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Background Robotic surgery is gaining acceptance for distal pancreatectomy (DP). Nevertheless, no multi-institutional data exist to demonstrate the ideal clinical circumstances for use and the efficacy of the robot compared to the open or laparoscopic techniques, in terms of perioperative outcomes. Methods The 2014 ACS-NSQIP procedure-targeted pancreatectomy data for patients undergoing DP were analyzed. Demographics and clinicopathological and perioperative variables were compared between the three approaches. Univariate and multivariable analyses were used to evaluate outcomes. Results One thousand eight hundred fifteen DPs comprised 921 open distal pancreatectomies (ODPs), 694 laparoscopic distal pancreatectomies (LDPs), and 200 robotic distal pancreatectomies (RDPs). The three groups were comparable with respect to demographics, ASA score, relevant comorbidities, and malignant histology subtype. Compared to the ODP group, patients undergoing RDP had lower T-stages of disease ( P  = 0.0192), longer operations ( P  = 0.0030), shorter hospital stays ( P  < 0.0001), and lower postoperative 30-day morbidity ( P  = 0.0476). Compared to the LDP group, RDPs were longer operations ( P  < 0.0001) but required fewer concomitant vascular resections ( P  = 0.0487) and conversions to open surgery ( P  = 0.0068). On multivariable analysis, neoadjuvant therapy ( P  = 0.0236), malignant histology ( P  = 0.0124), pancreatic reconstruction ( P  = 0.0006), and vascular resection ( P  = 0.0008) were the strongest predictors of performing an ODP. Conclusions The open, laparoscopic, and robotic approaches to distal pancreatectomy offer particular advantages for well-selected patients and specific clinicopathological contexts; therefore, clearly demonstrating the most suitable use and superiority of one technique over another remains challenging.

BackgroundAlthough a β-catenin mutated hepatocellular adenoma (HCA) is a benign liver tumor, it can cause bleeding, obstruction, pain, and hepatocellular carcinoma.1–3 Because surgery needs to balance these risks with its morbidity, a minimally invasive approach may be well suited.4–6 In this report, a strategic approach to minimally invasive resection of HCA encompassing segment 4a (S4a) is reviewed.PatientA 22-year-old woman with abdominal pain was found to have two liver lesions involving segment 4a (5 cm) and segment 8 (S8) (4.5 cm). Liver biopsy confirmed a β-catenin mutated HCA in the S4a lesion. After embolization, an anatomic S4a segmentectomy and a partial S8 resection were planned.TechniqueThree-dimensional modeling was used to perform a preoperative virtual hepatectomy; to visualize the spatial relationship between the HCA, the portal bifurcation, and the hepatic veins; and to preplan the port sites.7 With the patient in the French position, after port placement, intraoperative ultrasound was performed to identify the transection plane.8 The main left portal pedicle and Rex’s recessus were exposed, and the branches of S4a were dissected out, clipped, and divided. Using ultrasound, the middle hepatic vein was exposed to define the lateral border of the dissection plane.ConclusionAlthough a β-catenin mutated HCA in S4a does not necessitate a formal segmentectomy, understanding the anatomic structures outlining its borders can facilitate the resection, especially for a large HCA. Virtual hepatectomy helps to achieve a detailed comprehension of the complex borders of segment 4a. Preoperative embolization can firm up the tumor and minimize the risk of intraoperative rupture from manipulation.

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome—including Bacteroides, Selenomonas, and Prevotella species—is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.

BackgroundPrevious studies have found racial disparity in pancreatectomies for resectable pancreatic adenocarcinoma. The aim of this study was to investigate if racial disparities were worse in the performance of pancreaticoduodenectomy for borderline resectable pancreatic adenocarcinoma.MethodsThis study used the National Cancer Database (2004–2016) and included patients with non-metastatic and head of the pancreas borderline resectable pancreatic adenocarcinoma. Multivariable, Poisson regression models with robust standard errors evaluated the relative risk (RR) of undergoing a pancreaticoduodenectomy among non-White patients (Black, Asian, and non-White Hispanic) compared with White patients. A Poisson regression model with hospital fixed effects was performed to evaluate if findings were due to within-hospital or between-hospital variation. Interaction between race and neoadjuvant therapy was also evaluated.ResultsThere were 15,482 patients (median age 68 years, interquartile range 60–76 years; 48.6% male) with borderline resectable pancreatic adenocarcinoma who were predominantly White (84.3%, n = 13,058; non-White, 15.7%, n = 2424). Overall, 18.4% (n = 2853) had a pancreatic resection. Non-White patients had a significantly lower likelihood of undergoing a pancreatic resection for borderline resectable pancreatic adenocarcinoma when compared with White patients (RR 0.75, 95% confidence interval 0.68–0.83; p < 0.001). These findings persisted in the hospital fixed-effects model. In the interaction analysis, there were no significant differences in the likelihood of pancreatic resection if patients received neoadjuvant therapy.ConclusionsNon-White patients were 25% less likely to undergo a pancreatic resection for borderline resectable pancreatic adenocarcinoma compared with White patients. This racial disparity was due to variation in care within-hospitals and disappeared if non-White patients were treated with neoadjuvant therapy.

Background Liver-directed therapies have been used to treat neuroendocrine liver metastases (NELM) for both symptomatic improvement and tumor growth control. We reviewed our experience with NELM to investigate the outcomes of available treatment modalities and to identify prognostic factors for survival. Methods We identified all patients with NELM, who were managed at our institution, from a prospectively collected institutional database. Overall survival (OS) was determined for each treatment modality. Results Between 2003 and 2010, we identified 939 patients with neuroendocrine tumors, of whom 649 patients had NELM. The primary tumor site was the small intestine in 245 patients (38%) and pancreas in 194 patients (30%). With a median follow-up of 44 months, the median, 5 and 10 year OS for each treatment group was as follows: hepatic resection ( n  = 58, 9%), 160 months, 90%, 70%; radiofrequency ablation ( n  = 28, 4%), 123 months, 84%, 55%; chemoembolization ( n  = 130, 20%), 66 months, 55%, 28%; systemic therapy ( n  = 316, 49%), 70 months, 58%, 31%; and observation ( n  = 117, 18%), 38 months, 38%, 20%. Age [hazard ratio (HR) 1.0, p  < 0.001), small bowel primary site (HR 0.5, p  < 0.001), hepatic resection (HR 0.3, p  = 0.001), well-differentiated tumors (HR 0.3, p  < 0.001), alkaline phosphatase within normal limit (WNL) (HR 0.4, p  < 0.001), and chromogranin A WNL (HR 0.5, p  < 0.001) were significant independent prognosticators for OS. Conclusions This series represents one of the largest single-institution studies of NELM reported. We found that hepatic resection was associated with highly favorable OS. Our observations support hepatic resection in appropriately selected patients.

Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones. A wide range of clinical behavior can be seen, with the primary prognostic indicator being tumor grade as defined by the Ki67 proliferation index and mitotic index. Surgery is the primary treatment modality for PNETs. While functional PNETs should undergo resection for symptom control as well as potential curative intent, nonfunctional PNETs are increasingly managed nonoperatively. There is increasing data to suggest small, nonfunctional PNETs (less than 2 cm) are appropriate follow with nonoperative active surveillance. Evidence supports surgical management of metastatic disease if possible, and occasionally even surgical management of the primary tumor in the setting of widespread metastases. In this review, we highlight the evolving surgical management of local and metastatic PNETs.

Background Preoperative diagnosis of pancreatic cystic neoplasms is problematic. We evaluated our experience with endoscopic ultrasound (EUS) to determine the utility of fine-needle aspiration cytology (FNAC) in surgical decision-making. Methods Patients evaluated for pancreatic cysts with EUS fine-needle aspiration (FNA) from 3/1996–10/2003 were included. Patients undergoing both preoperative EUS-FNA and pancreatic resection were identified. FNAC read as a mucinous cystic neoplasm (MCN), suspicious for neoplasia, or mucinous epithelial/atypical cells were classified as “concerning.” Cytology with no malignant cells was negative. FNAC read as indeterminate, atypical cells of undetermined significance, or possible contamination was nondiagnostic. Results Of 95 patients evaluated with EUS FNAC, 29 underwent resection. On final pathology, 7/29 lesions (24%) were malignant [two neuroendocrine tumors, three adenocarcinomas, one invasive intraductal papillary mucinous neoplasm (IPMN), and one metastatic uterine tumor], 4/29 (14%) were benign (three serous cystadenomas and one chronic pancreatitis), and 18/29 (62%) were premalignant (ten MCNs and eight IPMNs). Seven patients had concerning FNAC. All seven harbored malignant or premalignant lesions. Nine patients had negative FNAC: three (33%) with benign lesions and six (67%) with premalignant lesions. Thirteen of the 29 patients (45%) had nondiagnostic FNAC with 12/13 (92%) harboring a malignant or premalignant lesion. Sensitivity, specificity, positive predictive value, and negative predictive value were 28%, 100%, 100%, and 18%, respectively. Conclusion The decision to proceed with nonoperative management should not be based on a negative or nondiagnostic FNAC alone, as 67% of negative and 92% of nondiagnostic specimens were associated with malignant or premalignant pathology.

BackgroundNeoadjuvant therapy has shown value in various cancer types. The role of neoadjuvant therapy in pancreatic ductal adenocarcinoma (PDAC), however, remains unknown. The aim of the present work is to evaluate the effect of neoadjuvant therapy on the survival of patients with borderline-resectable PDAC.Patients and MethodsBetween 2004 and 2015, 7730 patients with resectable PDAC and 1980 patients with borderline-resectable PDAC were identified from the National Cancer Database (NCDB). Survival was compared between resectable and borderline-resectable patients. Survival and pathologic characteristics were also compared within borderline-resectable patients who received neoadjuvant therapy and those who received adjuvant therapy alone. Kaplan–Meier method and Cox proportional-hazard models were used for analysis.ResultsMedian overall survival (mOS) of all patients with resectable PDAC was similar to that of patients with borderline-resectable disease treated with neoadjuvant therapy (26.5 versus 25.7 months, p = 0.78). Patients with borderline-resectable disease treated with neoadjuvant therapy had improved mOS compared with borderline-resectable patients treated with adjuvant therapy alone (25.7 versus 19.6 months, p < 0.0001). When comparing patients with borderline-resectable disease who received neoadjuvant therapy versus those who received adjuvant therapy alone, the former less often had node-positive pancreatic cancer (40.6% versus 76.3%, p < 0.001) and margin-positive resections (17.8% versus 44.4%, p < 0.001).ConclusionNeoadjuvant therapy is associated with enhanced survival in patients with borderline-resectable pancreatic cancer, which may be attributed to tumor downstaging.

Background The latest studies on surgical and cost-analysis outcomes after laparoscopic distal pancreatectomy (LDP) highlight mixed and insufficient results. Whereas several investigators have compared surgical outcomes of LDP vs. open distal pancreatectomy (ODP) for adenocarcinomas, few similar studies have focused on pancreatic neuroendocrine tumors (PNETs). Methods We reviewed the medical records of PNET patients undergoing distal pancreatectomy between 2004 and 2014. Patients were divided into LDP vs. ODP groups. Demographics, relevant comorbidities, oncologic variables, and cost-analysis data were assessed. Survival and Cox proportional hazards analyses were used to evaluate outcomes. Results Of the 171 distal pancreatectomies for PNETs, 73 were laparoscopic, whereas 98 were open. Patients undergoing LDP demonstrated significantly lower rates of postoperative complications ( P  = 0.028) and had significantly shorter hospital stays ( P  = 0.008). On multivariable analysis, positive resection margins ( P  = 0.046), G3 grade ( P  = 0.036), advanced WHO classification ( P  = 0.016), TNM stage ( P  = 0.018), and readmission ( P  = 0.019) were significantly associated with poor survival; however, method of resection (LDP vs. ODP) was not ( P  = 0.254). The median total direct costs of LDP vs. ODP did not differ significantly. Conclusions In response to the recent considerable controversy surrounding the costs and surgical outcomes of LDP vs. ODP, our results show that LDP for PNETs is cost-neutral and significantly reduces postoperative morbidity without compromising oncologic outcomes and survival.

Whole-exome sequencing of circulating tumor cells enables accurate and powered calling of somatic point mutations. Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two patients with prostate cancer, including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were present in matched tissue. Moreover, we identified 10 early trunk and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these mutations, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.