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Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic gastrointestinal cancers yet remain poorly characterized. We performed immunological screening against personalized neoantigens in combination with single-cell RNA sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that most neoantigen-reactive CD8 + T cells displayed an exhausted state with significant CXCL13 and GZMA co-expression compared with non-neoantigen-reactive bystander cells. Most neoantigen-reactive CD4 + T cells from a patient with bile duct cancer also exhibited an exhausted phenotype but with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancers harbor distinct transcriptomic signatures, which may provide new opportunities for harnessing these cells for therapy., Competing Interests: Declaration of interests E.T. is on the scientific advisory board of PACT Pharma, Genocea Biosciences, and Turnstone Biologics. C.B.B. reports a consultant/advisory relationship with BMS, has stock ownership in and is on the scientific board of PrimeVax, and is on the scientific board of BioAI and LunaPhore. Other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: There is early evidence that indocyanine green (ICG) fluorescence imaging has the ability to detect metastatic and primary malignancies in the liver that are too small to be identified by other methods. However, the rate of false positives and false negatives remains unknown., Materials and Methods: This is a single institution prospective single-arm study. Patients with suspected hepatic or pancreatic malignancies were intravenously injected with ICG one to three days prior to their scheduled surgical therapy. At the beginning of the procedure, the liver was assessed with fluorescence imaging and all identified lesions were biopsied and evaluated., Results: Twenty-three patients were enrolled from April 2015 through February 2016. Fifteen patients with confirmed malignancy had adequate fluorescence imaging evaluation of the liver; 10 with pancreatic primary malignancies and five with hepatic primaries. Fluorescence imaging was the only modality that identified nine concerning hepatic lesions, all of which were benign on pathology examination. Out of 11 malignant hepatic masses, six were visible on fluorescence imaging. Out of nine benign hepatic lesions, five were visible. No side effects or complications of the fluorescence imaging were encountered. The sensitivity for ICG fluorescence was 45.5%, the specificity 21.2%, the positive predictive value 25%, and the negative predictive value 40%., Conclusion: Intraoperative hepatic assessment with ICG fluorescence imaging to identify malignancy in the liver is feasible and safe. However, in this study the significant number of false positives limit the utility of the technique. Our preliminary data do not support its routine use for detection of malignancies in the liver.

Background: Clinical characteristics of patients with congenital myopathies (CM) are well known but there is a lack of knowledge about the natural history and course of disease of the different genetic subtypes. In 2010 we assessed the national cohort of Danish patients with CM to decide genetic diagnosing and describe genotype- phenotype relationships.AIM of this follow-up study was to evaluate the course of disease since the initial study and to evaluate the applicability of standard assessment methods to reflect change over time and patients own opinion on the course of disease., Methods: All available genetically diagnosed patients studied by us in 2010 (n = 41) were invited to the follow-up study; assessment of motor function (MFM-32), muscle strength (MRC %)and respiratory function (FVC %) and prime assessor were the same as in the initial study. Patients were asked whether the course of disease had progresses, was stable or had improved., Results: 23 patients (15-61 y) accepted the invitation. Mean follow-up time was 7.7 years. Loss of muscle strength was more prominent in patients with mutations in DNM2, RYR1 and TPM2/3 genes and deterioration in FVC % was more evident in patients carrying NEB and ACTA1 gene mutations. MFM-sum score was less sensitive to change compared to MRC-sum score. In general, agreement between the patient's own opinion of the course of disease and results of assessments was good., Conclusion: The number of patients in the study is too small to be conclusive, but the results indicate that CM can be stable or slowly progressive depending on the genetic subtype.

Background: Optimal treatment of pancreatic ductal adenocarcinoma of the neck, body and tail (PDAC-NBT) necessitates R0 surgical resection. Preoperative radiographic identification of patients likely to achieve successful oncologic resection remains difficult. This study seeks to identify preoperative imaging characteristics predictive of non-R0 resections or impaired survival for PDAC-NBT., Methods: Patients at five high-volume centers who underwent resection for PDAC-NBT were retrospectively analyzed. The most immediate preoperative cross-sectional scan was assessed along with outcome measures of overall survival and margin status., Results: 330 patients were treated between 2001 and 2016. Margin status included 247 R0 (78.2%), 67 R1 (21.2%), and 2 R2 (0.6%). A non-R0 resection predicted worse survival (p = 0.0002). On preoperative imaging, patients with tumors greater than 20 mm, tumor attenuation greater than 70 Hounsfield units, or who demonstrated pancreatic atrophy and/or calcifications also had worse survival (p = 0.010, p = 0.036, p = 0.025 respectively). Patients with tumors interfacing with the splenic artery or vein or extending posteriorly achieved fewer R0 resections (p = 0.0006, p = 0.0004, p = 0.001, respectively)., Conclusion: Preoperative cross-sectional imaging can identify tumor characteristics associated with poor survival and non-R0 resection. Further investigation is needed to identify the appropriate surgical and treatment modifications necessary to clinically benefit this subset of patients., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments): local parenchymal tumor destruction therapy . The expert panel proposed new nomenclature for 3 distinct disease categories of liver-dominant metastatic colorectal cancer that is consistent with other tumor types: (I) surgically treatable (resectable); (II) surgically untreatable (borderline resectable); (III) advanced surgically untreatable (unresectable) disease. Patients may present at any point in the algorithm and move between categories depending on their response to therapy. The broad intent of therapy is to transition patients toward individualized treatments where possible, given the survival advantage that resection offers in the context of a comprehensive treatment plan. This article reviews what is known about the role of SIRT with Y-90 as neoadjuvant, definitive, or palliative therapy in these different clinical situations and provides insight into when treatment with SIRT with Y-90 may be appropriate and useful, organized into distinct treatment algorithm steps., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo.2020.01.09). Authors received an honorarium for Advisory Board attendance that served as the basis for the modified Delphi consensus exercise. No payment was provided for the time spent authoring this manuscript. DR Jeyarajah, NJ Espat, BC Visser, DA Iannitti, Doyle MBM, J Kim, and T Thambi-Pillai are or have been consultants to Sirtex Medical, Inc. NJ Espat has served as a speaker on behalf of Sirtex. DR Jeyarajah has served as a consultant to Ethicon., (2020 Journal of Gastrointestinal Oncology. All rights reserved.)

Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019)., Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking., Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology., Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety., Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

Background: Pancreatic surgery outcomes are associated with surgeon and center experience. Anesthesiologists as potential value drivers for pancreatic surgery have not been explored. We sought to evaluate whether anesthesiologists impact perioperative costs for pancreatic surgery., Methods: Within an integrated health care system, 796 pancreatic surgeries (526 PDs and 270 DPs) were performed from January 2014 to June 2017. Mean direct operative and anesthesia costs driven by anesthesiologists (operating room (OR) time, anesthesia billing and anesthesia procedures) were determined for each case. The volumes of pancreatic cases per anesthesiologist were calculated, and those above the 75th percentile for volume (4 cases) were considered high-volume. A multivariable analysis of OR/anesthesia costs was performed., Results: Mean OR and anesthesia costs for PD were $7064 for low-volume anesthesiologists (LVA), higher than $5968 for high-volume anesthesiologists (HVA) (p < 0.001). By multivariable analysis, HVA were associated with decreased costs of $2278 (p < 0.001). Teams of HVA and high-volume surgeons (HVS) were also associated with decreased mean costs of $1790 (p = 0.04)., Conclusion: These data suggest that anesthesiologists experienced in the management of complex pancreatic operations such as PDs may contribute to improved efficiencies in care by reducing perioperative costs., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: An initiative was established to improve value-based care for pancreatic surgery in a large nonprofit health system. Cost data were presented bimonthly to a hepatobiliary clinical performance group via videoconference., Study Design: The direct costs were calculated for all patients undergoing distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) between January 2014 and July 2017. Median length of stay, 30-day and 90-day mortality rates, readmission rate, and costs were stratified by surgeon volume using 2 published criteria: "volume pledge" criteria (≥5 PDs/year) and Leapfrog criteria (≥11 PDs/year)., Results: There were 270 DPs and 526 PDs performed in 14 hospitals spanning 4 states. Median PD costs were lower for high-volume surgeons (≥5 PDs/year), $21,026 vs $24,706 (p = 0.005). High-volume surgeons had a shorter length of stay (9 days vs 11 days; p < 0.001) for PD and DP (6 days vs 7 days; p = 0.001). Increased costs for low-volume surgeons included operative/anesthesia costs ($7,321 vs $6,325; p = 0.03), room and board ($5,828 vs $4,580; p = 0.01), and intensive care costs ($4,464 vs $3,113; p = 0.04). Operating time was increased for high-volume surgeons for DP and PD (p < 0.001). There was no difference in 30-day or 90-day mortality rates or readmissions for DP or PD when stratified by volume pledge criteria. There was no difference in total costs for DP or PD when stratified by Leapfrog criteria., Conclusions: There was a significant cost reduction for PD but not DP when the threshold of 5 PDs was used as a definition of high volume. The sharing of detailed financial data with HPB surgeons on a regular basis provides an opportunity to evaluate practice patterns and thereby reduce direct costs., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: A novel 3-dimensional (3D) guidance system was developed to aid accurate needle placement during ablation., Methods: Five novices and 5 experienced hepatobiliary surgeons were recruited. Using an agar block with analog tumor, participants targeted under 4 conditions: in-line with the ultrasound plane using ultrasound, in-line using 3D guidance, 45° off-axis using ultrasound, and off-axis using 3D guidance. Time to target the tumor, number of withdrawals, and the National Aeronautics and Space Administration Task Load Index were collected. Initial and final parameters for each of the conditions were compared using a within-subjects paired t test., Results: A significant reduction was seen in the number of required withdrawals in all situations when using the 3D guidance (0.75 vs 3.65 in-line and 0.25 vs 3.6 for off-axis). Mental workload was significantly lower when using 3D guidance compared with ultrasound both for novices (29.85 vs 41.03) and experts (31.98 vs 44.57), P < .001 for both. The only difference in targeting time between first and last attempt was in the novice group during off-axis targeting using 3D guidance (115 vs 32.6 seconds, P = .03)., Conclusion: Though 3D guidance appeared to decrease time to target, this was not statistically significant likely as a result of lack of power in our trial. Three-dimensional guidance did reduce the number of required withdrawals, potentially decreasing complications, as well as mental workload after proficiency was achieved. Furthermore, novices without experience in ultrasound were able to learn targeting with the 3D guidance system at a faster pace than targeting with ultrasound alone.

Objectives: Literature addressing the significance of lymph node positivity in the management of nonfunctional pancreatic neuroendocrine tumors (PNETs) is conflicting., Methods: The National Cancer Data Base was queried for patients who underwent surgical resection of nonfunctional PNETs between 1998 and 2011. Clinical data and overall survival were analyzed using χ and Cox proportional hazards regression. Multiple imputation was used as a comparative analysis because of the high number of patients missing data on tumor grade., Results: Two thousand seven hundred thirty-five patients were identified. The overall incidence of lymph node metastasis was 51%. In the subset of patients with grade 1 tumors less than 1 cm, 24% had positive lymph nodes. Overall median survival for patients with negative lymph nodes was 11 years compared with 8 years for lymph node-positive patients (P < 0.001). On multivariate survival analysis, tumor grade, distant metastases, regional lymph node involvement, positive surgical margins, male sex, and older age were predictive of decreased overall survival., Conclusions: Lymph node positivity was associated with decreased overall survival. The incidence of lymph node involvement in resected low-grade tumors less than 1 cm is higher than previously reported. Patients selected for resection of PNETs should be offered lymphadenectomy for staging.

Introduction: Current literature addressing the treatment of solid pseudopapillary neoplasms (SPNs) of the pancreas is limited, particularly for patients with distant metastases. We aimed to define predictive indicators of survival in a large series of patients and assess the outcome of patients with distant metastases., Methods: The National Cancer Database was queried for patients diagnosed with SPNs of the pancreas between 1998 and 2011. Single predictor univariate analyses were performed on variables including demographics, tumor characteristics, and surgery outcomes, and multivariate Cox proportional hazards survival analysis was then completed with backward elimination., Results: Overall, 340 patients were identified: 82% were female, median age was 39 years, and 84% had no comorbidities. Patients undergoing any type of surgical resection experienced long-term survival (85% 8-year survival). Patients undergoing surgical resection (n = 296) had superior survival (hazard ratio [HR] 21 for no surgery, p < 0.0001), as did patients treated at academic centers and those with private insurance (HR 3.9, p = 0.009; HR 4.9, p = 0.007). Sex, age, tumor size, presence of lymph node metastases, positive surgical margins, and presence of distant metastases were not significant predictors of survival in multivariate analysis. Of 24 patients with distant metastases, seven were treated surgically and experienced long-term survival similar to that of patients without metastases treated surgically (HR 2, p = 0.48)., Conclusion: SPNs of the pancreas are rare neoplasms with excellent overall survival; however, in a low number of patients they metastasize. Of the few patients with metastatic disease selected for resection, most experienced long-term survival.

Background: Fistula Risk Score (FRS) is a previously developed tool to assess the risk of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD)., Methods: Prospectively collected databases from 4 university affiliated and non-affiliated HPB centers in United States and Canada were used. The influence of individual baseline characteristics, FRS and FRS group on CR-POPF was assessed in univariate and multivariate analyses. FRS calculator performance was assessed using a C-statistic., Results: 444 patients were identified. Pathology, soft pancreas texture and pancreatic duct size were associated with CR-POPF rates (p < 0.001 for each); EBL was not (p = 0.067). The negligible risk group consisted of 50 (11.3%) patients, low risk of 118 (26.6%), moderate 234 (52.7%) and high risk group of 42 (9.5%) patients. The overall rate of CR-POPF was 20%. Of the patients in the negligible risk group, 2% developed CR-POPF, 13.6% of the low risk, 23.1% moderate and 42.9% in the high risk group (p < 0.001). Overall C-statistic was 0.719., Conclusion: FRS is robust and able to stratify the risk of developing CR-POPF following PD in diverse North American academic and non-academic institutions. The FRS should be used in research and to guide clinical management of patients post PD in these institutions., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Background: There is a growing body of literature pertaining to minimally invasive pancreatic resection (MIPR). Heterogeneity in MIPR terminology, leads to confusion and inconsistency. The Organizing Committee of the State of the Art Conference on MIPR collaborated to standardize MIPR terminology., Methods: After formal literature review for "minimally invasive pancreatic surgery" term, key terminology elements were identified. A questionnaire was created assessing the type of resection, the approach, completion, and conversion. Delphi process was used to identify the level of agreement among the experts., Results: A systematic terminology template was developed based on combining the approach and resection taking into account the completion. For a solitary approach the term should combine "approach + resection" (e.g. "laparoscopic pancreatoduodenectomy); for combined approaches the term must combine "first approach + resection" with "second approach + reconstruction" (e.g. "laparoscopic central pancreatectomy" with "open pancreaticojejunostomy") and where conversion has resulted the recommended term is "first approach" + "converted to" + "second approach" + "resection" (e.g. "robot-assisted" "converted to open" "pancreatoduodenectomy") CONCLUSIONS: The guidelines presented are geared towards standardizing terminology for MIPR, establishing a basis for comparative analyses and registries and allow incorporating future surgical and technological advances in MIPR., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The introduction of minimally invasive pancreatic resection (MIPR) into surgical practice has been slow. The worldwide utilization of MIPR and attitude towards future perspectives of MIPR remains unknown., Methods: An anonymous survey on MIPR was sent to the members of six international associations of Hepato-Pancreato-Biliary (HPB) surgery., Results: The survey was completed by 435 surgeons from 50 countries, with each surgeon performing a median of 22 (IQR 12-40) pancreatic resections annually. Minimally invasive distal pancreatectomy (MIDP) was performed by 345 (79%) surgeons and minimally invasive pancreatoduodenectomy (MIPD) by 124 (29%). The median total personal experience was 20 (IQR 10-50) MIDPs and 12 (IQR 4-40) MIPDs. Current superiority for MIDP was claimed by 304 (70%) and for MIPD by 44 (10%) surgeons. The most frequently mentioned reason for not performing MIDP (54/90 (60%)) and MIPD (193/311 (62%)) was lack of specific training. Most surgeons (394/435 (90%)) would consider participating in an international registry on MIPR., Discussion: This worldwide survey showed that most participating HPB surgeons value MIPR as a useful development, especially for MIDP, but the role and implementation of MIPD requires further assessment. Most HPB surgeons would welcome specific training in MIPR and the establishment of an international registry., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Anastomotic leak after pancreaticoduodenectomy is the most important cause of postoperative morbidity and mortality. Histological studies of bowel anastomoses have provided valuable insights regarding causes of anastomotic failure. However, this crucial information is lacking for pancreatico-enteric anastomoses., Methods: Pancreaticoduodenectomy was performed in a porcine model. Animals were survived up to 10 days and then the pancreatico-enteral anastomosis specimen was resected en bloc. Anastomotic bursting pressure was measured and histological sections of the anastomoses were examined., Results: Six out of 8 animals had excellent healing of the anastomoses. One animal developed a clinically significant leak at the pancreaticoduodenal anastomosis (12.5%) and one animal had a subclinical duodeno-duodenal leak discovered on necropsy (12.5%). Both anastomoses that failed had a collagen-to-tissue ratio less than 40%. In contrast, none of the anastomoses with a ratio greater than 40% showed any evidence of disruption., Conclusion: Our results indicate that quantitative measurement of collagen deposition at the pancreatic anastomosis provides objective assessment of healing of the pancreatic anastomosis. A survival porcine model of pancreaticoduodenectomy results in a similar leak rate to published data on pancreaticoduodenectomy in humans and will be useful for future studies assessing novel pharmacologic or technical interventions aimed at improving outcomes.

