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Background & Aims: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance., Methods: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer., Results: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5)., Conclusions: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Weight change offers the simplest indication of a patient's recovery after an operation. There have been no studies that have thoroughly investigated postoperative weight dynamics after pancreatectomy. The aim of this study was to define postoperative weight change after a pancreatectomy and determine factors associated with optimal and poor weight trajectories., Methods: From 2004 to 2019, 1,090 proximal (65%) and distal (35%) pancreatectomies were performed in patients with adequate data in the medical records. Patient weights were acquired preoperatively and at postoperative months 1, 3, and 12. Optimal (top quartile, weight restoration) and poor (bottom quartile, persistent weight loss) postoperative weight cohorts were identified at 1 year postoperatively., Results: The median percentage weight change 1 year postpancreatectomy was -6.6% (interquartile range: -1.4% to -12.5%), -7.8% for proximal pancreatectomy, and -4.2% for distal pancreatectomy. For most patients (interquartile range cohort), the median percentage weight change at 1, 3, and 12 months was -6.2%, -7.2%, and -6.6%. The independent factors associated with weight restoration were age <65, nonobesity (body mass index <30kg/m 2 ), receiving total parenteral nutrition/total enteral nutrition preoperatively, experiencing preoperative weight loss >10%, distal pancreatectomy, not undergoing vascular resection, and no readmission within 30 days. Conversely, persistent weight loss was associated with American Society of Anesthesiologists classes III to IV, obesity, malignancy, proximal pancreatectomy, blood loss ≥350mL, and experiencing readmission within 30 days. Focusing on pancreatic ductal adenocarcinoma (n = 372) patients, the factors associated with persistent weight loss were obesity, proximal pancreatectomy, and experiencing recurrence within 1 year; however, weight cohorts were not associated with overall survival for pancreatic ductal adenocarcinoma patients., Conclusion: These data define weight kinetics after pancreatectomy. Ultimately, postoperative weight trajectories appear to be largely predetermined but may be mitigated by limiting readmissions and complications. Clinicians should use these data to identify patients who continue to lose weight between the first and third month postoperatively with a high suspicion for the requirement of nutritional monitoring or other interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate surgical performance in pancreatoduodenectomy using clinically relevant postoperative pancreatic fistula (CR-POPF) occurrence as a quality indicator., Background: Accurate assessment of surgeon and institutional performance requires (1) standardized definitions for the outcome of interest and (2) a comprehensive risk-adjustment process to control for differences in patient risk., Methods: This multinational, retrospective study of 4301 pancreatoduodenectomies involved 55 surgeons at 15 institutions. Risk for CR-POPF was assessed using the previously validated Fistula Risk Score, and pancreatic fistulas were stratified by International Study Group criteria. CR-POPF variability was evaluated and hierarchical regression analysis assessed individual surgeon and institutional performance., Results: There was considerable variability in both CR-POPF risk and occurrence. Factors increasing the risk for CR-POPF development included increasing Fistula Risk Score (odds ratio 1.49 per point, P < 0.00001) and octreotide (odds ratio 3.30, P < 0.00001). When adjusting for risk, performance outliers were identified at the surgeon and institutional levels. Of the top 10 surgeons (≥15 cases) for nonrisk-adjusted performance, only 6 remained in this high-performing category following risk adjustment., Conclusions: This analysis of pancreatic fistulas following pancreatoduodenectomy demonstrates considerable variability in both the risk and occurrence of CR-POPF among surgeons and institutions. Disparities in patient risk between providers reinforce the need for comprehensive, risk-adjusted modeling when assessing performance based on procedure-specific complications. Furthermore, beyond inherent patient risk factors, surgical decision-making influences fistula outcomes.

Background: Early invasive carcinoma may be encountered in association with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The natural history of these early invasive lesions is unknown., Methods: Pancreatic surgical databases from 4 high-volume centers were queried for IPMNs, with invasive components measuring 20 mm or less. All cases were reviewed by GI gastrointestinal pathologists, and pathologic features were analyzed to identify predictors of recurrence and survival., Results: A total of 70 small IPMN-associated invasive carcinomas (≤20-mm invasion) were identified, comprising 25% of resected IPMN-associated carcinomas (n = 280). Most of these small invasive cancers were multifocal (66%), less than 10 mm in size (73%), and arose in the setting of a main duct IPMN (96%). The most common adenocarcinoma subtypes were tubular (57%) and colloid (29%). Lymph node metastases were present in 19% of cases and 23% were T3 lesions. The overall recurrence rate was 24% (n = 17), and the median time to recurrence was 16 months (range: 4-132 months). Median and 5-year survival rates were 99 months and 59%. Recurrence patterns of invasive disease were local in 35%, distant in 47%, and both in 18%. Lymphatic spread and T3 stage were predictive of recurrence (univariate, P = 0.006), whereas tubular carcinoma type was the most predictive of poor overall survival (multivariate hazard ratio = 3.7, P = 0.04)., Conclusions: This study represents the largest multi-institutional experience of resected small IPMN-associated carcinoma. Although these malignancies may frequently be cured with resection, recurrence risk is significant. Lymphatic spread, increased T stage, and tubular type carcinoma were associated with the poorest outcome.

Background: The literature investigating pancreatic invasive intraductal papillary mucinous neoplasm (IPMN) has largely come from small institutional studies, preventing adequately powered comparisons of adjuvant therapy versus surgery alone (SA) within specific patient subgroups., Methods: Patients with resected, stage I through IV, invasive IPMN and conventional pancreatic ductal adenocarcinoma (PDAC) were identified in the National Cancer Data Base (1998-2010). Cox modeling of patients with invasive IPMN was used to compare overall survival (OS) between patients who received adjuvant therapy and those who underwent SA. A second model was used to compare OS between patients with invasive IPMN and those with PDAC., Results: For the 1220 patients with invasive IPMN, the median OS was 28.9 months; the 1-year and 5-year actuarial survival rates were 76% and 17%, respectively; and 47% received adjuvant therapy. Cox modeling associated SA with worse OS (hazard ratio, 1.36; 95% confidence interval, 1.17-1.58; P = .00005) as well as American Joint Committee on Cancer (AJCC) TNM stage III/IV disease, positive lymph node status, positive margins, and poor tumor differentiation (all P ≤ .05). In addition, Cox modeling stratified by the following characteristics demonstrated improved OS with adjuvant therapy: AJCC TNM stage II or III/IV, positive lymph node status, positive margins, and poorly differentiated tumors. There was no survival advantage from adjuvant therapy for patients who had AJCC TNM stage I or lymph node-negative disease. Patients who had invasive IPMN had improved risk-adjusted OS compared with those who had PDAC (hazard ratio, 0.73; 95% confidence interval, 0.68-0.78; P < .00001)., Conclusions: Invasive IPMN appears to be more indolent than conventional PDAC. Adjuvant therapy is associated with improved OS compared with SA in patients with invasive IPMN, especially for those with higher stage disease, positive lymph nodes, positive margins, or poorly differentiated tumors. Conversely, this benefit does not extend to patients with stage I or lymph node-negative disease., (© 2015 American Cancer Society.)

Background: The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy., Methods: During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience., Results: The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Ln's. Consensus was reached on selectively removing suspected Ln's outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive., Conclusion: Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Ln's outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, "extended" pancreatectomy that includes the resection of additional organs may be needed to achieve this goal. Our aim was to develop a common consistent terminology to be used in centers reporting results of pancreatic resections for cancer., Methods: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature on extended pancreatectomies and worked together to establish a consensus on the definition and the role of extended pancreatectomy in pancreatic cancer., Results: Macroscopic (R1) and microscopic (R0) complete tumor resection can be achieved in patients with locally advanced disease by extended pancreatectomy. Operative time, blood loss, need for blood transfusions, duration of stay in the intensive care unit, and hospital morbidity, and possibly also perioperative mortality are increased with extended resections. Long-term survival is similar compared with standard resections but appears to be better compared with bypass surgery or nonsurgical palliative chemotherapy or chemoradiotherapy. It was not possible to identify any clear prognostic criteria based on the specific additional organ resected., Conclusion: Despite increased perioperative morbidity, extended pancreatectomy is warranted in locally advanced disease to achieve long-term survival in pancreatic ductal adenocarcinoma if macroscopic clearance can be achieved. Definitions of extended pancreatectomies for locally advanced disease (and not distant metastatic disease) are established that are crucial for comparison of results of future trials across different practices and countries, in particular for those using neoadjuvant therapy., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Although the outcomes for pancreatic ductal adenocarcinoma (PDAC) remain disappointing, there has been considerable improvement in the 5-year survival rate of patients with resectable disease. As such, an R0 surgical resection (microscopic tumor clearance) offers patients with PDAC the greatest survival benefit. Carbohydrate antigen 19-9, the only US Food and Drug Administration-approved biomarker for PDAC, is a poor screening tool and is most informative after PDAC resection. Consequently, there has been a tremendous initiative to discover novel biomarkers that may aid in detecting the disease earlier, improving prognosis, and predicting response to available chemotherapy. The number of implicated biomarkers in PDAC is indeed staggering, with >2500 proposed candidates presented in the recent literature. A vast majority of these biomarkers, however, remain in the investigational phase. This review categorizes the most promising biomarkers--those closest to potential clinical application--into diagnostic and prognostic/predictive groups. The greatest challenge likely lies in the search for an effective diagnostic biomarker that can accurately discriminate between malignant and benign disease, and thereby facilitate earlier identification of those patients with PDAC who may benefit most from surgical resection.

Introduction: Survival after a resected pancreatic ductal adenocarcinoma (PDAC) appears to be improving. Yet, in spite of advancements, prognosis remains disappointing. This study analyses a contemporary experience and identifies features associated with survival., Methods: Kaplan-Meier analysis was conducted for 424 PDAC resections performed at two institutions (2001-2011). Multivariate analysis was performed to elicit characteristics independently associated with survival., Results: The median, 1-, and 5-year survivals were 21.3 m, 76%, and 23%, with 30/90-day mortalities of 0.7%/1.7%. 76% of patients received adjuvant therapy. Patients with major complications (Clavien Grade IIIb-IV) survived equivalently to patients with no complications (P = 0.33). The median and 5-year survival for a total pancreatectomy was 32.2 m/49%; for 90 'favourable biology' patients (R0/N0/M0) was 37.3 m/40%; and for IPMN (9% of series) was 21.2 m/46%. Elderly (>75 yo) and nonelderly patients had similar survival. Favorable prognostic features by multivariate analysis include lower POSSUM physiology score, R0 resection, absence of operative transfusion, G1/G2 grade, absence of lymphovascular invasion, T1/T2 stage, smaller tumor size, LN ratio <0.3, and receipt of adjuvant therapy., Conclusion: This experience with resected PDAC shows decreasing morbidity and mortality rates along with modestly improving long-term survival, particularly for certain subgroups of patients. Survival is related to pathological features, pre-operative physiology, operative results and adjuvant therapy., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: Traditional survival estimates after resection for pancreatic cancer are based on clinicopathological variables at the time of diagnosis. Estimates have not reflected time survived after resection, as investigated for other malignancies. The aim of the present study was to understand how survival estimates change after pancreatic resection for cancer based on time already survived (conditional survival)., Methods: Pancreatectomies performed for pancreatic ductal adenocarcinoma (PDAC) between 2001 and 2010 were reviewed. Clinicopathological variables were evaluated to identify predictors of survival. Expected survival according to a validated nomogram for pancreatic cancer as well as conditional survival estimates and actual survival were calculated., Results: In all, 186 patients underwent pancreatic resection for PDAC [154 (82.8%) Whipple, 26 (14.0%) distal and 6 (3.2%) total]. Median (range) survival was 22 (3.4-107.3) months. Predictors of overall survival were: absence of nodal disease [odds ratio (OR) 8.8], age <67 years (OR 8.4) and lower stage (OR 4.3). Expected survival according to the nomogram was 70% (1 year), 39.5% (2 years) and 24% (3 years). As time passed, and overall and expected survival decreased, conditional survival increased., Discussion: The available prognostic system for PDAC underestimated survival compared with actual survival in the present study. Conditional survival estimates, based on accrued lifespan, were better than either predicted or actual survival, suggesting that survival is a dynamic, rather than static, concept. Conditional survival may, therefore, be a useful tool to allow patients and clinicians to project subsequent survival based on time accrued since resection., (© 2011 International Hepato-Pancreato-Biliary Association.)