Non-Inferiority Trials in Surgical Oncology

The classical randomized controlled clinical trial is designed to prove superiority of an investigational therapy over an established therapy or placebo (here referred to as "superiority trial”). Although the randomized controlled superiority trial has its well-grounded role, clinical trials of non-inferiority are equally important in the advance of medical science. Non-inferiority trials test whether a new intervention is as good as a standard treatment with respect to curing the illness (e.g., overall survival) while offering other benefits over the standard therapy, such as lower toxicity, better side-effect profile, improved ease of administration, or reduced costs. The evaluation of non-inferiority is critical in many settings. In surgical oncology, for instance, treatments often combine advantages (e.g., survival benefit) with disadvantages (e.g., high post-operative morbidity due to extensive surgery, considerable toxic effects of an aggressive chemotherapy regimen). The various aspects of different therapeutic strategies may make a treatment decision difficult, requiring a non-inferiority trial to quantify risks and benefits. However, despite their great importance in clinical cancer research, the concept, design, and objectives of non-inferiority trials remain poorly understood in the surgical community. The goal of this review is to discuss the principles, strengths, and challenges of non-inferiority trials and introduce this highly relevant topic to the surgical reader, using examples from the field of surgical oncolog

TAPP or TEP? Population-Based Analysis of Prospective Data on 4,552 Patients Undergoing Endoscopic Inguinal Hernia Repair

Background: Whether total extraperitoneal inguinal hernia repair (TEP) is associated with worse outcomes than transabdominal preperitoneal inguinal hernia repair (TAPP) continues to be a matter of debate. The objective of this large cohort study is to compare outcomes between patients undergoing TEP or TAPP. Methods: Based on prospective data of the Swiss association of laparoscopic and thoracoscopic surgery, all patients undergoing unilateral TEP or TAPP between 1995 and 2006 were included. The following outcomes were compared: conversion rates, intraoperative and postoperative complications, duration of operation. Results: Data on 4,552 patients undergoing TEP (n=3,457) and TAPP (n=1,095) were collected prospectively. Average age and American Society of Anesthesiologists score were similar in the two groups. Patients undergoing TEP had a significantly higher rate of intraoperative complications (TEP 1.9% vs. TAPP 0.9%, p=0.029) and surgical postoperative complications (TEP: 2.3% vs. TAPP: 0.8%, p=0.003). The postoperative length of stay was longer for patients undergoing TAPP (2.9 vs. 2.3days, p=0.002), whereas the duration of the operation was longer for TEP (66.6 vs. 59.0min, p<0.001) and the conversion rate was higher (TEP 1.0% vs. TAPP 0.2%, p=0.011). Conclusions: This study is one of the first population-based analyses comparing TEP and TAPP in a prospective cohort of more than 4,500 patients. Intraoperative and surgical postoperative complications were significantly higher in patients undergoing TEP. TEP is also associated with longer operating times and higher conversion rates. Therefore, on a population-based level, the TAPP technique appears to be superior to the TEP repair in patients undergoing unilateral inguinal hernia repai

Active Antigen-specific Immunotherapy of Melanoma: from Basic Science to Clinical Investigation

Advanced-stage melanoma here dismal prognosis, and novel therapeutic approaches are urgently required. The possibility of taking advantage of the immune response of patients for its treatment has been an appealing concept for almost a century. Only during the last decade, however, has the molecular identification of tumor-associated antigens (TAAs) offered the possibility of vaccinating patients (e.g., active induction of TAA-specific immune responses). Active antigen-specific immunotherapy (AASIT) is currently being investigated in a number of clinical centers as a treatment option for advanced-stage melanoma. A large number of melanoma TAAs have been molecularly characterized and are being used in vaccination trials in various molecular forms and according to various immunization protocols. Here we provide a short overview on melanoma TAAs, the technologies currently in use to induce specific cytotoxic T-lymphocyte (CTL) responses in vivo, and their monitoring. We also propose a tentative AASIT agenda for the next few years, aiming at improving the capacity to induce and monitor TAA-specific immune responses and to verify their clinical effectivenes

