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IntroductionIncreasing hospital or surgeon volume is associated with improved outcomes among patients with pancreatic cancer. Promotion of regionalized care is based on this volume-outcome association. However, other research has exposed nuances and complexities inherent to this association that should be considered when promoting regionalized care models. We herein provide a critical review of the literature on the volume-outcome association and a discussion of areas of ongoing controversy.MethodsA PubMed literature search was conducted for the years 1995–2020. Peer reviewed original research studies were selected for critical review based on study design, potential to draw meaningful conclusions from the data, and discussion of current knowledge gaps.ResultsBased on the cumulative published literature, hospital/surgeon volume and patient mortality are inversely related. However, it remains unclear whether volume is a proxy for other more causative variables inherent in high-volume centers. Interpretation of the volume-outcome association is made more difficult to interpret due to the large variation in the definition of high volume, difficulty in isolating the individual impact of surgeon versus hospital volume, challenges in quantifying health system processes related to volume, and the fact that some low-volume centers consistently achieve excellent clinical results. Implementation of true regionalized care models has been rare, likely reflecting both health system and patient level challenges.ConclusionThe volume-outcome association has been consistently demonstrated to be important to the care of patients with pancreas cancer. The underlying mechanism of this association to explain the overall benefit is likely multifactorial. Better understanding of what drives the volume-outcome association may increase access to optimized care for a broader range of hospital systems and patients.

Background Pancreaticoduodenectomy (PD) has long been associated with high rates of morbidity and mortality. The objective of this study was to identify preoperative risk factors for serious complications and mortality after PD and to construct a prediction tool to facilitate risk stratification prior to surgery. Materials and Methods Patients who underwent elective PD from 2005 to 2009 were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Multivariate logistic regression identified predictors of 30-day serious complications and mortality. A prediction tool was created and validated in a sample of 1254 patients. Results Of 4945 patients who underwent PD, 1342 (27.1%) suffered a serious complication and 127 (2.6%) died within 30 days. The most frequent complications were sepsis (15.3%), surgical site infection (13.1%), and respiratory complications (9.5%). After adjusting for potential confounders, the significant predictors of morbidity included older age, male gender, overweight and obesity, dependent functional status, chronic obstructive pulmonary disease (COPD), steroid use, bleeding disorder, leukocytosis, elevated serum creatinine, and hypoalbuminemia. Significant predictors of 30-day mortality included COPD, hypertension, neoadjuvant radiation therapy, elevated serum creatinine, and hypoalbuminemia. Multivariable models were used to construct a preoperative risk stratification tool. Conclusions Preoperative factors are associated with perioperative outcomes after PD. The prediction tool estimates the probability of early morbidity and mortality for patients undergoing PD. The tool may be used to provide information for patient counseling during the informed consent process and to identify high-risk patients for the purpose of tailoring perioperative care.

Background This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes. Methods All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS). Results Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3–4, intermediate: 5–7, high: 8–10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS. Conclusions By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.

BackgroundThe impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA.MethodsPatients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status.ResultsAmong 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0–1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4–2.3; p = 0.829).ConclusionsAdditional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

Background While pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, many other histologic forms of pancreatic cancer are also recognized. These histologic variants portray unique characteristics in terms of patient demographics, tumor behavior, survival, and responsiveness to treatments. Materials and Methods Patients who underwent surgical resection of the pancreas for non-metastatic, invasive pancreatic cancer between 2004 and 2014 were selected from the National Cancer Data Base and categorized by histologic variant according to WHO classification guidelines. Patient demographics, tumor variables, treatment characteristics, and survival were compared between histologic groups and subgroups. Results A total of 57,804 patients met inclusion and exclusion criteria and were grouped into eight major histologic categories. Survival analysis by the histologic group showed median overall survival of 20.2 months for ductal adenocarcinoma, 20.5 months for squamous cell carcinoma, 26.8 months for mixed acinar-neuroendocrine carcinomas, 52.6 months for cystic mucinous neoplasms with an associated invasive carcinoma, 67.5 months for acinar cell carcinoma, and 69.3 months for mesenchymal tumors. Median survival was not reached for neuroendocrine tumors and solid-pseudopapillary neoplasms, with 5-year overall survival rates of 84% and 97% respectively. Conclusions Rare subtypes of pancreatic cancer present unique clinicopathologic characteristics and display distinct tumor biologies. This study presents data on demographic, prognostic, treatment, and survival outcomes between rare forms of pancreatic neoplasms in order to aid understanding of the natural history and behavior of these neoplasms, with the hope of serving as a reference in clinical decision-making and ability to provide accurate prognostic information to patients.

Background Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection. Methods A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late. Results With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y  = −0.465 x  + 16.99 and y  = −0.12 x  + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority ( n  = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p  = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p  < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p  = 0.021), microvascular invasion (HR 3.3, p  = 0.037), perineural invasion (HR 3.9, p  = 0.029), lymph node metastases (HR 5.0, p  = 0.004), and microscopic positive margin (HR 3.5, p  = 0.046) were independent risk factors associated with early recurrence. Conclusions Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.

Background The potential for malignant transformation varies among pancreatic cystic neoplasms (PCN) subtypes. Imaging and cyst fluid analysis are used to identify premalignant or malignant cases that should undergo operative resection, but the accuracy of operative decision-making process is unclear. The objective of this study was to characterize misdiagnoses of PCN and determine how often operations are undertaken for benign, non-premalignant disease. Methods A retrospective analysis of patients undergoing pancreatic resection for the preoperative diagnosis of PCN was undertaken. Preoperative and pathological diagnoses were compared to measure diagnostic accuracy. Results Between 1999 and 2011, 74 patients underwent pancreatic resection for the preoperative diagnosis of PCN. Preoperative classification of mucinous vs. non-mucinous PCN was correct in 74 %. The specific preoperative PCN diagnosis was correct in 47 %, but half of incorrect preoperative diagnoses were clinically equivalent to the pathological diagnoses. The likelihood that the pathological diagnosis was of higher malignant potential than the preoperative diagnosis was 7 %. In 20 % of cases, the preoperative diagnosis was premalignant or malignant, but the pathological diagnosis was benign. Diagnostic accuracy and the rate of undercall diagnoses and overcall operations did not change with the use of EUS or during the time period of this analysis. Conclusions Precise, preoperative classification of PCN is frequently incorrect but results in appropriate clinical decision-making in three-quarters of cases. However, one in five pancreatic resections performed for PCN was for benign disease with no malignant potential. An appreciation for the rate of diagnostic inaccuracies should inform our operative management of PCN.

The aim of this study was to characterize patients readmitted following inpatient general surgery procedures. We hypothesized that a decreased length of stay would increase risk for readmission. We utilized our institutional National Surgical Quality Improvement Project database from 2006 to 2011. The main outcome of interest was 30-day readmission. Univariate and logistic regression analyses identified risk factors for readmission. We identified 3,556 patients, with 322 (9%) readmitted within 30 days after discharge. Multivariable analysis demonstrated age, dyspnea, and American Society of Anesthesiologists class to be independent risk factors for readmission. In addition, patients who suffered multiple complications had a decreased risk for readmission as length of stay increased. Patients with <2 postoperative complications had an increased risk for readmission as length of stay increased. Contributors to postoperative readmissions are multifactorial. Perioperative factors predict risk for readmission and may help determine a target length of stay. Prevention of postoperative complications may reduce readmission rates.

Background Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival. Methods We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien–Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. Results Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications ( p  < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1–1.6, p  = 0.03 for OS; HR 1.3, 95 % CI 1.01–1.6, p  = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3–0.7, p  < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6–3.2, p  < 0.001). Conclusions Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.

Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate.