Patterns of Failure Following Preoperative Chemotherapy and Stereotactic Body Radiation Therapy and Resection for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer.

BACKGROUND: The role of neoadjuvant stereotactic body radiation therapy (SBRT) in the treatment of pancreatic adenocarcinoma (PDAC) is controversial and the optimal target volumes and dose-fractionation are unclear. The aim of this study is to report on treatment outcomes and patterns of failure of patients with borderline resectable (BL) or locally advanced (LA) pancreatic cancer following preoperative chemotherapy and SBRT. METHODS: We conducted a single-institution, retrospective study of patients with BL or LA PDAC. Patients received neoadjuvant chemotherapy and SBRT was prescribed to 30 Gy over 5 fractions to the pancreas planning tumor volume (PTV). A subset of patients received a simultaneous integrated boost to the high risk vascular PTV and/or elective nodal irradiation (ENI). Following neoadjuvant chemoradiation, all patients underwent subsequent resection. Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMPFS), and locoregional control (LRC) estimates were obtained using Kaplan-Meier analysis. RESULTS: Twenty-two patients with BL (18) or LA (4) PDAC were treated with neoadjuvant chemotherapy and SBRT followed by resection from 2011-2022. Following neoadjuvant treatment, 5 patients (23%) achieved a pathologic complete response (pCR) and 16 patients (73%) had R0 resection. At 24 months, there were no isolated locoregional recurrences (LRRs), 9 isolated distant recurrences (DRs), and 5 combined LRRs and DRs. Two LRRs were in-field, 2 LRRs were marginal, and 1 LRR was both in-field and marginal. 2-year median LRC, LRRFS, DMPFS, PFS, and OS were 77.3%, 45.5%, 31.8%, 31.8%, and 59.1%, respectively. For BL and LA cancers, 2-year LRC, DMPFS, and OS were 83% vs. 75%, (p = 0.423), 39% vs. 0% (p = 0.006), and 61% vs. 50% (p = 0.202), respectively. ENI was associated with improved LRC (p = 0.032) and LRRFS (p = 0.033). Borderline resectability (p = 0.018) and lower tumor grade (p = 0.027) were associated with improved DMPFS. CONCLUSIONS: Following preoperative chemotherapy and SBRT, locoregional failure outside of the target volume occurred in 3 of 5 recurrences; ENI was associated with improved LRC and LRRFS. Further studies are necessary to define the optimal techniques for preoperative radiation therapy.

The Elephant in the Room: Racial Microaggressions and Implicit Bias in Surgical Training.

OBJECTIVE: The aim of this study was to examine the association between race, experience of microaggressions, and implicit bias in surgical training. BACKGROUND: There is persistent underrepresentation of specific racial and ethnic groups in the field of surgery. Prior research has demonstrated significant sex differences among those who experience microaggressions during training. However, little research has been conducted on the association between race and experiences of microaggressions and implicit bias among surgical trainees. METHODS: A 46-item survey was distributed to general surgery residents and residents of surgical subspecialties through the Association of Program Directors in Surgery listserv and social media platforms. The questions included general information/demographic data and information about experiencing, witnessing, and responding to microaggressions during surgical training. The primary outcome was the prevalence of microaggressions during surgical training by self-disclosed race. Secondary outcomes were predictors of and adverse effects of microaggressions. RESULTS: A total of 1624 resident responses were obtained. General surgery residents comprised 825 (50.8%) responses. The female-to-male ratio was nearly equal (815:809). The majority of respondents identified as non-Hispanic White (63.4%), of which 5.3% of residents identified as non-Hispanic Black, and 9.5% identified as Hispanic. Notably, 91.9% of non-Hispanic Black residents (n=79) experienced microaggressions. After adjustment for other demographics, non-Hispanic Black residents were more likely than non-Hispanic White residents to experience microaggressions [odds ratio (OR): 8.81, P <0.001]. Similar findings were observed among Asian/Pacific Islanders (OR: 5.77, P <0.001) and Hispanic residents (OR: 3.35, P <0.001). CONCLUSIONS: Race plays an important role in experiencing microaggressions and implicit bias. As the future of our specialty relies on the well-being of the pipeline, it is crucial that training programs and institutions are proactive in developing formal methods to address the bias experienced by residents.

