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  • Platinum-based Chemotherapy in Primary Advanced Seminoma—a Retrospective Analysis: Treatment Results at the Northern Israel Oncology Center (1989-2010)

    Objective: Over the past 30 years, great strides have been made in the treatment of disseminated testicular tumors. Despite the low number of patients and the rarity of studies concerning primary advanced seminoma, the efficacy of chemotherapy is clear, mainly 3-4-cisplatin-based chemotherapy. Aiming to contribute to the understanding and implementation of proper chemotherapeutic management in advanced seminoma patients, we retrospectively summarized our experience with 26 patients who were referred for platinum-based chemotherapy, post-orchiectomy to the Northern Israel Oncology Center between 1989 and 2010. Response rate, side effects, and long-term outcome were investigated. Methods: Before chemotherapy, meticulous staging was done, including tumor markers (B-human chorionic gonadotropin (B-HCG), alpha-fetoprotein (AFP), and lactic dehydrogenase (LDH)), and abdominal and pelvic computerized tomography (CT) scans were carried out. Results: All 26 treated patients achieved complete remission, clinically and symptomatically, with normalization of their CT scans. At a median follow-up of 120 months (range, 24–268 months) all patients are alive, without evidence of recurrent disease. One patient whose disease recurred twice achieved a third complete remission following salvage treatment with high-dose chemotherapy and autologous peripheral stem cell transplantation. Another patient, who preferred surveillance, relapsed abdominally after 9 months but achieved long-standing complete remission with cisplatin-based chemotherapy. Both these patients are alive with no evidence of disease. Three patients recovered uneventfully from bleomycin-induced pneumonitis. Conclusions: Advanced seminoma is a highly curable disease using platinum-based chemotherapy. Our study confirms the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma.
  • Assessment of Margins in Transoral Laser and Robotic Surgery

    The growing practice of endoscopic surgery has changed the therapeutic management of selected head and neck cancers. Although a negative surgical margin in resection of neoplasm is the most important surgical principle in oncologic surgery, controversies exist regarding assessment and interpretation of the status of margin resection. The aim of this review was to summarize the literature considering the assessment and feasibility of negative margins in transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). Free margin status is being approached differently in vocal cord cancer (1–2 mm) compared with other sites in the upper aerodigestive tract (2–5 mm). Exposure, orientation of the pathological specimen, and co-operation with the pathologist are crucial principles needed to be followed in transoral surgery. Piecemeal resection to better expose deep tumor involvement and biopsies taken from surgical margins surrounding site of resection can improve margin assessment. High rates of negative surgical margins can be achieved with TLM and TORS. Adjuvant treatment decision should take into consideration also the surgeon’s judgment with regard to the completeness of tumor resection.
  • Transoral Laser Surgery for Laryngeal Cancer

    Transoral laser microsurgery (TLM) was pioneered in the early 1970s as an approach to treat laryngeal pathology with precision and minimal thermal damage to the vocal cords. Over the last four decades, TLM has become an integral part of the treatment paradigm for patients with laryngeal cancer. TLM is one of the primary treatment options for early-stage laryngeal tumors. However, in recent years, surgeons have begun to develop TLM into a more versatile approach which can be used to address advanced laryngeal tumors. Although functional outcomes following TLM for advanced laryngeal disease are scarce, survival outcomes appear to be comparable with those reported for organ preservation strategies employing external beam radiation therapy (EBRT) and chemotherapy. In addition, TLM plays an important role in the setting of recurrent laryngeal cancer following primary irradiation. TLM has been demonstrated to decrease the need for salvage total laryngectomy resulting in improved functionality while retaining comparable oncologic outcomes. The aims of this review are to elucidate the indications, techniques, and oncological outcomes of TLM for advanced laryngeal cancers.
  • The Surgical Management of Thyroid Cancer

    Thyroid cancer has been increasing in incidence, with the number of reported cases in the US rising by 25% over the last 3 years. With growing technological advances in the field and improved contributions of diagnostics, surgical decision-making and operative planning have taken on new challenges. Herein, we review the current clinical practice recommendations and active areas of surgical controversy, reflective of the most recently published professional consensus guidelines and a systematic review of the literature.
  • A New Paradigm Is Needed for Medical Education in the Mid-Twenty-First Century and Beyond: Are We Ready?

    The twentieth century witnessed profound changes in medical education. All these changes, however, took place within the existing framework, suggested by Flexner a century ago. The present paper suggests that we are approaching a singularity point, where we shall have to change the paradigm and be prepared for an entirely new genre of medical education. This suggestion is based upon analysis of existing and envisaged trends: first, in technology, such as availability of information and sophisticated simulations; second, in medical practice, such as far-reaching interventions in life and death that create an array of new moral dilemmas, as well as a change in patient mix in hospitals and a growing need of team work; third, in the societal attitude toward higher education. The structure of the future medical school is delineated in a rough sketch, and so are the roles of the future medical teacher. It is concluded that we are presently not prepared for the approaching changes, neither from practical nor from attitudinal points of view, and that it is now high time for both awareness of and preparation for these changes.
  • Vulvar Cancer in the North of Israel

    Purpose. This is a population study of patients who were treated for vulvar cancer in a tertiary center in northern Israel, aimed to report clinical findings, treatment, and outcome. Methods. A retrospective chart review of all medical records of consecutive patients who were treated for vulvar cancer in the years 1993–2012 was conducted. Data extracted from the medical records included demographics, histology, size of lesion, stage of disease at diagnosis, type of treatment, radiation dose, follow-up, recurrence, and survival. Results. The study included 44 patients with a median age of 69.8 years (range, 42–93 years). Thirty-five (79.5%) of the patients were of Jewish descent, five were Arabic, and four were of other descent. The most common histology type was squamous cell carcinoma in 35 (79.5%) patients. Most patients were staged FIGO II–III at time of diagnosis. Surgery was the most common primary treatment modality (54.2%). Twenty-three (52.2%) patients had recurrent disease. Older age and more advanced stage at diagnosis were associated with increased mortality. Conclusion. Vulvar cancer is common among elderly women with co-morbidities who present in advanced disease stage; all these factors are significant for survival.
  • Coagulation and Placenta-Mediated Complications

    Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women’s health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications.
  • The Role for Insulin and Insulin-like Growth Factors in the Increased Risk of Cancer in Diabetes

    Patients with type 2 diabetes (T2D) are at increased risk of developing cancer. This evidence arises from numerous epidemiologic studies that relate a positive association between T2D and cancer. In-vitro and several in-vivo experiments have attempted to discern the potential mechanistic factors involved in this relationship. Candidates include hyperinsulinemia, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-2 (IGF-2) signaling. These studies demonstrated that increased insulin, IGF-1, and IGF-2 signaling through the insulin receptor and IGF-1 receptor can induce cancer development and progression.
  • Heparanase – A Link Between Coagulation, Angiogenesis and Cancer

    Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis, and angiogenesis. Recently we have demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on the cell surface, leading to dissociation of TFPI from the cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. More recently, we have shown that heparanase directly enhances TF activity, resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased levels and possible involvement of heparanase in vascular complications in pregnancy. Taking into account the prometastatic and proangiogenic functions of heparanase, overexpression in human malignancies, and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel arena for further research.
  • Abstracts from Rambam Research Day