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PD-1 targeted therapy has dramatically changed advanced cancer treatment. However many questions remain, including specificity of T cells activated by PD-1 therapy and how peripheral blood analysis correlates to effects at tumor sites. In this study, we utilized TCR sequencing to dissect the composition of peripheral blood CD8 T cells activated upon therapy, comparing it with tumor-infiltrating lymphocytes. We report on a nonagenarian melanoma patient who showed a prominent increase in peripheral blood Ki-67+ CD8 T cells following brain stereotactic radiation and anti-PD-1 immunotherapy. Proliferating CD8 T cells exhibited an effector-like phenotype with expression of CD38, HLA-DR and Granzyme B, as well as expression of the positive costimulatory molecules CD28 and CD27. TCR sequencing of peripheral blood CD8 T cells revealed a highly oligoclonal repertoire at baseline with one clonotype accounting for 30%. However, the majority of dominant clones - including a previously identified cytomegalovirus-reactive clone - did not expand following treatment. In contrast, expanding clones were present at low frequencies in the peripheral blood but were enriched in a previously resected liver metastasis. The patient has so far remained recurrence-free for 36 months, and several CD8 T cell clones that expanded after treatment were maintained at elevated levels for at least 8 months. Our data show that even in a nonagenarian individual with oligoclonal expansion of CD8 T cells, we can identify activation of tumor-infiltrating CD8 T cell clones in peripheral blood following anti-PD-1-based immunotherapies.

With the proliferation of bariatric surgery, there is a need to learn “the new anatomy” in these patients and the possible scenarios surgeons could face when foregut surgery is indicated. In particular, some cases of bile duct injuries after laparoscopic cholecystectomy (and any biliary reconstruction) could occur in this population; thus a whole armamentarium of techniques are needed accordingly to manage this problem. Although it is important to know the bariatric technique used previously in each patient beforehand, this chapter presents the current surgical techniques that are critical to know in this setting.

Background: The role of laparoscopy for major hepatectomies remains a matter of development to be further assessed. The purpose of this study is to compare the short-and long-term outcomes between laparoscopic and open major hepatectomies meta-analyzing individual patient data from published comparative studies. Methods: All retrospective studies comparing between laparoscopic and open major hepatectomies published until March 2017 were identified independently by 2 reviewers by searching in PubMed and Cochrane Central Register of Controlled Trials. Individual patient data were sought from all selected studies. Postoperative outcomes, including intraoperative blood loss, operative time, hospital stay, postoperative complications, mortality rates, and long-term survival were analyzed. Results: A total of 917 patients were divided into the laparoscopic (427) and open (490) groups from 8 selected studies. The hospital stay was significantly shorter, and the total morbidity was lower in the laparoscopic group. When classified by severity, the incidence of postoperative minor complications was lower; however, that of major complications was not significantly different. The operative time was longer in the laparoscopic group; however, intraoperative blood loss, perioperative mortality, and blood transfusions were comparable between the 2 groups. The overall survival in the patients with colorectal liver metastases and hepatocellular carcinoma was not significantly different between the 2 groups. Conclusion: Laparoscopic major hepatectomies offer some perioperative advantages, including fewer complications and shorter hospital stay, without increasing the blood loss volume and mortality. Whether these results can anticipate the outcomes in future randomized controlled trials has not been determined. (C) 2018 Elsevier Inc. All rights reserved.

Background Management of pancreatic cancer (PC) in elderly patients is unknown; clinical trials exclude patients with comorbidities and those of extreme age. This study evaluated treatment patterns and survival outcomes in elderly PC patients using linked Surveillance, Epidemiology, and End Results (SEER) and Medicare data. Materials and Methods Histology codes 8140, 8500, 8010, 8560, 8490, 8000, 8260, 8255, 8261, 8263, 8020, 8050, 8141, 8144, 8210, 8211, or 8262 in Medicare Parts A and B were identified. Data regarding demographic, characteristics, treatments, and vital status between 1998 and 2009 were collected from the SEER. Determinants of treatment receipt and overall survival were examined using logistic regression and Cox proportional hazards models, respectively. Results A total of 5,975 patients met inclusion. The majority of patients were non-Hispanic whites (85%) and female (55%). Most cases presented with locoregional stage disease (74%); 41% received only chemotherapy, 30% chemotherapy and surgery, 10% surgery alone, 3% radiation, and 16% no cancer-directed therapy. Patients with more advanced cancer, older age, and those residing in areas of poverty were more likely to receive no treatment. Among patients 66–74 years of age with locoregional disease, surgery alone (hazard ratio [HR] = 0.54; 95% confidence interval [CI]: 0.39–0.74) and surgery in combination with chemotherapy (HR = 0.69; 95% CI: 0.53–0.91) showed survival benefit as compared with the no treatment group. Among patients ≥75 years of age with locoregional disease, surgery alone (HR = 2.04; 95% CI: 0.87–4.8) or in combination with chemotherapy (HR = 1.59; 95% CI: 0.87–2.91) was not associated with better survival. Conclusion Treatment modality and survival differs by age and stage. Low socioeconomic status appears to be a major barrier to the receipt of PC therapy among Medicare patients. Implications for Practice Elderly patients with cancer are under-represented on clinical trials and usually have comorbid illnesses. The management of elderly patients with pancreatic cancer is unknown, with many retrospective experiences but low sample sizes. Using Surveillance, Epidemiology, and End Results-Medicare linked data to analyze treatment patterns and survival of elderly patients with pancreatic cancer on a larger population scale, this study highlights treatment patterns and their effect on survival and proposes possible obstacles to access of care in elderly patients with pancreatic cancer other than Medicare coverage.