Phase 1 Study of Hypofractionated Proton Beam Radiation Therapy in Adjuvant Pancreatic Cancer (PROTON-PANC).

PURPOSE: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy. METHODS AND MATERIALS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2). RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%). CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.

Microaggressions and Implicit Bias in Surgical Training: An Undocumented but Pervasive Phenomenon.

OBJECTIVE: To examine the prevalence, nature, and source of microaggressions experienced by surgical residents during training. SUMMARY AND BACKGROUND DATA: The role of microaggressions in contributing to workplace culture, individual performance, and professional satisfaction has become an increasingly studied topic across various fields. Little is known about the prevalence and impact of microaggressions during surgical training. METHODS: A 46-item survey distributed to current surgical residents in training programs across the United States via the Association of Program Directors in Surgery listserv and social media platforms between January and May 2020. Survey questions explored the frequency and extent of events of experiencing, witnessing, and responding to microaggressions in the workplace. The primary outcome was the occurrence of microaggressions experienced by surgical residents. Secondary outcomes included the nature, impact, and responses to these events. RESULTS: A total of 1624 responses were collected, with an equal distribution by self-identified gender (female, n = 815; male, n = 809). The majority of trainees considered themselves heterosexual (n = 1490, 91.7%) and White (n = 1131, 69.6%). A majority (72.2%, n = 1173) of respondents reported experiencing microaggressions, most commonly from patients (64.1%), followed by staff (57.5%), faculty (45.3%), and co-residents (38.8%). Only a small proportion (n = 109, 7.0%) of residents reported these events to graduate medical education office/program director. Nearly one third (30.8%) of residents said they experienced retaliation due to reporting of micro-aggressions. CONCLUSIONS: Based on this large, national survey of general surgery and surgical subspecialty trainees, microaggressions appear to be pervasive in surgical training. Microaggressions are rarely reported to program leadership, and when reported, can result in retaliation.

Frequency and Characteristics of Social Media Use among General Surgery Trainees.

INTRODUCTION: With increased social isolation due to COVID-19, social media has been increasingly adopted for communication, education, and entertainment. We sought to understand the frequency and characteristics of social media usage among general surgery trainees. MATERIALS AND METHODS: General surgery trainees in 15 American training programs were invited to participate in an anonymous electronic survey. The survey included questions about demographics, frequency of social media usage, and perceptions of risks and benefits of social media. Univariate analysis was performed to identify differences between high users of social media (4-7 h per week on at least one platform) and low users (0-3 h or less on all platforms). RESULTS: One hundred fifty-seven of 591 (26.6%) trainees completed the survey. Most respondents were PGY3 or lower (75%) and high users of social media (74.5%). Among high users, the most popular platforms were Instagram (85.7%), YouTube (85.1%), and Facebook (83.6%). YouTube and Twitter were popular for surgical education (77.3% and 68.2%, respectively). The most reported benefits of social media were improving patient education and professional networking (85.0%), where high users agreed more strongly about these benefits (P = 0.002). The most reported risks were seeing other residents (42%) or attendings (17%) with unprofessional behavior. High users disagreed more strongly about risks, including observing attendings with unprofessional behavior (P = 0.028). CONCLUSIONS: Most respondents were high users of social media, particularly Instagram, YouTube, and Facebook. High users incorporated social media into their surgical education while perceiving more benefits and fewer risks of social media.

Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients with Moderate to Severe COVID 19: A Phase IIa Trial.

Background: A profound need remains to develop further therapeutics for treatment of those hospitalized with COVID-19. Based on data implicating the type 2 cytokine interleukin (IL)-13 as a significant factor leading to critical COVID-19, this trial was designed to assess dupilumab, a monoclonal antibody that blocks IL-13 and IL-4 signaling, for treatment of inpatients with COVID-19. Methods: We conducted a phase IIa randomized double-blind placebo-controlled trial to assess the safety and efficacy of dupilumab plus standard of care versus placebo plus standard of care in mitigating respiratory failure and death in those hospitalized with COVID-19. Subjects were followed prospectively for 60 days. The primary endpoint was the proportion of patients alive and free of invasive mechanical ventilation at 28 days. Findings: Forty eligible subjects were enrolled from June to November of 2021. There was no difference in adverse events nor in ventilator free survival at day 28 between study arms. However, for the secondary endpoint of mortality at day 60, subjects randomized to dupilumab had a higher survival rate compared to the placebo group (89.5% vs 76.2%, adjusted HR 0.05, 95% CI: 0.0-0.72, p=0.03). There were fewer subjects admitted to the ICU in the dupilumab group compared to placebo (33.3% vs 66.7%; adjusted HR 0.44, 95% CI: 0.09-2.09, p=0.30). Lastly, we saw downstream evidence of IL-4 and IL-13 signaling blockade in the dupilumab group through analysis of immune biomarkers over time. Interpretation: Dupilumab was well tolerated and improved 60-day survival in patients hospitalized with moderate to severe COVID-19. Trial Registration: This trial is registered with ClinicalTrials.gov, NCT04920916 . Funding: Virginia Biosciences Health Research Corporation, PBM C19, Henske Family Foundation, National Institutes of Health, National Cancer Institute.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).

How We Do It: Implementing a Virtual, Multi-Institutional Collaborative Education Model for the COVID-19 Pandemic and Beyond.

OBJECTIVE: To describe the implementation of a virtual, multi-institutional educational collaboration involving over 50 general surgery residency programs during the COVID-19 pandemic that enabled enhanced learning for surgical residents despite social-distancing requirements. DESIGN: Description of Virginia Commonwealth University's virtual educational augmentation program and the development of a collaborative teaching network during the coronavirus pandemic. SETTING: This collaboration was initiated by Virginia Commonwealth University's Department of Surgery, Richmond, VA, and grew to include general surgery residency programs from across the nation. PARTICIPANTS: General surgery residents and faculty from Departments of General Surgery were recruited locally via direct emails and nationally via the Association of Program Directors' listserv and Twitter. In total, 52 institutions participated from every part of the country. RESULTS: A virtual, multi-institutional collaborative lecture series was initiated that grew to involve over 50 general surgery residency programs, allowing for daily didactics by experts in their fields during the initial surge of the COVID-19 pandemic, while maintaining social distancing and the provision of essential clinical care. CONCLUSION: A multi-institutional collaboration enabled continued didactic education during the coronavirus pandemic, vastly broadening the expertise, scope and variety available to residents, while decreasing burden on faculty. We believe this can serve as a framework for future multi-institutional collaborations that extend beyond the COVID-19 era.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

General surgery involvement with ventriculoperitoneal shunt insertions reduces revision rates.

BACKGROUND: Ventriculoperitoneal shunts (VPS) are placed for a variety of etiologies. It is common for general surgery to assist with insertion of the distal portion in the peritoneum. OBJECTIVE: To determine if there is a difference in revision rates in patients undergoing VPS placement with general surgery as well as those undergoing laparoscopic insertion. METHODS: A retrospective review of all consecutive patients undergoing VPS placements was performed in a three-year period (2017-2019). Those that underwent placement with general surgery were compared to those without general surgery. Additionally, patients undergoing distal placement via mini-laparotomy versus laparoscopy were compared. Multivariable logistic regression was used to examine risk factors for distal VPS failure. RESULTS: 331 patients were included. 202 (61.0 %) underwent VPS placement with general surgery. 121 (36.6 %) patients underwent insertion via laparoscopic technique. General surgery involvement reduced operative times, decreased length of stay, and lowered overall revision rates with distal revision rates being most significant (1.5 % vs 8.5 %; p = 0.0034). Patients undergoing VPS placement via laparoscopic technique had decreased operative time, length of stay, in-hospital complications and revision rates, with significant decrease in shunt infection (1.7 % vs 7.1 %; p = 0.0366). A history of prior shunt or abdominal surgery (OR 3.826; p = 0.0282) and lack of general surgery involvement (OR 20.98; p = 0.0314) are independent risk factors for distal shunt revision in our cohort. CONCLUSION: The use of general surgeons in VPS insertion can be of benefit by decreasing operative time, length of stay, total revisions, and distal revision rates. Further prospective studies are warranted to determine true benefit.

