CivaSheet intraoperative radiation therapy for pancreatic cancer.

The treatment of borderline resectable (BR) pancreatic cancer is challenging and requires a multidisciplinary approach with chemotherapy, radiation and surgical resection. Despite using chemotherapy and radiotherapy in the neoadjuvant setting, achievement of negative surgical margins remains technically challenging. Positive margins are associated with increased local recurrences and worse overall survival and there are no standard options for treatment. The CivaSheet is an FDA-cleared implantable sheet with a matrix of unidirectional planar low-dose-rate (LDR) Palladium-103 (Pd-103) sources. The sources are shielded on one side with gold to spare radio-sensitive structures such as the bowel. The sheet can easily be customized and implanted at the time of surgery when there is concern for close or positive margins. The CivaSheet provides an interesting solution to target the region of close/positive margins after pancreatectomy. Here we discuss the physical properties, the dosimetry, clinical workflow and early patient outcomes with the CivaSheet in pancreatic cancer.

First report on the feasibility of a permanently implantable uni-directional planar low dose rate brachytherapy sheet for patients with resectable or borderline resectable pancreatic cancer.

BACKGROUND: Margin negative resection in pancreatic cancer remains the only curative option but is challenging, especially with the retroperitoneal margin. Intraoperative radiation therapy (IORT) can improve rates of local control but requires specially designed facilities and equipment. This retrospective review describes initial results of a novel implantable mesh of uni-directional low dose rate (LDR) Pd-103 sources (sheet) used to deliver a focal margin-directed high-dose boost in patients with concern for close or positive margins. METHODS: Eleven consecutive patients from a single institution with resectable or borderline resectable pancreatic cancer with concern for positive margins were selected for sheet placement and retrospectively reviewed. Procedural outcomes, including the time to implant the device and complications, and clinical outcomes, including survival and patterns of failure, are reported. A dosimetric comparison of the LDR sheet with hypothetical stereotactic body radiotherapy (SBRT) boost is reported. RESULTS: One patient had a resectable disease, and 10 patients had a borderline resectable disease and underwent neoadjuvant treatment. Sheet placement added 15 min to procedural time with no procedural or sheet-related complications. At a median follow up of 13 months, 64% (n = 7) of patients are alive and 55% (n = 6) are disease-free. Compared to a hypothetical SBRT boost, the LDR sheet delivered a negligible dose to kidneys, liver, and spinal cord with a 50% reduction in max dose to the small bowel. CONCLUSION: This is the first report of the use of an implantable uni-directional LDR brachytherapy sheet in patients with resected pancreatic cancer with concern for margin clearance, with no associated toxicity and favorable clinical outcomes.

Esophagus and Gastrointestinal Junction Tumors.

Esophageal squamous cell carcinoma and adenocarcinoma account for 95% of all esophageal malignancies. The rates of esophageal adenocarcinoma have increased in Western countries, making it the predominant type of esophageal cancer. Treatment of both types of cancer has transformed to a more minimally invasive approach, with endoscopic methods being used for superficial cancers and more frequent use of video-assisted and laparoscopic modalities for locally advanced tumors. The current National Comprehensive Cancer Network guidelines advocate a trimodal approach to treatment, with neoadjuvant chemoradiation and surgery for locally advanced cancers.

Simplified preoperative tool predicting discharge destination after major oncologic gastrointestinal surgery.