Emergency Preparedness: Perceptions of People with Disabilities

The prevalence of emergencies and disasters has increased over the past decade which has caused cities, states and countries to routinely develop emergency preparedness and management plans (Turk, 2016). Although these demands have increased, individuals with disabilities have been less represented in the development of the plans (Timmons, 2017; Turk, 2016). According to The World Bank Disaster Risk Management Report (2020), disasters (e.g., infectious disease outbreaks such as COVID-19, hurricanes, earthquakes, industrial accidents.) and post-disaster consequences have increased over recent years. Although individuals with disabilities have become more aware of emergency preparedness and its importance, researchers have noted that there is a huge disparity of awareness and preparedness related to emergencies and disasters in the disability community (UNISDR Global Assessment Report, 2019). Therefore, this issue could adversely affect individuals with disabilities in essential areas of life (e.g., quality of life, employability, mobility, maintaining their home, communication) (Fox, et al., 2010; Twigg, et al., 2018). In addition, most studies seem to focus on disaster recovery and post disaster information rather than prevention and planning strategies that could help alleviate, and at times prevent, post-disaster issues for people with disabilities and elderly. Similarly, a lack of awareness of individualized emergency planning strategies for individuals with specific healthcare needs continues to be a significant reason why individuals with disabilities and elderly are more likely to be negatively affected by emergencies than other populations (Charlton, 2000; UNISDR, 2014). The lack of access to participate in emergency preparedness teams or organizations results in persons without disabilities continuing to exclude people with disabilities in the planning efforts of proper and inclusive emergency plans in their communities at large. The purpose of this study was to measure the self-perceptions of individuals with disabilities related to their level of emergency preparedness as well as access to emergency preparedness information. This study used purposive sampling by recruiting individuals with disabilities who have received services from their local center for independent living (CIL) and reside in the state of Texas. This study utilized the Texas Hazard Mitigation Questionnaire-Revised and a demographic survey that were developed by the researcher to help gain an understanding of general preparedness intentions and behavior as well as personal and demographic factors influencing decision making (e.g., information sources, risk perception, age, dwelling type, socioeconomic status)

The distribution of robotic surgery in general and visceral surgery departments in Switzerland - a nationwide inquiry.

OBJECTIVES Since its introduction as a clinical technique, robotic surgery has been extended to different fields of surgery. However, the indications as well as the number of robotic procedures varied in different institutions. The aim of this investigation was to evaluate the current use of robotic surgery in general and digestive surgery in Switzerland. METHODS All Swiss surgical departments that are recognized training institutes for postgraduate training in surgery by the Swiss Institute of Medical Education (SIWF) were queried with a detailed questionnaire regarding the use of robotic surgery techniques and were analyzed regarding hospital size and type of hospital. RESULTS Ninety-three departments were queried, and 67 % (n=63) answered the survey. Fifty-eight were public, and five were private institutions. Seventeen (26 %) of the queried departments used robotic surgery in digestive surgery. Four out of 17 (23 %) of the departments that performed robotic surgery were private hospitals, while 13 (77 %) were public institutions. In the majority of departments, robotic surgery of the rectum (n=12; 70.6 %) and colon (n=11; 64.7 %) was performed, followed by hernia procedures (n=8; 47.1 %) and fundoplication (n=7; 41.2 %). Less frequently, pancreatic resections (n=5; 29.4 %), cholecystectomy (n=4; 23.5 %), adrenalectomy (n=4; 23.5 %), gastric bypass (n=3; 17.7 %), gastric sleeve (n=3; 17.7 %), hepatic procedures (n=2; 11.7 %), or small bowel resections (n=1; 5.9 %) were performed as robotic procedures. More than 25 procedures per year per department were performed for hernia surgery (n=5 departments), gastric bypass (n=2 departments), cholecystectomy, fundoplication, and colon surgery (each n=1 department). CONCLUSIONS The number and range of robotic procedures performed in Switzerland varied widely. Higher accreditation for general surgery or subspecialization of visceral surgery of the department was positively associated with the use of robotic techniques, reflecting an unequal availability of robotic surgery

Enhanced Recovery after Surgery (ERAS) and its applicability for major spine surgery

This article examines the relevance of applying the Enhanced Recovery after Surgery (ERAS) approach to patients undergoing major spinal surgery. The history of ERAS, details of the components of the approach, and the underlying rationale are explained. Evidence on outcomes achieved by using the ERAS approach in other orthopaedic and complex surgical procedures are then outlined. Data on major spinal surgery rates and current practice are reviewed and the rationale for the use of ERAS in major spinal surgery is discussed, and potential challenges to its adoption acknowledged. A thorough literature search is then undertaken to examine the use of ERAS pathways in major spinal surgery, and the results presented. The article then reviews the evidence to support the application of individual ERAS components such as patient education, multimodal pain management, surgical approach, blood loss, nutrition, and physiotherapy in major spinal surgery, and discusses the need for further robust research to be undertaken. The article concludes that given the rising costs of surgery and levels of patient dissatisfaction, an ERAS pathway that focuses on optimizing clinical procedures by adopting evidence-based practice, and improving logistics, should enable major spinal surgery patients to recover more quickly with lower rates of morbidity and improved longer term outcomes