Disease-free survival after pancreatectomy for pancreatic neuroendocrine tumors: A 17-year single-center experience of 223 patients.

BACKGROUND: Metastasis or recurrence of pancreatic neuroendocrine tumors (pNETs) after pancreatectomy is an important source of postsurgical morbidity. This study aimed to define disease-free survival (DFS) in this population. METHODS: Patients who underwent pancreatectomy for pNETs between January 2005 and January 2022 were included. Clinicopathologic and survival data were collected, and the primary endpoint was DFS. Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were performed. RESULTS: Of the 223 patients, 144 (65%) distal/subtotal/partial pancreatectomies, 71 (32%) pancreaticoduodenectomies, 6 (3%) total pancreatectomies, and 2 (1%) enucleations were performed. Of the 223 patients, 45 (20%) experienced disease recurrence or metastasis after index pancreatectomy during the 17 years of the study. Nonfunctional pNETs (162 [73%]) were more common than hormonally functional subtypes. The 2- and 5-year DFSs were 82% and 76%, respectively. Kaplan-Meier analysis demonstrated that N1 node positive disease, size of ≥ 4 cm, lymphovascular invasion, perineural invasion, Ki-67 of ≥ 20%, and nonfunctional pNETs are significantly associated with a lower DFS (P < .05). Univariate Cox analysis identified the following predictors to be significantly associated with poorer DFS: larger tumor size (hazard ratio [HR], 1.16; 95% CI, 1.04-1.28), Ki-67 index of ≥ 20% (HR, 4.93; 95% CI, 2.00-11.44), perineural invasion (HR, 3.23; 95% CI, 1.40-7.89), open surgery (HR, 3.34; 95% CI, 1.03-1.33), node-positive disease (HR, 5.27; 95% CI, 2.28-13.26), and increased body mass index (HR, 1.10; 95% CI, 1.03-1.17) (P < .05). CONCLUSION: Of note, 1 in 5 patients who underwent resection developed recurrence or metastasis after pancreatectomy. Prognostic predictors of DFS in pNETs could help optimize treatment and enhance follow-up protocols to improve quality and reduce morbidity.

Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy.

INTRODUCTION: Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes. METHODS: The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC. Patients with histologically confirmed advanced HCC treated with ICI at Memorial Sloan Kettering Cancer Center from 2012 to 2022 were included. Association between clinical, pathological, and genomic characteristics were assessed with univariable and multivariable Cox regression model for progression-free survival (PFS) and OS. RESULTS: Two-hundred and forty-two patients were treated with ICI-based therapy. Patients were predominantly male (82%) with virally mediated HCC (53%) and Child Pugh A score (70%). Median follow-up was 28 months (0.5-78.4). Median PFS for those treated in 1st line, 2nd line and ≥ 3rd line was 4.9 (range: 2.9-6.2), 3.1 (2.3-4.0), and 2.5 (2.1-4.0) months, respectively. Median OS for those treated in 1st line, 2nd line, and ≥ 3rd line was 16 (11-22), 7.5 (6.4-11), and 6.4 (4.6-26) months, respectively. Poor liver function and performance status associated with worse PFS and OS, while viral hepatitis C was associated with favorable outcome. Genetic alterations were not associated with outcomes. CONCLUSION: Clinicopathologic factors were the major determinates of outcomes for patients with advanced HCC treated with ICI. Molecular profiling did not aid in stratification of ICI outcomes. Future studies should explore alternative biomarkers such as the level of immune activation or the pretreatment composition of the immune tumor microenvironment.

Safety of Selective Operative Drainage After Pancreatic Resection: A Retrospective Analysis of 2,607 Patients.

OBJECTIVE: To assess whether selective omission of operative drains after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is associated with adverse perioperative outcomes. BACKGROUND: The routine use of operative drains after pancreatectomy is widely practiced; however, prospective randomized clinical trials and retrospective analyses have shown mixed results. METHODS: Patients who underwent PD or DP between November 2009 and May 2021 were reviewed and stratified by operative drain placement. Patient demographics, morbidity, the need for additional procedures, and mortality were compared between patients who did or did not develop a clinically relevant post-operative pancreatic fistula (CR-POPF). RESULTS: In total, 1,855 PD and 752 DP cases were analyzed. Among PD patients with a CR-POPF (N=259, 14%), 160 (62%) had an operative drain placed, of whom 141 (88%) required at least 1 additional procedure. Within this subgroup, grade ≥ 4 complications (7.5% vs. 11.1%, P=0.37), 90-day mortality (3.8% vs. 6.1%, P=0.54), length of stay (LOS) (median 12 vs. 13 d, P=0.19) and readmission rates (63.1% vs. 54.6%, P=0.19) were similar between drained and non-drained patients. Of note, drained PD patients without a CR-POPF had a longer hospital stay (8 vs. 7 d, respectively, P=0.004) and more thromboembolic events (2.4% vs. 1.1%, respectively, P=0.04) Among DP patients with a CR-POPF (n=129), 44 had an operative drain, with 37 (84%) requiring an additional procedure. Within this subgroup, grade ≥ 4 complications (4.6% vs. 5.9%, P>0.95), 90-day mortality (0%), LOS (median 7 d for both, P=0.88) and readmission rates (72.7% vs. 80%, P=0.38) were similar in drained and non-drained patients. CONCLUSION: This study confirms that selective omission of operative drains does not compromise perioperative outcomes, as initially reported in our prospective randomized trial.