BackgroundPancreatic ductal adenocarcinoma (PDAC) has yet to widely benefit from T cell-targeted immunotherapy and displays universally poor prognosis. Thus, enhancing the activity of immunotherapy is a high priority. Our laboratory recently reported that heat shock protein-90 (Hsp90) inhibition enhances the efficacy of PD-1 blockade in murine models of PDAC (Zhang Y. et al., Mol Cancer Ther, 2020). Hsp90 inhibitors can limit activation of cancer associated fibroblasts (CAF) and promote infiltration of T cells when combined with PD-1 blockade in preclinical systems.MethodsBased on these data, we are conducting a Phase Ib/II clinical trial to evaluate the combination of XL888 (Hsp90 inhibitor) and pembrolizumab in patients with metastatic pancreatic cancer. We hypothesize that this combination will be safe and elicit pronounced microenvironmental changes, leading to enhanced efficacy of checkpoint blockade in a tumor type that is otherwise refractory to this approach. During the phase II portion patients were randomized to receive a three week lead in with either pembrolizumab or pembrolizumab and XL888. Paired biopsies and blood samples were obtained at baseline and at week two on treatment and CyTOF was used to assess changes in circulating and tumor infiltrating immune populations. Further, CyTOF profiling of circulating immune cells was performed to assess impacts of XL888 on over thirty phenotypically defined immune populations (figure 1).ResultsAs of June 2021, paired liver biopsy specimens from sites of metastasis have been successfully obtained from a total of 8 patients and paired peripheral blood mononuclear cell samples have been analyzed in 24 patients. Our CyTOF analysis illustrated a surprising increase in myeloid cell populations within the tumor following treatment. Analysis of circulating immune cells illustrated a decrease in natural killer cells and Th17 populations following treatment while naïve B cells were increased. These data will be validated by immunohistochemical analysis of FFPE biopsy specimens obtained in parallel at the time of CyTOF analysis. The impact of XL888 on systemic cytokines and chemokines (n=48 total) in the peripheral blood from patients enrolled in the clinical trial is therefore being assessed as a potential mechanism to explain this observation.Abstract 403 Figure 1Clinical trial and correlative analysis schema. Patients were randomized to receive either pembrolizumab alone or in combination with the HSP90 inhibitor XL888 for a two week cycle prior to crossover to the combination arm. Plasma, peripheral blood mononuclear cells (PBMC), and biopsies were assayed to evaluate immunomodulatory effects of the therapies.ConclusionsClinical data from this trial indicates that this combination is safe in patients. As clinical data matures, changes in soluble and cellular biomarkers will be correlated with response to elucidate mechanisms of response or resistance to this combination therapy.Trial RegistrationThis clinical trial is underway and registered with the ID NCT03095781Ethics ApprovalThe study was approved by Emory University’s Ethics Board, approval IRB00087397.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Background: Patients with prior Roux-en-Y gastric bypass (RYGB) operations for weight loss present reconstruction challenges during a pancreaticoduodenectomy (PD). With over 60,000 RYGB performed annually, the increasing odds of encountering such patients during a PD make it imperative to understand the RYGB anatomy and anticipate reconstruction options. This article describes the possible reconstruction options and their rationale. Methods: We reviewed our PD reconstruction options, compared them to what have been described in the literature, and derived a consensus from internal conferences comprising bariatric and hepatopancreatobiliary surgeons to describe known reconstruction options. Results: In general, reconstruction options can include one of three options: (1) remnant gastrectomy, (2) preservation of gastric remnant, or (3) reversal of gastric bypass. Conclusion: This article describes individualized reconstruction options for RYGB patients undergoing PD. The reconstruction options can ...

The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade ( 3%), intermediate grade (3-20%), and high grade ( 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately.The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS).Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A ( 1%, n = 43), group B (1-1.99%, n = 23), and group C (2-2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1-2.99% was associated with decreased RFS compared with group A ( 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0-70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage.PanNETs with a Ki-67 of 1-2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future grading systems to guide both surveillance protocols and treatment strategies.

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P

Histologic classification of ampullary carcinomas as intestinal versus pancreatobiliary is rapidly becoming a part of management algorithms, with immunohistochemical classification schemes also being devised using this classification scheme as their basis. However, data on the reproducibility and prognostic relevance of this classification system are limited. In this study, five observers independently evaluated 232 resected ampullary carcinomas with invasive component >3 mm. Overall interobserver agreement was ‘fair’ (κ 0.39; P

BACKGROUND: The path of the biliopancreatic limb for reconstruction of the pancreatic anastomosis during pancreatoduodenectomy for pancreatic ductal adenocarcinoma can be trans-mesocolon or through the ligament of Treitz. Even after curative intent pancreatoduodenectomy, incidence of recurrence in the surgical bed remains high and may lead to obstruction of the biliopancreatic limb. However, the association between path of jejunal limb and incidence of biliopancreatic limb obstruction has not been studied. Primary aim was to determine whether path of reconstruction predisposes to biliopancreatic limb obstruction in the setting of local recurrence. METHODS: Patients who underwent pancreatoduodenectomy for pancreatic ductal adenocarcinoma (2008–2018) from a single institution were identified. As disease recurrence is the predominant cause of biliopancreatic limb obstruction, analysis was limited to patients with known recurrence at date of last follow-up. Given a known median time to recurrence of 8 to 10 months after resection for pancreatic ductal adenocarcinoma, analysis was further limited to patients with at least 8 months of follow-up. Primary outcome was incidence of biliopancreatic limb obstruction. RESULTS: Among the 517 patients identified, 182 were included. Median age was 65 years; 51% were male. Median follow-up was 22 months. Path of reconstruction was trans-mesocolon in 35% (n = 64) and through ligament of Treitz in 65% (n = 118). There was no difference between the two groups in clinicopathologic factors including age, tumor differentiation, grade, T-stage, N-stage, LVI, or PNI (all p > 0.05). Importantly, there was no difference in retroperitoneal margin positivity between groups (transmesocolon 8% vs ligament of Treitz 10%, p = 0.79). Both groups had similar post-operative outcomes including median length-of-stay (trans-mesocolon 6 days vs ligament of Treitz 6 days, p = 0.89) and median follow-up (trans-mesocolon 21 months vs ligament of Treitz 23 months, p = 0.68). Biliopancreatic limb obstruction was detected in 8% (n = 14) of which 14% (n = 2) were in the trans-mesocolon group and 86% (n = 12) were in the ligament of the Treitz group. Therefore, incidence of biliopancreatic limb obstruction was 3.1% in the trans-mesocolon group and 10.4% in the ligament of the Treitz group resulting in an absolute risk increase of 7.3%, risk ratio of 3.4, and relative risk increase of 2.3. There was no difference in median time to biliopancreatic limb obstruction between the groups (17.6 months vs 18.5 months, p = 1.0). Biliopancreatic limb obstruction was caused by locally recurrent pancreatic ductal adenocarcinoma in 93% (n = 13) and kinking of the duodenojejunal anastomosis in 7% (n = 1). Intervention was performed in 71% (n = 10) and included surgical bypass in 29% (n = 4), percutaneous drain in 21% (n = 3), and endoscopic/surgical decompression in 21% (n = 3). CONCLUSION: Biliopancreatic limb obstruction is a known complication after pancreatoduodenectomy for pancreatic ductal adenocarcinoma due to local recurrence in the surgical bed. This study shows that path of jejunal limb through the ligament of Treitz may be associated with a higher incidence of biliopancreatic limb obstruction compared with trans-mesocolon as the position of the biliopancreatic limb in the surgical bed may be more predisposed to obstruction after local recurrence. Larger studies are needed; however, given this potential risk of subsequent obstruction, these data suggest that the reconstruction paths may not be equivalent when performing pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

Rosai-Dorfman disease (RDD) is a rare entity characterized by proliferating S100-positive histiocytes. Originally described in lymph nodes, it can involve extranodal sites. Pancreatic involvement is rare, with

Background Postoperative emergency department (ED) visits represent fragmented care, are costly, and often evolve into readmission. Readmission rates after pancreatoduodenectomy (PD) are defined, while ED visits following PD are not. We examined the pattern of 30-day post-discharge ED visits for PD patients. Methods A quaternary institutional database analysis of adult patients who underwent PD between 2010–2017 was reviewed for ED utilization within 30 days from discharge. Results Of the 1,004 patients who underwent PD, 12% (N = 117) patients sought care in the ED within 30 days from postoperative discharge. The median time to ED presentation was 5 days post-discharge (IQR 3–9). Half of ED visits occurred during nights and weekends (N = 59, 50%). Of ED-utilizing patients, 64% (N = 76) were admitted to the hospital and 29% (N = 34) were discharged from the ED. ED visits were associated with a Clavien-Dindo Classification of 0 in 10.2% (N = 13) of patients, I-II in 62.4% (N = 73), and III-V in 26.5% (N = 31). Discussion Post-discharge ED utilization is a novel quality metric and represents a potential target population for reducing hospital readmissions. Over two-thirds (72%) of ED visits were associated with low acuity complications, and promoting institutional strategies addressing postoperative ED visits may improve patient care and efficient utilization of healthcare resources.

