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A triple-row stapler is widely used to divide the pancreas in distal pancreatectomy (DP). However, the selection criteria of the stapler cartridge to prevent postoperative pancreatic fistula (POPF) remain unclear. The objective of this study was to determine if factors concerning pancreatic thickness or staple size affect POPF after DP.Datasets of patients from the Mayo Clinic and National Cancer Center Hospital East who underwent DP using a triple-row stapler were merged. Risk of POPF was analyzed using clinicopathological variables, including data for pancreatic thickness and staple height. A compression index was defined as the designated staple height (mm) after closure divided by the pancreatic thickness (mm).Among the 277 patients, POPF occurred in 65 (23%) patients. The median pancreatic thickness was 13.7 mm and the median compression index was 0.137. Multivariable logistic models showed that a greater pancreatic thickness (odds ratio, 1.190, P 0.001) and a compression index ≤0.160 (odds ratio, 4.754, P 0.001) were independently related with POPF.In patients undergoing DP using a triple-row stapler, the thickness of the pancreas was related with the occurrence of POPF. Selection of the stapler cartridge with a compression index of ≤0.160 may reduce the occurrence of POPF.

Background Pancreatectomy with arterial resection (AR) is performed infrequently. As indications evolve, we evaluated indications, outcomes, and predictors of mortality, morbidity, and survival after AR. Study Design We performed a single-institution review of elective pancreatectomies with AR (from July1990 to July 2017). Univariate and multivariate analyses were performed for predictors of outcomes and survival. Results A total of 111 patients underwent pancreatectomy with AR including any hepatic (54%), any celiac (44%), any superior mesenteric (14%), or multiple ARs (14%), with revascularization in 55%. The majority of cases were planned (77%) and performed post-2010 (78%). Overall 90-day major morbidity (≥grade III) and mortality were 54% and 13%, respectively, due to post-pancreatectomy hemorrhage (PPH), postoperative pancreatic fistula (POPF), or ischemia in the majority of cases. There was a significant decrease in mortality post-2010 (9% vs 29%, p = 0.02), and this was protective on multivariate analysis (odds ratio [OR] 0.1, p = 0.004); PPH increased mortality (OR 6.1, p Conclusions Regardless of indication or type, pancreatectomy with AR is associated with risks greater than standard resections. Mortality has decreased in the modern era; however, morbidity remains high from hemorrhagic, fistula, or ischemia-related complications. Mitigation measures are needed if advanced resections are considered with increasing frequency given the potential oncologic benefit of AR in selected cases after modern chemotherapy.

BACKGROUND Morbidity and costs after pancreatoduodenectomy remain increased, driven by postoperative pancreatic fistula (POPF). A risk-based pathway for pancreatoduodenectomy (RBP-PD) was implemented and the clinical and cost outcomes compared with that of our historic practice. METHODS Prospective clinical and cost outcomes for our RBP-PD cohort treated from September 2014 to September 2015 were compared with a previously published cohort of pancreatoduodenectomies from January 2007 to February 2014. RESULTS A total of 128 RBP-PD cases were compared with 808 historic controls. Apart from less blood loss, there were no significant clinical differences between the 2 groups. Overall POPF rate did not change. Average duration of stay decreased to 10 days from 12 (P

The aim of this study was to investigate the impact of decreased skeletal muscle (SM) volume on survival outcomes in patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC).Between March 2000 and February 2015, 323 patients who underwent upfront surgical resection for PDAC were identified from the Mayo Clinic SPORE in Pancreatic Cancer. Body composition data, including SM area, subcutaneous adipose tissue area, and visceral adipose tissue area were calculated using an abdominal computed tomography (CT) image at the third lumbar spinal level. The body composition data were normalized by patients' height (e.g., SM index, cmBecause the median SM index was significantly different between males vs. females (49.9 cmA smaller sex-standardized SM index is a predictive factor for shorter overall and recurrence-free survival in PDAC patients undergoing surgery.

Background and Aims Malignant vascular invasion usually results from gross direct infiltration from a primary tumor and impacts cancer staging, prognosis, and therapy. However, patients may also develop a remote malignant thrombi (RMT), defined as a malignant intravascular thrombus located remote and noncontiguous to the primary tumor. Our aim was to compare EUS, CT, and magnetic resonance imaging (MRI) findings of RMT and to explore the potential impact on cancer staging. Methods Patients with RMT were identified from a prospectively maintained EUS database. Retrospective chart review was performed to obtain EUS, CT/MRI, clinical, and outcome data. Results A median of 3 FNAs (range, 1-8) was obtained from RMT in 17 patients (60 ± 14.1 years, 56% men) between April 2003 and August 2016, with the finding of malignant cytology in 12 patients (70.6%; 10 positive, 2 suspicious). CT/MRI detected the RMT in 5 patients (29.4%), 4 of whom had positive or suspicious EUS-FNA cytology. Among the 8 newly diagnosed pancreatic adenocarcinoma (PaC) patients, CT did not detect the RMT in 5 (63%), of whom 3 patients had positive or suspicious intravascular EUS-FNA cytology. For newly diagnosed PaC patients (n = 8), the EUS-FNA diagnosis of a biopsy specimen–proven RMT upstaged 3 patients (37.5%) and converted 2 patients (25%) from CT resectable to unresectable disease. No adverse events were reported. The mean follow-up was 18.9 ± 27.7 months. Conclusions Our study demonstrates the ability and potential safety of intravascular FNA to detect radiographically occult RMT, which substantially impacts cancer staging and resectability.

BACKGROUND AND OBJECTIVES Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC. METHODS The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis. RESULTS In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P

Intrahepatic lesions of mixed hepatocellular (HCC) and intrahepatic cholangiocellular carcinoma (ICC) histology are rare. The aim was to describe the natural history of these tumors relative to monomorphic ICC or HCC utilizing the National Cancer Data Base (NCDB).Patients with ICC, HCC, and mixed histology (cHCC-CCA) were identified in the NCDB (2004-2012). Inter-group comparisons were made. Kaplan-Meier and multivariable Cox Proportional Hazards analyzed overall survival.The query identified 90,499 patients with HCC; 14,463 with ICC; and 1141 with cHCC-CCA histology. Patients with cHCC-CCA histology were relatively young (61 vs. 62 (HCC, p = 0.877) and 67 (ICC, p 0.001) years) and more likely to have poorly differentiated tumor (29.2% vs. 10.3% (HCC) and 17.2% (ICC) p 0.001). Median overall survival for cHCC-CCA was 7.9 months vs. 10.8 (HCC) and 8.2 (ICC, all p 0.001). Stage-specific survival for mixed histology tumors was most similar to that of HCC for all stages. cHCC-CCA were transplanted at a relatively high rate, and transplant outcomes for mixed tumors were substantially worse than for HCC lesions.cHCC-CCA demonstrate stage-specific survival similar to HCC, but post-surgical survival more consistent with ICC. Patients with a pre-operative diagnosis of cHCC-CCA should undergo resection when appropriate.

Patient triage in anatomically resectable, early stage pancreatic ductal adenocarcinoma (PDAC) with elevated carbohydrate antigen 19-9 (CA 19-9) remains unclear. We hypothesized that any CA 19-9 elevation indicates biologically borderline resectability.The National Cancer Data Base (NCDB 2010 to 2012) was reviewed for PDAC patients with reported CA 19-9. Nonsecretors were analyzed separately. Early stage (I/II) patients were stratified by CA 19-9 above or below normal (37 U/mL). Unadjusted Kaplan-Meier and adjusted Cox proportional hazards survival modeling were performed.Of 113,145 patients, only 28,074 (24.8%) had CA 19-9 measured and reported, and this proportion was stage independent. Among early stage patients (n = 10,806), there were 957 (8.8%) nonsecretors, 2,708 (25.1%) with normal levels, and 7,141 (66.1%) with elevated levels. Demographics and perioperative outcomes were similar between these groups. Survival was worse in all stages in patients with CA 19-9 elevation. Nonsecretors had survival similar to that of patients with normal levels. Early stage patients with elevated CA 19-9 had decreased survival at 1, 2, and 3 years (56% vs 68%, 30% vs 42%, 15% vs 25%, all p0.001) relative to patients with normal levels. Adjusted modeling confirmed this finding (hazard ratio [HR] 1.26, p0.001). Repeat modeling in the neoadjuvant cohort demonstrated this to be the only treatment sequence to completely abrogate increased mortality due to CA 19-9 elevation (p = 0.11).The minority of PDAC patients have CA 19-9 measured and reported in NCDB. The CA 19-9 nonsecretors and normal-level patients achieve equivalent survival. Elevation of CA 19-9 is associated with decreased stage-specific survival, with the greatest difference in early stages. Neoadjuvant systemic therapy followed by curative intent surgery best mitigates the increased mortality hazard. Patients with PDAC who have elevated CA 19-9 levels at diagnosis are biologically borderline resectable regardless of anatomic resectability, and neoadjuvant systemic therapy is suggested.

Autoimmune pancreatitis (AIP) responds dramatically to corticosteroids treatment. We reviewed our experience to determine the safety and effectiveness of treating obstructive jaundice in definitive AIP with corticosteroids alone without biliary stenting.From our AIP database, we retrospectively identified type 1 AIP subjects whose jaundice was treated with corticosteroids alone without biliary stenting. Their medical records were reviewed and clinical data were evaluated to determine the outcomes.Fifteen AIP subjects (87% male, mean age 68.4 years) were treated with corticosteroids at initial presentation (n = 8), first (n = 5) or subsequent (n = 2) relapse. Mean values (upper limit of normal, ULN) of liver tests prior to corticosteroids were aspartate aminotransferase (AST) 203.5u/l (4 × ULN), alanine aminotransferase (ALT) 325.8u/l (6 × ULN), alkaline phosphatase (ALP) 567.4u/l (5 × ULN), and total bilirubin (TB) 5.9 mg/dl (5.9 × ULN). At first follow-up (mean 4 days) the decrease was 54.9% for AST, 51.6% for ALT, 33% for ALP and 47.2% for TB (all p 0.05). After 15-45 days, all patients had normal AST, 3/15 had ALT 1.5 × ULN, 1/15 had ALP 1.5 × ULN, 1/15 had TB 1.5 × ULN. No patient required biliary stent placement, or developed cholangitis or other infectious complications during steroid treatment.Under the supervision of an experienced pancreatologist and with close monitoring of patients, obstructive jaundice secondary to definitive AIP can be safely and effectively managed with corticosteroids alone, without the need for biliary stenting.

Efficacy and outcomes of resection for pancreatic neuroendocrine tumors (pNET) are well established; specific data on outcomes for pancreaticoduodenectomy (PD), either alone or with combined procedures, are limited. A retrospective review of PDs for pNET (1998–2014) at our institution was conducted. Patients were categorized into standard PD (SPD) alone or combined PD (CPD) defined as patients undergoing concurrent vascular reconstruction or additional organ resection for curative intent. Kaplan-Meier survival analyses were performed. PD for pNET was performed for 95 patients. Tumors were functional in 11 patients (9 %). Twenty-six patients (28 %) underwent CPD. The 30/90-day mortality was 1.1/5.3 % respectively and similar between SPD and CPD (p = 0.61/p = 0.24). Five-year overall survival after PD for pNET was 85.1/71.9 % and similar between SPD/CPD groups (p = 0.17). Recurrence-free and overall survival for low-grade tumors was 74.7/93.9 % at 5 years compared to only 14.8/49.7 % for high-grade tumors (p < 0.001) and not predicted by extent of resection (SPD/CPD, respectively). PD with or without concurrent resection provides an acceptable, perioperative and long-term oncologic, outcome for pNET. CPD is justified treatment modality, particularly for patients with low-grade tumors. The need for combinatorial procedures during PD is not contraindication alone for otherwise resectable patients with pNET.

In patients undergoing elective partial pancreatectomy, our aim was to evaluate the effect of metabolic syndrome (MS) on postoperative mortality, morbidity, and utilization of hospital resources. Our hypothesis was that MS is associated with worse surgical outcomes after pancreatectomy. Fifteen thousand eight hundred thirty-one patients undergoing elective pancreatectomy from 2005 to 2012 were identified in the Participant User File of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Univariable and multivariable analyses were performed examining the association of MS (defined as body mass index ≥30 kg/m2, hypertension requiring medications, and diabetes requiring medications and/or insulin) and risk of 30-day mortality, morbidity, and utilization of hospital resources (risk of blood transfusion in the first 72 h after pancreatectomy and prolonged hospital stay, defined as ≥13 days, which was the 75th percentile of this cohort). Multivariable logistic regression models controlled for age, sex, race, pancreatectomy type (distal versus proximal), smoking status, alcohol consumption, functional status, dyspnea, cardiovascular disease, hematocrit, INR, serum albumin, bilirubin, and creatinine. Stratified analyses were conducted by type of pancreatectomy and indication for pancreatectomy (benign versus malignant). On univariate analysis, 1070 (6.8 %) patients had MS. MS was associated with increased postoperative morbidity, major morbidity, surgical site infection, septic shock, cardiac event, respiratory failure, pulmonary embolism, blood transfusion, and prolonged duration of hospital stay (P

Background A delayed post pancreatoduodenectomy haemorrhage is associated with a significant increase in peri operative mortality. Endovascular techniques are frequently used for a delayed haemorrhage. However, limited data exists on the short and long term outcomes of this approach. A retrospective review over a 10 year period at a quaternary referral pancreatic centre was performed. Methods Between 2002–2012, 1430 pancreatoduodenectomies were performed, and 32 patients had a delayed haemorrhage (occurring >24 h post operatively) managed by endovascular techniques. The clinicopathological variables related to a haemorrhage were investigated. Results A total of 42 endovascular procedures were performed at a median of 25 days, with the majority of delayed haemorrhages occurring after 7 days. There were four deaths (13%) with three occurring in patients with a grade C haemorrhage. Seven patients (22%) experienced rebleeding, and two patients developed hepatic abscesses. Conclusion A delayed haemorrhage post pancreaticoduodenectomy can be managed by endovascular techniques with acceptable morbidity and mortality. Rebleeding and hepatic abscesses may occur and can be managed non operatively in most cases. The association of a delayed haemorrhage with a pancreatic fistula makes this a challenging clinical problem.

Background and study aims: Pancreas cyst fluid analysis does not provide optimal discrimination between mucinous and nonmucinous cysts. The aim of this study was to assess the performance characteristics of the “string sign” – a test performed at the time of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), for the diagnosis of mucinous pancreatic cysts (branch duct intraductal papillary mucinous neoplasms [bIPMN] and mucinous cystic neoplasms). Patients and methods: Patients undergoing EUS-FNA of pancreatic cystic lesions at one referral center between 2003 and 2012 were included. The string sign was performed prospectively, and was considered positive if ≥ 1 cm string formed in cyst fluid and lasted for ≥ 1 second. Performance characteristics of the string sign and a sequential cyst fluid test interpretation model were assessed. Results: For 98 histologically proven cases, the sensitivity, specificity, positive predictive value, and negative predictive value of the string sign for diagnosis of mucinous cysts were 58 % (95 % confidence interval [CI] 44 % – 70 %), 95 % (83 % – 99 %), 94 % (81 % – 99 %), and 60 % (46 % – 72 %), respectively. When string sign results and carcinoembryonic antigen (CEA) concentration (≥ 200 ng/mL) were combined, diagnostic accuracy improved from 74 % and 83 %, respectively, to 89 % (P ≤ 0.03). Among bIPMN, a positive string sign was associated with gastric and intestinal epithelial subtypes. The sequential cyst fluid test interpretation model (including cytology, mucin stain, CEA, and string sign) yielded an overall sensitivity for mucinous lesions of 96 %, with a specificity of 90 %. Conclusions: The string sign is highly specific for diagnosis of mucinous pancreatic cysts, and improves overall diagnostic accuracy of pancreatic cyst fluid analysis. Sequential cyst fluid test interpretation yields high diagnostic sensitivity and specificity for mucinous cysts.

BackgroundThe 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings.MethodsA single‐centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan–Meier estimates and log‐rank tests.ResultsA total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow‐up was 4.5 years. The median patient age was 58 years (range: 24–79 years). Median body mass index was 27 kg/m2 (range: 17–46 kg/m2). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001).ConclusionsThe AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC.