The aim of this study is to describe religious and spiritual beliefs of physicians and examine their influence on the decision to pursue medicine and daily medical practice. An anonymous survey was e-mailed to physicians at a large, multidisciplinary tertiary referral center with satellite clinics. Data were collected from January 2014 through February 2014. There were 2097 respondents (69.1 % men), and number of practicing years ranged from ≤1 to ≥30. Primary care physicians or medical specialists represented 74.1 %, 23.6 % were in surgical specialties, and 2.3 % were psychiatrists. The majority of physicians believe in God (65.2 %), and 51.2 % reported themselves as religious, 24.8 % spiritual, 12.4 % agnostic, and 11.6 % atheist. This self-designation was largely independent of specialty except for psychiatrists, who were more likely report agnosticism (P = 0.003). In total, 29.0 % reported that religious or spiritual beliefs influenced their decision to become a physician. Frequent prayer was reported by 44.7 % of physicians, but only 20.7 % reported having prayed with patients. Most physicians consider themselves religious or spiritual, but the rates of agnosticism and atheism are higher than the general population. Psychiatrists are the least religious group. Despite the influence of religion on physicians' lives and medical practice, the majority have not incorporated prayer into patient encounters.

Background: There has been a proliferation of gastrointestinal surgical fellowships; however, little is known regarding their association with surgical volume and management approaches., Methods: Surveys were distributed to members of GI surgical societies. Responses were evaluated to define relationships between fellowship training and surgical practice with pancreatoduodenectomy (PD)., Results: Surveys were completed by 889 surgeons, 84.1% of whom had completed fellowship training. Fellowship completion was associated with a primarily HPB or surgical oncology-focused practice (p < 0.001), and greater median annual PD volume (p = 0.030). Transplant and HPB fellowship-trained respondents were more likely to have high-volume (≥20) annual practice (p = 0.005 and 0.029, respectively). Regarding putative fistula mitigation strategies, HPB-trained surgeons were more likely to use stents, biologic sealants, and autologous tissue patches (p = 0.007, <0.001 and 0.001, respectively). Surgical oncology trainees reported greater autologous patch use (p = 0.003). HPB fellowship-trained surgeons were less likely to routinely use intraperitoneal drainage (p = 0.036) but more likely to utilize early (POD ≤ 3) drain amylase values to guide removal (p < 0.001). Finally, HPB fellowship-trained surgeons were more likely to use the Fistula Risk Score in their practice (29 vs. 21%, p = 0.008)., Conclusion: Fellowship training correlated with significant differences in surgeon experience, operative approach, and use of available fistula mitigation strategies for PD., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Preclinical studies have shown synergy between radiation therapy and immunotherapy. However, in almost all preclinical models, radiation is delivered in single doses or short courses of high doses (hypofractionated radiation). By contrast in most clinical settings, radiation is delivered as standard small daily fractions of 1.8-2 Gy to achieve total doses of 50-54 Gy (fractionated radiation). We do not yet know the optimal dose and scheduling of radiation for combination with chemotherapy and immunotherapy., Methods: To address this, we analyzed the effect of neoadjuvant standard fractionated and hypofractionated chemoradiation on immune cells in patients with locally advanced and borderline resectable pancreatic adenocarcinoma., Results: We found that standard fractionated chemoradiation resulted in a significant and extended loss of lymphocytes that was not explained by a lack of homeostatic cytokines or response to cytokines. By contrast, treatment with hypofractionated radiation therapy avoided the loss of lymphocytes associated with conventional fractionation., Conclusion: Hypofractionated neoadjuvant chemoradiation is associated with reduced systemic loss of T cells., Trial Registration: ClinicalTrials.gov NCT01342224, April 21, 2011; NCT01903083, July 2, 2013.