BACKGROUND: Preoperatively identifying patients who will require discharge to extended care facilities (ECFs) after major cancer surgery is valuable. This study compares existing models and derives a simple, preoperative tool for predicting discharge destination after major oncologic gastrointestinal surgery. METHODS: The American College of Surgeon National Surgical Quality Improvement datasets were used to evaluate existing risk stratification and frailty assessment tools between the years 2011 and 2015. A novel tool for predicting discharge to ECF was developed in the 2011-2015 dataset and subsequently validated in the 2016 dataset. RESULTS: Major resections were analyzed for 61 683 malignancies: 6.9% esophagus, 5.3% stomach, 20.0% liver, 21.0% pancreas, and 46.8% colon/rectum. The overall ECF discharge rate was 9.1%. The American Society of Anesthesiologist score, 11-point modified frailty index (mFI), and 5-point abbreviated modified frailty index (amFI) demonstrated only moderate discrimination in predicting ECF discharge (c-statistic: 0.63-0.65). In contrast, our weighted cancer cancer abbreviated modified frailty index (camFI) score demonstrated improved discrimination with c-statistic of 0.73. The camFI displayed >90% negative predictive value for ECF discharge at every operative site. CONCLUSION: The camFI is a simple tool that can be used preoperatively to counsel patients on their risk of ECF discharge, and to identify patients with the least need for ECF discharge after major oncologic gastrointestinal surgery.

Phase 1 Study of Neoadjuvant Short-Course Radiation Therapy Concurrent With Infusional 5-Fluorouracil for the Treatment of Locally Advanced Rectal Cancer.

PURPOSE: To assess the safety and feasibility of neoadjuvant short-course radiation therapy (RT) concurrent with continuous infusion 5-fluorouracil (5-FU) for the treatment of locally advanced rectal cancer. METHODS AND MATERIALS: Patients with cT3-4 or N + rectal adenocarcinoma based on ultrasound or magnetic resonance imaging were prospectively enrolled in this study. Study treatment consisted of continuous infusion 5-FU combined with short-course RT (5 Gy x 5 fractions) followed by 4 cycles of mFOLFOX, total mesorectal excision (TME), and 6 cycles of adjuvant mFOLFOX. To mitigate the potential added toxicity from concurrent 5-FU, intensity modulated RT was used. Using the continual reassessment method, the dose of 5-FU was escalated from 100 to a maximum-tolerated dose of 200 mg/m2/d. RESULTS: Fourteen patients were accrued. All patients completed continuous infusion 5-FU and short-course RT and the 5-FU dose was safely escalated to 200 mg/m2/d with no dose-limiting toxicity. Thirteen patients received the neoadjuvant mFOLFOX, and only 1 patient went straight to surgery after chemoradiation. Clinical response was 21% complete, 63% partial, 14% stable disease, and no patients had progression. Three patients with cCR had negative biopsies and did not have TME. Pathologic response was 64% partial response and 14% stable disease. No patients had pathologic progression. The most common grade 3 and 4 toxicities were cytopenias. The most common grade 1 and 2 toxicities were cytopenia, fatigue, diarrhea, and nausea. CONCLUSIONS: Our findings suggest that concurrent chemotherapy with neoadjuvant short-course RT is feasible and can be safely given with concurrent continuous infusion 5-FU. This works adds to the growing evidence that short-course RT is not only equivalent to long-course RT, but also may provide additional benefits, such as allowing for a transition to full dose systemic therapy in the neoadjuvant setting, selective organ preservation in complete responders, and providing a more convenient and cost-effective way of delivering pelvic RT.

Age-related risks of complications after distal pancreatectomy for neuroendocrine and cystic neoplasms.

BACKGROUND: Distal pancreatic neuroendocrine tumors (PNET) and pancreatic cystic neoplasms (PCN) are often incidentally found in older adults, requiring careful consideration between operative management and watchful waiting. This study analyzes the short-term complications associated with distal pancreatectomy (DP) for PNET and PCN in older adults to inform clinical decision-making. METHODS: Patients undergoing DP for PNET and PCN were analyzed using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database and the pancreatectomy procedure-targeted dataset. Associations between decade of age and 30-day outcomes were evaluated. RESULTS: 1626 patients were analyzed from 2014 to 2015. 692 (42.6%) were younger than 60 years, 507 (31.2%) were sexagenarians, 342 (21.0%) were septuagenarians, and 85 (5.2%) were octogenarians. Minimally invasive approaches were used in 62.7%. While septuagenarians and octogenarians constituted 26.3% of the cohort, they were affected by 55.6% of reintubations, 66.7% of failures to wean, 82.4% of myocardial infarctions, and 57.1% of septic shock. Septuagenarians and octogenarians had longer hospital stays, as compared to those younger than 60 years. CONCLUSION: Septuagenarians and octogenarians are disproportionately affected by perioperative complications after DP for PNET and PCN. Careful patient selection and thorough counseling should be provided when surgery is considered.

Predictors of Short-Term Readmission After Pancreaticoduodenectomy.

BACKGROUND: Readmissions are a common complication after pancreaticoduodenectomy and are increasingly being used as a performance metric affecting quality assessment, public reporting, and reimbursement. This study aims to identify general and pancreatectomy-specific factors contributing to 30-day readmission after pancreaticoduodenectomy, and determine the additive value of incorporating pancreatectomy-specific factors into a large national dataset. METHODS: Prospective American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) data were retrospectively analyzed for patients who underwent pancreaticoduodenectomy (PD) between 2011 and 2015. Additionally, a subset of patients with pancreatectomy-targeted data between 2014 and 2015 were analyzed. RESULTS: Outcomes of 18,440 pancreaticoduodenectomies were analyzed, and found to have an 18.7% overall readmission rate. Multivariable modeling with pancreatectomy-specific variables increased the predictive value of the model (area under receiver operator characteristic 0.66 to 0.73). Statistically significant independent contributors to readmission included renal insufficiency, sepsis, septic shock, organ space infection, dehiscence, venous thromboembolism, pancreatic fistula, delayed gastric emptying, need for percutaneous drainage, and reoperation. CONCLUSIONS: Large registry analyses of pancreatectomy outcomes are markedly improved by the incorporation of granular procedure-specific data. These data emphasize the need for prevention and careful management of perioperative infectious complications, fluid management, thromboprophylaxis, and pancreatic fistulae.

Desmoplastic Melanoma: Clinical Behavior and Management Implications.

INTRODUCTION: Desmoplastic melanoma is a rare variant of melanoma that has been reported to demonstrate unique clinical behavior when compared with other histological subtypes. In this study, we present the clinical course of patients with this unusual diagnosis. We hypothesized that desmoplastic melanoma would differ from nondesmoplastic melanoma with regard to its presentation, rate of regional metastasis, and recurrence pattern. METHODS: After institutional review board approval, a retrospective chart review was performed on all patients with a diagnosis of desmoplastic melanoma since 1998. The following data were collected: patient demographics, histopathological details of the lesion, initial treatment, and clinical course. In addition, the available slides were reviewed by a dermatopathologist. RESULTS: Twenty-eight patient charts were reviewed. Mean age at diagnosis was 65 years. Fifty-seven percent of patients were men, and 67% of the lesions originated from the head and neck. Of the 28 patients, 11 had pathology slides that were adequate for evaluation. Pure desmoplastic melanoma, defined by more than 90% of the specimen demonstrating desmoplastic features, was found in only 3 patients. Taking into account all cases, the mean Breslow thickness was 5.09 mm and ulceration was present in 12.5% of lesions. Regional disease was discovered in 18% of patients. The mean follow-up time was 43 months, and the overall recurrence rate was 32%. 66.7% of first recurrences were local. Two of 3 patients with pure desmoplastic melanoma developed regional metastasis. CONCLUSIONS: Our data largely support previous studies that suggest desmoplastic melanoma behaves differently compared with other histological subtypes. However, the incidence of regional disease among patients with pure desmoplastic melanoma appears to be higher in our study than in previous reports. Although this rare variant typically presents with advanced local disease, the rate of regional metastasis is less than what would be expected for similar thickness, nondesmoplastic cutaneous melanoma. The recurrence pattern is different compared with nondesmoplastic melanoma, and the most common site of recurrence is local. Discrepancy in the literature regarding the clinical behavior of this disease may be related to inconsistent pathological criteria for diagnosis. Further research will help clarify the optimal management of desmoplastic melanoma.

Changing paradigm in pancreatic cancer: from adjuvant to neoadjuvant chemoradiation.

BACKGROUND: Historically, management of pancreatic cancer has been determined based on whether the tumor was amenable to resection and all patients deemed resectable received curative intent surgery followed by adjuvant therapy with chemotherapy (CT) ± RT. However, patients who undergo resection with microscopic (R1) positive margins have inferior rates of survival. The purpose of this study is to identify patients who have undergone pancreatectomy for pancreatic cancer, determine the surgical margins, types of adjuvant therapies given and patterns of failure. Our hypothesis was that in patients who have surgery without pre-operative therapy, there is a high rate of R1 resections and subsequent local recurrence, despite adjuvant therapy. METHODS: Seventy-one patients with curative resections for pancreatic cancer between 2003 and 2015 were reviewed. Tumor stage, margin status, distance to closest margin, receipt of adjuvant therapy and length of survival were collected. Patients were divided into two groups based on whether they received adjuvant CT + RT (n=37) or CT alone (n=37). Patients were further divided based on whether resection was R1 (n=29) or R0 (n=42). Wilcoxon survival tests and Cox proportional hazards regression models were performed to determine the effects of CT + RT vs. CT alone, stratified by surgical margin status. RESULTS: Of the 29 patients (39%) who had R1, 15 received CT + RT and 14 received only CT. Patients who received CT + RT experienced a significantly longer period of PFS (13 vs. 7.5 mos, P=0.03) than patients who received CT alone. However, there was no significant difference found in time to death post cancer resection between CT + RT vs. CT alone (P=0.73). Of the 42 patients with R0, 21 received CT + RT and 21 received CT. There was a trend towards increase in PFS in patients treated with CT + RT (25 vs. 17 months, P=0.05), but there was no significant increase in time to death compared to patients treated with CT alone (P=0.53. Of the 36 patients with CT + RT, 21 had R0 and 15 had R1. Patients with R0 were more likely to have longer PFS (25 vs. 13 months, P=0.06), but there was no significant difference in time to death compared to patients with CT alone (P=0.68). CONCLUSIONS: After curative resection, the addition of RT to CT improves PFS in both R0 and R1 settings. However, patients with R1 have significantly worse PFS and OS compared to patients with R0 and even aggressive adjuvant therapy does not make up for the difference. The paradigm has shifted and now for patients with resectable pancreatic cancers we recommend neoadjuvant CT + RT to improve RT targeting and treatment response assessment and most importantly, improve chances of obtaining R0.

Using a Root Cause Analysis Curriculum for Practice-Based Learning and Improvement in General Surgery Residency.

OBJECTIVE: To describe and evaluate a root cause analysis (RCA)-based educational curriculum for quality improvement (QI) practice-based learning and implementation in general surgery residency. DESIGN: A QI curriculum was designed using RCA and spaced-learning approaches to education. The program included a didactic session about the RCA methodology. Resident teams comprising multiple postgraduate years then selected a personal complication, completed an RCA, and presented the findings to the Department of Surgery. Mixed methods consisting of quantitative assessment of performance and qualitative feedback about the program were used to assess the value, strengths, and limitations of the program. SETTING: Urban tertiary academic medical center. PARTICIPANTS: General surgery residents, faculty, and medical students. RESULTS: An RCA was completed by 4 resident teams for the following 4 adverse outcomes: postoperative neck hematoma, suboptimal massive transfusion for trauma, venous thromboembolism, and decubitus ulcer complications. Quantitative peer assessment of their performance revealed proficiency in selecting an appropriate case, defining the central problem, identifying root causes, and proposing solutions. During the qualitative feedback assessment, residents noted value of the course, with the greatest limitation being time constraints and equal participation. CONCLUSION: An RCA-based curriculum can provide general surgery residents with QI exposure and training that they value. Barriers to successful implementation include time restrictions and equal participation from all involved members.