Major vascular resection when necessary for margin control during pancreaticoduodenectomy is relatively universal with perioperative and oncological outcomes that are similar to those of patients undergoing a PD without venous involvement. The present study compares total laparoscopic pancreaticoduodenectomy (TLPD) versus open pancreaticoduodenectomy (OPD) with major vascular resection. We reviewed data for all patients undergoing TLPD or OPD with vascular resection at Mayo Clinic Rochester, between the dates of July 2007 and July 2013. A total of 31 patients undergoing TLPD and 58 patients undergoing OPD with major vascular resection were identified. Mean operative blood loss was significantly less in the laparoscopic (842 cc) compared to the open group (1,452 cc) (p

Outcomes of patients developing portal vein (PV) thrombosis (PVT) after distal pancreatectomy (DP) are unknown. The goal of this study was to identify risk factors for PVT and describe the long-term outcomes in these patients.Patients undergoing DP without repair or reconstruction of the PV between 2001 and 2011 were included. Patients that showed evidence of PVT on pre-operative imaging were excluded from the study. Location and extent of thrombosis was determined by post-operative computed tomography or ultrasound imaging in all patients. Evidence of systemic thrombosis (if present) in addition to PVT was also documented.In the study period, 991 patients underwent DP and 21 (2.1%) patients were diagnosed with PVT. Pancreatic neoplasm was the most frequent indication for operation (n = 11). Thrombus occurred in the main PV in 15 and the right branch of the PV in 8 patients. Complete PV occlusion occurred in nine patients with a median time to diagnosis of 16 days (range 5-85 days). Seventeen patients were anticoagulated for a median duration of 6 months (range 3.3-36 months) after the diagnosis of PVT. Over a median follow-up of 22 months, resolution of PVT occurred in seven patients. Predictors of non-resolution of PVT included anesthesia time180 min (p = 0.025), DM type II (p = 0.03), BMI 30 Kg/m(2) (p = 0.03), occlusive PVT (p 0.001), or thrombus in a sectoral branch (p = 0.02). Anticoagulation therapy did not influence the frequency of thrombus resolution and was complicated by gastrointestinal hemorrhage in four patients. There was no mortality as a direct result of PVT or anticoagulation.PVT after distal pancreatectomy is a rare complication. Serious complications as a direct result of PVT in this setting are uncommon and are not dependent on thrombus resolution. Although anticoagulation does not appear to influence the rate of PVT resolution in this small retrospective series, we support the use of anticoagulation until larger, controlled studies define clear advantages or disadvantages.

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

Background We aimed to identify staging parameters associated with survival in patients with hilar cholangiocarcinoma. Methods Clinicopathologic characteristics were obtained retrospectively for all resected patients with Bismuth-Corlette III cholangiocarcinoma between 1993 and 2011. Patients were stratified by the American Joint Commission on Cancer (AJCC) (7th edition) and Memorial Sloan-Kettering Cancer Center (MSKCC) staging systems. Survival analyses tested the effects of clinicopathologic factors and staging covariates on recurrence-free and overall survival. Results Eighty patients (mean age 63 ± 11 years, 63% male) underwent anatomic hepatectomy with bile duct resection/reconstruction for Bismuth-Corlette IIIa (53%) and IIIb (47%) cholangiocarcinoma. The median follow-up was 26 months (interquartile range = 12 to 50 months), and the median time to recurrence was 15 months (interquartile range = 6 to 38 months). Neither AJCC nor MSKCC staging systems were associated with recurrence-free survival (all P ≥ .059). MSKCC T-stage but not the AJCC staging system was associated with overall survival ( P ≤ .026). Conclusions MSKCC T-stage classification but not AJCC staging is independently associated with overall survival for patients after resection of hilar cholangiocarcinoma.

BackgroundNew‐onset diabetes mellitus after a pancreaticoduodenectomy (PD) remains poorly defined. The aim of this study was to define the incidence and predictive factors of immediate post‐resection diabetes mellitus (iPRDM).MethodsRetrospective review of patients undergoing PD from January 2004 through to July 2010. Immediate post‐resection diabetes mellitus was defined as diabetes requiring pharmacological treatment within 30 days post‐operatively. Logistic regression was conducted to identify factors predictive of iPRDM.ResultsOf 778 patients undergoing PD, 214 were excluded owing to pre‐operative diabetes (n= 192), declined research authorization (n= 14) or death prior to hospital discharge (n= 8); the remaining 564 patients comprised the study population. iPRDM occurred in 22 patients (4%) who were more likely to be male, have pre‐operative glucose intolerance, or an increased creatinine, body mass index (BMI), pre‐operative glucose, operative time, tumour size or specimen length compared with patients without iPRDM (P < 0.05). On multivariate analysis, pre‐operative impaired glucose intolerance (P < 0.001), pre‐operative glucose ≥ 126 (P < 0.001) and specimen length (P= 0.002) were independent predictors of iPRDM. A predictive model using these three factors demonstrated a c‐index of 0.842.DiscussionNew‐onset, post‐resection diabetes occurs in 4% of patients undergoing PD. Factors predictive of iPRDM include pre‐operative glucose intolerance, elevated pre‐operative glucose and increased specimen length. These data are important for patient education and predicting outcomes after PD.

Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD). The National Cancer Data Base (2004–2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression. Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90–1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870). Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.

Background and Aims Among the greatest hurdles to pancreatic cancer (PC) therapy is the limited tissue penetration of systemic chemotherapy because of tumor desmoplasia. The primary study aim was to determine the toxicity profile of EUS-guided fine-needle injection (EUS-FNI) with gemcitabine. Secondary endpoints included the ability to disease downstage leading to an R0 resection and overall survival (OS) at 6 months, 12 months, and 5 years after therapy. Methods In a prospective study from a tertiary referral center, gemcitabine (38 mg/mL) EUS-FNI was performed in patients with PC before conventional therapy. Initial and delayed adverse events (AEs) were assessed within 72 hours and 4 to 14 days after EUS-FNI, respectively. Patients were followed for ≥5 years or until death. Results Thirty-six patients with stage II (n = 3), stage III (n = 20), or stage IV (n = 13) disease underwent gemcitabine EUS-FNI with 2.5 mL (.7-7.0 mg) total volume of injectate per patient. There were no initial or delayed AEs reported. Thirty-five patients (97.2%) were deceased at the time of analysis with a median 10.3 months of follow-up (range, 3.1-63.9). OS at 6 months and 12 months was 78% and 44%, respectively. The median OS was 10.4 months (range, 2.7-68). Among patients with stage III unresectable disease, 4 (20%) were downstaged and underwent an R0 resection. Conclusions Our study suggests the feasibility, safety, and potential efficacy of gemcitabine EUS-FNI for PC. Additional data are needed to verify these observations and to determine the potential role relative to conventional multimodality therapy.

Outcomes of neoadjuvant systemic therapy versus an upfront operation for clinical, stage III pancreatic adenocarcinoma remain poorly defined. Our aim was to compare survival among patients receiving neoadjuvant chemotherapy versus surgery-first with an intention-to-treat analysis.The National Cancer Data Base was reviewed from 2002-2011 for patients with clinical, stage III adenocarcinoma of the head or body of the pancreas. Patients were categorized as neoadjuvant or surgery-first. The intention-to-treat analysis included all neoadjuvant therapy patients in whom a potentially curative operation was planned and all surgery-first patients for whom adjuvant therapy was recommended. Intention-to-treat overall survival was compared by Kaplan-Meier and Cox proportional hazards multivariable regression.A total of 593 patients were identified: 377 (63.6%) in the neoadjuvant cohort, wherein 104 (27.6%) experienced preoperative attrition, and 216 (36.4%) in the surgery-first cohort, of whom 30 (13.9%) failed to receive intended adjuvant chemotherapy. Intention-to-treat Kaplan-Meier analysis demonstrated superior survival for neoadjuvant compared to surgery-first (median overall survival 20.7 months vs 13.7 months, log rank P .001). Intention-to-treat multivariable regression analysis revealed a decreased mortality hazard (hazard ratio = 0.68, 95% confidence interval 0.53-0.86, P = .0012) for neoadjuvant compared to surgery-first.Despite preoperative attrition, neoadjuvant therapy in clinical, stage III pancreatic cancer patients is associated with improved overall survival when compared to patients receiving surgery-first.