Background: Preoperative risk stratification for postoperative pancreatic fistula in patients undergoing distal pancreatectomy is needed., Methods: Risk factors for postoperative pancreatic fistula in 220 consecutive patients undergoing distal pancreatectomy at 2 major institutions were recorded retrospectively. Gland density was measured on noncontrast computed tomography scans (n = 101), and histologic scoring of fat infiltration and fibrosis was performed by a pathologist (n = 120)., Results: Forty-two patients (21%) developed a clinically significant pancreatic fistula within 90 days of surgery. Fat infiltration was significantly associated with gland density (P = .0013), but density did not predict pancreatic fistula (P = .5). Recursive partitioning resulted in a decision tree that predicted fistula in this cohort with a misclassification rate less than 15% using gland fibrosis (histology), density (HU), margin thickness (cm), and pathologic diagnosis., Conclusions: This multicenter study shows that no single perioperative factor reliably predicts postoperative pancreatic fistula after distal pancreatectomy. A decision tree was constructed for risk stratification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Routine lymphadenectomy in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) is not routinely performed. We aim to define predictive indicators of survival in patients with positive lymph nodes., Methods: The National Cancer Data Base (NCDB) was queried for patients who underwent major hepatectomy for ICC between 1998 and 2011. Clinical and pathologic data were assessed using uni- and multi-variate analyses. A sub-analysis was performed on the 160 patients with positive lymph nodes., Results: Of 849 patients with lymph node data, 57% had at least one lymph node examined. Median survival for lymph node negative patients was 37 months versus 15 months for lymph node positive patients. In lymph node positive patients, poorer survival was associated with not receiving chemotherapy (HR 1.83, p = 0.003), tumor size > 5 cm (p = 0.029), and older age (p < 0.0001). Lymph node positive patients age less than 45 had a median survival of 27 months., Conclusions: Overall survival in patients with lymph node metastases from ICC is poor. Adjuvant therapy was associated with a longer survival in lymph node positive patients, although prospective data are needed. Routine lymphadenectomy should be strongly considered to provide prognostic information and guidance for adjuvant therapy., (Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Total pancreatectomy is infrequently performed for pancreatic cancer. Perceived operative mortality and questionable survival benefit deter many surgeons. Clinical outcomes, described in single-center series, remain largely unknown., Methods: The National Cancer Database was queried for cases of pancreatic ductal adenocarcinoma undergoing total pancreatectomy (1998-2011). Univariate survival analyses were performed for 21 variables: demographic (8), tumor characteristics (5), surgery outcomes (6), and adjuvant therapy (2). The Log-rank test of differences in Kaplan-Meier survival curves was used for categorical variables. Variables with p < 0.05 were included in a multivariate analysis. Cox proportional hazards regression was used to analyze continuous variables and multivariate models., Results: 2582 patients with staging and survival data made up the study population. 30-day mortality was 5.5%. Median overall survival was 15 months, with 1, 3, and 5-year survival rates of 60%, 22%, and 13%, respectively. Age, facility type, tumor size and grade, lymph node positivity, margin positivity, and adjuvant therapy significantly impacted survival in multivariate analysis., Conclusion: Although total pancreatectomy is a reasonable option for selected patients with pancreatic ductal adenocarcinoma, survival of the entire group is limited. Operative mortality is improved from prior reports. Greater survival benefits were seen in younger patients with smaller, node negative tumors resected with negative margins in academic research centers., (Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

A wide array of ablation technologies, in addition to the progressive sophistication of imaging technologies and percutaneous, laparoscopic, and open surgical techniques, have allowed us to expand treatment options for patients with liver tumors. In this article, technical considerations of chemical and thermal ablations and their application in hepatic oncology are reviewed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The Explorer Minimally Invasive Liver (MIL) system uses imaging to create a 3-dimensional model of the liver. Intraoperatively, the system displays the position of instruments relative to the virtual liver. A prospective clinical study compared it with intraoperative ultrasound (iUS) in laparoscopic liver ablations., Methods: Patients undergoing ablations were accrued from 2 clinical sites. During the procedures, probes were positioned in the standard fashion using iUS. The position was synchronously recorded using the Explorer system. The distances from the probe tip to the tumor boundary and center were measured on the ultrasound image and in the corresponding virtual image captured by the Explorer system., Results: Data were obtained on the placement of 47 ablation probes during 27 procedures. The absolute difference between iUS and the Explorer system for the probe tip to tumor boundary distance was 5.5 ± 5.6 mm, not a statistically significant difference. The absolute difference for probe tip to tumor center distance was 8.6 ± 7.0 mm, not statistically different from 5 mm., Discussion: The initial clinical experience with the Explorer MIL system shows a strong correlation with iUS for the positioning of ablation probes. The Explorer MIL system is a promising tool to provide supplemental guidance information during laparoscopic liver ablation procedures., (© The Author(s) 2013.)

Objectives: This study investigated the impact of neoadjuvant radiation therapy (XRT) on postoperative outcomes following pancreaticoduodenectomy for pancreatic cancer., Methods: The American College of Surgeons National Quality Improvement Program database was queried for the period 2005-2010 to assess complication rates following pancreaticoduodenectomy for pancreatic cancer. Two groups of patients were identified, comprising those who received neoadjuvant XRT and those who did not (control group)., Results: A total of 4416 patients were identified, including 200 in the XRT group and 4216 in the control group. There were differences in patient characteristics between the groups, including in age, hypertension and bilirubin level. Despite the fact that weight loss was more common, median operative time was longer (423 min versus 368 min; P < 0.001), and vascular reconstruction was more commonly required (20.5% versus 8.4%; P < 0.001) in the XRT group. In addition, the XRT group had a shorter median hospital stay than the control group (9 days versus 10 days; P = 0.005). Mortality (3.0% versus 2.7%; P = 0.818) and morbidity (40.5% versus 37.6%; P = 0.404) rates were not influenced by neoadjuvant XRT. Blood transfusion rates were increased in the XRT group (13.0% versus 7.4%; P = 0.003). Severe complications were influenced by age >70 years, American Society of Anesthesiologists (ASA) class >2, preoperative sepsis, dyspnoea, weight loss, impaired functional status, peripheral vascular disease and operative time of >8 h., Conclusions: Neoadjuvant XRT is not associated with an increase in complications after pancreaticoduodenectomy., (© 2013 International Hepato-Pancreato-Biliary Association.)

Background: Gallbladder cancer (GBC) carries an unfavorable prognosis with high mortality. This retrospective study was conducted to identify prognostic factors after resection of GBC, to assist in selecting appropriate surgical and adjuvant therapy., Methods: Sixty-two patients from two institutions were identified with GBC by pathology. In 25, the cancer was unresectable at presentation. The remaining 37 patients comprised the study population. Log-rank analysis was used to assess univariate association with disease-free survival (DFS) and disease-specific survival (DSS). Cox regression was used for multivariate analysis., Results: Median DFS and DSS were 22.6 and 28.5 months respectively, with a median follow-up of 44.2 months. On univariate analysis, bile duct (BD) involvement was significantly associated with decreased DFS (P ≤ .001) and DSS (P = .004). BD involvement was uniformly fatal. LN involvement was not significantly associated with DFS or DSS (P = .85, P = .54)., Conclusions: All patients with BD involvement in our population died of the disease. The subset of patients with resectable GBC and BD involvement is a group that is at high risk for recurrence and should be treated as such. In our small population, preoperative and intraoperative methods evaluating BD involvement were unreliable.

Background: Published results addressing the treatment of colorectal liver metastases (CRLM) with radiofrequency ablation (RFA) vary widely with local recurrence rates of 2-40% and 5-year survival of 14-55%. The goal of this study was to analyze our 10-year experience with laparoscopic RFA., Methods: From January 2000 to July 2010, 130 patients underwent laparoscopic RFA for CRLM. Kaplan-Meier analysis was used to assess survival. Univariate and multivariate analysis were performed to identify factors associated with survival and recurrence., Results: In this cohort, median survival was 40.4 months with 5-year survival of 28.8%. Overall, 9.2% of patients had a local recurrence (3.6% for tumors 3 cm or less). On univariate analysis, factors associated with decreased survival were BMI (P = 0.045), rectal primary (P = 0.005), and increased tumor size (P = 0.002). On multivariate analysis, increased tumor size (HR 1.29 [95% CI: 1.04-1.59]; P = 0.020) and bilobar disease (HR 2.06 [95% CI: 1.02-4.15]; P = 0.044) were associated with decreased survival. On univariate analysis, only BMI was found to be associated with disease recurrence (P = 0.025)., Conclusions: Our data demonstrate that laparoscopic RFA can achieve a median survival of 40.4 months with a low local recurrence rate. Patients with tumors 3 cm or less have a decreased risk of local recurrence., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Despite considerable data focused on the morbidity of pancreaticoduodenectomy (PD), the financial impact of complications has been infrequently analyzed. This study evaluates the impact of the most common complications associated with PD on the cost of care. Additionally, we identified cost centers that were significantly affected by complications., Methods: A retrospective analysis of a prospective database in a network of community-based teaching hospitals was performed. All patients (n = 145) who underwent PD were included for years 2005 to 2009. Of these, 144 had complete in-hospital cost data. Complications were assessed and classified into major and minor categories according to Dindo et al. Forty-nine cost centers were analyzed for their association with the cost of complications. Univariate and multivariate linear regression analyses were performed. Significance was reported for P < .05., Results: The median cost for PD was $30,937. Patients with major complications had significantly higher median cost compared with those without ($56,224 vs $29,038; P < .001). Independent predictors of increased cost included reoperation; sepsis; pancreatic fistula; bile leak; delayed gastric emptying; and pulmonary, renal, and thromboembolic complications. Cost center analysis showed significant added charges for patients with major complications for blood bank ($1,018), clinical laboratory ($3,731), a computed tomography scan ($4,742), diagnostic imaging ($697), intensive care unit ($4,986), pharmacy ($33,850) and respiratory therapy ($1,090) (P < .05, all)., Conclusions: This study identified the major complications of PD, which are significantly associated with a higher cost. Substantial cost center increases were associated with major complications, particularly in pharmacy ($33,850). Measures aimed at limiting complications through centralization of care or care pathways may reduce the overall cost of care for patients after pancreatic resection., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: With the advent of endoscopic retrograde choledochoduodenostomy, the need for choledochoduodenostomy to treat common bile duct obstruction is less common, but occasionally required., Methods: Patients considered for laparoscopic choledochoduodenostomy secondary to benign conditions between 1999 and 2009 at a single institution were included. Charts were retrospectively reviewed for preoperative, operative, and long-term outcomes data., Results: Twenty patients were identified; 15 with chronic choledocholithiasis causing benign biliary obstruction or chronic recurrent cholangitis, 3 with chronic relapsing pancreatitis, and 2 with distal common bile duct strictures. Mean operative time was 270 min. No major operative complications were reported. Five patients with severe adhesions or portal hypertension required conversion to laparotomy. Median hospital stay was 6 days (range, 2-32). Postoperatively, three (20%) patients completed laparoscopically and three (66.7%) patients converted to laparotomy had complications. In addition, one death due to myocardial infarction was reported 4 weeks after hospital discharge. With an average follow-up of 21 months, only one patient (5%) developed recurrent symptoms., Conclusion: Laparoscopic choledochoduodenostomy is a useful technique in patients with benign, refractory common bile duct obstruction. This technically demanding procedure is feasible; however, the associated comorbidities in this complex group of patients result in a relatively high complication rate.

