Potential Role for Observation in Small Solid Pseudopapillary Neoplasm (SPN).

BACKGROUND: Solid pseudopapillary neoplasms (SPN) are rare tumors of the pancreas, typically affecting young women. Resection is the mainstay of treatment but is associated with significant morbidity and potential mortality. We explore the idea that small, localized SPN could be safely observed. METHODS: This retrospective review of the Pancreas National Cancer Database from 2004 to 2018 identified SPN via histology code 8452. RESULTS: A total of 994 SPNs were identified. Mean age was 36.8 ± 0.5 years, 84.9% (n = 844) were female, and most had a Charlson-Deyo Comorbidity Coefficient (CDCC) of 0-1 (96.6%, n = 960). Patients were most often staged clinically as cT2 (69.5%, n = 457) followed by cT3 (17.6%, n = 116), cT1 (11.2%, n = 74), and cT4 (1.7%, n = 11). Clinical lymph node and distant metastasis rates were 3.0 and 4.0%, respectively. Surgical resection was performed in 96.6% of patients (n = 960), most commonly partial pancreatectomy (44.3%) followed by pancreatoduodenectomy (31.3%) and total pancreatectomy (8.1%). In patients clinically staged as node (N0) and distant metastasis (M0) negative, occult pathologic lymph node involvement was found in 0% (n = 28) of patients with stage cT1 and 0.5% (n = 185) of patients with cT2 disease. The risk of occult nodal metastasis significantly increased to 8.9% (n = 61) for patients with cT3 disease. The risk further increased to 50% (n = 2) in patients with cT4 disease. CONCLUSIONS: Herein, the specificity of excluding nodal involvement clinically is 99.5% in tumors ≤ 4 cm and 100% in tumors ≤ 2 cm. Therefore, there may be a role for close observation in patients with cT1N0 lesions to mitigate morbidity from major pancreatic resection.

Ampullary Neuroendocrine Tumors: Insight into a Rare Histology.

BACKGROUND: Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. METHODS: The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. RESULTS: Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p < 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p < 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p < 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p < 0.0001). CONCLUSIONS: Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.

Global Survey on Pancreatic Surgery During the COVID-19 Pandemic.

OBJECTIVE: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients' and clinicians' safety and safeguard health care capacity. SUMMARY BACKGROUND DATA: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. METHODS: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement. RESULTS: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2-5] to 1 (IQR 0-2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement. CONCLUSIONS: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.

The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection.

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

Endoscopic Management of Pancreatic Fluid Collections.

Pancreatic fluid collections (PFCs) may develop due to inflammation secondary to acute and/or chronic pancreatitis, trauma, surgery, or obstruction from solid or cystic neoplasms. PFCs can be drained percutaneously, surgically, or endoscopically with endoscopic ultrasound-guided cyst gastrostomy and/or transpapillary drainage through endoscopic retrograde cholangiopancreatography. There has been a paradigm shift in the endoscopic management of PFCs in the past few years with newer techniques including utilization of self-expanding metal stents and multiport devices. This review is a comprehensive update on the classification of PFC, indications for drainage, optimal approach, and techniques.

Cancer Survivorship: Defining the Incidence of Incisional Hernia After Resection for Intra-Abdominal Malignancy.

BACKGROUND: Cancer survivorship focuses largely on improving quality of life. We aimed to determine the rate of ventral incisional hernia (VIH) formation after cancer resection, with implications for survivorship. METHODS: Patients without prior VIH who underwent abdominal malignancy resections at a tertiary center were followed up to 2 years. Patients with a viewable preoperative computed tomography (CT) scan and CT within 2 years postoperatively were included. Primary outcome was postoperative VIH on CT, reviewed by a panel of surgeons uninvolved with the original operation. Factors associated with VIH were determined using Cox proportional hazards regression. RESULTS: 1847 CTs were reviewed among 491 patients (59 % men), with inter-rater reliability 0.85 for the panel. Mean age was 60 ± 12 years; mean follow-up time 13 ± 8 months. VIH occurred in 41 % and differed across diagnoses: urologic/gynecologic (30 %), colorectal (53 %), and all others (56 %) (p < 0.001). Factors associated with VIH (adjusting for stage, age, adjuvant therapy, smoking, and steroid use) included: incision location [flank (ref), midline, hazard ratio (HR) 6.89 (95 %CI 2.43-19.57); periumbilical, HR 6.24 (95 %CI 1.84-21.22); subcostal, HR 4.55 (95 %CI 1.51-13.70)], cancer type [urologic/gynecologic (ref), other {gastrointestinal, pancreatic, hepatobiliary, retroperitoneal, and others} HR 1.86 (95 %CI 1.26-2.73)], laparoscopic-assisted operation [laparoscopic (ref), HR 2.68 (95 %CI 1.44-4.98)], surgical site infection [HR 1.60 (95 %CI 1.08-2.37)], and body mass index [HR 1.06 (95 %CI 1.03-1.08)]. CONCLUSIONS: The rate of VIH after abdominal cancer operations is high. VIH may impact cancer survivorship with pain and need for additional operations. Further studies assessing the impact on QOL and prevention efforts are needed.

International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. METHODS: A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. RESULTS: Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. CONCLUSION: The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.

Defining intraoperative hypothermia in ventral hernia repair.

BACKGROUND: Intraoperative normothermia, a single measurement of core body temperature≥36°C, is an important quality metric outlined by the World Health Organization for the reduction of surgical site infections (SSIs). Hypothermia has been linked to SSI in colorectal and trauma patients, but the effect in ventral hernia repair (VHR) is unknown. MATERIALS AND METHODS: Patients who underwent VHR at a single institution between 2005 and 2012 were included. Temperature data were matched with National Surgical Quality Improvement Program SSI data. Novel definitions of hypothermia were explored: patient temperature nadir, percentage of time spent at the nadir, mean temperature, and time spent <36°C. Multivariable regression models were performed. RESULTS: Five hundred fifty-three patients were included with temperature recorded every 8-15 min. Mean temperature nadir was 35.7°C (±1.3°C [standard deviation]) and was not associated with SSI (odds ratio [OR], 0.938; 95% confidence interval, 0.778-1.131). The percentage of readings spent at the nadir was 31% (±31%) and was not predictive of SSI (OR, 1.471; 95% CI, 0.983-2.203). As mean temperature increased, the risk of SSI increased (OR, 1.115; 95% CI, 0.559-2.225). Percentage of temperature readings<36°C was 29% (±38%) and was not associated with SSI (OR, 1.062; 95% CI, 0.628-1.796). In all models, body mass index, smoking, and length of surgery were predictive of SSI. CONCLUSIONS: Our results demonstrate no association between temperature and SSI in VHR. Efforts to reduce SSI should focus on factors such as smoking cessation, weight loss, and length of surgery. Our study suggests that maintenance of perioperative normothermia may only decrease SSIs in certain at-risk populations.

Interventions for Pancreatitis-New Approaches, Knowledge Gaps, and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

ABSTRACT: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.

Disease-based mortality after percutaneous endoscopic gastrostomy: utility of the enterprise data warehouse.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) remains a mainstay of enteral access. Thirty-day mortality for PEG has ranged from 16 to 43 %. This study aims to discern patient groups that demonstrate limited survival after PEG placement. The Enterprise Data Warehouse (EDW) concept allows an efficient means of integrating administrative, clinical, and quality-of-life data. On the basis of this concept, we developed the Vanderbilt Procedural Outcomes Database (VPOD) and analyzed these data for evaluation of post-PEG mortality over time. METHODS: Patients were identified using the VPOD from 2008 to 2010 and followed for 1 year after the procedure. Patients were categorized according to common clinical groups for PEG placement: stroke/CNS tumors, neuromuscular disorders, head and neck cancers, other malignancies, trauma, cerebral palsy, gastroparesis, or other indications for PEG. All-cause mortality at 30, 60, 90, 180, and 360 days was determined by linking VPOD information with the Social Security Death Index. Chi-square analysis was used to determine significance across groups. RESULTS: Nine hundred fifty-three patients underwent PEG placement during the study period. Mortality over time (30-, 60-, 90-, 180-, and 360-day mortality) was greatest for patients with malignancies other than head and neck cancer (29, 45, 57, 66, and 72 %) and least for cerebral palsy or patients with gastroparesis (7 % at all time points). Patients with neuromuscular disorders had a similar mortality curve as head and neck cancer patients. Stroke/CNS tumor patients and patients with other indications had the second highest mortality, while trauma patients had low mortality. CONCLUSIONS: PEG mortality was much higher in patients with malignancies other than head and neck cancer compared to previously published rates. PEG should be used with great caution in this and other high-risk patient groups. This study demonstrates the power of an EDW-based database to evaluate large numbers of patients with clinically meaningful results.

An urban-rural blight? Choledocholithiasis presentation and treatment.

BACKGROUND: Exploration of urban-rural (UR) and regional differences is critical to developing effective healthcare delivery systems. Choledocholithiasis (CDL) remains a common problem with a range of therapeutic options and potentially severe complications. This study evaluated UR and regional differences of CDL presentation and treatment. We hypothesized that UR status contributes to differences in treatment of CDL. METHODS: This study examined patients from the 2007 Healthcare Cost and Utilization Project dataset. Inpatient discharges and interventions for CDL patients were identified. UR and regional designations were determined from National Center for Health Statistics guidelines. Patients with pancreatitis or cholangitis were designated as complicated CDL (cCDL) patients. Interventions for CDL were classified as endoscopic, surgical, or percutaneous. Complex-sample proportion analyses were performed. RESULTS: A total of 111,021 patients with CDL were identified; 81% of these patients lived in urban areas compared with 19% in rural areas; 61% had uncomplicated choledocholithiasis (uCDL) and 39% had cCDL. The overall distribution of uCDL and cCDL did not differ by UR status or region. A higher proportion of rural patients did not receive an intervention 45.1% (95%CI 41.8%-48.4%) versus urban patients 30.5% (28.8%-32.2%), P < 0.05. Interventions for urban patients were more likely endoscopic 87.7% (86.8%-88.6%) compared with rural 82.0% (79.3%-84.7%), P < 0.05. Rural patients were more likely to undergo surgery 10.5% (8.6%-12.4%) than urban patients 4.9% (4.4%-5.4%), P < 0.05. Regional variations did not impact the type of intervention received. CONCLUSION: Rural patients received CDL interventions less often and had a higher proportion of surgical interventions regardless of severity of presentation.

Predicting complicated choledocholithiasis.

INTRODUCTION: Management of choledocholithiasis and its complications is variable and often requires transfer to a specialty facility. This study links patient-specific characteristics with the outcome measure of complicated choledocholithiasis to identify high-risk patients who may require expedited treatment or transfer to a higher level of care. MATERIALS AND METHODS: Patients with a discharge diagnosis of choledocholithiasis (CDL) were identified from the 2009 Nationwide Inpatient Sample (NIS). Patient characteristics were identified associated with the primary outcome measure of complicated choledocholithiasis (cCDL), defined as acute pancreatitis or cholangitis during the admission for CDL. Predictors of mortality were also evaluated. Analysis was performed using complex-sample univariate and adjusted analyses. RESULTS: We identified 123,990 discharges with a diagnosis of CDL. The overall incidence of CDL was 314 per 100,000 NIS discharges. Forty-one percent of CDL discharges were for cCDL (acute pancreatitis 31%, cholangitis 12%). Risk factors for cCDL included age (risk increased 0.8% per year), male gender (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1-1.2), alcohol abuse (OR 1.5, CI 1.3-1.8), diabetes (OR 1.1, CI 1.0-1.2), hypertension (OR 1.1, CI 1.0-1.2), obesity (OR 1.2, CI 1.1-1.3), nonelective admission (OR 2.3, CI 2.0-2.6), and Asian/Pacific Islander race/ethnicity (OR 1.2, CI 1.0-1.5). Patients with cCDL had increased odds of mortality (OR 1.5, CI 1.2-2.0). CONCLUSIONS: Increased age, nonelective admission, and specific comorbid conditions are associated with cCDL, which has increased mortality. These factors can be used to identify patients needing timely access to treatment or transfer to a higher level of care.

Advance care planning in patients undergoing surgery to resect pancreatic adenocarcinoma: Underlying tension between balancing hope and realism.

BACKGROUND: The timing and the dose of Advanced Care Planning in patients with pancreatic ductal adenocarcinoma undergoing curative-intent resection are generally dictated by the surgeon performing the operation. METHODS: A qualitative investigation using 1:1 interviews with 40 open-ended questions was conducted with a convenience sample of 10 high-volume pancreatic surgeons from across the country. The grounded theory approach was used for data analysis. RESULTS: A total of 10 interviews were conducted with expert pancreatic surgeons-6 males and 4 females. During preoperative counseling, all surgeons attempt to motivate patients by emphasizing hope, optimism, and the fact that surgery offers the only opportunity for cure. All surgeons discuss the possibility of recurrence as well as postoperative complications; however, a majority perceived that patients do not fully appreciate the likelihood of recurrence or postoperative complications. All surgeons acknowledged the importance of end-of-life conversations when death is imminent. Seventy percent of surgeons had mixed opinions regarding benefits of preoperative Advanced Care Planning in the preoperative setting, while 20% felt it was definitely beneficial, particularly that delivery of care aligned with patient goals. All surgeons emphasized that Advanced Care Planning should be led by a physician who both knows the patient well and understands the nuances of pancreatic ductal adenocarcinoma management. Most common barriers to in-depth Advanced Care Planning discussion reported by surgeons include taking away hope, lack of time, and concern for sending "mixed messages." CONCLUSION: We identified that surgeons experience a fundamental tension between promoting realistic long-term goals and expectations versus focusing on hope and enabling an overly optimistic perception of prognosis.

Choledocholithiasis management in rural America: health disparity or health opportunity?

BACKGROUND: Choledocholithiasis (CDL) management is dictated by local expertise, individual training, and availability of appropriate staff. This study evaluates the management of CDL between urban and rural communities. MATERIALS AND METHODS: Patients undergoing inpatient management of CDL were identified from the 2007 Healthcare Cost and Utilization Project. Availability of endoscopic retrograde cholangiopancreatography (ERCP) was determined from the 2007 American Hospital Association survey. The proportion of common bile duct exploration (CBDE), ERCP, or percutaneous (PERC) interventions were compared across census regions and National Centers for Health Statistics (NCHS) urban-rural classes. The NCHS urban-rural classification scheme divides counties from most populous (NCHS 1) to rural (NCHS 6). Proportions were compared using the 95% confidence interval (95%CI) approach. RESULTS: We estimated 111,021 CDL hospitalizations in the U.S. in 2007. Of these, 67% had a coded intervention. Intervention frequencies were similar across census regions. Comparisons across NCHS classes revealed higher proportions of ERCP in urban areas (NCHS 1-4) while a higher proportion of CBDE was seen in rural areas (NCHS 5-6). ERCP availability was high in metropolitan areas (available in 35%-44% of hospitals NCHS 1-4) and low in rural areas (25% of NCHS 5 hospitals and 5% NCHS 6). PERC management was similar across NCHS classes. CONCLUSIONS: Rural hospitals and communities need surgeons trained in CBDE, where ERCP expertise may not be readily available. Feasible ways of expanding ERCP coverage to the nation's rural areas need to be explored. These observations may impact surgical training at least for those targeting careers in rural surgery.

Rare, long-term complication after pancreatoduodenectomy-a case report of cecal volvulus.

Complications after pancreatoduodenectomy are common, and range widely in timing of presentation, relation to pancreatobiliary pathology, and necessity of operative intervention. We present a case of a 74-year-old male with history of pancreatoduodenectomy for pancreatic adenocarcinoma who presented 11 months after index operation with cecal volvulus and required emergent right hemicolectomy. Prior history of pancreatoduodenectomy with mobilization of the right colon likely predisposed him to development of this surgical emergency. Patients have altered gastrointestinal anatomy after pancreatoduodenectomy and special care is necessary to protect the afferent biliopancreatic limb during intraoperative exploration, and particularly if right colectomy is necessary.

The effect of age on short-term outcomes after pancreatic resection: a population-based study.

OBJECTIVE: To use a large population-based cohort to determine age-dependent short-term outcomes after pancreatic resection. METHODS: We identified all pancreatic resections in Texas from 1999 to 2005. Patients were stratified into 4 age groups (<60, 60-69, 70-79, and 80+ years). Bivariate and multivariate analyses were performed to determine the effect of age on mortality, discharge to home versus requiring inpatient nursing care, and length of stay. RESULTS: Three thousand seven hundred and thirty-six patients underwent pancreatic resection. Unadjusted in-hospital mortality increased with each increasing age group from 2.4% in patients <60 to 11.4% in patients 80 years and older (P < 0.0001). Likewise, postoperative lengths of stay increased with each increasing age group (P = 0.02). Age group independently predicted the need for discharge to an inpatient nursing unit rather than home (P < 0.0001), with the odds ration (OR) increasing with each increasing age group. With each increasing age group, patients were less likely to be resected at high-volume (H-V) hospitals (>10 pancreatic resections/y). Whereas low-volume (L-V) hospitals (< or =10 pancreatic resections/y) had higher mortality rates (3.2% versus 7.3%, P < 0.0001), the difference in mortality between H- and L-V hospitals was more striking in older patients. With increasing age group, mortality increased from 3.0% to 9.5% to 11.4% to 14.7% at L-V hospitals. It increased from 2.0% to 3.5% to 4.5% to 8.7% at H-V hospitals (P < 0.0001). In the multivariate model controlling for gender, race, hospital volume, year of surgery, diagnosis, risk of mortality, severity of illness, admission status, and procedure type, older age group independently predicted increased mortality. The OR for patients 60-69 years was 2.5 (P = 0.0003), the OR for patients 70-79 years was 1.8 (P = 0.02), and the OR for patients 80+ years was 4.4 (P < 0.0001) when compared with patients <60 years. CONCLUSIONS: In contrast to some previous single-institution studies, we found that increased age is an independent risk factor for mortality after pancreatic resection. For all ages, mortality rates were higher at L-V hospitals, but the difference worsened significantly with increasing age. Older patients had longer lengths of stay, were less likely to be discharged home, and more likely to require care at an inpatient nursing or acute care facility at the time of discharge.

Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Incidence of additional primary cancers in patients with invasive intraductal papillary mucinous neoplasms and sporadic pancreatic adenocarcinomas.

BACKGROUND: Recent small studies have reported an incidence of 23% to 39% for additional primary cancers in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas. There have been no population-based studies evaluating this incidence rate. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (1983 to 1991), we identified all patients with primary pancreatic cancers (sporadic and adenocarcinomas arising in IPMNs). We determined the incidence of additional primary cancers that developed either before or after the diagnosis of invasive IPMN and compared it to the incidence of additional primary cancers in patients with sporadic pancreatic adenocarcinoma. RESULTS: Nineteen thousand six hundred forty-seven patients were reported with pancreatic cancer. Ninety-five percent of cancers were sporadic and 5.0% were invasive IPMNs. Ten point three percent had one or more extra-pancreatic primary cancers in addition to their pancreatic primary (10.3% in patients with sporadic adenocarcinoma and 10.1% in patients with invasive IPMNs, p = NS). The most common sites of additional primary cancers were colorectal (20.1%), breast (19.9%), prostate (16.6%), urinary system (11.1%), and lung (9.8%). In the 2,017 patients with additional primary cancer, 86% occurred before the diagnosis of pancreatic cancer and 14% occurred after the diagnosis of pancreatic cancer. CONCLUSIONS: Our population-based analysis shows that the incidence of additional primary malignancies in patients with invasive IPMNs is 10%. Although not as high as previously reported in smaller studies, the incidence is significant and comparable to the incidence seen in patients with adenocarcinoma. Surveillance for other common malignancies in patients with IPMNs and pancreatic adenocarcinomas should be performed.

Trends and disparities in regionalization of pancreatic resection.

BACKGROUND: The current recommendation is that pancreatic resections be performed at hospitals doing >10 pancreatic resections annually. OBJECTIVE: To evaluate the extent of regionalization of pancreatic resection and the factors predicting resection at high-volume centers (>10 cases/year) in Texas. METHODS: Using the Texas Hospital Inpatient Discharge Public Use Data File, we evaluated trends in the percentage of patients undergoing pancreatic resection at high-volume centers (>10 cases/year) from 1999 to 2004 and determined the factors that independently predicted resection at high-volume centers. RESULTS: A total of 3,189 pancreatic resections were performed in the state of Texas. The unadjusted in-hospital mortality was higher at low-volume centers (7.4%) compared to high-volume centers (3.0%). Patients resected at high-volume centers increased from 54.5% in 1999 to 63.3% in 2004 (P = 0.0004). This was the result of a decrease in resections performed at centers doing less than five resections/year (35.5% to 26.0%). In a multivariate analysis, patients who were >75 (OR = 0.51), female (OR = 0.86), Hispanic (OR = 0.58), having emergent surgery (OR = 0.39), diagnosed with periampullary cancer (OR = 0.68), and living >75 mi from a high-volume center (OR = 0.93 per 10-mi increase in distance, P < 0.05 for all OR) were less likely to be resected at high-volume centers. The odds of being resected at a high-volume center increased 6% per year. CONCLUSIONS: Whereas regionalization of pancreatic resection at high-volume centers in the state of Texas has improved slightly over time, 37% of patients continue to undergo pancreatic resection at low-volume centers, with more than 25% occurring at centers doing less than five per year. There are obvious demographic disparities in the regionalization of care, but additional unmeasured barriers need to be identified.