Diseases of the pancreas and periampullary region form an important clinical group of malignant and also benign diseases which still carry relatively high morbidity and mortality rates. Pancreatic ductal adenocarcinoma, in particular, is associated with very poor outcome as the number of new cases per year is just slightly higher than the number of deaths from this disease. Therefore, treatment of these conditions should always be based on both the highest level of evidence and technical expertise. Surgery for diseases of the pancreas and periampullary region has evolved substantially during the last 15 years and several new surgical techniques have been described. According to recent randomized trials and advances in medical treatment, several surgical dogmas have been refuted. The majority of patients with pancreatic and periampullary cancer at the time of diagnosis have advanced disease. However, in specialized centers, 10–15% of the patients with these malignances are suitable for resection. In these centers, the morbidity and mortality associated with major pancreatic resection have been reduced considerably in recent years. It is an undisputed fact that pancreatic resection ranks as one of the most, if not the most, complicated and technically challenging surgical procedures. It not only is a demanding technical exercise but also exerts a substantial logistical strain on healthcare resources. The group from Heidelberg addressed the importance of vascular resections during pancreatic surgery. The limits of resection in patients with pancreatic and periampullary cancers have been extended. The recently published consensus paper by the International Study Group for Pancreatic Surgery (ISGPS) provided up-to-date definitions of borderline and extended resections. These definitions help clinicians worldwide to apply extended surgical approaches to an increasing number of surgical candidates. These procedures include vascular and multivisceral resections. When dictated by tumor involvement, resection of portal and superior mesenteric and splenic veins should be performed routinely in patients if the patient's general condition allows and there are no major comorbidities. The decision for arterial resections should be strictly individualized. This type of surgery should be reserved for fit, younger patients, with preoperative careful examination of all aspects of this extended surgery. The majority of patients with infiltration of coeliac trunk or superior mesenteric artery should be considered for neoadjuvant therapy and then reevaluated for postponed surgical intervention and resection of infiltrated vessels. D. Hartmann and H. Friess addressed the current status of the role of the surgery in the treatment of chronic pancreatitis. Surgical intervention in patients with chronic pancreatitis is mainly performed to resolve the complications of disease. In the majority of patients, intractable pain is the major indication for surgery, although jaundice, duodenal obstruction, and portal vein thrombosis are not rare. The goal of the surgery is pain reduction and management of complications, while preserving exocrine and endocrine pancreatic function and improving quality of life. Timing of surgery is an important feature during the prolonged natural history of the disease. New findings support early surgery for pain management in chronic pancreatitis patients, since early surgical intervention is associated with an improved postoperative pain relief, a reduced risk of pancreatic insufficiency, and decreased reintervention rates in comparison to conservative step-up approaches. Duodenum-preserving pancreatic head resections (including Beger, Frey, and Berne procedures) seem to be superior in peri- and postoperative outcome parameters and quality of life compared to partial pancreatoduodenectomy (Whipple procedure) while being equally effective in postoperative pain relief, overall health, and postoperative endocrine sufficiency. Organ-sparing operation at the right point of time carries a better outcome than performing an extended resection as a last resort once all therapeutic options are exhausted. An early timing of surgical therapy is crucial for the outcome of patients with painful CP and the indication of surgery should be considered early once symptoms are unambiguous. The group from Verona evaluated technical aspects, indications, and results of the application of Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) on locally advanced pancreatic cancer (LAPC). RFA and IRE are the most frequently applied ablative techniques for the management of locally advanced pancreatic cancer. These techniques are versatile, since they can be performed at laparostomy, or via laparoscopic, endoscopic, or percutaneous routes. It has been demonstrated that their use is safe; however, since serious adverse events can occur, they are best performed at high volume centers and by high volume surgeons. The application of RFA and IRE is recommended in a multidisciplinary decision-making setting and they should be used especially on locally advanced tumors that have not demonstrated a propensity to metastasize. That said, properly designed studies are still needed to assess their efficacy. Finally, one of the most intriguing aspects of the application of RFA and IRE is their presumed stimulation of the immune system against the cancer. Once this aspect is further clarified and possibly confirmed, their use within the natural history of pancreatic cancer will become clearer. The group from Glasgow described the treatment of infected necrotizing pancreatitis. Treatment of acute pancreatitis is currently based on the definitions set forth in the 2012 Revised Atlanta Classification. Since the PANTER trial, there is now consensus that a “step-up approach” starting with catheter drainage and, if needed, followed by minimally invasive necrosectomy is the preferred treatment approach to infected necrotizing pancreatitis. The most commonly used minimally invasive strategies for necrosectomy are transgastric necrosectomy, percutaneous necrosectomy, and video-assisted retroperitoneal debridement (VARD). The recently completed TENSION trial compared transgastric necrosectomy with VARD within a “step-up approach,” but the final results are awaited. The advantage of transgastric necrosectomy is that it minimizes the risk of a pancreatocutaneous fistula which can be very problematic in case of “central gland necrosis.” The major disadvantage of transgastric necrosectomy is that multiple, often lengthy, procedures are required, whereas, with VARD via a 3–5 cm incision, only 1-2 procedures are sufficient in the majority of patients. Percutaneous necrosectomy probably holds the middle ground between these two options and several large series have described good outcomes. The group from Belgrade overviewed the role of interventional treatment of abdominal compartment syndrome (ACS) during severe acute pancreatitis (SAP). Some unresolved questions persist which include the role of medical treatment and the indications for and the timing of interventional techniques. Currently, there is no unanimity of opinion regarding surgical or other interventional treatments for ACS during the course of SAP. Critically ill patients with acute pancreatitis have a considerable risk for developing intra-abdominal hypertension. Routine measurement of intra-abdominal pressure is recommended, allowing the identification of patients at risk of abdominal compartment syndrome. First line therapy for this life-threatening complication is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Percutaneous catheter drainage should be the first step in interventional treatment which can relieve ACS. When ACS persists, surgery is indicated. Timing of abdominal decompression also remains uncertain in the treatment of these patients. However, the Finnish group published their experience with 26 patients regarding early and late decompression. Results clearly showed that early decompression (first 4 days) was associated with a significantly lower mortality rate, compared with late decompression (after 4 days). Midline laparostomy seems to be the method of choice, although full-thickness transverse subcostal bilateral laparostomy, subcutaneous linea alba fasciotomy, and fasciotomy of the anterior rectus abdominis sheath have been described as alternative options. Since laparostomy carries significant morbidity, randomized studies are needed to establish firm advantages over other techniques. Better understanding of pathophysiology of diseases of the pancreas and periampullary region has led surgeons to change some traditional surgical approaches and develop new innovative techniques. Technological advances which have improved the safety and efficacy of pancreatic surgery have been performed mainly in selected high volume centers. In order to improve both quality of life and duration of survival for our patients, novel surgical techniques should become more widely available and accepted. Studies with sound design and statistical methodology are urgently needed. In the present special issue, the authors have addressed new understanding of the pathophysiology of diseases of the periampullary region and pancreas. They have focused their interest in evidence-based, novel surgical techniques and approaches and challenging clinical settings have been emphasized. Dejan Radenkovic Michael B. Farnell Claudio Bassi Marc Besselink

We investigated the role of operative therapy in non-cirrhotic patients who developed metastatic hepatocellular carcinoma (HCC). This retrospective cohort study included consecutive non-cirrhotic patients with metastatic HCC after a prior hepatectomy treated between 1990 and 2009. Patients were stratified by operative therapy (resection, ablation, transcatheter therapy). Kaplan–Meier analyses with log-rank comparisons tested effects of operative therapy on overall survival (OS) and progression-free survival (PFS). Of 195 non-cirrhotic patients treated for HCC during the study period, 98 [median age 65, interquartile range (IQR) 53–71; 55 % male] subsequently developed metastatic HCC (55 intrahepatic only). Median time to development of metastases after the index operation was 10 months (IQR 5–20 months); median number of metastases was 3 (IQR 2–7). Half of these patients (n = 50) underwent operative treatment of metastases; 20 (40 %) underwent metastasectomy, 18 (36 %) ablation, and 12 (24 %) transcatheter therapy. Operative therapy was associated with improved OS (p

Summary Objective Islet autotransplantation (IAT) may decrease the morbidity and mortality of postpancreatectomy diabetes mellitus. The current systematic review and meta-analysis examined the rate of insulin independence (II) and mortality after IAT post-total (TP) or partial pancreatectomy (PP). Methods Ovid MEDLINE, EMBASE, Web of Science, SCOPUS and reference lists were searched until 31 January 2011. Eligible studies enrolled adult patients with IAT post-TP or PP, regardless of study design, sample size and language. Two investigators identified eligible studies and extracted data independently. From each study, 95% confidence intervals (CIs) were estimated and pooled using random effects meta-analysis. Results Fifteen observational studies were eligible (11 IAT post-TP, two post-PP and two including both). The II rates for IAT post-TP at last follow-up and transiently during the study were 4·62 per 100 person-years (95% CI: 1·53–7·72) and 8·34 per 100 person-years (95% CI: 3·32–13·37), respectively. In the later group, patients achieved transient II lasting 15·57 months (95% CI: 10·35–20·79). The II rate at last follow-up for IAT post-PP was 24·28 per 100 person-years (95% CI: 0·00–48·96). Whereas the 30-day mortality for IAT post-TP and post-PP was 5% (95% CI: 2–10%) and 0, respectively, the long-term mortality was 1·38 per 100 person-years (95% CI: 0·66–2·11) and 0·70 per 100 person-years (95% CI: 0·00–1·80) respectively. Conclusions IAT postpancreatectomy offers some patients a chance for insulin independence. Better data reporting are essential to establish the risks and benefits of IAT after pancreatic surgery.

To evaluate the role of neoadjuvant chemoradiation therapy and rescue surgery in the management of unresectable or recurrent duodenal adenocarcinoma.Retrospective review of all adults treated with neoadjuvant therapy and rescue surgery for locally unresectable or locally recurrent duodenal adenocarcinoma from 1994 to 2010.Ten patients received various forms of neoadjuvant therapy prior to operative exploration for potential resection. Six patients presented with locally unresectable disease, while four had local recurrences. Six patients had vascular encasement, three had retroperitoneal extension with vascular invasion, and one had invasion of surrounding organs. Of the six patients with locally advanced disease, preoperative therapy consisted of chemotherapy alone (3) or chemoradiotherapy (3). Of the four patients with local recurrences, preoperative therapy consisted of chemotherapy alone (1), chemoradiotherapy alone (1), chemoradiotherapy after chemotherapy (1), and chemoradiotherapy followed by combination chemotherapy (1). Nine of ten patients became resectable after neoadjuvant therapy. Clinically, two patients had complete responses, and four had partial responses. Histopathology revealed complete pathologic response in two patients and near-complete pathologic response in one (1 mm of residual disease). Currently, five patients are alive (range 18-83 months postoperatively). All have no evidence of disease.Neoadjuvant therapy may convert locally unresectable duodenal adenocarcinoma to resectable disease with subsequent prolonged survival.

Delayed or decreased computed tomography (CT) enhancement characteristics in pancreatic fibrosis have been described.A review of 157 consecutive patients with preoperative dual-phase CT between 2004 and 2009 was performed. Pancreatic CT attenuation upstream from the tumor was measured in the pancreatic and hepatic imaging phases. The ratio of the mean CT attenuation value [hepatic to pancreatic phase; late/early (L/E) ratio] and histological grade of pancreatic fibrosis was correlated with the development of a clinically relevant pancreatic anastomotic failure (PAF) and other clinical parameters.A clinically relevant PAF was observed in 21 patients (13.4%) with morbidity and mortality of 39.5% and 0%, respectively. The PAF group showed maximum enhancement in the pancreatic and washout in the hepatic CT phase, while the no PAF group showed a delayed enhancement pattern. Degree of pancreatic fibrosis and L/E ratio were significantly lower for the PAF group than the no PAF group (0.86 ± 0.14 vs. 1.09 ± 0.24; P 0.0001 and 21.0 ± 17.9 vs. 40.4 ± 29.8; P 0.0001); fewer PAF patients showed an atrophic histological pattern (14% vs. 39%; P = 0.046). The L/E ratio was positively correlated with pancreatic fibrosis. Pancreatic fibrosis and L/E ratio increased with larger duct size (P 0.001), the presence of diabetes (P 0.05), and the surgeon's assessment of pancreas firmness (P 0.001). In multivariate analyses, L/E ratio and body mass index were significant predictors for the development of a clinically relevant PAF; a 0.1-U increase of L/E ratio decreased the odds of a PAF by 54%.Pancreatic CT enhancement pattern can accurately assess pancreatic fibrosis and is a powerful tool to predict the risk of developing a clinically relevant PAF following PD.

Survival after resection for invasive intraductal papillary mucinous neoplasm (inv-IPMN) is superior to pancreatic ductal adenocarcinoma (PDAC). This difference may be explained by earlier presentation of inv-IPMN. We hypothesized that inv-IPMN has survival comparable with PDAC after resection when matched by stage.From 1999 to 2009, 113 patients underwent resection for inv-IPMN at 2 large academic institutions. These data were compared with 845 patients during the same period undergoing resection for PDAC. Demographics, pathology, and overall survival (OS) were compared according to current American Joint Committee on Cancer stage.Mean age with inv-IPMN and PDAC was 68 and 65 years, respectively. Follow-up was 33 and 24 months for inv-IPMN and PDAC, respectively. Median OS was 32 months for inv-IPMN and 17 months in PDAC (p0.001). Median OS in lymph node-negative inv-IPMN was 41 months and 24 months in PDAC (p = 0.003), with the greatest absolute difference in stage Ia patients with OS of 80 and 50 months in inv-IPMN and PDAC, respectively (p = 0.03). In node-positive patients, OS was 20 months in inv-IPMN and 15 months in PDAC (p = 0.06). Of inv-IPMN, 24% was colloid versus 75% of tubular subtype; 37(85%) of node-positive inv-IPMN were tubular subtype. Median OS was 23 and 127 months for tubular and colloid subtypes, respectively (p0.001).When matched by stage, inv-IPMN has superior survival after resection compared with PDAC. This disparity is greatest in node-negative and least in node-positive disease. These findings suggest the behaviors of inv-IPMN and PDAC, although different, converge with advancing American Joint Committee on Cancer stage because of a greater proportion of tubular subtype.

Background Hepatic resection of metastatic carcinoid cancer can prolong survival and control symptomatic endocrinopathy. Decompensated carcinoid heart disease (CHD) can develop in some patients with metastatic carcinoid cancers, which can preclude operation for resectable hepatic metastases. We hypothesized that outcomes after hepatic resection for patients with the carcinoid syndrome after valve replacement for CHD would be similar to carcinoid patients without CHD. Study Design We compared the survival and symptom control after hepatic resection for patients undergoing valve replacement for CHD to carcinoid patients without CHD matched for age, sex, and extent of hepatectomy. Results Fourteen patients with earlier valve replacement for CHD were compared with 28 carcinoid patients without CHD. All patients had hepatic resection for metastatic carcinoid disease and carcinoid syndrome. Mean age, sex distribution, and extent of hepatectomy (major hepatectomy, 78%) was similar between groups. Mean interval from valve replacement to hepatectomy was 101 days. There was no operative mortality. Major operative morbidity, inclusive of operative blood loss and cardiorespiratory events, occurred in 28.5% and 14.2% for CHD and non-CHD groups, respectively (p = 0.16). Symptom-free survival for CHD and non-CHD groups was 69% and 81% at 1 year (p = 0.22) and 61% and 44% (p = 0.17) at 5 years, respectively. Octreotide-free survival after hepatectomy 69% and 84% (p = 0.15) at 1 year and 62% and 52% (p = 0.29) 5 years, respectively. Overall survival CHD and non-CHD groups 100% at 1 year and 100% and 70% (p = 0.002) 5 years. Conclusions Valve replacement for severe CHD is safe and hepatic resection is associated with similar outcomes as patients without CHD undergoing hepatic resection for carcinoid syndrome. Identifying resectable hepatic metastases from carcinoids in patients with severe CHD should prompt valve replacement and interval hepatic resection.

Summary Introduction Total pancreatectomy (TP) has been associated with substantial metabolic abnormalities and poor glycaemic con- trol limiting its use. Because data reported to date are limited, we evaluated outcomes related to the diabetes mellitus obligated by TP. Methods A case series study of all patients who underwent TP from 01/01/1985 to 12/31/2006 at Mayo Clinic was conducted. TP cases were summarized according to perioperative procedures, mortality and morbidity after TP. To complement this retrospec- tive examination, a survey was developed to measure DM treat- ment modality, target organ failure and complications in patients alive in 2007. We performed a meta-analysis to compare our results with similar previous studies and provide overall estimates of out- comes. Results A total of 141 cases were studied (97 malignant diseases, 44 benign diseases). The median survival was much less for malig- nant pathology (2AE2 vs 8AE7 years, Log rank P =0 AE0009). In 2007, there were 59 patients that were presumed alive and 47 (80%) responded to the survey. Mean HbA1c at last follow-up was 7AE5% with 89% of respondents on a complex insulin programme (mean daily insulin requirement 35 ± 13 units). Episodic hypoglycaemia was experienced by 37 (79%); 15 (41%) experienced severe hypo- glycaemia. In contrast, diabetic ketoacidosis developed in only 2 (4%). Target organ complications and chronic diarrhoea devel- oped in 13 patients (28%) each. Conclusion The primary factor determining survival after TP is the aetiology necessitating TP, i.e. pancreatic malignancy. Most respondents used complex insulin programmes, but hypoglyca- emia continues to be a problem.

BackgroundAdjuvant treatment for pancreatic adenocarcinoma has been shown to improve survival. An increasingly recognized ‘subtype’ of pancreatic adenocarcinoma is invasive intraductal papillary mucinous neoplasm (IPMN). It is unclear whether adjuvant treatment for invasive IPMN improves survival. This study aimed to determine the impact of adjuvant treatment in invasive IPMN.MethodsWe conducted a retrospective analysis of merged clinical databases including 412 patients undergoing resection for IPMN at two academic institutions between 1989 and 2006.ResultsOf 412 patients with IPMN who underwent pancreatectomy, 98 had invasive carcinoma. Median survival in invasive IPMN was 32months. Adjuvant treatment did not affect median survival in node-positive or node-negative invasive IPMN. Biopsy-proven recurrence of invasive IPMN occurred in 45 patients (46%). The median disease-free interval from resection to recurrence was 27months. Treatment of recurrences with chemotherapy or radiation therapy was not associated with a difference in survival; however, a subgroup of patients with recurrence in the remnant pancreas who underwent re-resection appeared to have more favourable outcomes.ConclusionsAn invasive component measuring >2cm and lymph node involvement are associated with poorer prognosis. Adjuvant therapy in invasive IPMN appears to confer no survival benefit. In selected patients with recurrence of invasive IPMN in the remnant pancreas, re-resection should be considered.

The obesity epidemic coupled with epidemiologic evidence of the link between pancreatic cancer and obesity has raised the interest in the impact of body mass index (BMI) on outcomes for resected pancreatic cancer. All patients who underwent pancreatoduodenectomy (PD) for pancreatic adenocarcinoma from 1981 to 2007 were categorized into four groups according to their BMI (

Autoimmune pancreatitis (AIP) has been divided into subtypes 1 (lymphoplasmacytic sclerosing pancreatitis) and 2 (idiopathic duct centric pancreatitis). We compared clinical profiles and long-term outcomes of types 1 and 2 AIP.We compared clinical presentation, relapse, and vital status of 78 patients with type 1 AIP who met the original HISORt criteria and 19 patients with histologically confirmed type 2 AIP.At presentation, patients with type 1 AIP were older than those with type 2 AIP (62 +/- 14 vs 48 +/- 19 years; P.0001) and had a greater prevalence of increased serum levels of immunoglobulin G4 (47/59 [80%] vs 1/6 [17%]; P = .004). Patients with type 1 were more likely than those with type 2 to have proximal biliary, retroperitoneal, renal, or salivary disease (60% vs 0; P.0001). Inflammatory bowel disease was associated with types 1 and 2 (6% vs 16%; P = .37). During median clinical follow-up periods of 42 and 29 months, respectively, 47% of patients with type 1 and none of those with type 2 experienced a relapse. In type 1 AIP, proximal biliary involvement (hazard ratio [HR], 2.12; P = .038) and diffuse pancreatic swelling (HR, 2.00; P = .049) were predictive of relapse, whereas pancreaticoduodenectomy reduced the relapse rate (vs the corticosteroid-treated group; HR, 0.15; P = .0001). After median follow-up periods of 58 and 89 months (types 1 and 2, respectively), the 5-year survival rates for both groups were similar to those of the age- and sex-matched US population.Types 1 and 2 AIP have distinct clinical profiles. Patients with type 1 AIP have a high relapse rate, but patients with type 2 AIP do not experience relapse. AIP does not affect long-term survival.

Background Survival for pancreatic ductal adenocarcinoma is low, the role of adjuvant therapy remains controversial, and recent data suggest adjuvant chemoradiation (CRT) may decrease survival compared with surgery alone. Our goal was to examine efficacy of adjuvant CRT in resected pancreatic adenocarcinoma compared with surgery alone. Materials and Methods Patients with pancreatic adenocarcinoma at Johns Hopkins Hospital (n = 794, 1993–2005) and Mayo Clinic (n = 478, 1985–2005) following resection who were observed (n = 509) or received adjuvant 5-FU based CRT (median dose 50.4 Gy; n = 583) were included. Cox survival and propensity score analyses assessed associations with overall survival. Matched-pair analysis by treatment group (1:1) based on institution, age, sex, tumor size/stage, differentiation, margin, and node positivity with N = 496 (n = 248 per treatment arm) was performed. Results Median survival was 18.8 months. Overall survival (OS) was longer among recipients of CRT versus surgery alone (median survival 21.1 vs. 15.5 months, P

In immunosuppressed patients with branch duct intraductal papillary mucinous neoplasm (IPMN-Br) associated with solid organ transplantation, the risk of major pancreatic surgery has to be weighed against the risk of progression to malignancy. Recent studies show that IPMN-Br without consensus indications for resection (CIR) can be followed conservatively. We analyzed the course of IPMN-Br in patients with and without solid organ transplant.We compared clinical and imaging data at diagnosis and follow-up of 33 IPMN-Br patients with solid organ transplant (T-IPMN-Br) with those of 57 IPMN-Br patients who did not undergo transplantation (NT-IPMN-Br). In T-IPMN-Br, we noted pre- and post-transplant imaging and cyst characteristics. This case-control study was conducted in a tertiary-care hospital for patients with IPMN-Br.T-IPMN-Br patients were younger than the NT-IPMN-Br patients (63 vs. 68 years, P = 0.01). The median duration of follow-up for the groups was similar (29 vs. 28 months, P = NS). CIR were present in 24% (8/33) of T-IPMN-Br patients and 32% (18/57) of NT-IPMN-Br. New CIR were noted in 6% (2/33) of patients in the T-IPMN-Br group during a median follow-up of 17 months (range, 3-100 months) compared with 4% (2/57) of patients in the NT-IPMN-Br group (P = NS). Eleven patients (10 NT-IPMN-Br, 1 T-IPMN-Br) underwent surgery during follow-up. Only one NT-IPMN-Br patient was diagnosed with malignancy; all others had benign IPMN-Br.In participants with IPMN-Br, short-term follow-up after solid organ transplant was not associated with any significant change in cyst characteristics suggesting that incidental IPMN-Br, even in the setting of immunosuppression post-transplant, can be followed conservatively.

Organ failure (OF) is a main cause of death in severe acute pancreatitis (SAP). Our primary aim was to evaluate the morbidity and mortality of patients admitted with SAP with no OF (NOF), single OF (SOF), and multiple (or =2) OF (MOF).Medical records of 207 consecutive patients admitted with SAP to the Mayo Clinic between 1992 and 2001 were reviewed. OF was defined according to the Atlanta classification and patients were categorized in the three groups-NOF, SOF, and MOF. Primary outcomes were in-hospital mortality, duration of hospitalization, need for the intensive care unit (ICU), and the mean length of stay in the ICU.OF occurred in 108 patients (52%). Gastrointestinal bleeding occurred in 18%, respiratory failure in 36%, hypotension in 28%, and renal failure in 26%. Compared to patients with MOF, patients with NOF had shorter hospitalizations (28 vs. 55 days, P=0.02), less need for ICU care (50% vs. 90%, P=0.001), shorter time in the ICU (5 vs. 34 days, P0.05), and decreased in-hospital mortality (2% vs. 46%, P0.01). Odds ratios evaluating the risk of in-hospital mortality for subjects with any OF was 28 (7-186), 10 (2-69) for patients with SOF, and 64 (15-464) for patients with MOF.Patients with SAP and NOF have prolonged hospitalizations but low mortality. The Atlanta classification should be revised to include a patient group defined as "moderately severe acute pancreatitis" that identifies those patients currently classified as SAP without OF.

With improvements in the safety of Whipple resection in recent decades, surgeons have continued to explore the role of more extensive lymphadenectomy in hope of improving long-term survival. A systematic literature search of level I evidence addressing the role of the extent of lymphadenectomy was undertaken. Only reports of prospective, randomized controlled trials comparing pancreaticoduodenectomy with standard lymphadenectomy to pancreaticoduodenectomy with extended lymphadenectomy where information regarding survival, morbidity, mortality, the number of resected lymph nodes in each group and detailed operative technique were included. Four prospective, randomized trials comprising some 424 patients and one meta-analysis were identified. In aggregate, these studies confirmed that the number of resected lymph nodes was significantly higher in the pancreaticoduodenectomy with extended lymphadenectomy group. Morbidity and mortality rates were comparable. Postoperative diarrhea in the early months after operation was problematic in patients undergoing extended lymphadenectomy. In none of the studies was a benefit in long-term survival demonstrated. Standard pancreaticoduodenectomy continues to be the operation of choice for adenocarcinoma of the head of the pancreas.

Background A clinical risk score for pancreatic fistula (CRS-PF) was recently reported to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). An independent external validation has not been performed. Our hypothesis was that CRS-PF predicts POPF after both laparoscopic and open PD. Study Design The CRS-PF was calculated from a retrospective review of patients undergoing PD from January 2007 to February 2014. Postoperative pancreatic fistula was graded using International Study Group of Pancreatic Fistula criteria. Grade B and C leaks were defined as clinically significant. Performance was measured based on sensitivity, specificity, positive and negative predictive value, accuracy, and R 2 . Results There were 808 patients who met inclusion criteria; 539 (66.7%) had open and 269 (33.3%) had laparoscopic PD. The CRS-PF was high risk in 134 patients, intermediate in 492, low in 135, and negligible in 47. Postoperative pancreatic fistula occurred in 191 (23.6%) patients (grade A, 3.8%; B, 14.2%; and C, 5.6%), and it increased with risk category (R 2 = 0.935 all, 0.898 open, and 0.968 laparoscopic). High and intermediate risk categories were combined and classified as "test positive," and negligible and low risk categories were combined and classified "test negative," resulting in a CRS-PF with a sensitivity of 95% and a negative predictive value of 96% for predicting POPF. Contrary to previous studies, grade A POPF increased with increasing CRS-PF and POPF did not correlate with estimated blood loss (R 2 = 0.04). Conclusions The CRS-PF was validated independently by predicting POPF for both laparoscopic and open PD. Predictive performance was at least as good for laparoscopic PD as for open PD. Lack of correlation with estimated blood loss suggests CRS-PF might be tailored for improved performance. The CRS-PF is a clinically useful tool for POPF risk stratification after PD and allows for targeted intra- and postoperative measures to address patients at increased risk.

Venous resection and reconstruction is becoming more common during pancreaticoduodenectomy (PD). There are multiple options for reconstruction of the mesenteric venous system ranging from primary repair to grafting with autologous or synthetic material. Few studies report on the patency rates and long-term morbidity of these repairs. We sought to describe our experience with venous reconstruction during PD with specific attention to patency and long-term morbidity and mortality. Thrombosis rates of mesenteric venous reconstruction during PD are low, with low associated morbidity. In this retrospective cohort, clinical, operative, and pathologic data were collected from consecutive patients for 1988 through 2003. Graft patency on follow-up imaging studies was determined, and short- as well as long-term morbidity and mortality were recorded. Sixty-four patients underwent PD with venous resection/reconstruction from 1988 through 2003. Mean patient age was 63 years, with pancreatic ductal adenocarcinoma as the pathology in 88%. Reconstruction consisted of primary lateral venorrhaphy in 29 (45%), PTFE graft in 18 (28%), primary end-to-end repair in 13 (20%), and autologous vein graft in 4 (6%). There was one perioperative death (2%). Follow-up imaging to assess patency was available for a mean of 12.2 months postoperatively. Eleven thromboses were diagnosed at a mean of 11.9 months. Three thromboses (5%) were noted within 30 days and full anticoagulation was chosen. Fifty-three percent of patients received anticoagulation with aspirin, warfarin, or clopidogrel based upon surgeon preference. There was no difference in thrombosis rates between those receiving anticoagulation and those who did not (P=0.65). In those patients with thrombosis outside the acute time period, morbidity was limited to ascites in three patients and splenic vein thrombosis with uncomplicated esophageal varices in another patient. Mesenteric venous resection and reconstruction during PD has a high patency rate, and those reconstructions that do thrombose are associated with a low morbidity. The majority of reconstruction thromboses that occurred late were associated with recurrence.

Background & Aims: The Japan Pancreas Society criteria for diagnosis of autoimmune pancreatitis (AIP) mandate presence of characteristic imaging (diffuse pancreatic enlargement with diffusely irregular, narrow pancreatic duct). AIP has unique histologic features associated with infiltration of tissues of affected organs with abundant IgG4-positive cells. We propose expanded diagnostic criteria for AIP with a cohort of histologically confirmed AIP. Methods: We reviewed the pancreatic imaging findings on computed tomography scans, serum IgG4 levels, other organ involvement, and response to steroids in 29 consecutive patients who met histologic criteria for AIP. Results: Computed tomography scans (n = 22) showed diffuse pancreatic enlargement in 6 (27%) patients; the rest had focal enlargement, distinct mass, normal pancreas, or focal acute pancreatitis. Serum IgG4 level was elevated in 15 of 21 (71%) patients, and other organ involvement (eg, intrahepatic biliary strictures) was noted in 11 of 29 (38%) patients. All 17 patients treated with steroids exhibited resolution/marked improvement of pancreatic/extrapancreatic manifestation. On the basis of this experience we propose that diagnosis of AIP can be made in patients with ≥1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) response to steroid therapy of pancreatic/extrapancreatic manifestations of AIP. Twenty additional patients met expanded diagnostic criteria for AIP, and their demographic and clinical profile was similar to that of the 29 patients meeting histologic criteria. Conclusions: AIP defined by histological criteria shows a wide spectrum of radiologic features, with characteristic imaging seen only in a minority. Incorporation of additional features into current diagnostic criteria can identify the full spectrum of clinical presentations of AIP.

While selected pancreatic diseases may be best treated by total pancreatectomy (TP), the anticipated sequelae of pancreatic insufficiency make TP an undesirable alternative. Our aim was to determine if patients undergoing TP have a worse quality of life (QoL) than age- and gender-matched controls and poor long-term glycemic control. Ninety-nine patients undergoing TP from 1985 through 2002 were identified. The 34 survivors with no recurrent malignancy were surveyed with the Short Form-36 (SF-36), the Audit of Diabetes Dependent QoL (ADD QoL), the European Organization for Research and Treatment in Cancer Pancreas 26 (EORTC PAN 26), and our institutional questionnaire. Operative morbidity and mortality were 32% and 5%, respectively. Three late postoperative deaths (3%) were attributed to hypoglycemia. Of the 34 surviving patients, 27 (79%) agreed to participate at a mean of 7.5 years postoperatively. Seven patients had required 12 hospitalizations for poor glycemic control. Per the SF-36, two domains (role physical and general health) were decreased compared with an age- and gender-matched national population (P < .05). The ADD QoL demonstrated an overall decrease in QoL related specifically to the diabetes mellitus (P < .01), but comparison with insulin-dependent diabetics from other causes showed no significant difference in QoL. The EORTC PAN 26 instrument also showed measurable effects on QoL. Total pancreatectomy can be performed safely. QoL after TP is decreased compared with age- and gender-matched controls but not with diabetes from other causes; however, the changes are not overwhelming. TP should remain a viable option but in selected patients.

The study goal was to analyze outcome after distal pancreatectomy for three subtypes of adenocarcinoma to determine the role of en bloc resection in surgical management. A secondary aim was to identify those clinicopathologic factors correlating with survival in an analysis limited to ductal adenocarcinoma. Medical records of consecutive patients undergoing distal pancreatectomy for adenocarcinoma between 1987 and 2003 were reviewed. A comparative analysis was undertaken of the safety and outcome of patients undergoing standard and en bloc resections. Clinicopathologic factors for patients undergoing distal pancreatectomy for ductal adenocarcinoma were subjected to both univariate and multivariate survival analyses. Ninety-three patients underwent resection for ductal adenocarcinoma (66, 71%), mucinous cystadenocarcinoma (18, 19%), or adenocarcinoma associated with intraductal papillary mucinous neoplasm (IPMN) (9, 10%). En bloc resection was required in 33 (35%) patients. There was no operative mortality. Median survival was 15.5 months, 30.2 months, and 50.7 months for ductal adenocarcinoma, mucinous cystadenocarcinoma, and adenocarcinoma associated with IPMN, respectively. Patients undergoing en bloc resection had a higher overall complication rate, required more transfusions and more intensive care unit admissions, and had a higher rate of positive margins; however, there were no deaths. For ductal adenocarcinoma, tumor size greater than 3.5 cm, age greater than 60 years, and stage were factors that correlated with survival on a univariate analysis. None were significant on multivariate analysis. Four patients with ductal adenocarcinoma were actual 5-year survivors. While en bloc resections are associated with a higher rate of complications, the majority are self-limited and mortality is low. Resection, including adjacent organs, should be performed when appropriate. Long-term survival for patients with cystadenocarcinoma or IPMN-associated adenocarcinoma can be anticipated. While rare, long-term survival for patients with ductal adenocarcinoma after distal pancreatectomy can be achieved.

Pancreatic mucin-producing cystic neoplasms are classified into 2 distinct entities: mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN). In previous studies, MCN often has been defined loosely and has not always been distinguished clearly from IPMN. Our aims were to determine the demographics, clinical features, and prevalence of invasive cancer in MCN defined by the presence of characteristic ovarian stroma.By using the presence of ovarian stroma as a requisite criterion for diagnosis of MCN, a single pathologist, unaware of clinical information, identified 56 MCNs from 243 mucin-producing neoplasms resected at Mayo Clinic between 1986 and 2003. Medical records of the MCN patients were reviewed to obtain clinical and demographic data.Patients with MCN were almost exclusively (98%) women; we identified 1 man with a neoplasm containing ovarian stroma. The mean (+/-SD) age at resection was 48 +/- 15 years (84%60 y). Abdominal pain was the most common presenting symptom; 16% were asymptomatic. Most MCN (93%) were in the pancreatic body/tail region. Their median size was 5 cm (61%or =5 cm). Histologically, 50 (89%) were adenomas, 2 (4%) had carcinoma-in-situ, and 4 (7%) had invasive cancer. None of the 22 MCNs5 cm in size had invasive cancer. No patient with noninvasive disease had a recurrence after resection.MCN defined by ovarian stroma has a distinct demographic and clinical profile and a low prevalence of invasive cancer. These observations suggest that ovarian stroma should be used as the defining criterion for diagnosing MCN.

Background Morbidity associated with pancreaticoduodenectomy usually results from complications associated with the pancreaticojejunal anastomosis, in particular, a pancreatic leak. Four patients with retained transanastomotic pancreatic stent-induced complications after pancreaticduodenectomy were identified. Methods Medical records for the 4 patients were reviewed, and telephone interviews were conducted. Observations Each patient underwent pancreaticoduodenectomy for a peripapillary tumor with creation of a pancreaticojejunal anastomosis by using an internal 8F Silastic stent. Subsequent evaluation for steatorrhea (n=3) or recurrent pancreatitis (n=1) led to discovery of a retained pancreatic stent. In one patient, the stent was incidentally discovered. Steatorrhea significantly improved (n=1) or resolved (n=2) after stent removal. The patient with pancreatitis has not experienced another episode. Conclusions The possibility of a retained stent should be considered in patients presenting with steatorrhea or pancreatitis after pancreaticoduodenectomy.

Background & Aims: We have observed intraductal papillary mucinous neoplasm (IPMN) associated with pancreatic calcification. The aim of this study is to describe the profile of IPMN associated with calcification and gain insights into the pathogenesis of calcification in IPMN. Methods: We identified 10 patients with IPMN with pancreatic calcification, of whom 7 underwent pancreatic resection. We reviewed demographic data, history of previous pancreatitis, and radiological and histological features of these patients. Results: In patients with IPMN with calcification (mean age, 65 ± 12 yr; 50% men), a diagnosis of chronic calcifying pancreatitis was entertained in 5 of 10 patients; 2 patients had undergone previous endoscopic therapy for stone removal. There was no previous history of pancreatitis in 9 of 10 patients. Radiologically, calcifications were seen diffusely throughout the gland in 8 of 10 patients and interpreted as chronic calcific pancreatitis. Although 1 of the 7 patients who underwent resection had diffuse IPMN throughout the gland, 6 patients had IPMN confined to the head or uncinate process (mean size, 2.75 cm; range, 1.1–5 cm). Histologically, 6 of 7 IPMNs were adenomas, and 1 patient had invasive cancer. No patient had intratumoral calcification. All 7 patients had calcification within the main pancreatic duct and/or side branches, often within inspissated mucus. Conclusions: IPMN associated with pancreatic calcification can lead to misdiagnosis and inappropriate treatment for chronic calcifying pancreatitis. In the absence of intratumoral calcification or a previous history of long-standing chronic pancreatitis, calcification in IPMN likely represents a unique and hitherto unrecognized form of calcifying obstructive pancreatitis caused by prolonged partial obstruction of the pancreatic duct.

Little is known about subjects with idiopathic tumefactive chronic pancreatitis (TCP), that is, chronic pancreatitis whose clinical presentation, usually with a mass or obstructive jaundice, suggests cancer.We independently reviewed clinical data and histology of 45 TCP (27 idiopathic, 18 alcohol induced) resected at Mayo Clinic (January 1985-March 2001). Follow-up data were obtained from medical records and mailed questionnaires.Compared with alcoholic subjects, idiopathic TCP patients were older (58 +/- 2 vs. 48 +/- 3 yr, P0.001), had shorter symptom duration (median 3 vs. 24 wk, P0.001), were more likely to have no or mild abdominal pain (70% vs. 17%, P = 0.001), and were more often jaundiced (67% vs. 33%, P = 0.02). Three distinct histologic patterns were identified in TCP. Typical CP (n = 19) showed lobular atrophy, fat necrosis, and ductal changes (dilatation, protein plugs, and stones). Lymphoplasmacytic sclerosing pancreatitis (LPSP) (n = 14) was characterized by periductal lymphoplasmacytic infiltration, obliterative phlebitis, and cholangitis with edema. Idiopathic duct-centric CP (IDCP) (n = 12) had neutrophil-predominant lobular inflammation, without phlebitis. On correlation of clinical and histologic diagnosis, 17 of 18 (94%) patients with alcohol-induced TCP had typical CP, and 25 of 27 (93%) with idiopathic TCP had LPSP or IDCP. LPSP and IDCP were indistinguishable clinically except for higher incidence of jaundice in LPSP (93% vs. 42%, P = 0.005). In idiopathic TCP no recurrence of symptoms was observed after resection (median follow-up 49 mo).Idiopathic TCP is clinically and histologically distinct from alcohol-induced TCP. It is unclear whether LPSP and IDCP, 2 unique patterns of histologic injury observed in idiopathic TCP, are part of the spectrum of the same disease or represent 2 or more different entities. Resection of mass prevents recurrence of symptoms in idiopathic TCP.

Objectives Patients with severe necrotizing pancreatitis are at risk for infection, a major cause of morbidity and mortality. Most patients with infected pancreatic tissue require surgical intervention (necrosectomy), which is associated with high morbidity and mortality. A subset of these patients can be managed successfully with conservative management combined with prolonged courses of antibiotics. Methods Three cases of severe acute pancreatitis seen at our institution are described, in which the patients developed aspirate-proven pancreatic infections. The patients were nonetheless stable from a clinical standpoint and were treated with long courses of antibiotics known to penetrate the pancreas; emergent surgery was deferred. Results In two patients, surgery was completely avoided, with good clinical outcome. In the third patient, elective surgery was undertaken 12 wk after the episode of acute pancreatitis, to perform necrosectomy on organized pancreatic necrosis and to evaluate the patient’s biliary tree. There were no postoperative complications. Conclusions A subset of patients with severe acute pancreatitis complicated by infection can be successfully managed with long term antibiotics and other supportive measures. High risk necrosectomy can, in some instances, be delayed or avoided entirely.