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  • Transoral Robotic Surgery in the HPV Era

    The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades mostly due to human papillomavirus (HPV)-related infections. Cancers resulting from HPV infection bear a better prognosis than those that are smoking-related. Because HPV-positive patients are often younger, with lower rates of co-morbid illness and longer overall life expectancies, long-term sequelae of therapy have become an important issue. Treatment of oropharyngeal cancers has typically involved the use of radiation and chemotherapy to avoid the morbidity of open surgery which included mandibulotomy and composite resection. Transoral robotic surgery (TORS) is an emerging treatment option for this disease, avoiding the morbidity of open approaches while providing excellent oncologic and functional outcomes. With overall survival rate at 2 years exceeding 80%, and local failure rate of less than 3%, patients receiving TORS report relatively good health-related quality of life (QOL) scores. The aim of the current review is to provide a summary of the current literature with regard to the oncologic and functional outcomes following treatment of OPSCC with TORS.
  • Changes in the Management of Common Bile Duct Stones: 1980 to Date

    Objective: To compare the results of treating patients with common bile duct (CBD) stones by endoscopic sphincterotomy (ES), surgical exploration, or a combination of ES and surgical CBD exploration (the rendezvous technique). Methods: A narrative review of the literature. Summary of Data: Before 1990, 17 cohort studies indicated that ES cleared CBD stones in 92.0% of patients, with a mortality rate of 1.5%. Surgery removed CBD stones in 90.2% of patients, with a 2.1% mortality rate. A single randomized controlled trial in 1987 showed that ES removed CBD stones in 91% of 55 patients, with a 3.6% mortality rate and a 27% complication rate, whereas surgical CBD exploration removed CBD stones in 92%, with a 1.8% mortality rate and a 22% complication rate. Since 1991, 26 randomized controlled trials have shown that laparoscopic–ES rendezvous is as effective as ES alone and laparoscopic surgery alone but is associated with fewer complications, a reduced need for additional procedures, and a shorter hospital stay. Conclusions: A laparoscopic–ES rendezvous appears to be the optimal approach to the treatment of CBD stones in younger and fit patients. The choice between ES alone and laparoscopic–ES rendezvous in older or high-risk patients remains uncertain.
  • The “Immigrant Medical Services” Organization from the End of the British Mandate Through the First Years of Israel (1944–1953)

    The aftermath of the Second World War and the Holocaust triggered mass migration of Jewish refugees to British Mandatory Palestine and, after 1948, the nascent State of Israel. Responding to this crisis, Jews in the Diaspora increased their commitment to facilitate immigration to Israel, particularly by supporting medical services to the Yishuv (pre-state Jewish Settlement). This paper explores the critical role played by Hadassah and other organizations in establishing direct medical services for Jewish immigrants during two key periods of Israel’s history: the end of British Mandatory Palestine (1944–1948) and the early years of the State of Israel (1948–1953). While the Immigrant Medical Services organization faced numerous challenges, this organization was essential in addressing the pressing healthcare needs of a burgeoning population amid morbidity and mortality concerns. An emphasis is placed on the challenges faced by these organizations and the commitment and resourcefulness of all involved, which ultimately shaped the foundation of Israel’s healthcare infrastructure.
  • 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.
  • ADAMTS-13 in the Diagnosis and Management of Thrombotic Microangiopathies

    Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. For many years distinction between these TMAs, especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), remained purely clinical and hard to make. Recent discoveries shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), were found to cause TTP pathology, while Shiga toxins or abnormalities in regulation of the complement system causes microangiopathy and thrombosis in HUS. TMAs may appear in various conditions such as pregnancy, inflammation, malignancy, or exposure to drugs. These conditions might cause acquired TTP, HUS, or other TMAs, or might be a trigger in individuals with genetic predisposition to ADAMTS-13 or complement factor H deficiency. Differentiation between these TMAs is highly important for urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and anti-ADAMTS-13 antibody levels may advance this differentiation resulting in accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool for monitoring treatment efficacy and relapse risk, allowing consideration of therapy addition or change. In the past few years, great improvements in ADAMTS-13 assays have been made, and tests with increased sensitivity, specificity, reproducibility, and shorter turnaround time are now available. These new assays enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which may ultimately result in improvement of TMA management.
  • The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection

    Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained vir-al response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, pro-longed, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fi-brinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to pre-dict disease progression in HCV patients and be a logical target for the development of novel therapeu-tic approaches for the treatment of patients with HCV infection.
  • The Future of Children's Health in the Genomic Era

    The effects of genomic medicine on child health promise to be profound. Medical applications will eventually include characterizing patients’ genomes to detect predictive mutations for pre-symptomatic counseling where treatment exists; to search for causes of diseases of unknown etiology, and to detect carriers for prenatal counseling; to define cancer and other disease-based genomes to design individualized therapy; and to understand our microbiomes to modify these in health and disease. Rapid advances in technology and bioinformatics has reduced the cost and the time and increased the accuracy necessary to sequence whole genomes or whole exomes. However, complete understanding of disease will also require correlation of genomic information with high-quality phenotypic data. In addition, several critical ethical, psycho-social, and public policy issues will require clarity in the coming years. Ultimately these advances will improve the effectiveness of health care for children and for society.
  • Abstracts from the Fourteenth Rambam Research Day, December 7, 2017

    This Supplement of Rambam Maimonides Medical Journal presents the abstracts from the Fourteenth Annual Rambam Research Day. These abstracts represent the newest basic and clinical research coming out of Rambam Health Care Campus—research that is the oxygen for education and development of tomorrow’s generation of physicians. Hence, the research presented on Rambam Research Day is the foundation for understanding patient needs and improving treatment modalities. Bringing research from the bench to the bedside and from the bedside to the community is at the heart of Maimonides’ scholarly and ethical legacy.
  • Comparison of the Supraclavicular, Infraclavicular and Axillary Approaches for Ultrasound-Guided Brachial Plexus Block for Surgical Anesthesia

    Objective: We hypothesized that ultrasound (US)-guided technique of the supra- and infraclavicular and axillary approaches of brachial plexus block (BPB) will produce a high quality of surgical anesthesia for operations below the shoulder independently of the approach and body mass index (BMI). Intercosto-brachial and medial brachial cutaneous nerves will be blocked separately because they are not a part of the brachial plexus. Methods: This is a prospective randomized observer-blinded study. The three approaches of the US-guided BPB without neurostimulation were compared for quality, performance time, and correlation between performance time and BMI. Intercostobrachial and medial brachial cutaneous nerve blocks were used in all patients. Results: A total of 101 patients were randomized into three groups: SCL (supraclavicular), ICL (infra-clavicular), and AX (axillary). Seven patients were excluded due to various factors. All three groups were similar in demographic data, M:F proportion, preoperative diagnosis and type of surgery, anesthesiologists who performed the block, and surgical staff that performed the surgical intervention. The time between the end of the block performance and the start of the operation was also similar. The quality of the surgical anesthesia and discomfort during the operation were identical following comparison between groups. No direct positive correlation was observed between BMI and the block performance time. The time for the axillary block was slightly longer than the time for the supra- and infraclavicular approaches, but it had no practical clinical significance. Transient Horner syndrome was observed in three patients in the SCL group. No other adverse effects or complications were observed. Conclusions: All three approaches can be used for US-guided BPB with similar quality of surgical anesthesia for operations of below the shoulder. A block of the intercostobrachial and medial brachial cutaneous nerves is recommended. Obesity is not a significant factor in relation to the time of US-guided BPB performance, or the quality of surgical anesthesia. (ClinicalTrials.gov number, NCT01442558.)
  • Quality Assurance of Undergraduate Medical Education in Israel by Continuous Monitoring and Prioritization of the Accreditation Standards

    External accreditation reviews of undergraduate medical curricula play an important role in their quality assurance. However, these reviews occur only at 4–10-year intervals and are not optimal for the immediate identification of problems related to teaching. Therefore, the Standards of Medical Education in Israel require medical schools to engage in continuous, ongoing monitoring of their teaching programs for compliance with accreditation standards. In this paper, we propose the following: (1) this monitoring be assigned to independent medical education units (MEUs), rather than to an infrastructure of the dean’s office, and such MEUs to be part of the school governance and draw their authority from university institu¬tions; and (2) the differences in the importance of the accreditation standards be addressed by discerning between the “most important” standards that have been shown to improve student well-being and/or patient health outcomes; “important” standards associated with student learning and/or performance; “possibly important” standards with face validity or conflicting evidence for validity; and “least important” standards that may lead to undesirable consequences. According to this proposal, MEUs will evolve into entities dedicated to ongoing monitoring of the education program for compliance with accreditation standards, with an authority to implement interventions. Hopefully, this will provide MEUs and faculty with the common purpose of meeting accreditation requirements, and an agreed-upon prioritization of accreditation standards will improve their communication and recommendations to faculty.