Burnout and its relationship with perceived stress, self-efficacy, depression, social support, and programmatic factors in general surgery residents.

BACKGROUND: Burnout affects surgical residents' well-being. OBJECTIVE: We sought to identify factors associated with burnout among surgery residents. METHODS: An electronic/anonymous survey was sent to surgical residents at 18 programs, consisting of demographic/programmatic questions and validated scales for burnout, depression, perceived stress, self-efficacy, and social support. Residents were grouped into quartiles based off burnout, and predictors were assessed using univariate and multivariate analyses. RESULTS: 42% of residents surveyed completed it. Burnout was associated with depression, higher perceived stress/debt, fewer weekends off, less programmatic social events, and residents were less likely to reconsider surgery if given the chance. Low burnout was associated with lower depression/stress, higher social support/self-efficacy, more weekends off per month, program mentorship, lower debt, and residents being more likely to choose surgery again if given the chance. On multivariate analysis, higher depression/perceived stress were associated with burnout, and lower burnout scores were associated with lower stress/higher self-efficacy. CONCLUSIONS: Burnout in surgery residents is associated with higher levels of depression and perceived stress. The addition of programmatic social events, limiting weekend work, and formal mentoring programs may decrease burnout.

Intestinal Obstruction: Evaluation and Management.

Acute intestinal obstruction occurs when the forward flow of intestinal contents is interrupted or impaired by a mechanical cause. It is most commonly induced by intra-abdominal adhesions, malignancy, and herniation. The clinical presentation generally includes nausea, emesis, colicky abdominal pain, and cessation of passage of flatus and stool, although the severity of these clinical symptoms varies based on the acuity and anatomic level of obstruction. Abdominal distension, tympany to percussion, and high-pitched bowel sounds are classic findings. Laboratory evaluation should include a complete blood count, metabolic panel, and serum lactate level. Imaging with abdominal radiography or computed tomography can confirm the diagnosis and assist in decision making for therapeutic planning. Management of uncomplicated obstructions includes intravenous fluid resuscitation with correction of metabolic derangements, nasogastric decompression, and bowel rest. Patients with fever and leukocytosis should receive antibiotic coverage against gram-negative organisms and anaerobes. Evidence of vascular compromise or perforation, or failure to resolve with adequate nonoperative management is an indication for surgical intervention.

Subdiaphragmatic Vagotomy With Pyloroplasty Ameliorates the Obesity Caused by Genetic Deletion of the Melanocortin 4 Receptor in the Mouse.

Background/Objectives: We tested the hypothesis that abolishing vagal nerve activity will reverse the obesity phenotype of melanocortin 4 receptor knockout mice (Mc4r-/-). Subjects/Methods: In two separate studies, we examined the efficacy of bilateral subdiaphragmatic vagotomy (SDV) with pyloroplasty in the prevention and treatment of obesity in Mc4r-/- mice. Results: In the first study, SDV prevented >20% increase in body weight (BW) associated with this genotype. This was correlated with a transient reduction in overall food intake (FI) in the preventative arm of the study. Initially, SDV mice had reduced weekly FI; however, FI normalized to that of controls and baseline FI within the 8-week study period. In the second study, the severe obesity that is characteristic of the adult Mc4r-/- genotype was significantly improved by SDV with a magnitude of 30% loss in excess BW over a 4-week period. Consistent with the first preventative study, within the treatment arm, SDV mice also demonstrated a transient reduction in FI relative to control and baseline levels that normalized over subsequent weeks. In addition to the accompanying loss in weight, mice subjected to SDV showed a decrease in respiratory exchange ratio (RER), and an increase in locomotor activity (LA). Analysis of the white fat-pad deposits of these mice showed that they were significantly less than the control groups. Conclusions: Altogether, our data demonstrates that SDV both prevents gain in BW and causes weight loss in severely obese Mc4r-/- mice. Moreover, it suggests that an important aspect of weight reduction for this type of monogenic obesity involves loss of signaling in vagal motor neurons.

Stereotactic Body Radiation Therapy (SBRT) Combined With Chemotherapy for Unresected Pancreatic Adenocarcinoma.

OBJECTIVES: The role of radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to conventional radiation therapy, stereotactic body radiation therapy (SBRT) delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here, we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer. MATERIALS AND METHODS: Thirty-eight patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable pancreatic cancer at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over 5 days. Toxicities were scored using the Common Terminology Criteria for Adverse Events version 3. Survival was calculated using the Kaplan-Meier method. RESULTS: The median age was 70 years (range, 45 to 90 y). Eastern Cooperative Oncology Group performance status ranged from 0 to 3. Thirty-four patients received concurrent chemotherapy. Four patients received sequential chemotherapy. Median overall survival was 14.3 months and median progression-free survival was 9.2 months from diagnosis. From radiation, overall survival and progression-free survival were 12.3 and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included 1 grade 3 gastric outlet obstruction, 1 grade 4 biliary stricture, and 1 grade 5 gastric hemorrhage. CONCLUSIONS: SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible, and generally well tolerated. Outcomes of SBRT combined with chemotherapy compare favorably to results obtained with chemotherapy and conventional radiation therapy.

Pancreaticoduodenectomy hospital resource utilization in octogenarians.

BACKGROUND: Although pancreaticoduodenectomy (PD) is feasible in patients greater than or equal to 80 years, little is known about the potential strain on resource utilization. METHODS: Outcomes and inpatient charges were compared across age cohorts (I: ≤70, II: 71 to 79, III: ≥80 years) in 99 patients who underwent PD (2005 to 2013) at our institution. The generalized linear modeling approach was used to estimate the impact of age. RESULTS: Perioperative complications were equivalent among cohorts. Increasing age was associated with intensive care unit use, increased length of stay (LOS), and the likelihood of discharge to a skilled facility. After controlling for covariates, hospital charges were significantly higher in Cohort III (P = .006) and Cohort II (P = .035) when compared with Cohort I. However, hospital charges between Cohorts II and III were equivalent (P = .374). Complications (P = .005) and LOS (P < .001) were associated with higher hospital charges. CONCLUSIONS: Increasing age was associated with increased intensive care unit, LOS, and discharge to skilled facilities. However, octogenarians had equivalent PD charges and outcome measures when compared with septuagenarians and future studies should validate these findings in larger national studies.

Robotic, laparoscopic and open surgery for gastric cancer compared on surgical, clinical and oncological outcomes: a multi-institutional chart review. A study protocol of the International study group on Minimally Invasive surgery for GASTRIc Cancer-IMIGASTRIC.