BACKGROUND: Both minimally invasive surgery (MIS) and open approaches for distal pancreatectomy are acceptable. MIS options include total laparoscopic/robotic (TLR) and hand-assist laparoscopy (HAL). When considering safety profile and specimen quality, the optimal approach is unknown. METHODS: Patients who underwent distal pancreatectomy from 2010–2018 at two major academic institutions were included. Converted procedures were categorized into final approach. Ninety-day perioperative/pathologic outcomes of MIS and open were compared. Subset analyses between TLR vs HAL and HAL vs open were performed. Intent-to-treat analysis was performed. RESULTS: Among 1006 patients, resection was performed by MIS in 35% (n = 352), open in 65%(n = 654). MIS had similar patient comorbidity profile as open but had increased operative time (183 vs 162 min; p < 0.01), lower estimated-blood-loss (EBL; 131 vs 341 mL; p < 0.01), fewer intraoperative blood transfusions (1.4 vs 5%; p < 0.01), shorter LOS (5.2 vs 7.2 days; p < 0.01). Tumor size was smaller (3.2 vs 4.4 cm; p < 0.01) with lower lymph node (LN) yield (14 vs 16; p < 0.01). When comparing HAL (n = 109) to TLR (n = 243), despite increased prior abdominal operations (60 vs 43%; p = 0.008), HAL had shorter operative time (167 vs 191 min; p < 0.01), similar length-of-stay (LOS; 5.4 vs 5.1 days; p = 0.27), and readmission rate (15 vs 13%; p = 0.47). When comparing HAL to open, the advantages of TLR approach persisted including lower EBL (171 vs 342 mL; p < 0.01), and shorter LOS (5.4 vs 7.2 days; p < 0.01). Although HAL had smaller tumors, it had a similar LN yield (16 vs 16; p = 0.80), and higher R0-rate (97 vs 83%; p < 0.01). CONCLUSION: Hand-assist laparoscopy is safe and feasible for distal pancreatectomy as operative time, complication profile, lymph node yield, and R0-rates are similar to open procedures, while maintaining the associated the advantages of a total laparoscopic/robotic approach with reduced blood loss and shorter length-of-stay.

WOS: 000474496100006, PubMed: 31177317, Sarcomatoid carcinomas recently came into the spotlight through genetic profiling studies and also as a distinct model of epithelial-mesenchymal transition. The literature on sarcomatoid carcinomas of gallbladder is limited. In this study, 656 gallbladder carcinomas (GBC) were reviewed. Eleven (1.7%) with a sarcomatoid component were identified and analyzed in comparison with ordinary GBC (O-GBC). Patients included 9 females and 2 males (F/M = 4.5 vs. 3.9) with a mean age-at-diagnosis of 71 (vs. 64). The median tumor size was 4.6 cm (vs. 2.5; P = 0.01). Nine patients (84%) presented with advanced stage (pT3/4) tumor (vs. 48%). An adenocarcinoma component constituting 1-75% of the tumor was present in nine, and eight had surface dysplasia/CIS; either in situ or invasive carcinoma was present in all cases. An intracholecystic papillary-tubular neoplasm was identified in one. Seven showed pleomorphic-sarcomatoid pattern, and four showed subtle/bland elongated spindle cells. Three had an angiosarcomatoid pattern. Two had heterologous elements. One showed few osteoclast-like giant cells, only adjacent to osteoid. Immunohistochemically, vimentin, was positive in six of six; P53 expression was >60% in six of six, keratins in six of seven, and p63 in two of six. Actin, desmin, and S100 were negative. The median Ki67 index was 40%. In the follow-up, one died peri-operatively, eight died of disease within 3 to 8 months (vs. 26 months median survival for O-GBC), and two were alive at 9 and 15 months. The behavior overall was worse than ordinary adenocarcinomas in general but was not different when grade and stage were matched. In summary, sarcomatoid component is identified in < 2% of GBC. Unlike sarcomatoid carcinomas in the remainder of pancreatobiliary tract, these are seldom of the "osteoclastic" type and patients present with large/advanced stage tumors. Limited data suggests that these tumors are aggressive with rapid mortality unlike pancreatic osteoclastic ones which often have indolent behavior.

Purpose A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.

Undifferentiated carcinomas with osteoclastic giant cells of the pancreas (OGC) are rare tumors. The current impression in the literature is that they are highly aggressive tumors similar in prognosis to ductal adenocarcinomas. In this study, the clinicopathologic characteristics of 38 resected OGCs were investigated and contrasted with 725 resected pancreatic ductal adenocarcinomas without osteoclastic cells (PDCs). The frequency among systematically reviewed pancreatic cancers was 1.4%. OGCs showed a slight female predominance (62.9%, vs. 51.4% in PDCs). The mean age was 57.9 years (vs. 65.0). The mean size of invasive cancer was 5.3 cm (vs. 3.2). They were characterized by nodular, pushing-border growth, and 8 arose in tumoral intraepithelial neoplasms (4 in mucinous cystic neoplasms, 4 in intraductal papillary mucinous neoplasms type lesions), and 23 (61%) also showed prominent intraductal/intracystic growth. Twenty-nine (76%) had an invasive ductal/tubular adenocarcinoma component. Osteoid was seen in 12. Despite their larger size, perineural invasion and nodal metastasis were uncommon (31.6% and 22.6%, vs. 85.5% and 64.0%, respectively). Immunohistochemistry performed on 24 cases revealed that osteoclastic cells expressed the histiocytic marker CD68, and background spindle cells and pleomorphic/giant carcinoma cells often showed p53 and often lacked cytokeratin. Survival of OGCs was significantly better than that of PDCs (5 yr, 59.1% vs. 15.7%, respectively, P=0.0009). In conclusion, pancreatic OGCs present with larger tumor size and in slightly younger patients than PDC, 21% arise in mucinous cystic neoplasms/intraductal papillary mucinous neoplasms, and 61% show intraductal/intracystic polypoid growth. OGCs have a significantly better prognosis than is currently believed in the literature.

Background Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO-001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P

Background Enucleation and anatomic resection (central, distal, or pancreaticoduodenectomy) are surgical options for pancreatic neuroendocrine tumors. Depending on nodal-status, enucleation alone may not be oncologically appropriate. Preoperative factors predictive of nodal-involvement are not well defined. Methods Patients who underwent curative-intent enucleation or resection of non-metastatic, well/moderately differentiated tumors at a single institution (2000–2014) were included. The aim was to determine factors associated with nodal-metastases and recurrence-free survival. Results Of 195 patients undergoing resection, 164 met inclusion-criteria. Lymphadenectomy was performed in 131 (80%), and 32 (24%) had nodal-metastases. Receiver-operative-characteristics analysis revealed tumor size ≥2 cm was associated with nodal-involvement (AUC: 0.689; Sensitivity: 90%; Specificity: 53%). On multivariable analysis, male gender (OR: 3.16; 95%CI: 1.18–8.46; P = 0.02), head/uncinate location (HR: 5.37; 95%CI: 2.07–13.96; P = 0.001), and size ≥2 cm (HR: 6.52; 95%CI: 1.75–24.30; P = 0.005) were associated with nodal-positivity. Nodal-metastases (HR: 3.04; 95%CI: 1.04–8.91; P = 0.043) and advanced T-stage (HR: 5.39; 95%CI: 1.46–19.95; P = 0.012) were independently associated with decreased recurrence-free survival. Enucleation (n = 17; 10%) had more positive margins and similar complication rates, pancreatic fistula rates, and lengths of stay as anatomic resections. Conclusion For pancreatic neuroendocrine tumors, male gender, head/uncinate location, and size ≥2 cm are associated with nodal-metastases. Nodal involvement is associated with decreased recurrence-free survival. Anatomic resection may be preferred in patients with these characteristics, as enucleation alone may under-stage patients and does not appear to be associated with an improved complication profile. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

The literature on "variants" and "malignant" counterparts of pancreatic serous cystic neoplasms (SCNs) is highly conflicted. Clinicopathologic characteristics of 193 SCNs were investigated, along with a critical literature review. For the macrocystic (oligocystic) variant, in this largest series, a demographic profile in contrast to current literature was elucidated, with 21% frequency, predominance in female individuals (4:1), body/tail location (1.7×), younger age of patients (mean age, 50 y), and frequent radiologic misdiagnosis as other megacystic neoplasms. Solid SCNs were rare (n=4, 2%) and often misinterpreted radiologically as neuroendocrine tumors. Available fine-needle aspiration in 11 cases was diagnostic in only 1. Radiologic impression was "malignancy" in 5%. Associated secondary tumors were detected in 13% of resections, mostly neuroendocrine. Secondary "infiltration" (direct adhesion/penetration) of spleen, stomach, colon, and/or adjacent nodes was seen in 6 (3%) fairly large SCNs (mean, 11 cm) with no distant metastasis. Three SCNs recurred locally, but completeness of original resection could not be verified. Our only hepatic SCN lacked a concurrent pancreatic tumor. Literature appraisal revealed that there are virtually no deaths that are directly attributable to dissemination/malignant behavior of SCNs, and most cases reported as "malignant" in fact would no longer fulfill the more recent World Health Organization criteria but instead would represent either (1) local adhesion/persistence of tumor, (2) cases with no histologic verification of malignancy, or (3) liver SCNs with benevolent behavior (likely representing multifocality, rather than true metastasis, especially considering there was no fatality related to this and no reported metastases to other remote sites). In conclusion, in contrast to the literature, the clinicopathologic characteristics of solid and macrocystic SCN variants are similar to their microcystic counterpart, although their radiologic diagnosis is challenging. Recurrence/secondary invasion of neighboring organs occurs rarely in larger SCNs but seems innocuous. An SCN should not be classified as "malignant" unless there is clear-cut evidence of histologic malignancy or documented distant metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is rarely detected early, instead presenting in patients as advanced metastatic disease once symptoms are evident. Given the central role of metastasis in pancreatic tumor progression and mortality, there is an urgent need for further investigation of how PDAC metastasizes and for novel treatment strategies targeting PDAC metastasis. A prominent histopathologic feature of PDAC is a desmoplastic, fibrotic stroma consisting of extracellular matrix components, immune cells, and activated fibroblasts termed “pancreatic stellate cells” (PSCs) that often compose a majority of cellular content in many PDAC tumors. Data from recent studies demonstrate multiple phenotypic PSC populations in the stroma (Ohlund et al., 2017); however, the influence of individual PSC populations on metastasis and disease progression is not fully understood. We hypothesized that PSCs promote pancreatic tumor metastasis through secretion of soluble factors and accompany these metastasizing tumor cells to distal sites using collective invasion mechanisms. Tumor spheroids were formed by centrifugation of HPAC cells (a human PDAC cell line) in low adhesion round bottom plates. Spheroids were embedded in both collagen- and Matrigel-based matrices and z-stacks were collected every 24hrs for 72hrs using a Lecia SP8 confocal microscope. Live cell imaging was performed in an incubation chamber for 72hrs using a Leica SP8 confocal microscope. Human pancreatic stellate cells were isolated from surgically resected tumor specimens at Emory University Hospital under IRB-approved protocols and grown to ~70% confluency before supernatants were collected. Utilizing innovative 3D invasion assays, we demonstrate the ability of human PSC conditioned media to initiate and promote invasion of HPAC pancreatic tumor spheroids. HPAC spheroids exposed to 10% PSC supernatants showed significantly decreased roundness in comparison to media alone. Further investigation of possible soluble factors mediating this interaction indicated a protein-based interaction, although alternative mechanisms by which metastasis may be initiated were also identified. Phenotypic analysis of invasion through live cell imaging led to observations of unique invasion mechanisms by which hyperactive cells at the leading edge seemingly guide invasion of large groups of cells. Additionally, we observed co-culture interactions between PSCs and HPAC cells. In comparison to HPAC cells alone, ratios of 10:1 PSCs to HPAC cells increased circularity (less invasive) while inverse ratios decreased circularity of spheroids (more invasive). This study supports the hypothesis that PSCs can promote collective invasion and migration of pancreatic tumor cells through both contact-dependent and -independent means. Further identification of mechanisms mediating this interaction may reveal novel therapeutic targets for the treatment of PDAC and present new strategies for targeting metastasis of this deadly disease. Citation Format: Michael B. Ware, Jerry Yue, Bassel El-Rayes, Shishir K. Maithel, Juan Sarmiento, Gregory B. Lesinski. Pancreatic stellate cells promote pancreatic cancer invasion and metastasis by secretion of soluble factors and through contact-mediated mechanisms [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A55.

