Long-term follow-up experience with adjuvant therapy after irreversible electroporation of locally advanced pancreatic cancer.

BACKGROUND: Irreversible electroporation (IRE) expands the surgical options for patients with unresectable pancreatic cancer. This study evaluated for differences in survival stratified by type of IRE and receipt of adjuvant chemotherapy. METHODS: Patients with locally advanced pancreatic cancer treated by IRE (2012-2020) were retrospectively included. Overall survival (OS) and recurrence-free survival (RFS) were compared by type of IRE (in situ for local tumor control or IRE of potentially positive margins with resection) and by receipt of adjuvant chemotherapy. RESULTS: Thirty-nine patients had IRE in situ, 61 had IRE for margin extension, and 19 received adjuvant chemotherapy. Most (97.00%) underwent induction chemotherapy. OS was 28.71 months (interquartile range [IQR] 19.17, 51.19) from diagnosis, with no difference by IRE type (hazard ratio [HR] 1.05 for margin extension [p = 0.85]) or adjuvant chemotherapy (HR 1.14 [p = 0.639]). RFS was 8.51 months (IQR 4.95, 20.17) with no difference by IRE type (HR 0.90 for margin extension [p = 0.694]) or adjuvant chemotherapy (HR 0.90 [p = 0.711]). CONCLUSION: These findings suggest that adjuvant therapy may have limited benefit for patients treated with induction chemotherapy followed by local control with IRE for unresectable pancreatic cancer. Further study of the duration and timing of systemic therapy is warranted to maximize benefit and limit toxicity.

Perioperative and persistent opioid utilization following pancreatectomy in the United States.

BACKGROUND: Opioids are central to analgesia for pancreatic diseases. Individuals undergoing pancreatectomy have largely been excluded from studies of opioid use, because of malignancy or chronic use. Surgeons need to understand usage patterns, and practices that may incline patients toward persistent post-operative use. METHODS: A retrospective study using IBM Watson Health MarketScan database examined patterns of peri-pancreatectomy opioid use between 2009 and 2017. Patients were grouped by opioid use 12 months to 31 days prior to pancreatectomy and followed for persistent use (refills 90-180 days postoperatively). Morphine milligram equivalents (MME) were calculated. Multivariable models explored associations between clinical characteristics, perioperative use and persistent use. RESULTS: Opioids were used within the year prior to surgery by 35.6% of 8325 patients. The median MME for opioid naïve patients (400 mg) was a fraction of the 1800 mg prescribed to chronic opioid users for peri-operative analgesia. The rate of persistent opioid use was 15.1% among naïve, 27.2% among intermittent and 77.3% among chronic opioid users. Multivariable models demonstrated naïve and intermittent users who filled a prescription within 30 days prior to pancreatectomy, those who were prescribed total MME ≥1500 mg, and a ≥14 day supply were most at risk of persistent opioid use. Almost 23% of chronic users stopped using opioids post-operatively, suggesting surgery can provide relief. CONCLUSION: Preoperative and persistent opioid use after pancreatectomy is substantially greater than expected based on other operations. Providers may mitigate this by recognizing the issue, managing expectations, and altering the timing and quantities of opioids prescribed.

Long term quality of life amongst pancreatectomy patients with diabetes mellitus.

BACKGROUND: Pancreatogenic diabetes is common after pancreatectomy, and the impact on quality of life (QOL) is poorly understood. The objective of this study was to investigate QOL between diabetic and non-diabetic patients at least five years after pancreatectomy. METHODS: Patients were recruited from a prospectively maintained institutional database. Participants were administered the Audit of Diabetes-Dependent Quality of Life (ADDQOL). Quality of life was compared between diabetics and non-diabetics using validated European Organization for Research and Treatment of Cancer questionnaires. RESULTS: 80 individuals completed surveys. 55% were female, 80% non-Hispanic white, 44% underwent Whipple, 48% were cystic neoplasms and 39% were adenocarcinoma. Diabetic patients (42.5%) reported comparable EORTC QLQ-C30 and Pan26 scores to non-diabetic patients. Pre-operative diabetic patients reported more dyspnea (p = 0.02) and greater pain (p = 0.02) than new-onset diabetics. Diabetic patients reported an overall ADDQOL quality of life score 'very good' (IQR: excellent, good) though felt life would be much better without diabetes (IQR: very much better, little better). While operation type was not influential, patients diagnosed with cystic neoplasms were almost twice as likely as those with other pathologies to report that life would be much better without diabetes (p < 0.01). CONCLUSION: At a median of 9.3 years from pancreatic surgery, ADDQoL scores of patients were similar to cohorts of non-pancreatogenic diabetics in the general population. Patients without cancer were more likely to report that diabetes affected their overall QOL, regardless of operation. This study provides nuanced understanding of long-term QOL to improve the informed consent process and post-operative long-term care.

Long-term health after pancreatic surgery: the view from 9.5 years.

BACKGROUND: Discussing the impact of pancreatic surgery on long-term health is poorly understood, but necessary for informed consent. Given the increased number of pancreatic operations being performed annually, further investigation is necessary. METHODS: Patients surviving longer than 5 years after pancreatic surgery were surveyed for postoperative hospitalizations, operations, pain, nutrition and diabetes. Variables were analyzed according to patient and peri-operative variables, and validated using medical records. RESULTS: Eighty individuals completed the survey; median follow-up was 9.5 years (IQR:6.43,12.73). 47.5% underwent a pancreatoduodenectomy, and 25.0% a distal pancreatectomy; 40.0% had adenocarcinoma. 57.1% reported long-term weight loss, of which 65.9% was unintentional. While 1.3% took pancreatic enzymes before surgery, 38.8% utilized after. 12.5% had diabetes before, and 28.6% after surgery; 22 of 30 patients required insulin replacement therapy (73.3%). 41.3% reported hospitalizations, 17.5% required endoscopies and 28.8% additional operations after full recovery. Need for additional interventions were not related to pathology or post-operative complications, but were more common among patients undergoing a Whipple. CONCLUSION: More than half of patients will have a long-term medical complication attributable to pancreatectomy. In comparison to the literature, it may be inferred that consequences occur within the first few years after surgery, and do not compound over time.

Optimal Timing of Total Gastrectomy to Prevent Diffuse Gastric Cancer in Individuals With Pathogenic Variants in CDH1.

BACKGROUND & AIMS: Carriers of pathogenic variants in CDH1 have a high risk of hereditary diffuse gastric cancer (HDGC). Guidelines recommend prophylactic total gastrectomy (PTG) at age 20-30 years, although there is controversy over the optimal age. We developed a simulation model to analyze the effects of PTG at different ages on quality-adjusted life-years (QALYs), cancer mortality, and life expectancy. METHODS: We used a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes of hypothetical cohorts with different ages at time of PTG (ages 20-79 years). Model inputs including health state transition probabilities, mortality and complication rates, quality of life utility values, and endoscopic surveillance sensitivity were derived from publications. The primary outcome, used to determine the optimal strategy, was age at which PTG yielded the highest QALYs. Secondary outcomes were cancer mortality and unadjusted life-years. RESULTS: Our model found that for men, the optimal age for PTG is 39 years, resulting in 32.01 incremental QALYs, 58.81 life-years (biologic age, 72.81 years), and lifetime cancer mortality of 8.5%. Incorporating endoscopic surveillance prior to PTG decreased cancer mortality to 6.7%, but had lower QALYs (31.59). PTG at age 30 reduced cancer mortality to 3.2%, with 31.45 incremental QALYs. For women, the optimal age for PTG was calculated to be 30 years, with 33.09 incremental QALYs, 66.17 life-years (biologic age, 80.17 years), and lifetime cancer mortality of 1.6%. Addition of endoscopic surveillance did not decrease the risk of HDGC mortality in women. CONCLUSIONS: Using a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes, we found the optimal ages for PTG to be 39 years for men and 30 years for women, when QALYs are the primary endpoint. These ages for PTG are older than those of current recommendations.

New onset diabetes predicts progression of low risk pancreatic mucinous cysts.

BACKGROUND: Patients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts. METHODS: We evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method. RESULTS: The 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5-57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%-20.2%), compared to only 0.8% (95%CI, 0.0%-2.3%) for patients without NODM. Among patients with the largest cysts (20-29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%-89.9%) compared to only 7.5% (95%CI, 1.6%-15.2%) for patients without NODM. CONCLUSION: New onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.

Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria.

BACKGROUND & AIMS: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSIONS: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Long-Term Surveillance and Timeline of Progression of Presumed Low-Risk Intraductal Papillary Mucinous Neoplasms.

OBJECTIVE: The purpose of this study was to assess risk of progression and rate of growth of presumed low-risk branch duct intraductal papillary mucinous neoplasms surveyed for more than 4 years. MATERIALS AND METHODS: A keyword search of electronic medical charts was performed for the years 2001-2013. Cystic lesions that met the criteria for clinical branch duct intraductal papillary mucinous neoplasm, lacked baseline high-risk or worrisome features, and had more than 4 years of surveillance were included in this study. Two radiologists performed cyst size measurements to assess interreader variability. Cyst progression was defined either as 2-mm or greater or 20% or greater increase in diameter or as development of worrisome features. Kaplan-Meier curves were generated to evaluate cyst progression time and linear mixed models to evaluate growth rates. RESULTS: The search revealed 2423 patients with cystic pancreatic lesions. Among these patients 228 had imaging follow-up for 4 or more years, and 131 met the clinical criteria for branch duct intraductal papillary mucinous neoplasms. Among the 131 cysts, 73 (55.7%) progressed: 61 (46.6%) increased in size, 10 (7.6%) increased in size and developed worrisome features, and two (1.5%) developed worrisome features only. Of the 71 cysts that increased in size, 50 (70.4%) did so within the first 5 years, and 21 (29.6%) grew after 5 years. No patient had adenocarcinoma. There was no significant difference in growth rate based on cyst size within the first 50 months. After 50 months, cysts larger than 20 mm continued to increase in size (p < 0.05) and had faster growth rates. CONCLUSION: Among presumed low-risk branch duct intraductal papillary mucinous neoplasms, most increased in size, approximately 30% after 5 years. Cysts with baseline size larger than 20 mm continued to grow beyond 5 years at a faster rate.

Single-Institution Experience with Irreversible Electroporation for T4 Pancreatic Cancer: First 50 Patients.

BACKGROUND: Irreversible electroporation (IRE) for treatment of locally advanced pancreatic tumors is garnering increasing attention. This study was conducted to determine perioperative morbidity and mortality for locally advanced pancreatic cancer. METHODS: Prospective data of 50 consecutive patients receiving IRE for T4 lesions at a single tertiary center were analyzed. The primary end point was Clavien-Dindo complications at 90 days, and the secondary outcomes were survival and recurrence. RESULTS: A total of 50 patients underwent 53 IRE procedures for primary treatment (n = 29) or margin extension (n = 24), and 47 patients had adenocarcinoma. Six patients died within 90 days after the procedure (5 in the primary control group). Mortality occurred a median of 26 days (range, 8-42 days) after the procedure. Five patients in both the margin-extension and primary control groups experienced grade 3 or 4 morbidity (p = 0.739). The incidences of grades 3 to 5 complications did not differ significantly based on the adjustable parameters of IRE, tumor size, or primary treatment versus margin extension. After a median follow-up period of 8.69 months [interquartile range (IQR), 0.26-16.26 months], the median overall survival period for the primary control group was 7.71 months [95 % confidence interval (CI), 6.03-12.0 months) and was not reached in the margin-extension group (p = 0.01, log-rank). CONCLUSIONS: At the authors' center, the mortality rate after IRE was higher than reported in other series, with the majority occurring in the primary control group. Major morbidity trended around upper gastrointestinal bleeding, visceral ulcerations/perforations, and portal vein thromboses. This favors further investigation of the safety and efficacy of IRE.

Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma.

BACKGROUND: This prospective study was undertaken to assess toxicity, resectability, and survival in pancreatic adenocarcinoma patients presenting with locally advanced, unresectable disease treated with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX) and gemcitabine and capecitabine (GX)/radiation therapy (RT). METHODS: All patients presenting to the Pancreas Center were evaluated for eligibility. Forty-five patients (mean age, 64 years; range, 44-83 years)-34 patients deemed unresectable because of arterial involvement and 11 patients deemed unresectable because of extensive venous involvement-were treated with 6 cycles of GTX. Those with arterial involvement were treated with GX/RT after chemotherapy. RESULTS: The GTX and GX/RT treatments were tolerated with the expected drug-related toxicities. There were no bowel perforations, cases of pancreatitis, or delayed strictures. Among those with arterial involvement, 29 underwent subsequent resection, with 20 (69%) achieving R0 resections. All 11 patients with venous-only involvement underwent resection, with 8 achieving R0 resections and 3 achieving complete pathologic responses. For the arterial arm, the 1-year survival rate was 71% (24 of 34 patients), and the median survival was 29 months (95% confidence interval, 21-38 months). Thirteen patients (38%) have not relapsed (range, 5-49+ months). For the venous arm, the median survival has not been reached at more than 42 months. Six patients (55%) in the venous arm did not experience recurrence (range, 6.2-42+ months). CONCLUSIONS: GTX plus GX/RT is an effective neoadjuvant regimen that can be safely administered to patients up to at least the age of 83 years. It is associated with a high response rate, a high rate of R0 resections, and prolonged overall survival.

Quality of life in patients after total pancreatectomy is comparable with quality of life in patients who undergo a partial pancreatic resection.

BACKGROUND: Quality of life after total pancreatectomy (TP) is perceived to be poor secondary to insulin-dependent diabetes and pancreatic insufficiency. As a result, surgeons may be reluctant to offer TP for benign and premalignant pancreatic diseases. METHODS: We retrospectively reviewed presenting features, operative characteristics, and postoperative outcomes of all patients who underwent TP at our institution. Quality of life was assessed using institutional questionnaires and validated general, pancreatic disease-related, and diabetes-related instruments (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30 and module EORTC-PAN26], Audit of Diabetes Dependent Quality of Life), and compared with frequency-matched controls, patients after a pancreaticoduodenectomy (PD). Continuous variables were compared using Student t-test or analysis of variance. Categorical variables were compared using χ(2) or Fisher exact test. RESULTS: Between 1994 and 2011, 77 TPs were performed. Overall morbidity was 49%, but only 15.8% patients experienced a major complication. Perioperative mortality was 2.6%. Comparing 17 TP and 14 PD patients who returned surveys, there were no statistically significant differences in quality of life in global health, functional status, or symptom domains of EORTC QLQ-C30 or in pancreatic disease-specific EORTC-PAN26. TP patients had slightly but not significantly higher incidence of hypoglycemic events as compared with PD patients with postoperative diabetes. A negative impact of diabetes assessed by Audit of Diabetes Dependent Quality of Life did not differ between TP and PD. Life domains most negatively impacted by diabetes involved travel and physical activity, whereas self-confidence, friendships and personal relationships, motivation, and feelings about the future remained unaffected. CONCLUSIONS: Although TP-induced diabetes negatively impacts select activities and functions, overall quality of life is comparable with that of patients who undergo a partial pancreatic resection.

Limitations of ACS-NSQIP in reporting complications for patients undergoing pancreatectomy: underscoring the need for a pancreas-specific module.

BACKGROUND: Large centralized databases are used with increasing frequency for reporting hospital-specific and nationwide trends and outcomes after various surgical procedures in order to improve quality of surgical care. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) is a risk-adjusted, case-weighted complication tracking initiative that reports 30-day outcomes from more than 400 academic and community institutions in the US. However, the accuracy of event reporting specific to pancreatic surgery has never been examined in depth. METHODS: We retrospectively reviewed medical records of patients, the information on whose postoperative course was originally reported through ACS-NSQIP between 2006 and 2010. Preoperative characteristics, operative data, and postoperative events were recorded after review of electronic medical records including physician and nursing notes, operative room records and anesthesiologist reports. Fidelity of reported clinical events was assessed. Accuracy, sensitivity, and specificity were calculated for each variable of interest. RESULTS: Two hundred and forty-nine pancreatectomies were reviewed, including 145 (58.2 %) Whipple procedures, 19 (7.6 %) total pancreatectomies, 65 (26.1 %) distal pancreatectomies, and 15 (6.0 %) central or partial resections. Median age was 65.7, males comprised 41.5 % of the group, and 74.3 % of patients were Caucasian. The overall rate of complications reported by NSQIP was 44.0 %, compared with 45.0 % in our review, however discordance was observed in 27.3 % of the time, including 34 cases of reporting a complication where there was not one, and 34 cases of missed complication. The most frequently reported event was postoperative bleeding requiring transfusion, however this was also the event most commonly misclassified. Additionally, three procedures unrelated to the index operation were recorded as reoperation events. While a pancreas-specific module does not yet exist, ACS-NSQIP reports a 7.6 % rate of organ-space surgical site infections; when compared with our institutional rate of Grades B and C postoperative fistula (10.4 %), we observed discordance 4.4 % of the time. Delayed gastric emptying, a common post-pancreatectomy morbidity, was not captured at all. Additionally, there were significant inaccuracies in reporting urinary tract infections, postoperative pneumonia, wound complications, and postoperative sepsis, with discordance rates of 4.4, 3.2, 3.6, and 6.8 %, respectively. CONCLUSIONS: ACS-NSQIP data are an important and valuable tool for evaluating quality of surgical care, however pancreatectomy-specific postoperative events are often misclassified, underscoring the need for a hepatopancreatobiliary-specific module to better capture key outcomes in this complex and unique patient population.

Evolving Technique for Puestow-Type Procedure for Chronic Pancreatitis: The Combined Roux-en-Y Proximal End-to-Side and Distal Longitudinal Pancreatojejunostomy.

BACKGROUND The goal of surgical procedures in chronic pancreatitis is to establish drainage of the duct throughout the gland as well as resect any inflammatory masses if present. Conventionally, for patients with a dilated pancreatic duct without inflammatory masses, a drainage procedure in the form of a longitudinal pancreatojejunostomy (or Partington-Rochelle modification of the Puestow procedure) is the procedure of choice. CASE REPORT In present case, a patient with chronic pancreatitis was evaluated for surgical management, but extensive intraductal and parenchymal pancreaticolithiasis throughout the entire gland considerably restricted access to the duct. A novel combined Roux-en-Y partial longitudinal pancreatojejunostomy of the body and tail with an end-to-side pancreatojejunostomy of the head was fashioned to facilitate drainage of the entire pancreas, without resection of any parenchyma. The patient's immediate postoperative course was uncomplicated, and at her 30-day follow-up, she had been without pain and had been tolerating a diet, with additional pancreatic enzyme supplementation. CONCLUSIONS Roux-en-Y partial longitudinal pancreatojejunostomy (or modified Puestow procedure) should be considered a viable option for the surgical management of chronic pancreatitis with extensive pancreaticolithiasis, with good short-term outcomes. It underscores the importance of leveraging anatomic limitations to expand the choice of drainage procedure for chronic pancreatitis. This procedure should be considered in those patients with significant pancreaticolithiasis, where clear visualization of the main pancreatic duct is limited, precluding a lengthy pancreatojejunostomy.

Readmission after pancreatic resection is not an appropriate measure of quality.

BACKGROUND: Hospital readmission has been proposed as a metric for quality of medical and surgical care. We examined our institutional experience with readmission after pancreatic resection, and assessed factors predictive of readmission. METHODS: We reviewed 787 pancreatic resections performed at a single institution between 2006 and 2010. Univariate and multivariate logistic regression models were used to assess the relationships between preoperative and postoperative characteristics and readmission. Reasons for hospital readmission were examined in detail. RESULTS: We found the 30-day readmission rate after pancreatic resection to be 11.6 %. In univariate analysis, young age, pancreaticoduodenectomy versus other operations, open versus laparoscopic technique, fistula formation, the need for reoperation, and any complication during the index hospitalization were predictive of readmission. In multivariate analysis, only young age and postoperative complication were predictive of readmission. Vascular resection, postoperative ICU care, length of stay, and discharge disposition were not associated with readmission. The most common reasons for readmission were leaks, fistulas, abscesses, and wound infections (45.1 %), delayed gastric emptying (12.1 %), venous thrombosis (7.7 %), and GI bleeding (7.7 %). CONCLUSIONS: We found the vast majority of readmissions after pancreatic resection were to manage complications related to the operation and were not due to poor coordination of care or poor discharge planning. Because evidence-based measures to prevent these surgical complications do not exist, we cannot support the use of readmission rates themselves as a quality indicator after pancreatic surgery.

Associations Between Patient Characteristics and Whipple Procedure Outcomes Before and After Implementation of an Enhanced Recovery After Surgery Protocol.

PURPOSE: The Enhanced Recovery After Surgery (ERAS) protocol is a multimodal perioperative care bundle aimed to improve pancreatic surgery outcomes. This work evaluates whether a Whipple ERAS protocol can be safely implemented at a quaternary care center. We also aimed to assess if race and socioeconomic factors are associated with disparities in outcomes in patients undergoing a Whipple ERAS protocol. METHODS: A retrospective review identified demographic and clinical data for 458 patients undergoing pancreaticoduodenectomies (PDs) at a single institution from October 2017 to May 2022. Patients were split into two cohorts: pre-ERAS (treated before implementation) and ERAS (treated after). Outcomes included length of stay (LOS), 30-day readmission and mortality rates, and major complications. RESULTS: There were 213 pre-ERAS PD patients, and 245 were managed with an ERAS protocol. More ERAS patients had a BMI > 30 (15.5% vs. 8.0%; p = 0.01) and received neoadjuvant chemotherapy (15.5% vs. 4.2%; p < 0.001). ERAS patients had a higher rate of major complications (57.6% vs. 37.6%; p < 0.001). Medicaid patients did not have more complications or longer LOS compared to non-Medicaid patients. On univariate analysis, race/ethnicity or gender was not significantly associated with a higher rate of major complications or prolonged LOS. CONCLUSION: A Whipple ERAS protocol did not significantly change LOS, readmissions, or 30-day mortality. Rate of overall complications did not significantly change after implementation, but rate of major complications increased. These outcomes were not significantly impacted by race/ethnicity, gender, tumor staging, or insurance status.

Chemotherapy and Immune Checkpoint Blockade for Gastric and Gastroesophageal Junction Adenocarcinoma.

Importance: Combining immune checkpoint blockade (ICB) with chemotherapy improves outcomes in patients with metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma; however, whether this combination has activity in the perioperative setting remains unknown. Objective: To evaluate the safety and preliminary activity of perioperative chemotherapy and ICB followed by maintenance ICB in resectable G/GEJ adenocarcinoma. Design, Setting, and Participants: This investigator-initiated, multicenter, open-label, single-stage, phase 2 nonrandomized controlled trial screened 49 patients and enrolled 36 patients with resectable G/GEJ adenocarcinoma from February 10, 2017, to June 17, 2021, with a median (range) follow-up of 35.2 (17.4-73.0) months. Thirty-four patients were deemed evaluable for efficacy analysis, with 28 (82.4%) undergoing curative resection. This study was performed at 4 referral institutions in the US. Interventions: Patients received 3 cycles of capecitabine, 625 mg/m2, orally twice daily for 21 days; oxaliplatin, 130 mg/m2, intravenously and pembrolizumab, 200 mg, intravenously with optional epirubicin, 50 mg/m2, every 3 weeks before and after surgery with an additional cycle of pembrolizumab before surgery. Patients received 14 additional doses of maintenance pembrolizumab. Main Outcomes and Measures: The primary end point was pathologic complete response (pCR) rate. Secondary end points included overall response rate, disease-free survival (DFS), overall survival (OS), and safety. Results: A total of 34 patients (median [range] age, 65.5 [25-90] years; 23 [67.6%] male) were evaluable for efficacy. Of these patients, 28 (82.4%) underwent curative resection, 7 (20.6%; 95% CI, 10.1%-100%) achieved pCR, and 6 (17.6%) achieved a pathologic near-complete response. Of the 28 patients who underwent resection, 4 (14.3%) experienced disease recurrence. The median DFS and OS were not reached. The 2-year DFS was 67.8% (95% CI, 0.53%-0.87%) and the OS was 80.6% (95% CI, 0.68%-0.96%). Treatment-related grade 3 or higher adverse events for evaluable patients occurred in 20 patients (57.1%), and 12 (34.3%) experienced immune-related grade 3 or higher adverse events. Conclusion and Relevance: In this trial of unselected patients with resectable G/GEJ adenocarcinoma, capecitabine, oxaliplatin, and pembrolizumab resulted in a pCR rate of 20.6% and was well tolerated. This trial met its primary end point and supports the development of checkpoint inhibition in combination with perioperative chemotherapy in locally advanced G/GEJ adenocarcinoma. Trial Registration: ClinicalTrials.gov Identifier: NCT02918162.

Socioeconomic Predictors of Access to Care for Patients with Operatively Managed Pancreatic Cancer in New York State.

PURPOSE: We evaluated how race and socioeconomic factors impact access to high-volume surgical centers, treatment initiation, and postoperative care for pancreatic cancer in a state with robust safety net insurance coverage and healthcare infrastructure. METHODS: The New York Statewide Planning and Research Cooperative System was analyzed. Patients with pancreatic cancer resected from 2007 to 2017 were identified by ICD and CPT codes. Primary outcomes included surgery at low-volume facilities (< 20 pancreatectomies/year), time to therapy initiation, and time to postoperative surveillance imaging (within 60-180 days after surgery). RESULTS: In total, 3312 patients underwent pancreatectomy across 124 facilities. Median age was 67 years (IQR 59, 75) and 55% of patients were male. Most (72.7%) had surgery at high-volume centers. On multivariable analysis, odds ratios for surgery at low-volume centers were increased for Black race (2.21 (95% CI 1.69-2.88)), Asian race (1.64 (95% CI 1.09-2.43)), Hispanic ethnicity (1.68 (95% CI 1.24-2.28)), Medicaid insurance (2.52 (95% CI 1.79-3.56)), no insurance (2.24 (95% CI 1.38-3.61)), lowest income quartile (3.31 (95% CI 2.14-5.32)), and rural zip code (2.49 (95% CI 1.69-3.65)). Patients treated at low-volume centers waited longer to initiate treatment (hazard ratio (HR) 0.91 (95% CI 0.81-1.01)). Black patients underwent the least surveillance imaging (50.4%; p < 0.0001), while Asian (HR 2.04, 95% CI 1.40-2.98)) and Hispanic patients (HR 1.36 (95% CI 1.00-1.84)) were more likely to have surveillance imaging. CONCLUSIONS: Race independently affected access to high-volume facilities and surveillance imaging. When considered in light of other accumulating evidence, future efforts might investigate the perceptions and logistical considerations noted by providers and patients alike to identify the etiology of these disparities and then institute corrective measures.

Prevalence and Risk Factors for Pancreatic Insufficiency After Partial Pancreatectomy.

BACKGROUND: This study aimed to determine the rate, timing, and predictors of diabetes and exocrine pancreatic insufficiency after pancreatectomy in order to inform preoperative patient counseling and risk management strategies. METHODS: Using prescription claims as a surrogate for disease prevalence, IBM Watson Health MarketScan was queried for claims patterns pre- and post-pancreatectomy. Multivariable models explored associations between clinical characteristics and medication use within 2 years of surgery. RESULTS: In total, 18.96% of 2,848 pancreaticoduodenectomy (PD) patients and 18.95% of 1,858 distal pancreatectomy (DP) patients had preoperative diabetic medication prescription claims. Fewer (6.6% and 3.88%, respectively) had pancreatic enzyme replacement therapy (PERT) claims. Diabetic medication claims increased to 28.69% after PD and 38.59% after DP [adjusted relative risk (aRR) = 1.36 (95% CI 1.27, 1.46)]. Other associated factors included age > 45, medical comorbidity, and obesity. The incidence of new diabetic medication claims among medication naïve patients was 13.78% for PD and 24.7% for DP (p < 0.001) with a median 4.7 and 4.9 months post-operatively. The prevalence of PERT claims was 55.97% after PD and 17.06% after DP [aRR = 0.32 (0.29, 0.36)]. The incidence of postoperative PERT claims 53.98% (PD) and 14.84% (DP) (p < 0.0001). The median time to new PERT claim was 3.0 (PD) and 3.2 (DP) months, respectively. Claims for both diabetic medications and PERT rose sharply after surgery and plateaued within 6 months. CONCLUSIONS: This study defines prevalence, timing, and predictors for post-pancreatectomy insufficiency to inform preoperative counseling, risk modification strategies, and interventions related to quality of life.