Hypothesis: Current literature evaluating radiofrequency ablation (RFA) for treatment of colorectal liver metastases describes high-risk surgical candidates or patients with unresectable disease. This creates bias when comparing RFA and hepatic resection. A Markov analysis would define theoretical outcomes necessary for RFA to demonstrate equivalence to resection., Design: A multistate Markov decision analytic model was constructed. Second-order Monte Carlo analysis was used to simulate a randomized controlled trial. Sensitivity analyses were performed to determine the projected outcomes necessary for RFA to achieve equivalence with resection., Setting: Tertiary care teaching hospital., Patients: A systematic review of published literature was performed, identifying studies involving patients with colorectal liver metastases treated with RFA or resection. Data were also included from a prospective database of patients undergoing laparoscopic RFA at our institution., Interventions: Percutaneous or laparoscopic RFA and hepatic resection., Main Outcome Measures: Quality-adjusted life expectancy and quality of life-adjusted survival., Results: The base-case analysis (60-year-old man) demonstrated a mean ± SD quality-adjusted life expectancy of 5.67 ± 0.71 years and a 5-year survival of 38.2% following resection. Based on current literature, the mean ± SD quality-adjusted life expectancy for RFA was 3.61 ± 0.49 years, with a 5-year survival of 27.2%. Sensitivity analyses demonstrated that RFA becomes the preferred strategy if the median disease-free survival reaches 1.42 years. When limited to patients from our institution with resectable lesions, the quality-adjusted life expectancy for RFA improved to a mean ± SD of 5.72 ± 0.50 years., Conclusions: Classical Markov analysis demonstrates that based on current literature, resection is superior to RFA in the treatment of colorectal liver metastases. When input is limited to laparoscopic RFA in patients with resectable lesions, projected 5-year survival is superior to that of hepatic resection.

Background: There continues to be controversy surrounding the appropriate use of radiofrequency ablation (RFA) for the treatment of colorectal liver metastases (CRLM). This study analyzes outcomes data of CRLM patients who underwent laparoscopic RFA. Outcomes of patients determined to be technically resectable were compared to patients with unresectable disease., Methods: Data from all patients with CRLM who underwent laparoscopic RFA between 1996 and 2006 were retrospectively reviewed. A blinded independent hepatobiliary-trained surgical oncologist reviewed preoperative diagnostic imaging studies to determine resectability. Outcomes data for patients with disease deemed anatomically resectable and unresectable were analyzed and compared. Survival was calculated by the Kaplan-Meier method. The log rank test was performed to assess significance in survival., Results: A total of 113 patients who underwent laparoscopic RFA for CRLM were identified. Twelve patients who underwent concurrent hepatic resection were excluded. Of the remaining patients, 64 were determined to have disease that was be technically resectable and 37 unresectable as a result of tumor number and/or distribution. Median and 5-year survival of the potentially resectable group was 4.3years and 48.7%, compared to 2.2 years and 18.4% in the unresectable group (P = 0.002). Median disease-free survival in the resectable group was 15.0 months, compared to 16.4 months in the unresectable group (P = 0.796). No postoperative mortality was reported in the technically resectable group, and the rate of major complications was 3.1%., Conclusions: Laparoscopic RFA of resectable CRLM can produce comparable long-term survival to hepatic resection in carefully selected patients, with favorable morbidity and mortality.

Objective: To compare short-term surgical outcomes and quality of life (QOL) between single-port laparoscopic cholecystectomy (SPLC) and classic 4-port laparoscopic cholecystectomy (CLC)., Background: There is significant interest in further reducing the trauma associated with surgical procedures. Although a number of observational studies have suggested that SPLC is a feasible alternative to CLC, there is a lack of data from randomized studies validating any benefit over CLC., Methods: Eligible patients were randomized to receive SPLC or CLC. Operative and perioperative outcomes, including cosmesis and QOL were analyzed., Results: Forty-three patients were randomized to SPLC (n = 21) or CLC (n = 22). There were no significant differences between groups for most preoperative demographics, American Society of Anesthesiology score, gallstone characteristics, local inflammation, blood loss, or length of stay. Patients undergoing SPLC were older than those receiving CLC (57.3 years vs. 45.8 years, P < 0.05). Operative times for SPLC were greater than CLC (88.5 minutes vs. 44.8 minutes, P < 0.05). Overall and cosmetic satisfaction, QOL as determined by the SF-36 survey, postoperative complications, and post-operative pain scores between discharge and 2-week postoperative visit were not significantly different between groups. Wound infection rates were similar in both groups. The SPLC group contained 1 retained bile duct stone, 1-port site hernia, and 1 postoperative port site hemorrhage., Conclusions: SPLC procedure time was longer and incurred more complications than CLC without significant benefits in patient satisfaction, postoperative pain and QOL. SPLC may be offered in carefully selected patients. Larger randomized trials performed later in the learning curve with SPLC may identify more subtle advantages of one method over another.

Background: Computed tomography (CT)-guided radiofrequency ablation (RFA) is presumed to be less morbid and less costly than laparoscopic RFA. This analysis investigates the 30-day morbidity, hospital cost, and reimbursement for CT-guided RFA versus laparoscopic RFA used to manage hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM)., Methods: A retrospective review was performed for all patients with CRLM or HCC who underwent CT-guided RFA or laparoscopic RFA between January 2002 and August 2008. Demographics, risk stratification, and procedural data were analyzed. Hospital financial data were queried for total cost, reimbursement, and itemized departmental charges. The CRLM and HCC patients were evaluated separately., Results: The study analyzed 18 RFA procedures for the treatment of HCC (8 CT-guided RFA; 10 laparoscopic RFA) and 25 RFA procedures for the treatment of CRLM (6 CT-guided RFA; 19 laparoscopic RFA). Immediate local failures were reported for 33.3% and 12.5% of the CT-guided RFA procedures for CRLM and HCC and for 5.2% and 0.0% of the laparoscopic RFA procedures for CRLM and HCC, respectively. The mean hospital cost was higher for the patients who underwent laparoscopic RFA ($11,808.70 ± $7,238.90 for HCC vs $9,882.40 ± $1,926.90 for CRLM) than for those who underwent CT-guided RFA ($7,186.10 ± $3,899.60 for HCC vs $5,767.50 ± $2,869.00 for CRLM). The mean reimbursement was lower than the mean hospital cost for the patients who underwent CT-guided RFA for CRLM ($4,329.10 vs $5,767.50)., Conclusion: Although CT-guided RFA is less expensive, it is poorly reimbursed. Also, CT-guided RFA is associated with a higher immediate local failure rate for both CRLM and HCC and a higher complication rate for patients with CRLM. For patients with HCC, CT-guided RFA is associated with a lower complication rate. Our data suggest that laparoscopic RFA should be used for most patients with CRLM and only selectively for patients with HCC.

Introduction: Selected patients with isolated breast cancer liver metastases (BCLM) may benefit from surgical management; however, indications remain unclear and the risks may outweigh the benefits in patients with a generally poor prognosis., Methods: Between 1998 and 2006, 17 patients diagnosed with BCLM were considered for surgical management (<4 tumours, tumour <4 cm in diameter and no/stable extrahepatic metastases). Peri-operative and outcomes data were analysed and compared., Results: Eight patients were found to have extensive or untreatable disease on staging laparoscopy and intra-operative ultrasound (SL/IOUS). The remaining nine patients underwent surgical management [seven laparoscopic radiofrequency ablations (RFA) and two hepatic resections]. Median length of follow-up for patients treated surgically was 40.0 months, median disease-free survival (DFS) was 32.2 months and median time to disease progression was 17.7 months. Of the eight patients not amenable to surgery, median length of follow-up was 21.8 months., Conclusion: SL/IOUS prevented unnecessary laparotomy in half of the patients taken to the operating room for surgical treatment of BCLM. In patients with BCLM, SL/IOUS should be considered standard of care before surgical intervention. The small number of patients and short follow-up may be inadequate to determine the true value of surgical management in this group of patients with BCLM., (© 2011 International Hepato-Pancreato-Biliary Association.)

Background: Intrahepatic cholangiocarcinoma (ICC) remains a rare tumour, although its incidence is increasing. Surgical resection is the mainstay of treatment. Published data regarding prognostic factors and optimal patient selection for resection are scant. We sought to determine the clinicopathologic characteristics of resectable ICC and outcomes following surgical treatment., Methods: We reviewed prospectively collected clinical data including patient, pathologic and operative details. Survival and recurrence outcomes were analysed using Cox hazard models and the Kaplan-Meier method., Results: We identified 31 surgically treated patients. Their 3-year overall survival rate (OS) was 40.1%; median follow-up was 16.2 months (range: 0.2-86.9 months). R0 resection was associated with significantly improved OS compared with R1/R2 resection (3-year OS was 68.6% in R0 vs. 24.0% in R1/R2; P= 0.042). The postoperative complication rate was 58.1%. Two patients died of postoperative liver failure within 30 days. Preoperative hypoalbuminaemia was significantly associated with worse survival., Conclusions: Surgical therapy for ICC is associated with longterm survival in the subset of nutritionally replete patients in whom an R0 resection can be achieved. Surgical mortality is significant in patients undergoing extended resection. The margin involvement rate is high and surgeons should consider the infiltrative nature of the disease in operative planning., (© 2010 International Hepato-Pancreato-Biliary Association.)

Background: Despite trends toward regionalization of care, the majority of pancreaticoduodenectomies (PD) are performed in community hospitals by surgeons with varying degrees of experience. We analyzed the impact of several variables, including surgeon volume, on outcomes following PD within a high-volume community-based teaching hospital system., Methods: Patients who underwent PD from 2005 to 2008 were reviewed retrospectively. Perioperative data, complications, and hospital financial data was queried. A high-volume (HV) surgeon was defined as an average of 10 or more PD per year., Results: Ninety-four patients underwent PD with an overall operative mortality rate of 9.6% (HV 2.2%, LV 16.0%), major complication rate of 32% (HV 18%, LV 44%), and median cost of $30,860 (HV $27,185, LV $33,007). Factors predictive of death were age (p < 0.02), body mass index (p < 0.01), and surgeon volume (p < 0.05). Factors predictive of major complication were surgeon volume (p < 0.01) and body mass index (p < 0.01). Factors predictive for increased length of stay for patients discharged from the hospital were surgeon volume (p < 0.02) and preoperative ASA classification (p < 0.05)., Conclusions: Surgeon volume and patient body mass index have a significant impact on perioperative morbidity following PD in a community teaching hospital.