The standard of care for patients with resected stage I to stage III pancreatic ductal adenocarcinoma (PDAC) is adjuvant gemcitabine-based chemotherapy. The role of adjuvant treatment in patients with subcentimeter, stage IA PDAC is unknown. The current study evaluated the effect of adjuvant treatment on survival outcomes among patients with American Joint Committee on Cancer/International Union Against Cancer stage IA (T1N0) resected PDAC using the National Cancer Data Base (NCDB).A retrospective review of the NCDB was conducted for patients diagnosed with T1 (tumor limited to the pancreas and measuring ≤2 cm in greatest dimension), lymph node-negative (N0), resected PDAC between 2004 and 2013. Patient demographics, histology, adjuvant treatment, and survival trends were examined. Kaplan-Meier analysis and log-rank tests were performed to determine the unadjusted association between overall survival (OS), tumor size, and treatment.A total of 876 patients met the inclusion criteria. The patients had a mean age of 66.2 years (range, 32-90 years); approximately 83.3% were white (730 patients) and 53.1% were female (465 patients). Approximately 45.9% of the patients had moderately differentiated tumor histology (402 patients); 70.0% (613 patients) had tumors measuring 1 to 2 cm (T1c) and 30.0% (263 patients) had tumors measuring1 cm (T1a/T1b). Approximately 94.2% of patients had negative surgical margins (815 patients) and 46.9% (410 patients) received adjuvant therapy. The median OS was significantly different for patients who received adjuvant therapy compared with patients who did not (70.7 months vs 46.9 months; P = .0001). For patients with tumors measuring1 cm, survival was not found to be significantly different between patients who received adjuvant treatment compared with those who did not (not reached vs 85.3 months; P = .54). In the multivariable analysis, none of the covariates (treatment group, Charlson-Deyo Score, age, insurance, and facility status) demonstrated significant differences for patients with tumors measuring1 cm.The current study is the first to demonstrate no survival benefit for adjuvant therapy in patients with resected subcentimeter PDAC.

Background Minimally invasive approaches for major hepatectomy have been marred by significant rates of conversion and associated morbidity. This study aimed to determine risk factors for conversion as well as postoperative morbidity in patients undergoing minimally invasive right-sided hepatectomy (MIRH). Methods Data for patients undergoing MIRH between 2008 and 2017 at Emory University were reviewed. Risk factors for conversion were determined using multivariate regression analysis. Outcomes of conversion patients were compared with those who underwent successful MIRH or elective open surgery. Results Unplanned conversion occurred in 7 (6.25%) of 112 patients undergoing MIRH. Primary reason for conversion was difficult dissection secondary to inflammation and severe adhesions. No preoperative clinical factor was identified that predicted conversions. Converted cases had higher EBL and pRBC transfusion compared to non-converted cases however morbidity was similar to those undergoing primary open surgery. Conclusion Difficult dissection and adhesions remained the only clinically applicable parameter leading to unplanned conversions. While these did offset benefits of a successful minimally invasive approach, it did not increase risk of postoperative complications compared with planned open surgery.

With current emphasis on improving cost-quality relationship in medicine, it is imperative to evaluate cost-value relationships for surgical procedures. Previously the authors demonstrated comparable clinical outcomes for minimally invasive right hepatectomy (MIRH) and open right hepatectomy (ORH). MIRH had significantly higher intraoperative cost, though overall costs were similar.MIRH was decoded into its component critical steps using value stream mapping, analyzing each associated cost. MIRH technique was prospectively modified, targeting high cost steps and outcomes were re-examined. Records were reviewed for elective MIRH before (pre-MIRH n = 50), after (post MIRH n = 25) intervention and ORH (n = 98), between January 1, 2008 and November 30, 2016.Average overall cost was significantly lower for post-standardization MIRH (post-MIRH $21 768, pre-MIRH $28 066, ORH $33 020; p 0.001). Average intraoperative blood loss was reduced with MIRH (167, 292 and 509 mL p 0.001). Operative times were shorter (147, 190 and 229 min p 0.001) and LOS was reduced for MIRH (3, 4, 7 days p 0.002).Using a common quality improvement tool, the authors established a model for cost effective clinical care. These tools allow surgeons to overcome personal or traditional biases such as stapler choices, but most importantly eliminate non-value added interventions for patients.

The value of routine primary (intraoperative) drain placement after major hepatectomy remains unclear. We sought to determine if primary drainage led to decreased rates of complications, specifically, intra-abdominal biloma or infection requiring a secondary (postoperative) drainage procedure.All patients who underwent major hepatectomy (≥3 hepatic segments) at 3 institutions, from 2000 to 2012, were identified. Patients with biliary anastomoses were excluded. Primary outcomes were any complication, rate of secondary drainage procedures, bile leak, and 30-day readmission.There were 1,041 patients who underwent major hepatectomy without biliary anastomosis; 564 (54%) had primary drains placed at the surgeon's discretion. Primary drain placement was associated with increased complications (56% vs 44%; p0.001), bile leaks (7.3% vs 4.2%; p = 0.048), and 30-day readmissions (16.4% vs 8.0%; p0.001), but was not associated with a decrease in secondary drainage procedures (8.0% vs 5.9%; p = 0.23). Patients with primary drains demonstrated higher American Society of Anesthesioloigsts (ASA) class, greater blood loss, more transfusions, and larger resections. After accounting for these significant clinicopathologic variables on multivariate analysis, primary drain placement was not associated with increased risk of any complications. Primary drainage was, however, independently associated with increased risk of bile leak (hazard ratio [HR] 2.04; 95% CI1.02 to 4.09; p = 0.044) and 30-day readmission (HR 1.79; 95% CI1.14 to 2.80; p = 0.011). There still was no reduction in the need for secondary drainage procedures (HR 0.98; p = 0.96).Primary intraoperative drain placement after major hepatectomy does not decrease the need for secondary drainage procedures and may be associated with increased bile leaks and 30-day readmissions. Routine drain placement is not warranted.

Clinicians may order Octreoscan or positron emission tomography (PET) scan for staging patients with neuroendocrine tumors (NETs). (111)In-Octreoscan (Octreoscan) identifies tumors by radiolabeled targeting of somatostatin receptors, while 18F-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) measures differential tissue glucose transport. We assessed the sensitivity of both nuclear imaging modalities with pathologic correlation to define the best initial choice for NET staging after standard cross-sectional imaging.We identified all patients diagnosed with NETs of gastrointestinal or pancreatic origin who underwent nuclear imaging staging by Octreoscan and/or PET from 2000 to 2013. Imaging results were correlated with tumor differentiation and grade of pathology specimens.Imaging and pathology results were identified for 153 patients. Of these, 131 underwent Octreoscan, 43 underwent PET, and 21 patients had both performed. Overall sensitivity of Octreoscan and PET for NET detection was similar (77 vs. 72 %; p = not significant). For well-differentiated NETs, Octreoscan (n = 124) demonstrated sensitivity of 80 vs. 60 % (p = 0.28) for PET (n = 30). For poorly-differentiated NETs, Octreoscan (n = 7) proved significantly less sensitive than PET (n = 13) (57 vs. 100 %; p = 0.02). The sensitivity of Octreoscan versus PET varied similarly when analyzed by WHO tumor grade: Grade 1 (79 vs. 52 %; p = 0.16), Grade 2 (85 vs. 86 %; p = not significant), and Grade 3 (57 vs. 100 %; p = 0.02).Tumor differentiation can be used to guide selection of nuclear imaging modalities for staging gastrointestinal and pancreatic NETs. Octreoscan appears more sensitive than (18)FDG-PET for well-differentiated NETs, whereas (18)FDG-PET demonstrates superior sensitivity for poorly-differentiated NETs.

The literature is highly conflicting on hepatobiliary mucinous cystic neoplasms (MCNs), aka "hepatobiliary cystadenoma/cystadenocarcinoma," largely because ovarian stroma (OS) was not a requirement until WHO-2010 and is not widely applied even today. In this study, MCNs (with OS) accounted for 24 of 229 (11%) resected hepatic cysts in one institution. Eight of the 32 (25%) cysts that had been originally designated as hepatobiliary cystadenoma/cystadenocarcinoma at the time of diagnosis proved not to have an OS during this review and were thus re-classified as non-MCN. In total, 36 MCNs (with OS) were analyzed-24 from the institutional files and 12 consultation cases. All were women. Mean age was 51 (28 to 76 y). Mean size was 11 cm (5 to 23 cm). Most (91%) were intrahepatic and in the left lobe (72%). Preoperative imaging mentioned "neoplasm" in 14 (47%) and carcinoma was a differential in 6 (19%) but only 2 proved to have carcinoma. Microscopically, only 47% demonstrated diffuse OS (>75% of the cyst wall/lining); OS was often focal. The cyst lining was often composed of non-mucinous biliary epithelium, and this was predominant in 50% of the cases. Degenerative changes of variable amount were seen in most cases. In situ and invasive carcinoma was seen in only 2 cases (6%), both with small invasion (7 and 8 mm). Five cases had persistence/recurrence, 2 confirmed operatively (at 7 mo and 15 y). Of the 2 cases with carcinoma, one had "residual cyst or hematoma" by radiology at 4 months, and the other was without disease at 3 years. In conclusion, many cysts (25%) previously reported as hepatobiliary cystadenoma/cystadenocarcinoma are not MCNs. True MCNs are uncommon among resected hepatic cysts (11%), occur exclusively in females, are large, mostly intrahepatic and in the left lobe (72%). Invasive carcinomas are small and uncommon (6%) compared with their pancreatic counterpart (16%). Recurrences are not uncommon following incomplete excision.

Clinicopathologic characteristics of paraduodenal (groove) pancreatitis (PDP) remain to be fully unraveled. In this study, 47 PDPs with preoperative enhanced images available were subjected to detailed comparative analysis in conjunction with pathologic findings. PDP were predominantly in males (3:1) with a mean age of 50 years, and 60% had a preoperative diagnosis of cancer. Mean lesional size was 3.1 cm. Three distinct subtypes were identified by imaging. Solid-tumoral (type-1) with groove-predominant (type-1A, 36%) forming a distinct solid band between the duodenum and pancreas often with histologic microabscesses (69% vs. 33% in others), and pancreas-involving (type-1B, 19%) forming a pseudotumoral mass spanning into the head-groove area, always diagnosed preoperatively as "cancer," but often lacked parenchymal atrophy of the body (44% vs. 92%). Cyst-forming (type-2) had groove-predominant (type-2A, 15%), often accompanied by Brunner gland hyperplasia, and pancreas-predominant (type-2B, 15%) were in younger (mean: 44 y) females (57% vs. 18%) and had less alcohol/tobacco abuse (50/33% vs. 81/69%). Ill-defined (type-3; 15%) often had main pancreatic duct dilatation (mean: 5.6 vs. 2.8 mm). The capricious presentations of PDP could be attributed to variable effects of different mechanistic and precipitative etiopathogenetic factors such as disturbed accessory duct outflow (dilated Santorini duct, 87%), aggravated by alcohol (77%) with superimposed stasis in the main ampulla (previous cholecystectomy, 47%; choledocholithiasis, 9%), strictured Wirsung duct (68%), and some likely exacerbated by ischemia (hypertension [59%], tobacco abuse [64%], arteriosclerosis in the tissue [23%]). In conclusion, our study identified 3 distinct types of PDP and each may reflect different pathogenetic contributing factors.

BACKGROUND Postoperative pancreatic fistula (POPF) is a potentially debilitating complication following pancreatoduodenectomy (PD). There are limited data correlating pancreatic parenchymal histopathologic features specifically fat and fibrosis content with development of POPF after PD. METHODS Patients who underwent PD (January 2010-May 2015) with archived pathologic slides were included. Each pancreatic neck transection margin was histologically graded for fat and fibrosis, scored from 0 to 4, and grader was blinded to clinical outcomes. Main pancreatic duct diameter and duct wall thickness were microscopically measured. Patients were dichotomized into high and low categories with respect to pancreatic fat and fibrosis and primary outcome of POPF. RESULTS Of 301 patients, 24 developed POPF (8.0%). One hundred ten patients (36.5%) had low fat (score

Background: In comparison with open distal pancreatectomy (ODP), laparoscopic distal pancreatec- tomy (LDP) is associated with fewer complications and shorter hospital stays, but comparative cost data for the two approaches are limited. Methods: Records of all distal pancreatectomies carried out from January 2009 to June 2013 were reviewed and stratified according to operative complexity. Patient factors and outcomes were recorded. Total variable costs (TVCs) were tabulated for each patient, and stratified by category (e.g. 'floor', 'operating room' (OR), 'radiology'). Costs for index admissions and 30-day readmissions were compared between LDP and ODP groups. Results: Of 153 procedures, 115 (70 LDP, 45 ODP) were selected for analysis. The TVC of the index admission was US$3420 less per patient in the LDP group (US$10 480 versus US$13 900; P = 0.06). Although OR costs were significantly greater in the LDP cohort (US$5756 versus US$4900; P = 0.02), the shorter average hospitalization in the LDP group (5.2 days versus 7.7 days; P = 0.01) resulted in a lower overall cost. The total cost of index hospitalization combined with readmission was significantly lower in the LDP cohort (US$11 106 versus US$14 803; P = 0.05). Conclusions: In appropriately selected patients, LDP is more cost-effective than ODP. The increased OR cost associated with LDP is offset by the shorter hospitalization. These data clarify targets for further cost reductions.

Laparoscopic-assisted extended hepatectomy and laparoscopic hepaticojejunostomy reconstruction can be performed for hilar cholangiocarcinoma by combining our existing protocols for laparoscopic anatomic hepatectomy and laparoscopic hand-sewn bilio-enteric anastomosis.Our first patient was a 42-year-old man with cholangitis and jaundice from tumor obstructing the hepatic duct bifurcation who underwent a right extended hepatectomy for hilar cholangiocarcinoma (Bismuth IIIa), radical portal lymphadenectomy, and Roux-en-Y hepaticojejunostomy using laparoscopic techniques. A four-trocar, one 6-cm wound protector laparoscopic technique was used. Inflow and outflow exclusion was achieved first, followed by liver transection. Radical portal lymphadenectomy was performed. A Roux-en-Y hepaticojejunostomy was constructed laparoscopically. We have performed three other cases using the same technique: two requiring right extended hepatectomy and one requiring left extended hepatectomy.No intraoperative complications occurred during the 4.0-hour procedure. Tumor margins were clear. The patient was given oral diet on Day 1 and discharged on Day 3 after surgery. No blood transfusions were necessary. A cholangiogram performed 10 days after surgery demonstrated patent hepaticojejunostomy, and magnetic resonance imaging performed during week 3 demonstrated the normal caliber of the intrahepatic biliary system. At 6 months, the patient was completely without symptoms and exhibited normal liver function tests.Laparoscopic-assisted right extended hepatectomy for hilar cholangiocarcinoma with laparoscopically hand-sewn hepaticojejunostomy in select patients can be achieved with good outcomes.