INTRODUCTION: Gastric cancer represents a great challenge for healthcare providers and requires a multidisciplinary treatment approach in which surgery plays a major role. Minimally invasive surgery has been progressively developed, first with the advent of laparoscopy and recently with the spread of robotic surgery, but a number of issues are currently being debated, including the limitations in performing an effective extended lymph node dissection, the real advantages of robotic systems, the role of laparoscopy for Advanced Gastric Cancer, the reproducibility of a total intracorporeal technique and the oncological results achievable during long-term follow-up. METHODS AND ANALYSIS: A multi-institutional international database will be established to evaluate the role of robotic, laparoscopic and open approaches in gastric cancer, comprising of information regarding surgical, clinical and oncological features. A chart review will be conducted to enter data of participants with gastric cancer, previously treated at the participating institutions. The database is the first of its kind, through an international electronic submission system and a HIPPA protected real time data repository from high volume gastric cancer centres. ETHICS AND DISSEMINATION: This study is conducted in compliance with ethical principles originating from the Helsinki Declaration, within the guidelines of Good Clinical Practice and relevant laws/regulations. A multicentre study with a large number of patients will permit further investigation of the safety and efficacy as well as the long-term outcomes of robotic, laparoscopic and open approaches for the management of gastric cancer. TRIAL REGISTRATION NUMBER: NCT02325453; Pre-results.

Current status of minimally invasive surgery for gastric cancer: A literature review to highlight studies limits.

BACKGROUND: Gastric cancer represents a great challenge for health care providers and requires a multidisciplinary approach in which surgery plays the main role. Minimally invasive surgery has been progressively developed, first with the advent of laparoscopy and more recently with the spread of robotic surgery, but a number of issues are currently being investigate, including the limitations in performing effective extended lymph node dissections and, in this context, the real advantages of using robotic systems, the possible role for advanced Gastric Cancer, the reproducibility of completely intracorporeal techniques and the oncological results achievable during follow-up. METHOD: Searches of MEDLINE, Embase and Cochrane Central Register of Controlled Trials were performed to identify articles published until April 2014 which reported outcomes of surgical treatment for gastric cancer and that used minimally invasive surgical technology. Articles that deal with endoscopic technology were excluded. RESULTS: A total of 362 articles were evaluated. After the review process, data in 115 articles were analyzed. CONCLUSION: A multicenter study with a large number of patients is now needed to further investigate the safety and efficacy as well as long-term outcomes of robotic surgery, traditional laparoscopy and the open approach.

Bowel perforation associated with robust response to BRAF/MEK inhibitor therapy for BRAF-mutant melanoma: a case report.

Combination BRAF/MEK inhibition has shown improved response rates and longer progression-free and overall survival for patients with BRAF-mutant metastatic melanoma. A 63-year-old female with widely metastatic BRAF V600E-mutant melanoma was treated with dabrafenib/trametinib. Ten weeks into therapy, she was treated conservatively for a partial bowel obstruction involving a lesion in the distal ileum. She presented two weeks later with CT evidence of a high-grade bowel obstruction with perforation. Emergent surgery was performed. Intraoperative inspection and pathologic analysis of the resected specimen revealed no evidence of melanoma. Seven months postoperatively she is disease free and fully functional. Rapid BRAF/MEK inhibitor-induced regression of small bowel lesions can result in bowel perforation, which is critical to distinguish from the consequences of disease progression.

Human Pancreatic Cancer-Associated Stellate Cells Remain Activated after in vivo Chemoradiation.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibrotic reaction or desmoplasia and complex involvement of the surrounding tumor microenvironment. Pancreatic stellate cells are a key mediator of the pancreatic matrix and they promote progression and invasion of pancreatic cancer by increasing cell proliferation and offering protection against therapeutic interventions. Our study utilizes human tumor-derived pancreatic stellate cells (HTPSCs) isolated from fine needle aspirates of pancreatic cancer tissue from patients with locally advanced, unresectable pancreatic adenocarcinoma before and after treatment with full-dose gemcitabine plus concurrent hypo-fractionated stereotactic radiosurgery. We show that HTPSCs survive in vivo chemotherapy and radiotherapy treatment and display a more activated phenotype post-therapy. These data support the idea that stellate cells play an essential role in supporting and promoting pancreatic cancer and further research is needed to develop novel treatments targeting the pancreatic tumor microenvironment.

Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety.

BACKGROUND: Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC. METHODS: Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires. RESULTS: Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment. CONCLUSIONS: SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity.