Thoracocentesis, minimal pleurotomy or thoracoscopy in malignant pleural effusion

 David Achim, Natalia Motaş, Mihnea Davidescu, Corina Bluoss, Ovidiu Rus, Elena Jianu, Bogdan Tănase, Vlad Alexe, Alin Burlacu, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

 Neoplastic pleural effusion is always an indicator of advanced disease in the oncology patient. Its approach depends on the patient’s general condition and comorbidities, the need for a histopathological diagnosis (unexplained pleural metastasis, patients with multiple history of anaphylaxis), the clinician’s experience and the technical possibilities of diagnosis and treatment which the latter has at his disposal. The three therapeutic procedures discussed (thoracocentesis, pleural drainage and thoracoscopy) do not exclude one from another, but can be used either in succession (puncture after pleural drainage or thoracoscopy), or concomitantly (pleural drainage on one side and thoracoscopy on the other, when pleural effusion is bilateral). The present paper tries to bring to light the indications of the various therapeutic options in malignant pleural effusions, in relation to the advantages and disadvantages of each of the procedures, criteria that help us choose the most suitable variant for each patient.

Rare cause of cataclysmic upper gastrointestinal tract hemorrhage – generalized amyloidosis

 Vlad Alexe, Ion Timaru, Corina Bluoss, Costina Diaconu, Mădălina Gabriela Radu, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

 We present the case of a 37-year-old patient, whose suffering started 9 months prior to the admission to “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, when he was hospitalized in another hospital for melena, altered general state, weight loss, physical and mental asthenia, being discharged with the diagnosis of internal hemorrhoids, mild anemia, biliary lithiasis, renal lithiasis, and left adrenal cystic tumor. The persistence and accentuation of the symptoms caused the reinvestigation of the patient, after eight months, and referral to our clinic, with the aforementioned diagnostics. Continuous intense epigastric pain, bloating and feverish syndrome have triggered urgent patient evaluation to exclude an organ perforation. The CT examination raised the suspicion of acute cholecystitis, also revealing a gastric parietal stroke. Superior digestive endoscopy revealed a stenotic vegetative antral tumor. Surgical intervention was performed and cholecystitis gangrene, gastric tumor, multiple entero-mesenteric and duodenal-pancreatic tumor nodules were observed. After cholecystectomy, suddenly, the patient entered a hypovolemic shock. Under the suspicion of a gastric tumor haemorrhage, gastrostomy was performed, with the antral tumor massively bleeding. Haemostasis in situ was impossible. The patient entering in cardiac arrest, external cardiac massage was initiated, which was later converted to internal cardiac massage by left thoracotomy in the 5th intercostal space and pericardiotomy. The heart was restarted with difficulty, followed by repeated cardiac arrests and restarts. Hemorrhage control was possible only through total gastrectomy out of necessity, without the reconstruction of digestive tract continuity (guided eso­phageal fistula). Shortly after the transfer to Intensive Care, the patient entered the cardiac arrest again, and we weren’t able to resuscitate him. The etiological diagnosis was obtained following necropsy examination: generalized amyloidosis (amyloid deposits in the stomach, small intestine, liver, heart, vessels, kidneys, and lung). This case study aims to draw the attention to this rare disease, generalized amyloidosis, whose multiorganic impairment complicates early diagnosis, mimicking a gastrointestinal neoplasm, and whose severity cannot be appreciated and can suddenly evolve catastrophically. Generalized amyloidosis generally has an unfavourable prognosis in digestive affections. In the case of digestive haemorrhage, the mortality reaches 100%.

News and innovations in the treatment of gynaecological cancers

 Rodica Anghel

“Prof. dr. Al. Trestioreanu” Institute of Oncology, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest

 Gynaecological cancers are a major health problem, with more than 1.1 million new cases being diagnosed each year. Latest statistics show that neoplasm of the uterine body is the fourth cause of cancer, and ovarian cancer is the fifth cause of death among women. In surgery, major progress has been made in the last decade, minimally invasive interventions, and even operations using the da Vinci robot for cervical cancer, uterine and ovarian cancer proving to be as effective in terms of patient progress, but with less adverse effects, a shorter hospitalization, a lower quantity of blood being lost and a lower need for blood transfusion, and also a lower incidence of postoperative complications compared to classical surgery. Radiotherapy has also made significant progress by incorporating imaging (PET-CT and MRI) into the treatment plan, as well as by implementing new conformational 3D techniques. Intensity Modulated Radio Therapy (IMRT) and Image-Guided Radio Therapy (IGRT) improve dose distribution, tumor control and reduce toxicity to risk organs. Immunotherapy is a new and innovative way to eliminate the immunosuppression status that the tumour induces by interacting with immune cells of the body. Monoclonal antibodies against CTLA4 (ipilimumab) and anti-PD (nivolumab and pembrolizumab) as well as anti-PDL1 (atezolizumab, avelumab and durvalumab) are successfully tested for gynaecological cancers, with response rates around 25%. Importantly, we can identify a predictive biomarker to identify patients who will respond to these therapies. Anti-angiogenic therapy using monoclonal antibodies against VEGF has been shown to be highly effective in the treatment of ovarian cancer, where the interval to progression of the disease and overall survival increased in patients with increased risk factors, and in cervical cancer, where survival increased by almost 4 months. Also, PARP inhibitors are another category of targeted therapies that increase the time to disease progression in BRCA mutation. In conclusion, immunotherapy, new targeted therapies and the personalization of treatment with the implementation of minimally invasive surgery and new radiotherapy techniques improve the outcome of patients with genital cancers.

Debulking surgery in combination with intraperitoneal chemohyperthermia in ovarian neoplasms resistant to platinum-based chemotherapy

 Nicolae Bacalbaşa1,2, Irina Bălescu3, Ionuţ Dumitru Suciu4, Oana Toader1,4, Nicolae Suciu1,4

1. “Carol Davila” University of Medicine and Pharmacy, Bucharest

2. Center for Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest

3. Ponderas Academic Hospital, Bucharest

4. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

Once the benefit of debulking surgery has been de­mon­strated on a large scale in patients diagnosed with advanced regional or recurrent ovarian cancer, the researchers’ attention has been focused on maximizing this effect by introducing intraperitoneal chemo­hyperthermia. The method provides better cellular diffusion of chemotherapeutic agents, thus increasing the cytotoxic effect on all visible and microscopic lesions. This ensures more efficient local disease control, which leads to a decrease in the recurrence rate over time. The advantages of intraperitoneal chemotherapy were originally demonstrated in patients diagnosed with platinum-sensitive ovarian neoplasms. Later, however, it has been shown that the method can also play a role in patients diagnosed with refractory ovarian neoplasms or platinum-based chemotherapy. This is of particular importance given the limitation of therapeutic possibilities in such cases. The present paper discusses the main mechanisms of action and distant effects in the case of intraperitoneal chemohyperthermia in combination with debulking surgery in platinum-resistant cases.

The role of miRNA in the stratification of female patients with liver metastases of mammary origin

 Nicolae Bacalbaşa1,2, Irina Bălescu3, Andrei Voichiţoiu4, Lucian Pop4, Oana Toader1,4, Nicolae Suciu1,4

1. “Carol Davila” University of Medicine and Pharmacy, Bucharest

2. Center for Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest

3. Ponderas Academic Hospital, Bucharest

4. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

 Breast cancer is one of the most common gynecological neoplasms that can lead to the appearance of liver metastases, the occurrence of which is most often associated with an extremely poor long-term prognosis. However, recent advances in the stratification of female patients based on the risk of recurrence have successfully led to the implementation of personalized therapies, thus creating the premises for improving the remote prognosis of such cases. One of the most important parameters on which this stratification can be accomplished is the miRNA signature. Thus, if several years ago the most significant prognostic factors in such a case were related to the number of secondary liver determinations, their size, the degree of differentiation and the existence of other extrahepatic secondary determinations, it seems that the miRNA signature plays a defining role in prognosis, as well as in establishing the therapeutic strategy of such a patient. This paper aims to present the role of miRNA in the stratification of patients with liver metastases of mammary origin, depending on the risk of recurrence after liver resection.

High-dose rate brachytherapy in Kaposi sarcoma

Ancuţa Elena Baciu1,3, Lucia Elena Enciu1,3, Mădălina Croitoriu1, Gabriel Baranga1, Laurenţiu Busuioc1, Xenia Elena Bacinschi1,2

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

2. “Carol Davila” University of Medicine and Farmacy, Bucharest

3. Faculty of Physics, University of Bucharest

Kaposi sarcoma (SK) is a conjuctivo-vascular neoplasia with multifocal, systemic character and metastatic capability. The lesions are present in various stages: spot, wound and nodule. The affection is often found in the average-age adult, with an incidence of approximately 2-6 cases in one million individuals. The treatment consists of: radio-chemotherapy, high activity antiretroviral therapy, surgical or laser therapy. The evolution is variable, ranging from several skin lesions to extensive skin forms, but also internal damage. This study presents the case of a 63-year-old male. The patient was hospitalized and treated in the radiotherapy department. The patient presented lesions in the lower limbs. A total dose of 30 Gy was administered, with 3 Gy per fraction, two fractions per week. The device used was GammaMedPlus with Ir192 source. The duration of treatment was five weeks. Five applicators were inserted into the mold and loaded on different lengths (16-23.5 cm). The dose normalization was made at 0.7 cm. After significant wound irradiation, significant local improvements were observed. High-dose rate brachytherapy can be a good option in SK irradiation.

Comparative oncology – the basic model of the One Health concept structure

Emilia Balint, Sabin Cinca, Ana-Maria Coman, Nicolae Manolescu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

The authors present an overview of both historical data and current aspects of comparative oncology from the point of view of fundamental investigations and medical practice. Romania can be considered a true precursor to the One Health concept, because, both in 1937 and 1968, in Romania there were established the national and international foundations of comparative oncology (Radu Codreanu – 1937; Octavian Costăchel and Nicolae Manolescu – 1968). Once founded, comparative oncology studied human cancer in parallel with animal and plant cancer, all related to the existence in the environment of the biotic and abiotic oncoinductor factors. Thus, the One Health concept demonstrates the imperative necessity of a new medical way of thinking, through the reunion of the two medicines – the human medicine and the veterinary medicine –, together with more domains of activity which include the same notion of medicine, namely, the environmental medicine, alongside with the food and nutrition medicine, as well as the occupational medicine.

Anesthesia for rigid interventional bronchoscopy. The possibilities of the year 2018 in the “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Adriana Bene, Sorela Rădoi, Carmen Brânduşa Pantiş

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

 The interventions of tracheobronchial disobstruction by rigid bronchoscopy in the patient with neoplastic pathology located in the respiratory tract require a careful anesthetic and surgical assessment, balancing the risks and benefits that the procedure brings in the conditions of an often limited functional reserve. The large variability regarding the pathological field and, on the other hand, the complications that may occur during or after the procedure make it difficult to make anesthetic protocols for rigid interventional bronchoscopy. In the first part of the paper we present the data found in specialized literature regarding the evaluation, ventilation techniques, monitoring, used anesthetics, as well as indications, contraindications and periprocedural complications. Later, we will outline the technical anesthetic possibilities that we currently have at the institute, and we will discuss the perspectives offered and the limits that they impose, especially since the role of the Intensive Care physician in the immediate prevention, monitoring and sanctioning of possible complications is major. Thus, the interventions in the thoracic surgery operating unit, close monitoring of the patient, the administration of intravenous anesthesia, the adaptation of the ventilation technique to the respiratory status of the patient both during and after the end of the bronchoscopy, and the intensive care monitoring are essential for a good evolution of the case.

Modulation of chemotherapy response by resveratrol in human pharynx tumor cells

Marinela Bostan1, Georgiana Gabriela Petrică-Matei1,2, Viviana Roman1, Mirela Mihăilă1, Camelia Hotnog1, Lorelei Irina Braşoveanu1

1. Center of Immunology, “Ştefan S. Nicolau” Institute of Virology, Bucharest

2. Department of Cytogenetics, Personal genetics – Medical Genetics Center, Discipline of Medical Genetics, Bucharest

Malignant lesions arising in the pharynx are mainly asymptomatic initially, and then they are aggressive and frequently invade and migrate to distant organs, making them difficult to treat. Current treatment for pharynx cancer used a chemotherapeutic agent – cispla­tin (CisPt) – which induced some toxic effects at the renal and bone morrow level. However, it’s possible that cisplatin efficacy will be greatly increased in combination with natural phytoalexin resveratrol (RSV), with antineoplastic activities. We examined the morphological and functional changes in tumor cells when natural compound RSV is added to CisPt treatment of human pharyngeal carcinoma cell line (FaDu). Proliferation versus cytotoxicity induced by CisPt and/or RSV treatments in FaDu cells were studied using CellTiter 96 Non-Radioactive Cell Proliferation assay. Also, we investigated the effect of CisPt and/or RSV on p53 expression and apoptosis response in the Fadu cells. The apoptosis procceses were assessed by flow cytometry, using propidium iodide (PI) and Annexin V-FITC staining. In addition, we analyzed the role of p38 Mitogen-Activated Protein Kinase (p38MAPK) in the modulation of the response to CisPt and/or RSV treatments in FaDu cells. Moreover, we explored whether the activation of p38MAPK is associated with p53 phosphorylation status in FaDu cells, using SB203580 specific p38MAPK inhibitor. We investigated the phosphorylation status of p38 MAPK and p53 proteins by ELISA assays, using antibodies that recognize their dual forms (the active, phosphorylated and the total one). Data obtained after CisPt treatment showed its pro-apoptotic activity on FaDu cells, and RSV treatment induced an increased apoptosis in a manner dependent of concentration. Co-treatment of tumor cells with CisPt and RSV appeared to be most effective and was correlated with strong apoptosis activation. RSV enhanced the cytotoxic effect of CisPt in FaDu cells, having a synergic effect and the ability to promote p53 phosphorylation, suggesting a possible link between the p38MAPK and p53 activation pathways. In conclusion, the effects induced by RSV on FaDu cells seem to be due to the activation of different cellular and molecular mechanisms, which might encourage the use of this compound as a potential adjuvant to CisPt treatment.

Keywords: HNSCC, cisplatin, resveratrol, p38MAPK, p53, SB203580

Thoracic approach in hepato-biliary surgery

Alexandru Mihail Boţianu, Petre Vlah-Horea Boţianu, Olivia Batog, Adrian Cristian Dobrică, Alexandra Butiurcă

Surgical Clinic no. 2, Târgu-Mureş, Romania

The authors present a series of 18 consecutives cases operated in 28 years, between 1985 and 2013: eight cases of thoraco biliary hyidatid fistulae; one case of thoraco biliary lithiasic fistula; right pulmonary hydatid cysts + hydatid hepatic cyst – thoracotomy double Toty + right thoracophrenotomy (one case); left hydatid pulmonary cyst (left thoracotomy) + right pulmonary hydatid cyst + hepatic hydatid cyst (right thoracophrenotomy) – bilateral thoracotomy in the same session surgery (one case); left thoracic approach (two pacients): a) left pulmonary hydatid cyst (ideal Perez-Fontana-Bakulev cystectomy) + four hydatid hepatic cysts through left thoracophrenotomy including four hydatid hepatic cystectomies, tactical cholecystectomy and Halsted transcystic drainage b) left pulmonary hydatid cyst associated with hepatic hydatid cyst operated through left thoracophrenotomy; total post-traumatic hepato thorax through unknown diaphragmatic rupture and colesterolosis of the gallbladder operated by transthoracic way, intrathoracic cholecystectomy and polipropilen mesh phrenoplasty; three patients with right subphrenic abcesses operated previously using the abdominal approach which could not be utilised again; right thoraco-phreno-hepatic gunshot wound operated through right thoraco-phrenotomy. Every patient has a personal particular story. The advantages were: very good access for the postero-superior liver – good light; re-operation after the abdominal approach with abdominal parietal insuficienty and adherences; difficult lesions; shorter hopsitalization and economic benefits.

Left hemidiaphragm agenesis associated with agenesis of the second phalanx of the 5th finger and bilateral sindactily of second and third toe

Alexandru Mihail Boţianu, Petre Vlah-Horea Boţianu, Olivia Batog, Adrian Cristian Dobrică, Alexandra Butiurcă

Surgical Clinic no. 2, Târgu-Mureş, Romania

The authors present a new syndrom: left hemidiaphragm agenesis associated with agenesis of the second phalanx of the 5th finger and bilateral sindactily of second and third toe, resolved through phrenoplasty with collar mesh, in a 34-year-old pacient sent to our clinic after a thoracic trauma with suspicion of diaphragmatic lesion. The diaphragma has a very elevated “left hemidiaphragm”, with the stomach and the colon completly intrathoracic. Very good functional recovery.

Veterinary medical applications of photostimulated chemotherapy with methotrexate in the treatment of malignant solid tumours

V. Budascu, R. Fumărel, Adina Căluşaru

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Introduction. In photodynamic therapy (PDT), optical radiation is used in conjunction with certain photosensitizers to treat malignant solid tumors. More recent research show that, besides these photosensitizers (mostly, hematoporphyrin derivatives), certain chemotherapy commonly used in oncology practice have the structural capacity to generate singlet oxygen molecules or other free radicals under the action of light which has well determined parameters. This is the functioning principle of photo-stimulating cytostatic chemotherapy (PSChT). The objective of the research is to study the effects of the PSChT versus classical chemotherapy (ChT) on laboratory rats at clinical and cell levels. Materials and method. The experimental group consisted of male, isogenic Wistar rats. We used Walker 256 solid tumor, 0.9% saline methotrexate solution, 10-6 M concentration, and irradiation equipment having an optical source of 250 W mercury vapor lamp and the highest centered emission around the 365 nm line. Results. The animals’ average survival through conventional chemotherapy was 33 days, and the average survival of the animals treated with photo-stimulating chemotherapy was over 70 days, with complete tumor remission in 65% of them. In order to deepen the study, an animal that experienced a relapse after 30 days from the start of PSChT was sacrificed for necropsy and afterwards for histological examination, showing that the tumor was characterized as a neoplastic process with a solid pattern from poorly individualized cells outlined by a pseudo-capsule infiltrated with lymphocytes (neoplastic cells with malignant morphology, anisokaryosis, and anisocytosis).

Pulmonary resections adjusted by minimally invasive approach

Alin Burlacu, Bogdan Tănase, Natalia Motaş, Mihnea Davidescu, Corina Bluoss, Ovidiu Rus, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Minimally invasive thoracic surgery is a current approach to the surgical treatment of benign or malignant lesions of primary or secondary etiology, and a large number of patients may benefit from it, with oncological outcomes at least comparable to patients treated with classical surgery, but also a wide range of benefits, such as rapid social reintegration, the possibility of immediate post-operative oncological adjuvant treatment, the lack of algic post-thoraco­tomy syndrome, as well as aesthetic criteria. Also, assisted video thoracic surgery brings real benefits to patients with marginal pulmonary reserve who do not undergo pulmonary resection through thoracotomy (thoracotomy itself temporarily reduces respiratory functional reserve by about 25%), thus becoming eligible for curative treatment. In the treatment of benign or malignant lesions of primary or secondary etiology, it can be used the minimally invasive approach for non-anatomical resections with stapler or laser and for resected segments: segmentectomy, lobectomy, bilobectomy or pneumonectomy. In this paper we present the advantages of resection thoracic surgery adjusted by the minimally invasive approach, with examples of cases operated in our clinic, thus considering the minimally invasive thoracic surgery a method of approach which, by the benefits it offers, becomes a present surgery for the selected cases, without excluding the classical approach.

Multidisciplinary approach in synchronous colorectal cancers – oral presentation

Ciprian Cirimbei, Vlad Rotaru, Simona Cirimbei, Elena Chitoran, Mihnea Alecu, Oana Isac, Eugen Bratucu, Sorela Rădoi, Costina Diaconu, Monica Olaru, Adriana Bene, Elena Moisescu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Synchronous colorectal (CRC) cancers represent two or more neoplasms diagnosed at the colorectal level, simultaneously or in less than 6 months post-diagnosis of a first lesion, raising multiple diagnostic and therapeutic problems. Objectives. We decided to emphasize the particular aspects regarding the diagnosis, surgical strategy, evolution and monitoring of these patients with special forms of CRC. Method. Between January 2011 and December 2015, at the Surgical Oncology Clinic I from the “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, 521 patients with colorectal cancers were operated, out of which 21 cases (4.03%) presented synchronic lesions; twelve cases had rectal and colonic tumors, and nine cases had only colonic lesions. All cases presented two neoplastic lesions, the diagnosis of concomitant cancers being established preoperatively in 17 cases, based on the complementarity of colonoscopy and computer tomography. Results. The preoperative diagnosis was incomplete in four cases, due to the impossibility of pancolonoscopy – the presence of occlusive/subclusive syndromes (two cases) or the conformation of the colon (two cases). The diagnosis was established intraoperatively in three cases; in a single case with laparoscopic approach, the diagnosis was not established intraoperatively, but six months later, by colonoscopy. The therapeutic strategy consisted in an initial surgical approach in all cases, with the resection of colonic lesions; the rectal lesions were resected during the same intervention in eight cases, the other four cases requiring preoperative radiotherapy before the resection, performed in a second surgical time. Conclusions. The experience accumulated in these cases underlines the importance of complete colonoscopy. When colonoscopy cannot be performed, CT is not a loyal investigation, virtual colonoscopy completing the diagnosis effectively. Surgical tactics should be modeled in each case, depending on tumor location and the degree of extension, with the principle of colon resection, and then the surgery-radiotherapy balance to resolve the subsequent therapeutic steps for the concomitant rectal neoplasia. The presence or absence of neoplastic stenosis at one of the locations modifies radically the treatment sequence, surgery initially addressing the dominant, occlusive lesion.

The rodent model – a valuable tool for human cancer

Ana Maria Coman, Nicolae Manolescu, Daniela Frăţilă, Antonela Buşcă, Radu Fumărel, Valentin Budascu, Alexandra Dumitru, Marieta Elena Panait

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

For over a century, rodents (especially mice and rats) have substantially contributed for cancer research. Despite the significant differences, the similarities between humans and rodents were considered sufficient to investigate the mechanisms underlying the onset of malignancy and to discover improved methods to prevent, diagnose and treat this disease. Worldwide, the rodent models are used as experimental systems in a variety of potential therapies for different types of cancer, including: tiny nanoparticles that deliver toxins to ovarian cancer cells, vaccine to prevent breast cancer, or radiolabeled antibodies to tumor-specific antigens. Although precise dose and schemes cannot be directly extrapolated to humans, the mouse and rat models provide relevant conceptual information for clinical application. In this review, we summarize the importance of using rodent models in human cancer with focus on their advantages and limitations. Also, we present some of the important research studies of cancer therapies on rodents conducted over time in the Cancer Research Department from “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, including: nanoparticles which deliver drugs into cancer cells with minimum drug leakage into normal cells, radiolabeled peptides which bind to the receptors overexpressed by cancer cells, or phototherapy that delivers light which destroy the deep tumors.

Which must prevail: molecular target or tumor type?

Răzvan Curcă

Almost all of the new targeted therapy registrations in the last years are based on molecular target definition and tumor type. And all this registrations changed entirely the paradigm of treatment of many cancers, from the management of one frequent disease (e.g., lung cancer) to the therapy of many rare diseases defined by molecular biomarkers (e.g., EGFR-mutant non-small cell lung cancer, ALK-positive non-small cell lung cancer, ROS1-mutation non-small cell lung cancer etc). So, the molecular target increased in power, to change the therapy of certain cancers. But the experience of one molecular subtype of one cancer can be translated without a further scientifical investigation in another type of tumor carrying the same molcular aberration? We reviewed in our presentation the current management of HER-2 positive cancers, BRAF-mutant tumors, and also the new registrations of drugs which are tumor agnostic (irrespective of the tumor type, but carrying the same molecular aberration).

Minimally invasive laser-assisted pulmonary resections

Mihnea Davidescu, Natalia Motaş, Bogdan Tănase, David Achim, Alin Burlacu, Olivia Batog, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Laser technology has a well-established role in lung resections. The most well-known and used application is the resection of metastases with maximum preservation of pulmonary parenchyma, but also having other applications: pulmonary biopsies, typical and atypical resections, reconstruction of sciatica, haemostasis and others. Internationally, there is an obvious orientation in the thoracic surgery towards minimally invasive surgery due to its advantages: for the health system – low hospitalization, with cost reduction, and for the patient – reduction of postoperative pain, low morbidity, rapid recovery and aesthetic advantages. The use of free fiber allows the use of laser in the minimally invasive approach of thoracic pathology, and also in interventional bronchology. This paper presents our experience in minimally invasive use of the Nd: YAG Limax Laser in 14 patients out of the 156 patients with laser applications.

Late effects of treatment for childhood cancer require follow-up for the whole life

Monica Desiree Dragomir

Department of Pediatric Oncology, “Prof. Dr. Al. Trestioreanu” Institute of Oncology; “Carol Davila” University of Medicine and Pharmacy, Bucharest

The initial priority of oncologists was to cure. After the 1940s, multimodal treatment associations (surgery, radiotherapy, chemotherapy) were sought to achieve the longest survival rate on long-term periods. During the pioneering phase of multidisciplinary treatment, acute side effects have been studied in the short term. Integral therapeutic advances over the last 40 years have led to a spectacular increase in long-term survi­val. Currently, the survival rate in cancer cases is over 80%. There are currently around 300,000 childhood cancer survivors in Europe and they are estimated to be 500,000 in the year 2020. With the increase in the number of childhood cancer survivors, there were observed and studied the late effects due to either the disease by itself, or to oncological treatments. Late effects may be defined as any adverse reaction that does not disappear after the discontinuation of treatment or any new problem arising after the discontinuation of therapy. Many of these effects become evident with maturation (puberty), growth and normal aging. Approximately 60% of survivors accuse medical problems secondary to cancer. The spectrum of late effects is broad, including both organic functions (cardiac, pulmonary, renal, endocrine, gastrointestinal, visual/auditory), as well as somatic and psychological development (linear growth, skeletal maturation, intellectual function, emotional/social maturation, sexual development), fertility and reproduction. Monitoring childhood cancer survivors is necessary throughout their whole life. The late effects should be known by pediatricians and family doctors, who have the task of monitoring their treatment, as well as doctors of other specialties (endocrinology, ENT, cardiology, neurology, orthopedics etc.). Conclusion. The multidisciplinary approach of late effects in childhood cancer survivors is the premise of a life quality as close as possible to normality.

Software-aided multidisciplinary approach to cancer treatment. Part 1: Medical imaging

Iolanda Dumitrescu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Five main subjects aiming to assist the multidisciplinary approach to cancer treatment are presented: medical image enhancement, computer-aided detection of calcifications, computer-aided diagnosis of breast masses, computer-aided assessment (2D, 3D) of cancer treatment response and computer-aided radiation therapy. The image enhancement of the perceptual quality of X-ray images was issued by histogram equalization, intensity adjustment, a multiscale approach and retinex-based techniques. Computer-aided detection of calcifications was based on the fact that these lesions have higher mass attenuation coefficients than any other structure in the breast, so they appear as bright areas in the image. Two software techniques have been implemented: one based on local binary patterns and the other by quantizing a combination of a signal-suppressed and a signal-enhanced image. Computer-aided diagnosis of breast masses involves image processing and analysis. The features characterizing a mass were issued following the recommendations of the BI-RADS Atlas, namely shape, contour and textural features. The extraction of the mass features involves the collection and characterization of relevant normal and pathological cases. Each new case would be classified on a nearest neighbor basis in one of the classes assigned during the training step. Computer-aided assessment of 2D/3D changes in size and shape of the tumor burden during treatment implies image processing, analysis and quantization of structures achieved tomographically. Tracking the changes and assessing treatment response is done much more sensitively than by visual interpretation alone, evaluating tumor shrinkage (objective response) and disease progression as useful endpoints in clinical trials. Computer-aided radiation therapy may issue accurate segmentation of the tumor, imaging data correlation from different time moments during treatment, modeling isodose curves and surfaces. The developments in computerized image analysis have to improve the interpretation stage of the medical imaging exam. The output from a computer-aided analysis of medical images has to be used as a “second opinion” in detecting and characterizing lesions, as well as in making diagnostic decisions.

Software-aided multidisciplinary approach to cancer treatment. Part 2: Cancer statistics

Iolanda Dumitrescu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Statistical data on cancer worldwide, issued by the World Health Organization (WHO) and the In­ter­na­tio­nal Agency for Research on Cancer (IARC), for the last years available, have been examined. The estimated cancer incidence, mortality and prevalence have been analyzed considering the more and less developed regions of the world and the main WHO regions, for men, women and both sexes. The differences in age-standardized rates of cancer between the more and less developed regions of the world and worldwide, and also for the countries with the 50 highest rates have been considered, for men, women and both sexes. The WHO projections until 2030 of deaths by cancer in the whole world, in the European region and the Eastern Mediterranean region have been considered, including age and sex. For these regions, the places of the main forms of cancer deaths among the top 20 number of deaths by the leading causes of disease have been presented. For Romania, the statistical data issued by the World Health Organization and the International Agency for Research on Cancer have been analyzed. Data for cancer incidence and mortality as age standardized rates and as numbers, for men, women and both sexes, each for 10 age intervals and by considering the main cancer localizations, have been addressed. After analyzing the statistical data for cancer disease, the conclusion was that the burden of cancer is continuously rising, reaching alarming counts by 2035. In this view, the multidisciplinary approach to cancer treatment should be carefully considered.

HER2 – theranostic target in solid tumors

Mirela Dumitru, Antonela Buşcă, Marieta Elena Panait

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Theranostics (therapy + diagnostics) combines a diagnostic test with targeted therapy based on the test results. Overexpression of HER2 (human epidermal growth factor 2) in tumor cells is associated with more aggressive disease, poor prognosis and shorter overall survival in cancer. The development of HER2 targeted therapy has significantly improved the patients’ survival. The need to identify as accurately as possible the expression of HER2 both in the tumor and in the metastases, as well as the precise targeting of HER2-positive tumor cells led to the development of new compounds for the molecular imaging and HER2-directed therapy. In this study, there are discussed different approaches (experimental and clinic) that use the HER2 as a specific target for imaging and for anti-tumor therapies. Viewing the molecular image of HER2 increases the potential of linking the target identified with therapy, and thus the personalization of treatment. It also increases the potential for in vivo tissue characterization, improving prediction, prognostication and monitoring of the therapy. The application of anti-HER2 theranostic agents could lead to minimizing systemic toxicity and to the optimization of drug efficiency and safety.

Psychiatric-legal aspects in the oncological pathology

Cătălina Florescu

Psychiatry specialist, MD

The oncological patient is a fragile patient, both somatically and psychologically. As any medical approach, informed consent precedes any diagnostic or therapeutic intervention. The informed consent must meet the three basic characteristics set out in the CIOMS 2002 guide, i.e., to be given by a competent person who: 1) receives the information, 2) understands the information, 3) decides in the interest of his/her own person, without being subject to coercion of intimidation or in a state of vulnerability. The particularity of the oncological patient is that the oncological vulnerability is added to the disease response, generally seen as having a poor prognosis, represented by acute stress-response changes, depressive or anxious reactions, with or without psychotic changes etc. The psychiatric-legal issue refers precisely to the validity of the informed consent, beginning with the competence of the person and following the understanding of the information under the conditions of the changes of anxiety that limit this understanding. In the case of a psychotic reaction, the validity of the consent is virtually null. The other psychiatric-legal aspect refers to the delirium syndromes that appear postoperatively in intensive care services. The psychiatric assessment should specify the changes occurring in all psychic spheres, balancing the need for the establishing discernment, possibly only through the psychiatric-legal committee or the possibility of continuing the medical treatment, which can be delayed only with the risk of affecting the somatic state of the patient, ta­king into account the legislation and the ethical norms that must be respected all over the world. The fragile boundary between normality and abnormality in psychiatry, the possibility of periods with low or absent discernment (psychosis, delirium), alternating with periods of discernment, make it difficult to practice oncological psychiatry, which must be guided by the principle of benefit, of the patient’s wellbeing as a primary objective.

Keywords: psychic competence, informed consent, benefit

Monitoring and quantification of CTEC correlated with overexpression of PD-L1 in RI modulation

Daniela Frăţilă, Ana-Maria Coman, Nicolae Manolescu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

CTEC (Circulating Tumor Cells) is a predictive biomarker for the early detection of relapses. Aggressive tumors can release thousands of tumor cells in the circulation, but only a small proportion of these cells survive in the bloodstream. However, 0.01% of them can cause metastases. CTEC are isolated from peripheral blood, and disseminated from a primary or metastatic tumor. For a correct CTEC identification in peripheral blood, besides classical detection criteria (antibody-based detection, detection based on physical properties and PCR-based detection), other molecular detection criteria were considered, such as a positivity for certain surface antigens, a high rate of CTEC mutations being correlated with an increased number of modified proteins called neo­antigens, that are recognized by the immune system as non-self, allowing the triggering of an RI against them. Overexpression of PD-L1 – the transmembrane protein from the active immune cells (NK, CTEC, macrophages, dendritic cells) – can provide information from an early stage in a series of malignant tumors. CTEC mutation analysis in certain types of leukemia and Hodgkin’s lymphoma, where the PD-L1 protein is highly expressed, may serve as a model for a subsequent target therapy to monitor the immune response to therapy.

Geriatric assessment of cancer patient – part of treatment decision

Laurenţia Galeş, Oana Trifănescu, Xenia Bacinschi, Rodica Anghel

Most newly diagnosed cancers occur in older adults, and it’s important to understand the patient’s underlying health status when making treatment decisions. The treatment decisions in older patients with cancer can be challenging, as other co-morbidities may limit life expectancy and the ability to tolerate the oncologic treatments. Because the biological age often does not correspond to the chronological age, it is difficult to define the chronological age above which a geriatric assessment should be done systematically. Given the time and resource barriers that are associated with geriatric asses­sment, the use of a geriatric screening tool to identify frail and/or vulnerable patients who are most likely to benefit from a geriatric assessment is appealing. Although the time commitment and burden on patients and caregivers are concerns, recently developed cancer-specific geriatric assessment tools can gather a wealth of information in a relatively short amount of time. Geriatric assessment should be performed in older patients with cancer for multiple reasons. First, it has been shown that geriatric assessment can identify areas of vulnerability that may otherwise be missed in routine oncology visits. Secondly, geriatric assessment can predict survival and adverse events of treatment to assist clinical decision making. Thirdly, geriatric assessment identifies areas where interventions can be performed, which can help patients tolerate and complete the prescribed therapy. A geriatric assessment includes an assessment of several domains such as functional status, psychological health, polypharmacy, comorbidity, nutrition, social support and cognition. The assessment includes tests that are grouped into three categories: tests examining general physical health, tests measuring ability to perform basic self care (ADLs – activity of daily living), tests measuring the ability to perform more complex activities (IADLs – instrumental activity of daily living), reflecting the ability to live independently in the community. The severity of the disability may be measured in terms of whether a person: does not perform the activity at all; can only perform the activity with the help of another person, or he can perform the activity with the help of a special equipment. All oncologists should strive to include some form of geriatric assessment in their everyday clinical practice. We believe that it is not only feasible, but necessary to provide older patients with high-quality cancer care. In summary, understanding the health status of an older adult is just as important as understanding the underlying tumor biology. Ideally, all older patients who are being considered for cancer treatments should receive a geriatric assessment as part of their evaluation.

Tumor markers utility and prognostic relevance of cathepsin D and sialic acid in Walker 256 carcinosarcoma and breast carcinoma

Daniela Glăvan, Maria Iuliana Gruia, Valentina Negoiţă

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Because cancer is a disease with global importance, it becomes imperative to find new therapeutic targets or new molecules with therapeutic potential for tumors. Tumor cells produce and release several proteolytic enzymes, which are involved in tumor invasion and metastasis. A lot of solid tumors have been reported to have increased levels of proteolytic enzymes in cancer tissue, strongly suggesting that proteases may be important in tumor progressions. Lysosomal proteinase and cathepsin D have been implicated in the progression of several human tumors. The majority of serum proteins are glycosylated, and elevated sialic acid in glycoproteins has been described in malignant cells and studies suggest that sialic acid may be a useful tumor biomarker. An investigation of the total serum sialic acid levels and cathepsin D in rats bearing Walker 256 carcinosarcoma and breast carcinoma patients versus control healthy individuals reported a positive corelation between stage of cancer, metastasis grade and poor prognosis. These markers with other clinical and biochemical criteria may play an important metabolic role in tumor progression.

Stages for the sanitary-veterinary authorization of the Breed, Supply and Use Unit for the scientific usage of animals at “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

I. Gruia, A. Căluşaru, V. Negoiţă

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

The use of animals for experimental purposes is a concept that has been and continues to retain the attention of society, often sparking disputes generated by the extent to which the ethical and moral requirements are met in this field. The need to authorize the Breed, Supply and Use Unit (bio-base) emerges as a major change in the field of laboratory animals’ science, based on the enforcement of Law 43/2014 and of the President Order of the National Sanitary-Veterinary Authority for Animal Safety (ANSVSA). These legal regulations are transposed from the EU Directive 2010/63/EU and entitle the following: projects involving the use of animals in procedures may only be carried out within a sanitary-veterinary unit authorized by the Veterinary Directorate. For running the projects, it is mandatory to receive a favorable resolution both from the Ethics Commission for evaluating projects that use animals to scientific purposes and from the Sanitary-Veterinary and Food Safety County Directorate/Bucharest Municipality Directorate.

Effects of quercetin on experimental cancer in rats following oxidant/antioxidant balance

Maria Iuliana Gruia, Valentina Negoiţă, Marieta Panait, Monica Vasilescu, Daniela Glăvan, Şerban Marinescu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Various types of antioxidant compounds are active against reactive oxygen species produced during metabolism and reduce oxidative damage of DNA, proteins, amino acids, and lipids. Quercetin is a type of polyphenol and a renowned antioxidant that effectively prevents cancer by removing free radicals. In this paper we try to demonstrate in vivo the biological action of quercetine and highlight the role of the concentration and the time of the administration of this compound to keep the antioxidant/pro-oxidant balance, the latter being responsible for the toxicity of the investigated flavonoid. For this purpose, there were used as experimental animals Wistar rats bearing tumors (Walker carcinoma and RS-hepatoma) treated three times a week with 50 mg/kg body of quercetine in DMSO at 7 and 21 days respectively from the tumoral graft, for three weeks. We investigated biochemical parameters of serum oxidative stress (lipid peroxides, copper-oxidative activity of ceruloplasmin, albumin thiol groups and the ability of serum to reduce iron) in dynamics of treatment. Also, in tissue sample with flow cytometry analysis we follow the S-phase fraction, proliferative index, and DNA index. All treated groups revealed some therapeutic benefits in contrast with controls, consisting in loss of aneuploid population, decrease of DNA synthesis to the normal rate and accumulation of cells into G1 phase. The obtained results indicate an antioxidant action of the compound in the first week of the treatment, followed by a number of side effects that led to the death of the animal along with the extension of the treatment. The antioxidant capability of quercetine strongly depends on the intracellular availability of GSH. Thus, the capability of quercetine to induce apoptosis in cancer cells undoubtedly renders this molecule an interesting tool in the oncology field. Any compound that attends oxide-reduction metabolic reactions may come from an antioxidant to a pro-aggressive oxidizer when is outdated and time scales in the optimum necessary treatment.

Characterization of angiogenic profile in colon cancer cells with different p53 mutational status by microarray technique

Camelia Mia Hotnog, Mirela Mihăilă, Marinela Bostan, Lorelei Irina Braşoveanu

“Ştefan S. Nicolau” Institute of Virology, Center of Immunology, Bucharest

A critical aspect of tumor progression is the ability of tumor cells to switch on the angiogenic phenotype. Tumor angiogenesis process is a result of pro- and antiangiogenic factors ratio, tumor cell invasion and metastasis being promoted by the up-regulation of angiogenic factors, such as vascular endothelial growth factor (VEGF). Angiogenesis may be regulated by the function of TP53 gene: the wild-type form of TP53 gene induces the down-regulation of angiogenic factor expression, whereas a dysfunctional mutated p53 stimulates angiogenesis by up-regulating VEGF. In the recent years, significant progress has been made in finding antiangiogenic strategies for tumor therapy. Recent studies focused on the discovery of new biological agents, since many natural compounds displayed anticarcinogenic and antiproliferative effects towards colon cancer cells, and might increase the effect of chemotherapy. Among them, resveratrol (Rsv) and curcumin (Crm) were reported to be used as additives in colon cancer prevention and treatments. In the present study, we investigated the effect of added bioactive compounds (like Rsv, Crm or Gst) to anti-cancer drugs on protein expression of molecules related to angiogenesis in LoVo (wild-type p53) and HT-29 (mutated p53) colon cancer cell lines. The cells were treated with 25 uM 5-FU or 50 uM Rsv, Crm or Gst; after 24 hours, the cells were processed to obtain cell lysates and total protein amount was quantified. The relative protein expression was determined by protein microarray technique, using RayBio® Human Angiogenesis Antibody Array kit. The obtained results showed a differential expression of angiogenic markers in treated versus untreated colon cell lines under study, depending also on their p53 mutational status.

Hypoxia and cervical cancer

Iulia V. Iancu1, Anca Botezatu1, Adriana Pleşa1, Demetra Socolov2, Irina Huică1, Alina Fudulu1, Adrian Albulescu1, Gabriela Anton1

1. “Ştefan S. Nicolau” Institute of Virology, Bucharest

2. “Gr. T. Popa” University of Medicine and Pharmacy, Iaşi

Background. It has now been established that in tumors progression, aggressiveness and resistance to treatment, an important role is played by cellular hypoxia. Low oxygen levels have been detected in numerous types of malignancies, including cervical cancer, where there were associated with tumor invasion and aggressiveness. The present study aims to investigate the expression levels of hypoxia inducible factors (HIF1, HIF2A and HIF3A) in cervical carcinoma as potential biomarkers of such tumors. Method. The study group consisted of 29 specimens with squamous cell carcinoma (SCC) (21-48 years old, median: 38.5 years old). Also, as controls, there were included 20 patients with negative cytology (NILM) and negative for HPV infection. From cervical samples, total RNA was isolated using TRIzol reagent and hypoxia-related genes expression levels were estimated by qRT-PCR. Results. The data obtained show high levels for all three hypoxia genes in cervical samples compared with the control group. The best results were noticed for HIF1 (mean n-fold: 0.85; p=0.043) and HIF2A (mean n-fold: 1.825; p=0.0062). Moreover, it was observed that for SCC patients, HIF2A levels were associated significantly with tumour metastasis (p=0.025) and FIGO stage (p= 0.039). Conclusions. Our results show an important role for hypoxia inducible factors in cervical cancer and emphasize their potential to investigate tumor invasion and aggressiveness.

Acknowledgements: Project POS-CCE O2.2.1. 433/ 2012 and Romanian Academy funding.

Brachytherapy as a new therapeutic standard in prostate cancer

Gabriel Kacsó1,2, Cătălin Iacob2, Noemi Schultes2, Dan Dordai2

1. “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca

2. Amethyst Clinic, Cluj-Napoca

Recent randomized trials have validated the superiority of brachytherapy as a dose complement (boost) associated to external radiation radiotherapy (RTE) compared to exclusive TTE in prostate cancer with intermediate D’Amico risk or increased relapse. Numerous non-randomized prospective studies, as well as a vast, retrospective post-treatment follow-up experience of 10-20 years attest the BT equivalence to radical surgery or RTE as monotherapy in the D’Amico low-risk group regarding relapse, but with a favorable toxicity for surgery, particularly in relation to the more imminent risk of urinary incontinence or impotence. Therefore, all major therapeutic guidelines (NCCN, EAU, ESMO) included in 2018 brachytherapy as a standard option in all cases of non-metastatic prostate cancer. With more than 400 brachytherapy implants in the past 10 years, both LDR (permanent, with Iodine 125) or HDR (temporarily, with Iridium 192), our team has continuously improved its expertise in this field by offering this cutting-edge technology in Romania.

Vascular proximity in retroperitoneal tumor surgery

Angela Mădălina Lazăr, Eugen Bratucu, Claudiu Daha

“Carol Davila” University of Medicine and Pharmacy, Bucharest; “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, First Surgical Clinic

Currently, the only treatment of curative intent in retroperitoneal tumor surgery is represented by radical/supraradical surgery, that is however extremely difficult to technically achieve. The evolving features of retroperitoneal tumors with a frequent involvement of important vascular structures impose limits to the surgical act, associating formidable risks and complications. The target of the current study was the identification of superior defining methods for the relationships between the tumor and main vascular structures, with the analysis of its significance for the prognosis and therapeutic response of retroperitoneal neoplasias. Patients and method. This study was conducted on a group of 160 patients operated for different histopathologic types of retroperitoneal tumors in “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, First Surgical Clinic. The medical imaging, the operative and histopathologic data were reviewed, with 3D reconstructions of the tumor and its relationships to blood vessels whenever necessary. The effect of the vascular proximity and type of vascular involvement on surgical results, the tendency to tumor recurrence and response to adjuvant therapies were studied. Results. Vascular involvement represented the main limiting factor to radical surgery. Vascular engulfment/compression by the tumor, even though surgically surpassed, was associated with a higher risk of local tumor recurrence, but not with distant metastases. Tumor vascular involvement did not represent an independent negative prognostic factor, but an indirect one, decreasing surgical radicalness. Conclusion. Retroperitoneal neoplasias frequently involve important vascular structures that determined the complexity of the surgical act and a limitation to surgical radicalness. The direct relation and the pronounced proximity between the tumor and blood vessels can be efficiently evidenced by 3D medical imaging reconstructions that will guide the type of surgical approach or even the decision to apply neoadjuvant therapies. The pronounced tendency towards locoregional recurrence of the tumors that have been dissected directly off the blood vessels should lead to a careful long-time follow-up.

The significance of retroperitoneal tumor grading

Angela Mădălina Lazăr, Eugen Bratucu, Claudiu Daha

“Carol Davila” University of Medicine and Pharmacy, Bucharest; “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, First Surgical Clinic

Knowledge on retroperitoneal tumor biology still remains in a cone of discouraging obscurity. Excepting the impact of radical surgery on patient prognosis, there is a lack of consensus regarding other prognostic factors for these tumors, useful in deciding the therapeutic approach and the delivery of adjuvant treatments. The aim of the present study consisted in the analysis of retroperitoneal tumor grade significance for the therapeutic act and overall prognostic of the patient, as there are only a few studies regarding this aspect. Patients and method. The present work was conducted on a group of 160 patients operated for various types of retroperitoneal tumors in “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, First Surgical Clinic, during a pe­riod of 16 years. We carefully analyzed the histopathologic reports and studied the impact of tumor grade on tumor characteristics of development, surgical approach and patient overall prognostic. Results. An accurate definition of tumor histopathologic grade depends on the type of surgery. Only radical surgery provided an adequate tumor specimen for the determination of tumor grade. A non-determined histopathologic grade was significantly associated to non-radical surgical interventions and represented a negative prognostic factor in survival analysis. Conclusion. Usually, the histopathologic type of a tumor has a major impact on tumor progression and patient response to therapies. However, in the case of retroperitoneal tumors, the histopathologic grading seems to require a different definition or it holds a smaller significance for the patient and the therapeutic approach. Still, a poorly differentiated/undetermined grading for retroperitoneal tumors is usually not detected in surgically curative stages and the definition of the best type of adjuvant therapeutic protocol should be updated.

Primary HPV testing in the setting of routine cervical cancer screening

Johanna Mäenpää1,2, Olga Veijalainen2, Saara Kujala3, Paula Kujala3

1. Department of Obstetrics and Gynecology, Tampere University Hospital, Finland

2. Faculty of Medicine and Life Sciences2, University of Tampere, Finland

3. Fimlab Laboratories Ltd., Tampere, Finland

Introduction. The aim of the study was to evaluate the performance of HPV-based screening as compared to conventional cytology in the framework of routine cervical cancer screening. Materials and method. 46,708 women, aged 35-60 years old, participated in the regional cervical cancer screening program of the city of Tampere and its surroundings in 2012-2014. The screening method used in Tampere was Abbot RealTime HPV test with cytology triage, while in the surroundings, conventional cytology was used. All women with LSIL or worse cytology were referred to colposcopy, while women with either borderline cytology or hrHPV+ and normal or borderline cytology were invited to a reflex screening in the following year. All other women were referred to the next screening round after five years. Results. The attendance rate was similar in both goups (72% and 71%). The detection rates of CIN 2+ and 3+ were greater in the HPV than in the PAP group during the index screening years (2012-2014), or 3.2/1000 and 2.3/100 versus 1.9/1000 and 1.1/1000, and in the reflex re-screening years (2013-2015), 4.4/1000 and 2.4/100 versus 1.2/1000 versus 0.6/100, respectively, with the total outcomes of 7.5/1000 and 4.7/1000 versus 3.1/1000 and 1.7/1000, respectively (p<0.0001). Due to a high persistence rate of HPV infection, the total colposcopy rate was higher in the HPV than in the PAP group, or 43.8/1000 and 18.4/1000 (p<0.0001), respectively. Conclusion. Primary hrHPV testing with cytology triage is more sensitive than conventional cytology in the routine screening of precursors for cervical cancer. However, HPV testing is associated with greater colposcopy rate in the reflex screening round.

Robotic-assisted laparoscopic surgery in gynecological oncology

Johanna Mäenpää1,2, Minna Mäenpää1

1. Department of Obstetrics and Gynecology, Tampere University Hospital, Finland

2. Faculty of Medicine and Life Sciences, University of Tampere, Finland

Robotic-assisted gynecological laparoscopic surgery was approved for medical use by FDA in 2005, and has quickly become more widely used globally ever since. In Finland, the first gynecological robotic-assisted surgery was performed in 2009 at Tampere University Hospital. The aim of Dr. Minna Mäenpää’s Thesis (2018) was to explore the practicality of the implementation of robotic-assisted surgery and its suitability for gynecological surgery. The first retrospective study consisted of the first 300 robotic-assisted laparoscopic surgeries in chronological order. Out of these, 81% were performed due to gynecological cancer (mainly endometrial cancer) and 19% due to benign indications. In operations for endometrial cancer, the learning curve for robotic-assisted surgery was short, approximately 10 operations. In addition to shortening of the operation time, more lymph nodes were removed after the learning curve. Preparation of the operating room was also found to be faster, and operating room time shortened significantly already after the first months. A randomized, prospective study was started, at the end of 2010, and the recruitment was complete in the fall of 2013. One hundred and one patients with endometrial cancer scheduled for surgery were randomized into two groups: robotic-assisted and traditional laparoscopic operation. The median operation time was 139 minutes (range: 86-197 minutes) in the robotic group (n=50), and 170 minutes (range: 126-259 minutes) in the traditional laparoscopy group (n=49) (p<0.001). No conversions to open surgery were made in the robotic group, but there were five conversions in the traditional group. In the robotic group, there were fewer intraoperative complications and more postoperative complications. The costs of both surgical techniques and complications during the 6-month follow-up period were examined. The total costs of surgical treatment were 1,928 euro, higher in the robotic-assisted group (median costs of traditional laparoscopy: 5,487 euro, versus median costs in robotic-assisted laparoscopy: 7,415 euro; p<0.001). The cost difference is mainly explained by more expensive instruments and devices used in robotic-assisted surgery, as well as more expensive operating room time and monitoring in the recovery room. The success rate of paraaortic lymphadenectomy using the robotic-assisted technique was studied using 7-year retrospective material on patients with gynecological cancer. Paraaortic lymphadenectomy succeeded in 83% (235/283) of operations to a high level; the area below the left renal vein and above the inferior mesenteric artery (IMA). The number of removed lymph nodes increased in the paraaortic area, as the surgeon performed more operations, and a learning curve was evident. In conclusion, robotic-assisted laparoscopic surgery is very suitable for the surgical treatment of patients with gynecological cancer. The relatively high costs can be balanced against successful challenging operations. The implementation of robotic-assisted surgery has been smooth, and the operations have been effective and safe to perform.

Sentinel lymph node in vulvar and ovarian cancers

Johanna Mäenpää1,2, Reita Nyberg1

1. Department of Obstetrics and Gynecology, Tampere University Hospital, Finland

2. Faculty of Medicine and Life Sciences, University of Tampere, Finland

The sentinel lymph node (SLN) method is widely used in melanoma and breast cancer. Among gynecological malignancies, vulvar cancer was the first cancer for which the method was used. At present, cervical and endometrial cancer are the most potential new indications for SLN. We have studied SLN for vulvar and ovarian cancer in the Thesis of Dr. Reita Nyberg (2017). In 2001-2004, the SLN method was adopted for the assessment of vulvar cancer at the Tampere University Hospital. The SLNs of 47 patients, regardless of clinical stage, were located with blue dye and radiocolloid injections and dissected separately for analysis, and a complete lymph node dissection was performed. In early stage vulvar cancer, the detection rate with the combined method (dye and radiocolloid) was 100%, and there were no false negative SLNs. Thus, the SLN method accurately predicted the nodal stage of patients with early vulvar cancer. In the next stage, the paraffin blocks of samples from the same vulvar tumors were used for evaluating associations between lymphangiogenesis, SLN metastasis, surgical stage and clinical course of the disease. Forty-four tumor samples and 17 metastatic SLNs were available for retrospective immunohistochemical analysis. 67% of the malignant vulvar tumors expressed vascular endothelial growth factor C (VEGF-C) in their invasive edges. This expression was also seen in 76% of SLN metastases. Positive tumoral VEGF-C expression did not significantly associate with higher surgical stage, the presence of SLN metastasis, higher recurrence rate or poorer prognosis, although some trends were observed. Negative VEGF-C expression in SLN metastases might serve as an indicator of metastasis-free non-SLN. The second objective of the thesis was to establish a SLN technique for the intraoperative use in ovarian cancer. Sixteen women with high-risk endometrial cancer and scheduled for laparotomy were enrolled in a prospective pilot study. Blue dye and radiocolloid were injected into a healthy ovary at the beginning of laparotomy. After removal of uterus and adnexa, the blue and hot SLNs were mapped during lymph node dissections (LND). In 94% of patients, 1-3 SLNs were detected with the combined method. All SLNs were located in the paraaortic area; those related to the left ovary were mostly (64%) detected above the inferior mesenteric artery (IMA), whereas almost all right-ovary-related SLNs (94%) were located under the IMA level (p=0.001). The pilot study confirmed that it is feasible to use conventional tracers intraoperatively for the mapping of ovarian SLN and a feasibility study followed, conducted in 20 patients with ovarian tumors. At the beginning of each operation, blue dye and radiocolloid were injected next to the ovarian mass into the mesovarium. If the mass was benign and radical surgery was not required, the SLNs were mapped transperitonally. When LND was performed, all SLNs were mapped and removed separately for analysis after opening of the retroperitoneum. The final histopathology of the SLNs and non-SLNs were compared. The SLN detection rate with the combined method was 100%, and 1-3 SLNs per patient were detected. Most of the SLNs (90%) were located in the paraaortic area; in 60% of the cases no SLNs were detected in other regions, and in 30% there were also pelvic SLNs. Isolated pelvic SLNs were rare (10%). In three women, LND was indicated due to the early ovarian cancer. One patient had nodal metastasis, and a positive SLN predicted correctly her nodal stage. SLN concept deserves further investigation in relation to the surgical treatment of early ovarian cancer.

PET-positive latero-cervical lesion in an oncological patient – multimodal treated mammary neoplasm

Veronica Manolache, Ovidiu Rus, Ioan Timaru, Mădălina Iliescu, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest 

We present the case of a 61-year-old patient with left-handed left mammary neoplasm, who received polychemo­therapy following primary tumor resection and which, following subsequent investigations, is found with a left cervical tumor. The PET-CT examination reveals that the left, metabolic active supraclavicular adenopathy with SUV 3.11 is unique. Surgical intervention was performed and a thrombosed vascular formation was revealed in the left outer jugular vein, which was excised. Postoperatively, the patient’s progression was favorable, without complications, with good overall condition. The histopathological examination specifies the diagnosis of thrombosis of the external jugular vein. The case is oncologically instructive: not any positive PET damage is automatically a malignant primitive tumor metastasis or another malignant tumor. In this situation, surgical consultation is required, followed by the surgical intervention, excision of the positive PET formation and histopathological examination. The diagnosis of vascular tumor was an intraoperative surprise, and the tumor proved to be a thrombosed hemangioma. The farmacon was captured due to the aseptic inflammatory process of the hemangioma. Thrombosed hemangiomas of the external jugular vein are rare vascular malformations with positive and differential diagnosis problems.

The importance of nutritional factor in postoperative fistula in patients with gastric cancer

Augustin Marian Marincaş, Virgiliu Mihail Prunoiu, Claudiu Daha, Ciprian Cirimbei, Sânziana Ionescu, Carmen Pantiş, Adriana Bene, Eugen Bratucu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

In patients with gastric cancer, the risk of postoperative complications is increased, due to malnutrition and protein deficit and to the long-term preoperative anaemia. Aim. The authors wish to analyze the impact of the preoperative nutritional nursing on the postoperative evolution, regarding both the appearance of postoperative fistula and the costs. Materials and method. We made a retrospective analysis of a batch formed out of 158 patients treated surgically in the First Clinic of Digestive and Oncologic Surgery from the “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, in the past six years. Results. The overall incidence of fistulas was 11.36%, out of which 8.22% were duodenal duct fistulas and 3.19% were eso-jejunal anastomosis fistulae. Out of the 30 patients with weight loss and pre- and postoperative parenteral nutrition, four patients made the fistula (13%). Out of the 36 patients with weight loss and parenteral nutrition only postoperatively, five patients made the fistula (13.88%). Out of 24 patients with weight loss and without nutritional therapy, five patients made the fistula (20.84%). Out of the 68 pacients without weight loss, four patients made the fistula (5.88%). The average cost was three times higher in patients with fistula. Conclusions. We appreciate that the preoperative nutritional nursing of the patients with gastric cancer is very necessary and it must be the consequence of the cooperation between the surgeon and the ICU specialist, regarding the improvement of the biologic parameters. The abrupt surgical intervention, apart from an emergency, in a patient without any assessment of the nutritional needs, may cause an important prejudice and increase the rate of specific complications.

Keywords: gastric cancer, preoperative nutritional balance, fistula

Gastric lesions of neoplastic etiology – problems of diagnosis and therapeutic approach

A.M. Marincaş, G.D. Subţirelu, V.M. Prunoiu, Sânziana Ionescu, E. Bratucu

First Department of General and Oncologic Surgery, “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

We present three cases of gastric lesions of neoplastic etiology, which have as a common denominator gastric ulceration and other bizarre gastric lesions, which have posed us particular problems of diagnosis and therapeutic attitude. Although patients were investigated according to current standards and benefited from endoscopy with biopsy, computer tomo­graphy and endoscopic ultrasonography in selected cases, the diagnosis could only be specified on the gastric specimen and, in some cases, the certainty of diagnosis, as well as the severity of the lesions could be determined only by the immunohystochemical examination. The main methods of preoperative evaluation are appreciated and the therapeutic approach and its support under the conditions of the morphopathological diagnosis uncertainty are discussed. We present these cases underlying the difficulty of the surgical decision despite the progress of the investigative means, and the decisive importance of interdisciplinary collaboration.

Keywords: gastric ulcer, primary gastric lymphoma, preoperative endoscopy, gastrectomy

The influence of micro-media on the glioblastoma cells features

Lilia Matei1, Corina Dinică1, Laura Denisa Dragu1, Felix Brehar2, Laura Georgiana Necula1, Mihaela Economescu1, Carmen Cristina Diaconu1, Coralia Bleotu1

1. “Ştefan S. Nicolau” Institute of Virology, Bucharest

2. “Bagdasar-Arseni” Emergency Clinical Hospital, Bucharest

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor, for which an effective pharmacotherapy remains unavailable. Several targeted therapies and chemotherapeutic agents have failed to increase survival or enhance patient outcomes in GBM. In order to understand this pathology, the aim of our study was to evaluate the influence induced by different micro-media on the expression of some biomarkers as fundamental aspects of niche influence on cells fate. Materials and method. The cell lines were obtained from glioblastoma multiforme through mechanically dissociation and maintenance in two different media: DMEM supplemented with epidermal growth factor (EGF), B27, and N2 (STON-BEN line), or DMEM supplemented with fetal bovine serum (FBS) (STONa line). On DMEM supplemented with EGF, B27 and N2, STON formed neurospheres, while in the presence of serum, the cells became adherent, forming monolayer. The specific characteristics of cells cultured in different media were evaluated using Protein Profiler Array and real time PCR. Results. In STON-BEN, the line that, accordingly to our previously in vivo studies, has a high metastatic potential and produce very aggressive tumors, the anti-angiogenic ADAMTS-1 protein was less expressed, whereas its antagonist, the pro-angiogenic protein TIMP, presented a very high level of expression. Also, in BEN culture media, higher levels of angiogenin (an activator of genes that inhibit apoptosis, supporting the tumor process by proliferation, invasion and migration) and vascular endothelial growth factor (VEGF; a great stimulator of vasculogenesis and angiogenesis) were observed, as well as PDGF-AA, insulin-like growth factor-binding protein (IGFBP) etc. On the other hand, STONa line showed slightly increased levels of endotelin-1, trombospondin-1, endoglin CD105, angiopoietin, endostatin etc. Conclusions. Our results demonstrate that niche microenvironment influenced the cell fate and complicated signaling paths, and the multitude of processes occur simultaneously in the tumor cells. Some established biomarkers could represent potential targets for a more effective treatment of aggressive forms, but further studies are needed.

Acknowledgements: This work was supported by CNCSIS-UEFISCSU project PCCDI III-116 BG/2016 and structural funds POS CCE O2.2.1.433/2012.

Treatment of advanced NSCLC with actionable mutations

Laura Mazilu

Constanţa Clinical Emergency Hospital, “Ovidius“ University of Constanţa, Romania

Lung cancer is one of the most common cancers and a leading cause of cancer deaths worldwide. 85% of lung cancer cases are non-small cell lung cancer (NSCLC). The standard of care (SoC) for stage IV NSCLC is systemic therapy. Biomarkers divide NSCLC into three groups: patients with molecularly defined actionable targets, PD-L1-defined immunosensitive populations, and patients without actionable biomarker targets. For most of the patients, histology still guides the therapeutic choice. For patients with stage IV NSCLC and adenocarcinoma component, molecular testing is the standard of care. All non-squamous NSCLC should be tested for EGFR and BRAF V600E mutations, ALK and ROS1 rearrangements. Testing for a broader array of mutations with next-generation sequencing (NGS) should be considered. For newly diagnosed EGFR-mutant NSCLC, treatment with an EGFR TKI is SoC. EGFR sensitizing mutations predict higher response rate, better progression-free survival (PFS) and better quality of life (QoL) if pacients are treated with EGFR TKI in first line. Post-progression biopsy is critical to establish the mechanism of resistance, and liquid biopsy for the detection of EGFR T790M is an option. Osimertinib is approved for patients with EGFR T790M-positive disease. ALK rearrangements predict higher overall response rate (ORR) and PFS if patients are treated with ALK TKI in first line. Next-generation ALK inhibitors are active in central nervous system (CNS) disease. For ALK-mutant NSCLC, many patients may benefit from sequential use of ALK inhibitors; however, the most effective sequencing strategy remains to be determined.

Ruthenium (III) compounds as potential therapeutic agents in human colorectal cancer

Mirela Mihăilă1, Camelia Hotnog1, Viviana Roman1, Marinela Bostan1, Valentina Uivarosi2, Lorelei I. Braşoveanu1

1. “Ştefan S. Nicolau” Institute of Virology, Bucharest, Center of Immunology, Romanian Academy, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Department of General and Inorganic Chemistry, Bucharest

Colorectal cancer is the third of the most common human cancers in the world, and involves genetic alterations, aberrant progression of the cell cycle, resistance to growth inhibition, evasion of apoptosis, induction of angiogenesis and modification of cell adhesion. Platinum compounds are effective anticancer agents used to treat colon cancer, but the resistance developed represents an obstacle against the full success of chemotherapy. Therefore, our study focused on characterization of ruthenium (RuIII) compounds with co-solvents that might be taken into account as alternative anticancer agents. Drug-mediated cytotoxity levels of novel ruthenium (III) complexes with co-solvents were tested in LoVo human colon cancer cell line as compared to CisPt and OxlPt by using end-point MTS colorimetric assay or the real-time cell analysis (RTCA) by xCELLigence System that continuously monitored compound cytotoxity versus cell proliferation. In addition, the biological effects of treatments were evaluated in terms of proliferation through cell cycle phases and apoptotic events, assessed by flow cytometry approaches. Data obtained showed increased levels of apoptosis in colon tumor cells treated with the Ru (III) complexes, while a major decrease of proliferation was found for S phase of the cell cycle. New synthesized Ru (III) complexes demonstrated a better biological activity based on diminishing cell proliferation, induction of apoptosis and modulation of cell cycle phases in colon tumor cells.

Molecular analysis of the TP53 gene and infrastructural particularities in mamar tumor tissue

Corina-Elena Mihalcea1, Ana-Maria Moroşanu2, Daniela Murăraşu1, Liliana Puiu1, Sabin Cinca1, Silviu-Cristian Voinea1, Nicolae Mirancea2

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

2. Institute of Biology, Romanian Academy, Bucharest

The p53 protein plays an essential role in regulating the cell cycle, thus acting as a tumor suppressor gene that prevents the occurrence of cancer, DNA repair and apoptosis. Mutations in TP53 gene may be a biomarker to chemotherapy response in advanced breast cancers, especially to tamoxifen. We investigated the TP53 gene, exons 4-9, using fresh tumor tissue samples, and we tried also to identify some particular ultrastructural aspects of the tissue. The study included 22 tumor tissues: all of them were invasive ductal ductal carcinomas, with various stages. Genomic DNA was extracted using QIAamp DNA Mini Kit, and DNA concentration and purity were evaluated using NanoDrop ND 1000. The samples were amplified by a PCR me­thod and subsequently sequenced by the Sanger method using the 3500 Genetic Analyzer. Data analysis was performed with the Variant Reporter v2 software. In order to investigate ultrasonic transmission electron microscopy (TEM), small fragments (1-3 mm) of normal breast and tumor tissue were used. Results. TP53 somatic mutations had a rate of 27.3% (6/22); most mutations were of deletion type (66.67%), localized in exon 4 (c.213_214del2), exon 5 (c.398delT) and exon 7 (c.739_747delAACCGGAGG and c.731delG). The substitutions were detected in two cases (33.33%): a missense mutation in exon 5 (R175H; c.524G>A) and a nonsense mutation in exon 6 (pR213 * c.637C>T). Five polymorphic variations were identified; three in the coding regions of the gene (rs1042522-R72P, rs372397095-P82P in exon 4 and rs1800372-R213R in exon 5) and two in intron 6 (rs1625895 and rs17880604). The mutated alleles corresponding to the SNPs rs1042522 and rs1625895 were detected in all samples, both homozygous and heterozygous, while the remaining TP53 variants were detected only in a few samples. The electron microscopy analysis at the ultrastructural level showed interesting aspects:

  • In invasive ductal carcinomas, epithelial tumor cells frequently have intracellular micro-channels with a multitude of microvilloid extensions.
  • Membrane vesicles (carrier proteins, lipids, microRNAs, DNA fragments etc.) that are released by some tumor cells at the stromal tumor interface can be observed.
  • The presence of telocytes was detected.                    

New approaches in triple negative breast cancer

Lucian Miron

“Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Regional Cancer Institute, Medical Oncology Department

Triple-negative breast cancers (TNBCs), defined by the lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers, and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease, encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. TNBC has an aggressive natural history, with an increased mortality rate during the first five years, most deaths occurring in this period. Typically, there is a high risk of early recurrence, and this tends to occur within the first four years after diagnosis. Compared with other subtypes, TNBC is also characterized by molecular heterogeneity. There is a diversity in the histologic patterns and transcriptional subtypes. Letherman et al. proposed a classification that defined several molecular subtypes of TNBC. These include: 1) basal-like (BL1 and BL2); 2) immunomodulatory;
3) mesenchymal; 4) mesenchymal stem-like; 5) luminal androgen receptor (LAR) subtype. Similarly, another gene expression analysis suggested the following subgroups: luminal/androgen receptor, mesenchymal, BL/immune-suppressed, and BL/immune-activated. These classifications help to increase our understanding of the TNBC biology and identify rational therapeutic strategies for TNBC subtypes. TNBC is a very heteroge­nous disease. Many studies clearly indicate that TNBC cannot be treated in a uniform way. Chemotherapy is the current standard-of-care treatment of TNBC in the adjuvant, neoadjuvant and metastatic settings. TNBCs are highly sensitive to chemotherapy, as evidenced by the pathologic complete response (pCR) rates ranging from 30% to 40% after neoadjuvant chemotherapy, compared with complete response (CR) rates for ER-positive breast cancer which range from 10% to 25%. The basal-like genotype is more likely to be sensitive to chemotherapy. However, TNBC has higher rates of relapse, which has been referred to as the triple-negative paradox. Platinum salts including carboplatin and cisplatin lead to the cross-link breaks, which may be especially important in the cells that are deficient in BRCA and in TNBC. Taxanes are also active agents in breast cancer. In the phase III trial of carboplatin versus docetaxel in triple-negative or BRCA1/2-positive metastatic breast cancer (TNT trial), germline BRCA-mutation carriers had a much better response rate to carboplatin than docetaxel, but lacking a germline mutation, while carboplatin and docetaxel were equally effective. PARP1 is an enzyme critical to base excision repair pathway and is a key for repairing single-strand DNA breaks. PARP inhibitors are a new class of medicines that include olaparib, veliparib, rucaparib and imiparib, which are active in treating TNBC basal-like tip 1. More recently, a single arm phase II study of neoadjuvant gemcitabine, carboplatin and imiparib in patients with TNBC or BRCA1/2 mutation associated breast cancer showed impressive responses in BRCA 1/2 carriers. The subset of TNBC patients who express the androgen receptor (AR) generally demonstrates a longer disease-free interval in early-stage disease. In a single-arm, stage II, phase II trial of hormonal therapy with enzalutamide (Xtandi®), the median PFS was 12.6 weeks (95% CI; 8.1-15.7). For patients with AR expression ≥10%, the median PFS was 14.7 weeks, and in patients with low AR expression (<10%), the median PFS was 8.1 weeks. A phase II trial of abiraterone acetate in a cohort of TNBC AR positive demonstrated a 6-month clinical benefit rate of 20% and a PFS of 2.8 months. Similarly, a phase II trial with enzalutamide demonstrated a 24-week clinical benefit of 29%. The paucity of actionable targets, the lack of targeted therapies, and the relatively poor prognosis of patients with TNBC have created ample opportunity to evaluate novel treatment approaches. An improved understanding of the immunogenicity of TNBC has led to clinical studies of several immunotherapeutic agents. Early phase I trials with immune checkpoint inhibitors in TNBC reported an overall response rate of up to 19%, with durable clinical responses and a tolerable safety profile. A phase III study demonstrated that adding pembrolizumab to standard neoadjuvant therapy for high-risk HER2-negative breast cancer increased the rates of pathologic complete responses, especially in women with triple-negative breast cancer – 50% higher rates (Nanda R et al. J Clin Oncol. 2017, 35; 506). We hope that immunotherapy strategies will provide new therapeutic options for TNBC. Triple-negative breast cancer is a breast cancer subtype which has only chemo­therapy as a conventional treatment. Many clinical trials of immunotherapy agents (nivolumab, permbrolizumab, atezolizumab) are in progress for the treatment of TNBC. Emerging data in the phase I setting with checkpoint inhibitors demonstrate a tolerable safety profile. Ongoing and future trials will define the role of immune checkpoint blockade in the treatment of TNBC. The hope is that immune checkpoint blocking antibodies will change the standard of care for TNBC. Conclusions. Triple-negative breast cancer remains the major challenge for breast cancer medical oncologists. Many therapeutic strategies are being explored and we hope that newer DNA repair inhibitors, immunotherapies and antibody-drug conjugates will lead to a better survival. Combined two or more targeted agents may required for more rationale and optimal approach to TNBC treatment.

Imagistic evaluation of benign and malignant breast lesions histopathologically confirmed

Alina Moldovan, Florin Radu

Introduction. Breast cancer is the most common cancer in women and has the second highest mortality among cancers in women worldwide. Also, breast cancer is by far the most common malignant tumor diagnosed in women in Romania, with over 8981 new cases diagnosed and about 3244 reported deaths in 2016. The incidence of breast cancer is 66.2 per 100,000 inhabitants, and the mortality rate is 21.6/100,000 in the female population. In Europe, breast cancer incidence ranked first in 2012, with 13.45%, with a death rate of 7.48%, being the third cause of mortality after lung and gastrointestinal cancers. Belgium, Denmark and France have the highest number of new cases of breast cancer, with 112, 105 and 104 cases per 100,000 inhabitants, respectively. Unfortunately, the incidence of breast cancer continues to increase slightly each year, and mortality has not changed much in the past 20 years, remaining extremely high. The increasing trend of the incidence of malignant mammalian pathology closely follows the general trend of the incidence of cancer cases in general, the latest estimates predicting a tripling of the number of cases by 2030 in both developed and developing countries. Promoting screening programs through appropriate public health policies in Western countries have favored the early diagnosis of breast cancer at an early stage, requiring a more conservative and effective therapeutic approach, with a consequent reduction in mortality and morbidity. The risk factors involved in breast cancer are: gender; age; family history; breast density; hormonal status: menopausal women with high circulating estrogen have a 2-3 times higher risk than low-estrogen women. Reproductive status, menstrual status, and the use of exogenous hormones are associated and increase the risk (RR: 1.25-1.99) of developing breast cancer. Other risk factors for breast cancer are: age at menopause; hormone replacement therapy; use of oral contraceptives; the appearance of menarche at young age; increased circulating levels of androgens; circulating levels of IGF-1 and IGFBP-3. The factors that reduce the risk are: breastfeeding for at least 12 months; increased number of births. Environmental and daily factors: exposure to ionizing rays from young ages; tobacco consumption; excessive obesity at menopause; alcohol consumption; exposure to pollution; using traumatic bras; stress; recurrent trauma. The pathophysiological elements responsible for the patient’s prognosis include: tumor size – clinical staging; histopathological subtype; degree of cell differentiation; the number of invaded lymph nodes; the existence of vascular invasion. Thus, the discovery and identification of the new markers led to a more accurate description of tumor biology and to substantial amplification of the role in establishing the therapeutic course. The treatment of breast cancer is challenging, due to genotyping, phenotyping, diagnosis and prognosis, because of many cell types that can be difficult to quantify with the usual imaging methods. Thus, in recent years, minimally invasive and laboratory imaging has been developed for the structural and morphological differentiation of lesions. The gold standard is the early and correct detection of malignant or potentially malignant lesions, often silent but with a major socioeconomic and psychological impact. In recent years, besides digital mammography with tomosynthesis, magnetic resonance, sonograms and sonoelastograms are developed as highly accessible non-invasive techniques and integrated in the paraclinical assessment of mammary lesions. Regardless of the tumor’s size, sonoelastography has a specificity of 93% and a sensitivity of 80%, a predictive positive power of 85.3% and a negative predictive power of 90.3%. The sensitivity is better for lesions less than 5 mm and the specificity is better for lesions over 10 mm. In the next study, I will show the concordance between the histopathological examination of the lesion and the imaging interpretation of the mammary lesions. The study was performed in a group of patients admitted in the Third Surgery Department of the “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, between 3.01.2016 and 31.12.2017. The objective of the study was to identify the cases with potentially malignant tumors, in order to develop diagnostic imaging strategies as accurate as possible, then confirmed histopathologically, necessary to develop an adequate therapeutic course. We studied cases that have been diagnosed by mammography, mammographic ultrasound and sonoelastography, in order to establish the contribution of each imaging investigation method in establishing a concise diagnosis, assessing the benefits and limitations of each individual investigation. Two groups of patients were studied, namely: Group I – patients who presented with imaging investigations showing benign lesions (BIRADS 1-3) confirmed or histopathologically infirmed; Group II – patients presenting with malignant or potentially malignant (BIRADS 3B-5) imaging investigations confirmed or histopathologically infirmed.

Conclusions

  1. Patients who were investigated by imaging methods showed an oscillatory distribution. There was an increased addressability in the age groups of 40-55 years old and 56-72 years old.
  2. Out of a total of 653 patients presented, 252 (38.59%) presented histopathologically confirmed malignant lesions, of which 244 patients presented both clinical and imagistic malignant and histopathologically confirmed lesions. Eight patients had only clinical and non-imaging features of malignancy.
  3. By analyzing the patients who presented themselves only with mammography and those who presented with ultrasound, and especially with sonoelastography, a higher rate was found in the early discovery of the incipient cases by associating the investigations.
  4. In patients with dense breasts, ultrasound and sono­elastographic examination is indispensable, being useful for the additional characterization of the mammographically or clinically diagnosed lesion.
  5. Early detection and determination of the therapeutic course depend largely on the confirmed or finally refuted imagistic features through the histopathological outcome.
  6. By developing radiology, we can get a specificity and sensitivity of more than 90% in detecting occult or malignant lesions, with major impact in decreasing mortality.

Left paraxifoid pericardic drainage – minimally invasive approach for biopsy and drainage of the pericardium

Natalia Motaş, Elena Jianu, Adriana Bene, Mihnea Davidescu, Ovidiu Rus, Corina Bluoss, Sorela Rădoi, Marilena Romoşan, Carmen Zamfir, Luminiţa Udrea, Monica Olaru, Carmen Pantiş, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Introduction. Liquid pericarditis has a multitude of causes. In patients with known malignancy, pericarditis can be caused either directly by the tumor (neoplastic pericarditis), or indirectly, for example, by blocking lymphatic drainage (paraneoplastic pericarditis). Materials and method. The Left Paraxifoidian Approach, published by us (C. Motaş and colab. – Interactive Journal of Cardio-Thoracic Surgery) for the first time in 2010, offers immediate and rapid pericardial access, and it can be achieved even in vigilant patients (under local anesthesia). Results. For the last 38 cases, operated between August 2008 and December 2017, we did not have post-procedural intraoperative and hospital deaths. On average, 850 ml of pericardium fluid were discharged intraoperatively. In three cases, general anesthesia was performed with orotracheal intubation, 25 patients were operated with local anesthesia and intravenous sedation, and 10 patients were operated only with local anesthesia. In 11 cases, we also underwent pericardioscopy. Intrapericardial cisplatin instillation was performed in two patients; the recurrence rate of pericarditis was 5.26%, corresponding to the series from literature in which the cytostatic was instilled – these aspects are discussed in the presentation. Conclusions. In cardiac tamponade especially, in cases where biopsy of the pericardium is required, the left paraxifoidian approach proves to be the best option that can be performed under local anesthesia.

Borderline ovarian tumors – management

Gheorghe Peltecu, Anca Maria Panaitescu, Radu Botezatu, Nicolae Gică, Raluca Chirculescu, Mioara Ionescu, Dragoş Median

Borderline ovarian tumors (BOT) comprise a heterogeneous group of tumors with a specific non-invasive histology, a low malignant potential and an uncertain outcome. Borderline ovarian tumors still remain a topic of controversy not only for optimal terminology, but also for frozen section and paraffin pathologic assessment, surgical treatment (especially for young patients wishing to preserve their fertility), the type of operative approach (open versus laparoscopy), need of chemotherapy, radical surgery after completion of childbearing plan and follow-up strategies. Borderline ovarian tumors have a low incidence, occurring at younger age, are diagnosed in early stage, are associated with infertility, and have a better prognosis when compared with epithelial ovarian cancer. The management of BOT should take into consideration the oncologic safety, but well balanced, with less radical treatment in selected cases. The various clinical, histological and pathological aspects of BOT should guide the surgeon, the oncologist and the pathologist to take the best decision for the patient, and to be as radical as necessary.

Cancer – a chance to be closer to life or death?

Geanina Pruteanu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Life seems to be a longer or a shorter journey which has an end. No one knows when he will face his own end, or when he will see the end of the loved ones, and this unknown fact produces what psychologists call death anxiety. If we do not perceive death as something so frightening, we may realize that her perspective is only a chance to be present, spontaneous and creative in our lives. This presentation represents an incursion of the objectives pursued within the pediatric oncology department, from the perspective of the psychological approach. On the one hand, the purpose of psychological evaluation and intervention is to increase the quality of life, the life length being affected by the diagnosis or oncological history. On the other hand, the goal is to accept human ephemerality in a healthy and assumed way. These are lengthy processes that require perseverance, delicacy and authenticity from the specialist, but also a bidirectional approach: for oncological patients and for their parents.

Challenges in the therapeutic approach of a patient with trachea neuroendocrine tumor – case presentation 

Laura Rebegea1,2, Iuliana Ivan3, Mihaela Crăescu1,4, Dorel Firescu5,6, Mihaela Dumitru1, Gina Patriche1

1. Radiotherapy Department, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi, Romania

2. Clinical Medical Department, Faculty of Medicine, “Dunărea de Jos” University of Galaţi, Romania,

3. Oncolgy Clinical Department, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi, Romania

4. Morphopathological Department, Faculty of Medicine, “Dunărea de Jos” University of Galaţi, Romania

5. Clinical Surgery Department, Faculty of Medicine, “Dunărea de Jos” University of Galaţi, Romania

6. 2nd Surgery  Clinical Department, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi, Romania

Motivation. Neuroendocrine tumors contain a heterogeneous population of tumors, 25% of these being localized in the upper respiratory tract. Materials and method. We present the case of a 52-year-old patient with lung adecarcinoma who performed surgery in 2005. In December 2016 he was histopathologically and immunohistochemically diagnosed with trachea neuroendocrine tumor, Ki67=15%, and positive specific neuroendocrine markers. The patient performed external beam radiotherapy (EBRT) on thoracic target volume, chemotherapy with carboplatin and etoposid, and after that with ocreotid, which was interrupted at his choice. Bone scintigraphy with 99Th revealed secondary bone lesions in December 2017; more suggestive would have been scintigraphy for somatostatin receptors. The treatment with bisphosphonates and EBRT on left iliac bone target volume was initiated. At computed tomography with positron emission (PET-CT), in April 2018, there were evidenced multiple metabolic active lesions: at the 3rd liver segment, soft/hard palate, and skeletal. Discussion and conclusions. There are many questions arising here regarding the starting point of bone metastasis and what would be the therapeutic approach. We present this case due to the rarity of tracheal neuroendocrine carcinoma associated with lung adenocarcinoma, and due to the disease progression and difficulties regarding the therapeutic decision.

Keywords: neuroendocrine tumor, bone metastasis, therapeutic decision

VIA – mobile application for adolescents and young adults affected by cancer

Katie Rizvi

Founder, “Little People Romania & Temerarii” Association; The Romanian Community of Cancer Survivor Adolescents and Young Adults 

Isolation is known to be the number one issue that young people experience when faced with a cancer diagnosis. With 78,700 new cancers diagnosed every year in Romania (GLOBOCAN 2012, IARC – 7.01.2016), 3,700 of them occur in the 15-39 year-old population, meaning that tens of thousands of cancer survivors in Romania under the age of forty are looking for others who won’t judge or stigmatise them, when cancer turned their world upside down. There might be many young adults with cancer in Romania, but the chances of meeting other collage students, young singles who live near or have the same type of cancer or treatment, are very minimal. This is why “Little People” will bring young adults’ cancer care into the 21st century, into the digital age, by offering a safe, private and completely anonymous 1-1 peer matching app for cancer patients in their teens, twenties and thirties in Romania, for tens of thousands of young people, who just need to know that they are not alone. We present you: VIA. “Little People” created a brand new, unique mobile application for young adults affected by cancer, aged between 18 and 39 years old, being identified in the UK as the most vulnerable patients. “Adolescents and young adults aged 15-39 with cancer are gaining an increasing emphasis in recent years. This is because cancer is the leading cause of non-accidental death in this group and the incidence of cancers in this age group is rising steadily year-on-year. They have an interface position between adult and children’s cancer care, and their poor survival compared to related cancers at a younger age remains apparent” (Stark et al., in press, EJC, August 2015). VIA, the new mobile app for adolescent and young adult cancer patients in Romania, will be the ultimate peer support network for potentially every cancer patient in the 18-39 age group.

Pulmonary nodules – Janusian aspect

Ovidiu Rus, Natalia Motaş, Veronica Manolache, Mihnea Davidescu, Corina Bluoss, Elena Jianu, David Achim, Vlad Alexe, Mădălina Iliescu, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

The vast majority of investigated and surgically treated lung nodules are found to be pulmonary metastases or primary pulmonary cancers in early stages. In a smaller percentage, the lesions are benign. But what if the nature of the nodules does not fit them into the category of tumor? We present the cases of two patients imagistically diagnosed with pulmonary nodules, with aspects that supported the possible malignant etiology. The surgical interventions resulted in totally unexpected conclusions, which could hardly be anticipated. The confrontation of preoperative and intraoperative diagnosis remains essential, and the lesional findings during surgery can alter both therapeutic and patient prognosis.

What’s new in 2018 regarding melanoma staging and surgery?

Angela Sandru1, Silviu Voinea1,2

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

In January 2018, the eighth edition of the American Joint Committee on Cancer (AJCC) melanoma staging system was formally implemented worldwide, after being revised by Melanoma Expert Panel. Based on analyses of a large international melanoma database, key changes have been made in the old staging system from 2009, in order to improve prognostication, risk stratification and selection of patients for clinical trials. With the ever-growing list of effective treatments available today, it is more important than ever to stage patients accurately, so that the monotherapies and combination therapies approved across different stage levels can be used most effectively. Thus, patients can be optimally informed about their options and considered for the most promising and appropriate clinical trials. Are there any changes in surgical indications too? Quite a lot. The guidelines have been revised to recommend against SLNB if a patient’s pretest probability of finding a positive SLN is less than 5%. Completion lymph node dissection looks increasingly like a procedure in search of an indication in the post-MSLT-II and DeCOG-SLT era. Surgery after immunotherapy seems to be effective in advanced melanoma. Checkpoint blockade for metastatic melanoma and the ability to surgically resect all disease after treatment are associated with an estimated survival of 75%, better than what’s been previously reported. So, many things are changing, everything is evolving, we just need to be informed and open-minded.

The place of nutritional support in oncology and palliative care

L. Simion1,2, Alexandra Cecilia Nicolăescu2, V. Poroch3,4, M. Alecu1,2

1. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

2. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, Romania

3. “Gr. T. Popa” University of Medicine and Pharmacy, Iaşi, Romania

4. Regional Institute of Oncology, Iaşi, Romania

Patient’s nutrition is all-important for both curative therapy and palliative care. The multimodal treatment of cancer, involving the association of radiotherapy, oncologic surgery and chemotherapy, cannot be successfully performed in patients with nutritional deficiency. The nutritional support is also an essential component of palliative care, centered on the quality of the patient’s life, which has the role of a variable component since the oncological disease onset. Ensuring an enteral nutrition is the preferred option when the patient should be sustained for an average or long period. In case of patients who can no longer be fed through bone but whose digestive tract is still functional, the options available for the enteral nutrition are: classic gastrostoma, classical jejunostoma, percutaneous endoscopic gastrostoma (PEG), or PEG options performed surgically (by minilaparotomy or by laparoscopy). In patients with abdominal surgery, there is the possibility to install during the surgery an enteral nutritional device similar to the naso-gastric tube, the classical example being the enteral nutrition tube inserted trans-anastomotically in the jejunum in a gastrically resected patient, but it is not a medium- and long-term solution. Another condition for the proper nutritional support is to provide the digestive transit, where a surgery focused to remove or to by-pass a tumor barrier also solves the nutrition problems. Radiotherapy for the otolaryngology-related or oro-maxillofacial-related oesophageal neoplasia cannot be conducted without providing an effective nutritional method that could be used throughout the treatment and at least until the oncological reassessment. Chemotherapy also requires good nutrition of the patient, both for therapeutic support and for controlling adverse reactions. Parenteral nutrition is not a long-term viable option and is usually recommended for maximum two weeks. PEG and its options represent the optimal solution of enteral nutrition over a medium and long period, invasiveness, costs and complications rates being significantly lower than in case of other techniques. The devices used are easily tolerated by patients, and they allow a fast recovery and an early resumption of nutrition.

Imbalance between matrix metalloproteinases and their tissue inhibitors is associated with metastatic spread via lymphatic pathways in head and neck squamous cell carcinomas

Adina Elena Stanciu1, Adina Zamfir-Chiru-Anton2, Marcel Marian Stanciu3, Cristian Radu Popescu4, Dan Cristian Gheorghe5

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, Department of Carcinogenesis and Molecular Biology

2. “Grigore Alexandrescu” Emergency Hospital for Children, ENT Department, Bucharest

3. Politehnica University of Bucharest, Faculty of Electrical Engineering, Bucharest

4. Colţea Clinical Hospital, Head and Neck Surgery Clinic, Bucharest

5. “Maria Sklodowska Curie” Emergency Clinical Hospital for Children, ENT Department, Bucharest

Background. Aberrant extracellular matrix (ECM) degradation by matrix metalloproteinases (MMPs) or an imbalance between MMPs and their tissue inhibitors (TIMPs) is considered to be a promoter of tumor invasion and metastasis. The purpose of the study was to determine MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in the sera of patients with head and neck squamous cell carcinoma (HNSCC) in relation to clinicopathological features. Method. Serum samples from seventy patients with HNSCC were measured by ELISA, before and two days after surgery. Forty healthy volunteers were selected as controls. Results. Preoperative MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were significantly higher in HNSCC patients than in the controls (p<0.001 and p=0.002, respectively). Our results were unexpected, because the highest ratio values for MMP-9/TIMP-1 were associated with the highest levels of MMP-9 and TIMP-1, while the highest ratio values for MMP-2/TIMP-2 were associated with normal levels of MMP-2 and TIMP-2. After surgery, a new balance was established and the changes in circulating TIMP-1 level were positively correlated with lymph node involvement (p=0.006), whereas the changes in MMP-9 level and MMP-9/TIMP-1 ratio were negatively correlated (p=0.021 and p=0.013, respectively). We found a positive correlation between the changes in circulating TIMP-2 serum concentrations and the degree of differentiation of the tumor cells (p=0.021), but no correlation was noticed with the tumor stage, tumor size and nodal involvement. Conclusions. Our results suggest that MMP‐9/TIMP‐1 imbalance contributes to the aggressive biologic behavior of HNSCC. Statistically significant association between MMP-9/TIMP-1 ratio and lymph node-positive HNSCC shows its direct involvement in cancer cell invasion and dissemination. Because a positive correlation was found between TIMP-2 and the degree of differentiation of the tumor cells, TIMP-2 could help segregate subsets of aggressive HNSCC into clinically meaningful subtypes.

Therapeutic novelties in epithelial ovarian cancer

Dana Lucia Stănculeanu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Epithelial ovarian cancer accounts for 90% of all ovarian tumors. Over the past decade, as a result of the improvement of each therapeutic stratagem in the multidisciplinary treatment, the survival of advanced stage patients has increased. Integrating clinical trials and translational research into clinical practice led to an increase in survival in advanced stages from 12 months in 1980 (GOG 3) to more than 120 months in the 21st century. Surgical treatment, R0 cytoreduction, has prognostic value, and lymphadenectomy according to the LION study does not appear to be necessary in patients with R0 and N0 clinical, which has changed medical practice in locoregional advanced disease. Adjuvant medical treatment is standardized, and chemotherapy with paclitaxel and platinum salts plus/minus bevacizumab in maintenance remains the standard of care. In the last years, the somatic genetic signature BRCA-like has an important role in establishing the therapeutic pathway. The most important oncology societies (ASCO, NCCN, SGO) recommend that women diagnosed with ovarian cancer be tested for BRCA-like regardless of family history. The classification of high grade ovarian cancer patients in three subgroups (wild BRCA, BRCA-like and BRCA mutant) allows the redefinition of treatment based on these biomarkers. The ARIEL 2 study defined using the NGS technique a category of patients with HRD (homologous recombination deficiency). Currently, FDA and EMA approved three categories of PARP inhibitor molecules: niraparib (NOVA study) – maintenance treatment in relapsed patients and resumed chemotherapy after platinum salt therapy; rucaparib (ARIEL 2 and ARIEL 3 studies) in monotherapy in platinum-sensitive patients with two or more treatment lines, who could no longer receive platinum-based chemotherapy, and olaparib (Study 19, Solo2) as maintenance treatment in patients with complete or partial response to platinum-based chemotherapy. The therapeutic decision to use in the maintenance sequence PARP inhibitors therapy or bevacizumab, both active and approved molecules in the treatment of ovarian cancer, is a reality. The sequence of these treatments is complicated. HRR mutations have a predictive role for the PARP inhibitor response, whereas for bevacizumab they have only prognostic value. The role of immunotherapy and treatment combinations is the subject of numerous clinical trials and remains to be defined, with promising results.

Borderline ovarian tumors – critical study

G.D. Subţirelu, A.M. Marincaş, V.M. Prunoiu, Sânziana Ionescu, E. Bratucu

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, 1st Department of General and Oncologic Surgery

Borderline ovarian tumors (BOT) are a heterogeneous group of epithelial tumors of the ovaries with both malignant and non-malignant aspects. They are characterized by cellular proliferation and nuclear atypia, but they usually do not show infiltrative growth pattern. BOT comprise about 15% of all epithelial ovarian malignancies. Patients with BOT are, in general, 10 years younger than women with epithelial ovarian cancer. Approximately one-third of all BOT are diagnosed in patients with child-bearing potential. Balancing radicality between oncologic safety and fertility-sparing treatment is a challenging task. We evaluated the clinical parameters of BOT patients treated between 1.01.2014 and 31.12.2017 in the 1st Department of General and Oncologic Surgery, “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest. The median age of the 37 patients was 48.2 years old, 14 patients were under 40 years old (37.8%), and fertility-preserving surgery was carried-out in 57.1% of the cases (8 patients). As they affect more frequently younger patients, the clinical management of BOT is complicated by aspects regarding the preservation of fertility. Despite a more favourable overall survival, young BOT patients with fertility-preserving surgery are at higher risk for disease recurrence. A better characterization of high-risk subtypes is crucial to better understand long-term risk of BOT and to avoid recurrences in those patients undertreated by the current management strategies. Fertility-sparing approach can be justified for younger patients after a thorough consultation.

Keywords: borderline ovarian tumor, surgical treatment, fertility preservation, recurrence

The role of PARP inhibitors in the treatment of ovarian neoplasms

Nicolae Suciu1,2, Nicolae Bacalbaşa2,3, Irina Bălescu4, Ionuţ Dumitru Suciu1, Oana Toader1,2

1. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

3. Center for Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest

4. Ponderas Academic Hospital, Bucharest

Once the principles of debulking surgery have been applied, the main therapeutic strategy that provides good control of advanced ovarian neoplasms is platinum-based adjuvant chemotherapy. However, most patients will develop recurrences at some point in their existence. The main therapeutic strategy that can delay this has been represented for a long time by inhibitors of angiogenesis. Recently, however, a new therapeutic class, that of PARP inhibitors (polyADP ribose polymerase – an enzyme activated in cells presenting DNA structures lesions), has been highlighted. Initially, these molecules were evaluated in negative BRCA ovarian neoplasms; however, recent studies have shown that this therapeutic class also plays an important role in positive-BRCA tumors. This study describes the main mechanisms of action of PARP inhibitors as part of the treatment of advanced ovarian neoplasms. Thus, it appears that the main current benefit of associating these molecules in the treatment of recurrent ovarian neoplasms is to increase the duration of the disease-free period.

The role of miRNA in the evaluation of breast neoplasm

Nicolae Suciu1,2, Nicolae Bacalbaşa2,3, Irina Bălescu4, Andrei Voichiţoiu1, Lucian Pop1

1. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

3. Center for Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest

4. Ponderas Academic Hospital, Bucharest

MicroRNA represents a class of small molecules of 21 to 25 non-protein nucleotides that regulate post-transcriptional target gene expression. In humans, it is estimated that there are over 2000 genomic miRNAs that regulate approximately 60% of genes, playing an important role in the differentiation, proliferation and subsequent apoptosis of various cell lines. Moreover, miRNA plays a key role in the metastasis of various neoplasms, including breast neoplasm; as a result, miRNA is considered an important marker on the basis of which a new stratification of patients diagnosed with breast cancer can be performed in order to predict metastatic risk, as well as resistance to various therapeutic strategies. The main particularities of miRNA that made them a very useful biomarker are related to the stability of these molecules in serum levels, as well as the resistance to repeated freezing and thaw cycles. This paper aims to present the role of miRNA in the initial assessment of breast cancer.

Minimally invasive surgical treatment in uterine cervical neoplasm

Bogdan Tănase, Alin Burlacu, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

The neoplasm of the cervix represents a major public health problem in Romania, being on the first place regarding prevalence among cancers in females, and the second cancer-related death cause in women. The surgical treatment remains one of the benchmarks for multimodal treatment in cervical neoplasm, but is recognized for its major impact on the body and for postoperative complications. We mention that in the case of the combination of radiotherapy and multimodal treatment, the morbidity can reach up to 20 percent – a controversial value in the literature. In an attempt to minimize this impact of radio-surgical treatment, we tried to practice and standardize surgical treatment by minimally invasive approach, being stimulated by the net benefits of this method in well-selected patients. This paper aims to discuss the advantages and disadvantages of the technique and to present the efforts made at our clinic on the treatment of cervical cancer.

Mammography – limits and benefits in breast cancer screening

Oana Daniela Toader1,2, Andrei Voichiţoiu1,2, Alexandra Vintea1,2, Ramona Dragomir1, Nicolae Suciu1,2

1. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

Breast cancer is one of the most common cancers in women and the second cause of cancer death after lung cancer. Due to its impact, it is necessary to develop programs for screening. Mammography represents a breast screening test which involves X-ray examination. The test has no upper age limit, but the onset of the screening is recommended to be at the age of 40 years in women with medium risk of breast cancer. The major advantage is the early detection of breast cancer, which allows an increased survival and the possibility of a conservative treatment. The introduction of mammography as a screening method has led to a reduction of mortality in breast cancer with 30%. Mammography can also be used to detect small abnormal tissue growths confined to the milk ducts in the breast, namely the ductal carcinoma in situ. It is also useful in detecting all types of breast cancer, including invasive ductal and invasive lobular cancer. Mammography has also some limits, such as the existence of false negative results in cases with excess of dense breast with glandular tissue, especially in women under the age of 35. Other limitations can be the presence of some mammographically occult neoplasm, peripheral lesions and false positive results. It’s not always possible to distinguish between a benign and a malignant tumor and it’s not possible to specify the nature of an image, thus being absolutely necessary to complete the exam with a mammary ultrasound in order to establish the diagnosis. The widespread use of mammographic screening, with huge benefits all over the world, depends on the technique, the films and the quality of the equipment. Despite its limitations, mammography remains a vital tool in breast cancer screening, being able to recognize incipient changes, with high sensitivity in postmenopausal women.

Circulant miRNA as a biomarker in metastatic mammary neoplasm

Oana Toader1,2, Nicolae Bacalbaşa2,3, Irina Bălescu4, Ionuţ Dumitru Suciu1, Nicolae Suciu1,2

1. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

3. Center for Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest

4. Ponderas Academic Hospital, Bucharest

The use of circulating miRNA as a biomarker in metastatic breast cancer played a key role in recent years, the most common such particles being miR-10b, followed by miR-34a, miR-373 and miR-155. Moreover, it appears that miR10b and miR-373 show significantly higher circulating levels among patients presenting metastasis in the lymph nodes, whereas increased levels of miR-10b represent a significant prognostic factor for the occurrence at some point of cerebral and bone metastases. Other molecules that play a key role in the occurrence of remote metastases are miR-105, miR-17 and miR-155. Thus, it appears that the existence of elevated levels of miR-105 even in the case of premature diagnosed mammary neoplasms is associated with an increased risk of metastasis, whereas the presence of miR-17 and miR-155, respectively, can differentiate mammary neoplasms with high metastatic potential from those with minimal risk remote dissemination. The present paper aims at presenting the main biomarkers and the usefulness of translating information about their existence or absence at the clinical level, thus offering the possibility of early identification of patients at risk of developing various metastases. Once identified, they will have the chance to undergo specific treatment to limit the development of metastatic lesions.

The role of miRNA in assessing ovarian neoplasms

Oana Toader1,2, Nicolae Bacalbaşa2,3, Irina Bălescu4, Andrei Voichiţoiu1, Lucian Pop1, Nicolae Suciu1,2

1. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

3. Center for Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest

4. Ponderas Academic Hospital, Bucharest

Ovarian neoplasm is one of the most common neoplasms affecting women worldwide, being responsible for the greatest number of oncological and gynecological causes of death. Since the 1930s it has become clear that one of the most important factors influencing the prognosis is the achievement of maximum cytoreduction. However, it has been widely demonstrated that the evolution of patients, even after maximal cytoreduction, is not a similar one, only a part of these patients decaying at a certain point in their recurrence evolution. As a result, the researchers’ attention was focused on the understanding of the molecular mechanisms responsible for these differences, as well as on identifying new therapeutic strategies that could improve the long-term prognosis of such cases. Thus, it seems that, as with mammary neoplasms, the determination of circulating miRNA plays a key role in promoting ovarian tumour genesis. This paper aims to present the main biomarkers in this class, as well as their impact on distance prognosis. Once these issues have been established, new personalized therapeutic strategies can be applied to reduce the risk of developing systemic recurrences.

Sentinel lymph node biopsy – limits and benefits in breast cancer management

Oana Daniela Toader1,2, Andrei Voichiţoiu1,2, Alexandra Vintea1,2, Ramona Dragomir1, Nicolae Suciu1,2

1. “Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

Breast cancer represents a major health problem and it is the most common cancer in women, being able to spread through the lymphatic system. Sentinel lymph node biopsy is a safe and accurate method for predicting the status of axillary lymph nodes, being widely used in breast cancer management. It consists in identifying and analyzing the first satellite tumor node, in order to determine if malignant cells are present or not, allowing their removal only when it’s necessary. Sentinel lymph node biopsy has major benefits, but also limitations. Using this technique, the side effects of lymph node surgery (lymphedema or tissue swelling, seroma, numbness, tingling or pain at the site of the surgery and difficulty moving the affected body part) can be prevented or reduced. However, the sentinel lymph node biopsy, as well as other surgical procedures can lead to complications – such as short-term pain, swelling and bruising at the surgical site – and increase the risk of infections. Another inconvenience is the false negative result of the biopsy which can mislead the treatment options. Although in early stages this technique is very useful, in advanced stages, where invaded lymph nodes are identified using imagistic or clinical methods, the sentinel lymph node is no longer necessary. Therefore, sentinel lymph node biopsy is not recommended in extensive tumors, inflammatory breast cancer, or in cases of metastasis in axillary lymph nodes. Data about the effects of using this technique in pregnancy are limited, making pregnancy a relative contraindication for sentinel lymph node biopsy. The sentinel lymph node biopsy in breast cancer allows us to know the status of axillary lymphatic with great precision, and because of selective axillary surgery, it reduces the morbidity associated with radical surgery.

News in the treatment of ovarian cancer

Oana Trifănescu, Rodica Anghel

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest

Globally, over 240,000 women are diagnosed annually with ovarian adenocarcinoma, which is the leading cause of death by gynaecological tumours. Due to the fact that until now there are no effective screening and detection methods in the early stages, most patients (more than 70%) are diagnosed in advanced stages. The risk factors involved in the pathogenesis of ovarian cancer are early menarche, late menopause, obesity and nulliparity, and also heredo-collateral ovarian cancer antecedents. The multidisciplinary approach is particularly important; the team treating the patient must include a surgeon specialized in oncology surgery, an oncologist, a radiotherapist, an imagist, and a specialist in palliative care. The purpose of surgery should be full tumour resection (R0), which is the most important outcome factor. It is recommended to administer platinum-based adjuvant chemotherapy, post operatory, in all patients diagnosed with IC stage or with poorly differentiated tumors. Anti-angiogenic targeted therapies have been successfully tested in ovarian adenocarcinoma, bevacizumab, an anti-VEGF monoclonal antibody, demonstrating its effectiveness in increasing the interval to disease progression and overall survival in ovarian adenocarcinoma patients and predicted prognostic factors. PARP inhibitors are a new category of targeted agents that, when administered as maintenance therapy, they increase the range until disease progression for patients who have mutations in BRCA 1 and BRCA 2 genes. In conclusion, the multidisciplinary approach and the use of targeted therapies can improve the prognosis of patients with ovarian adenocarcinoma.

The role of reactive oxygen species in patients with ovarian adenocarcinoma

Oana Trifănescu1,2, Maria Gruia1, Laurenţia Galeş1,2, Rodica Anghel1,2

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

Introduction. Epithelial ovarian cancer is the second cause of gynecological cancer worldwide, but the commonest cause of gynaecological cancer-associated death. The aim of this study was to determine the intensity of oxidative stress in ovarian cancer patients and to establish a connection between the presence of the tumor and reactive oxygen species (ROS). Patients and method. Thirty-five patients diagnosed in our centre with epithelial ovarian carcinoma stage II-IV between January 2010 and December 2017, who underwent multimodality treatment (surgery and chemotherapy), were included in the study. Reactive oxygen species measured in dynamic (four determinations between every cycle of chemotherapy) were malondialdehyde – to evaluate the lipid peroxidation, ceruloplasmin, SH albumin thiols groups, and in order to evalate the equilibrium of oxidative stress, total antioxidants were measured. Results. There was a systematic increase in the value of ROS: malondialdehyde mean value was 8.12 μmol/100 ml compared to less than 4 μmol/100 ml (normal value); ceruloplasmin mean value was 144.78 U.I. compared to normal value of 120 U.I., both showing an active oxidative process in patients with ovarian cancer. A small decrease of the normal value was noticed in thyols groups (395 versus 450 μmol/l) and that difference may be due to endogenous activation of the antioxidants. An increase of total antioxidants was noticed (1.8 versus 1.6 μmol). All these four compounds decreased between the first determination and the fourth one. There was a strong correlation between lipid peroxides levels and ceruloplasmin (Pearson correlation: 0.315; p=0.005) and between lipid peroxides and thiols groups (Pearson correlation: 0.23; p=0.039). There was a correlation between thiols and antioxidants (Pearson correlation: 0.33; p=0.003). Lipid peroxidation and ceruloplasmin were significantly higher in patients with residual disease (p=0.039 and p=0.046), emphasizing that the tumor is a generator of oxidative stress. Conclusion. The tumor produces reactive oxygen species in patients with advanced ovarian adenocarcinoma. This reactive oxygen species are corelated and acts as signalling molecules in tumor cells.

Rigid and interventional bronchoscopy – beginnings at IOB

Mădălin Ţeţu, Natalia Motaş, Adriana Bene, Mihnea Davidescu, Olivia Batog, Alin Burlacu, Carmen Pantiş, Teodor Horvat

“Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

Introduction. Interventional bronchoscopy can be practiced by flexible bronchoscopy or rigid bronchoscopy. Materials and method. In the Bronchology Laboratory of the “Prof. Dr. Al. Trestioreanu” Institute of Oncology (IOB), flexible bronchoscopy has been practiced since 2010; so far, over 3300 examinations have been performed. Results. There have been practiced: diagnostic explorations (for tracheo-broncho-pulmonary or neighboring pathology – thyroid, esophagus, mediastinum), bronchial and bronchiolo-alveolar lavages, bronchial and tracheal biopsies, transborder peripheral biopsies, foreign body extractions, postoperative therapeutic bronchoscopies, diagnosis of eso-tracheal and eso-bronchial fistulas, trans-bronchial aspirations. Recently, the collaboration between the Bronchoscopy Laboratory, the Intensive Care Unit and the Thoracic Surgery Clinic has resulted in the onset of rigid bronchoscopy for the patients of the institute. A real help in rigid interventional bronchoscopy is the laser of the Thoracic Surgery Operator Block (donated by the Amazonia Foundation to the Thoracic Surgery Clinic). To date, mechanical and laser dissection has been practiced by rigid bronchoscopy in patients with main airway broncho-pulmonary stenosing neoplasm. Conclusions. Interventional bronchoscopy in oncology patients provides a real benefit in obtaining diagnosis, maintaining airway or in the palliative treatment of tumors.

Evaluation of topoisomerase I and II status in human breast cancer cell lines

Maria Monica Vasilescu1, Maria Iuliana Gruia1, Camelia Hotnog2, Mirela Mihăilă2, Marieta Elena Panait1, Lorelei Irina Braşoveanu2

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology Bucharest

2. “Ştefan S. Nicolau” Institute of Virology, Center of Immunology, Bucharest

DNA topoisomerases are nuclear enzymes, essential for a wide range of processes related to DNA metabolism, such as replication and transcription, DNA repair, recombination, chromosome condensation and segregation. The human cells have six topoisomerases, three of them (topoisomerase I, topoisomerase II alpha, and topoisomerase II beta) being of great interest for researchers, proving to be cellular targets for many chemotherapeutic agents commonly used in cancer therapy. Because the cellular level of topoisomerases determines the proportion of the cleavage complexes during the treatment with chemotherapeutic agents and thus their cytotoxicity level, knowing the status of these proteins in the tumor has a great clinical importance for the response to chemotherapy. The objective of this study was to measure the cellular expression of topoisomerase I and topoisomerase II alpha and beta isoform in a panel of human breast cancer cell lines by flow cytometry method. The expression of topoisomerase I, topoisomerase II alpha and beta proteins could be detected in all of the breast cancer cell lines, and some differences of expression have been observed. The results of this study showed that in these cell lines there is no directly or inversely correlation between the levels of expression for all three topoisomerases, a proof of the fact that topoisomerases are regulated differently. In the context of the existence of a different pattern of topoisomerases sensitivity to chemotherapeutic agents, the levels of these proteins in cancerous tissues represent important factors when trying to make more selective treatment regimes for cancer patients.

The management of locally advanced cervical cancer (T1b2-T4a)

Silviu Voinea1,2, Cristian Bordea1,2, Angela Şandru1, Alexandru Blidaru1,2

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest

Cervical cancer is the third most common cancer in women worldwide, but in Romania the incidence and mortality by cervical cancer are the highest in Europe. These are due to the advanced stages at the diagnosis and because of the absence of a national screening program. For these reasons, the cervical cancer still represents a major public health concern in Romania. Although no formal definition exists, a broad definition is based on the risk of local and distance recurrence and requirement for more aggressive therapy (stage T1b2-T4a). In these conditions, is there a place for radical surgey? Surgery may control microscopic disease or may salvage poor responders, or because current imaging is not reliable in detecting microscopic disease, or in case when radiotherapy is technically not feasible. However, surgery has a high complication rate and may be unnecessary in pacients with complete response. Radiotherapy failed to sterilize the primary tumor in nearly half of the cases, although we do not know the real significance of this residual tumor for cervical cancer prognosis. For best local control, should the surgery be performed after chemoradiation? For Romania, with poor network radiotherapy conditions, we consider that surgery should be warranted and also effective.