Pancreaticoduodenectomy (PD) specimens present a challenge for surgical pathologists because of the relative rarity of these specimens, combined with the anatomic complexity. Here, we describe our experience on the orientation, dissection, and sampling of PD specimens for a more practical and accurate evaluation of pancreatic, distal common bile duct (CBD), and ampullary tumors. For orientation of PDs, identification of the "trapezoid," created by the vascular bed at the center, the pancreatic neck margin on the left, and the uncinate margin on the right, is of outmost importance in finding all the pertinent margins of the specimen including the CBD, which is located at the upper right edge of this trapezoid. After orientation, all the margins can be sampled. We submit the uncinate margin entirely as a perpendicular inked margin because this adipose tissue-rich area often reveals subtle satellite carcinomas that are grossly invisible, and, with this approach, the number of R1 resections has doubled in our experience. Then, to ensure proper identification of all lymph nodes (LNs), we utilize the orange-peeling approach, in which the soft tissue surrounding the pancreatic head is shaved off in 7 arbitrarily defined regions, which also serve as shaved samples of the so-called "peripancreatic soft tissue" that defines pT3 in the current American Joint Committee on Cancer TNM. With this approach, our LN count increased from 6 to 14 and LN positivity rate from 50% to 73%. In addition, in 90% of pancreatic ductal adenocarcinomas there are grossly undetected microfoci of carcinoma. For determination of the primary site and the extent of the tumor, we believe bisectioning of the pancreatic head, instead of axial (transverse) slicing, is the most revealing approach. In addition, documentation of the findings in the duodenal surface of the ampulla is crucial for ampullary carcinomas and their recent site-specific categorization into 4 categories. Therefore, we probe both the CBD and the pancreatic duct from distal to the ampulla and cut the pancreatic head to the ampulla at a plane that goes through both ducts. Then, we sample the bisected pancreatic head depending on the findings of the case. For example, for proper staging of ampullary carcinomas, it is imperative to take the sections perpendicular to the duodenal serosa at the "groove" area, as ampullary carcinomas often extend to this region. Amputative (axial) sectioning of the ampulla, although good for documentation of the peri-Oddi spread of the intra-ampullary tumors, unfortunately disallows documentation of mucosal spread of the papilla of Vater tumors (those arising from the edge of the ampulla, where the ducts transition to duodenal mucosa and extending) into the neighboring duodenum. Axial sectioning also often fails to document tumor spread to the "groove" area. In conclusion, knowledge of the gross characteristics of the anatomic hallmarks is essential for proper dissection of PD specimens. The approach described above allows practical and accurate documentation and staging of pancreas, distal CBD, and ampullary cancers.

Background Chronic kidney disease (CKD) is known to adversely affect cardiac and vascular surgery outcomes. We examined the effect of preoperative renal insufficiency on postoperative outcomes after pancreatic resection. Study Design All patients who underwent pancreatic resection between January 2005 and July 2012 were identified. Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease formula. Severe CKD (stages 4–5) was defined as eGFR 2 . Renal function also was analyzed using serum creatinine (sCr) dichotomized at 1.8 mg/dL. Primary outcomes were any complication, major complications, and respiratory failure. Multivariate models for each endpoint were constructed by including all variables with p value ≤0.10 on univariate analysis. Results There were 1,061 patients identified; 709 underwent pancreaticoduodenectomy, 307 distal pancreatectomy, and 45 central or total pancreatectomy. Median sCr value was 0.86 mg/dL (range 0.30 to 14.1 mg/dL). Eighteen patients (1.7%) had severe CKD and 31 (2.9%) had sCr ≥ 1.8 mg/dL. Complications occurred in 622 patients (58.6%), major complications in 198 (18.7%), and respiratory failure in 48 (4.5%). Both severe CKD and sCr ≥ 1.8 mg/dL were associated with any complication, major complications, and respiratory failure on univariate analysis. On multivariate analysis, severe CKD was associated with increased complications (odds ratio [OR] 5.5; 95% CI 1.3 to 25.5; p = 0.02) and respiratory failure (OR 6.1; 95% CI 1.8 to 20.5; p = 0.03), but not major complications. Using sCr ≥ 1.8 mg/dL as a surrogate marker for renal insufficiency, patients with sCr ≥ 1.8 mg/dL had increased risk of any complication (OR 3.5; 95% CI 1.3 to 9.3; p = 0.01), major complications (OR 2.2; 95% CI 1.04 to 4.8; p = 0.04), and respiratory failure (OR 4.7; 95% CI 1.8 to 12.6; p = 0.002). Conclusions Few patients with significant renal insufficiency are candidates for pancreatic resection. Severe CKD (stages 4–5) is associated with increased risk of complication and respiratory failure. Serum creatinine ≥1.8 mg/dL may serve as a useful marker of renal insufficiency and identifies patients at significantly increased risk of any complication, major complication, and respiratory failure after pancreatic resection.

Pancreatic ductal adenocarcinoma (PDAC) has dismal five-year survival ( Citation Format: Matthew R. Farren, Walid Shaib, Mohammad Zaidi, Layal Sayegh, David Kooby, Shishir Maithel, Alyssa Krasinskas, Olatunji Alese, Juan Sarmiento, Bassel El-Rayes, Gregory B. Lesinski. Comparison of neoadjuvant FOLFIRINOX alone vs FOLFIRINOX + stereotactic body radiation as immune-modulators of the pancreatic adenocarcinoma microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3967.

e15693 Background: Resection of the primary tumor in metastatic neuroendocrine tumor (NET) is controversial. The aim of this study is to evaluate survival outcomes and identify prognostic variables of surgical resection of the primary tumor in metastatic NET patients. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Chi-square and ANOVA tests were done to identify factors associated with surgical modality. Univariate and multivariate cox proportional hazards models were used for association between patient characteristics and survival. Kaplan-Meier curves were generated and log-rank tests conducted to compare the survival difference of patient characteristics. Results: A total of 2,361 patients between 18 and 90 years of age with stage IV well/intermediate-differentiated NET were identified. The mean age was 62.1 years (SD±13), with an equal male to female ratio (50.0%). Majority of NET primaries were in the small intestine (33.0%), pancreas (26.3%), and lung (24.4%). The majority were well differentiated tumors (69.6%) and 42.5% of patients underwent surgery at the primary site. On multivariate analysis total surgical resection of the primary (HR 0.44; 0.22-0.90; p < 0.001), female sex, year of diagnosis 2010-2014, negative surgical margin, Charlson-Deyo score < 2, and age < 51 years at diagnosis were associated with better overall survival (OS). Conclusions: Resection of the primary in stage IV well/intermediate-differentiated NET was associated with improved 5-year OS compared to patients with no surgery in small intestine (60.1% vs 44.2%), lung (70.0% vs 20.2%), and pancreas tumors (59.3% vs 30.6%).

Background Limited literature is available on the development of impaired glucose tolerance and diabetes mellitus after pancreaticoduodenectomy. The primary aim was to define the diabetic phenotype and correlate preoperative glycemic laboratory results to new-onset diabetes after pancreaticoduodenectomy. Study Design In this prospective study, perioperative fasting and postprandial (oral glucose tolerance test) plasma glucose, glycated hemoglobin, insulin, and c-peptide were measured in consecutive patients undergoing pancreaticoduodenectomy by the senior author from 2006 to 2017. American Diabetes Association definitions were used for glycemic classifications. Multivariate risk factor analysis was performed. Results Of 774 identified patients, 371 diabetics were excluded and 403 patients were included: 167 and 236 were preoperatively classified as nondiabetic and prediabetic, respectively. The incidence rates of diabetes at 120 months post pancreaticoduodenectomy were 9.0% (nondiabetics), 22.0% (prediabetics), and 16.6% (overall). Patients in whom diabetes developed demonstrated a 3-fold larger difference between oral glucose tolerance test and fasting glucose (Δ), and 2-fold larger Δinsulin and Δc-peptide values. Tiered multivariate analysis identified glycated hemoglobin >5.4% with a relative risk (RR) of 2.944 (p = 0.047) as an independent predictor of impaired glucose tolerance and diabetes mellitus. Analysis of patients stratified by preoperative classification identified fasting glucose >95 mg/dL (nondiabetics, RR 1.925; p = 0.002), and glycated hemoglobin ≥5.4% (prediabetics, RR 3.125; p = 0.040) as independent risk factors for diabetes. Compared with nondiabetics, prediabetics classified by any laboratory results demonstrated an RR of 2.471 (p = 0.001) for diabetes developing postoperatively. There was no association between primary pathology, advancing age, or BMI and increased risk of diabetes development. Conclusions Diabetes will develop after pancreaticoduodenectomy in approximately 16.6% of patients. A preoperative glycated hemoglobin >5.4% independently predicts new-onset diabetes. Pre- and postoperative endocrine analysis remains paramount for proper patient risk stratification.

Background Management of hepatocellular carcinoma (HCC) in the Model for End-Stage Liver Disease (MELD) exception era remains regionally variable. Outcomes were compared for patients undergoing transplant versus resection at a single institution in a UNOS region with short wait times for organ availability.

Our investigation suggests that MR imaging is accurate for identification of paraduodenal pancreatitis and for differentiation of this entity from ductal carcinoma of the pancreatic head.

Purpose We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. Methods and Materials The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. Results The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, −34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. Conclusions Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before routine integration into the treatment planning process.

Minimal changes have been made in regard to management of pancreatic pseudocysts, and drainage remains the treatment of choice for large (more than 6 cm), symptomatic, and persistent pseudocysts. Laparoscopic techniques have been increasingly employed with success and continue to be favored when possible. Laparoscopic Roux-en-Y cystjejunostomy is an appropriate and effective drainage procedure, especially when cystgastrostomy cannot be performed. We review the literature and describe the technique in this review.

Context.—There are virtually no data in the literature regarding the incidence, patterns, and clinicopathologic characteristics of mucinous carcinomas (MCs) of the gallbladder (GB).Objective.—To determine the incidence of mucinous differentiation in invasive GB carcinomas and the clinicopathologic characteristics of those that qualify as MC.Design.—Primary invasive GB carcinomas (n = 606) were reviewed for mucinous differentiation. Some degree of mucin production was identified in 40 cases (6.6%); however, only 15 (2.5%) were qualified for the World Health Organization definition of MC (stromal mucin deposition constituting >50% of the tumor).Results.—The mean age was 65 years, and the female to male ratio was 1.1 (versus 3.9 for conventional pancreatobiliary-type GB adenocarcinomas; P = .04). A significant proportion of the cases (8 of 12, 67%) presented with the clinical picture and intraoperative findings that were interpreted as acute cholecystitis. Mean and median tumor sizes were larger than those of conventional adenocarcinomas (4.8 and 3.4 cm versus 2.9 and 2.5 cm, respectively; P = .01). Most (13 of 15, 87%) cases presented with pT3 tumors (versus 48% for ordinary GB carcinomas; P = .01). Two cases had almost an exclusive colloid pattern (>90% composed of well-defined stromal mucin nodules that contained scanty carcinoma cells, most of which were floating within the mucin). Eight cases were of mixed-mucinous type, showing a mixture of colloid and noncolloid patterns. Five others had prominent signet-ring cells, both floating within the mucin (which constituted >50% of the tumor by definition) and infiltrating into the stroma as individual signet-ring cells in some areas. Immunohistochemical analysis performed on the 7 cases that had available tissue revealed CK7 in 4 of 7 (57%), CK20 in 2 of 7 (29%), MUC1 in 4 of 7 (57%), MUC2 in 6 of 7 (86%), CDX2 in 1 of 7 (14%), MUC5AC in 6 of 7 (86%), MUC6 in 0 of 7 (0%), and loss of E-cadherin in 6 of 7 (86%). The MLH1 and MSH2 were retained in 6 of 7 cases (100%). Follow-up information was available for 13 cases: 11 (85%) died of disease (1–37 months) and 2 (15%) were alive (23 months and 1 month). Overall survival of MCs was significantly worse than that of conventional adenocarcinomas (13 versus 26 months; P = .01); however, that did not seem to be independent of stage.Conclusions.—Mucinous carcinomas constitute 2.5% of GB carcinomas. They present with an acute cholecystitis-type picture. Most MCs are a mixed-mucinous, not pure colloid, type. They are typically large and advanced tumors at the time of diagnosis and thus exhibit more-aggressive behavior than do ordinary GB carcinomas. Immunophenotypically, they differ from conventional GB adenocarcinomas by MUC2 positivity, from intestinal carcinomas by an often inverse CK7/20 profile, from pancreatic mucinous carcinomas by CDX2 negativity, and from mammary colloid carcinomas by a lack of MUC6. Unlike gastrointestinal MCs, they appear to be microsatellite stable.

Ampullary (AMP) carcinomas comprise a heterogeneous group of cancers lacking adequate subcategorization. In the present study, 249 strictly defined primary AMP carcinomas (ACs) identified in 1469 malignant pancreatoduodenectomy specimens were analyzed for defining features. Gross and microscopic findings were used to determine tumor epicenter and extent of preinvasive component. ACs were classified into 4 distinct subtypes based on location: (1) Intra-AMP (25%): Invasive carcinomas arising in intra-ampullary papillary-tubular neoplasms with zero to minimal, duodenal surface involvement (