Hemorrhage Sites and Mitigation Strategies After Pancreaticoduodenectomy.

Importance: Postpancreatectomy hemorrhage is an uncommon but highly morbid complication of pancreaticoduodenectomy. Clinical evidence often draws suspicion to the gastroduodenal artery stump, even without a clear source. Objective: To determine the frequency of gastroduodenal artery bleeding compared to other sites and the results of mitigation strategies. Design, Setting, and Participants: This cohort study involved a retrospective analysis of data for consecutive patients who had pancreaticoduodenectomy from 2011 to 2021 at Memorial Sloan Kettering Cancer Center (MSK) and Thomas Jefferson University Hospital (TJUH). Exposures: Demographic, perioperative, and disease-related variables. Main Outcomes and Measures: The incidence, location, treatment, and outcomes of primary (initial) and secondary (recurrent) hemorrhage requiring invasive intervention were analyzed. Imaging studies were re-reviewed by interventional radiologists to confirm sites. Results: Inclusion criteria were met by 3040 patients (n = 1761 MSK, n = 1279 TJUH). Patients from both institutions were similar in age (median [IQR] age at MSK, 67 [59-74] years, and at TJUH, 68 [60-75] years) and sex (at MSK, 814 female [46.5%] and 947 male [53.8%], and at TJUH, 623 [48.7%] and 623 male [51.3%]). Primary hemorrhage occurred in 90 patients (3.0%), of which the gastroduodenal artery was the source in 15 (16.7%), unidentified sites in 24 (26.7%), and non-gastroduodenal artery sites in 51 (56.7%). Secondary hemorrhage occurred in 23 patients; in 4 (17.4%), the gastroduodenal artery was the source. Of all hemorrhage events (n = 117), the gastroduodenal artery was the source in 19 (16.2%, 0.63% incidence in all pancreaticoduodenectomies). Gastroduodenal artery hemorrhage was more often associated with soft gland texture (14 [93.3%] vs 41 [62.1%]; P = .02) and later presentation (median [IQR], 21 [15-26] vs 10 days [5-18]; P = .002). Twenty-three patients underwent empirical gastroduodenal artery embolization or stent placement, 7 (30.4%) of whom subsequently experienced secondary hemorrhage. Twenty percent of all gastroduodenal artery embolizations/stents (8/40 patients), including 13% (3/13 patients) of empirical treatments, were associated with significant morbidity (7 hepatic infarction, 4 biliary stricture), with a 90-day mortality rate of 38.5% (n = 5) for patients with these complications vs 7.8% without (n = 6; P = .008). Ninety-day mortality was 12.2% (n = 11) for patients with hemorrhage (3 patients [20%] with primary gastroduodenal vs 8 [10.7%] for all others; P = .38) compared with 2% (n = 59) for patients without hemorrhage. Conclusions and Relevance: In this study, postpancreatectomy hemorrhage was uncommon and the spectrum was broad, with the gastroduodenal artery responsible for a minority of bleeding events. Empirical gastroduodenal artery embolization/stent without obvious sequelae of recent hemorrhage was associated with significant morbidity and rebleeding and should not be routine practice. Successful treatment of postpancreatectomy hemorrhage requires careful assessment of all potential sources, even after gastroduodenal artery mitigation.

Salvage Ablative Radiotherapy for Isolated Local Recurrence of Pancreatic Adenocarcinoma following Definitive Surgery.

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98-100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan-Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37-87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6-71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26-56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46-72%) and 22% (95%CI, 14-37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17-40%) and 36% (95%CI 24-48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3-4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.

Morbidity and mortality in patients with stage IV pancreatic adenocarcinoma and acute cholangitis: Outcomes and risk prognostication.

BACKGROUND: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC. METHODS: We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality. RESULTS: One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0-5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3-92.5), 37 % (95 % CI, 29.3-46.6 %) and 18.9 % (95 % CI, 13.1-27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC. CONCLUSIONS: AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Advances in Surgery and (Neo) Adjuvant Therapy in the Management of Pancreatic Cancer.

A multimodality approach, which usually includes chemotherapy, surgery, and/or radiotherapy, is optimal for patients with localized pancreatic cancer. The timing and sequence of these interventions depend on anatomic resectability and the biological suitability of the tumor and the patient. Tumors with vascular involvement (ie, borderline resectable/locally advanced) require surgical reassessments after therapy and participation of surgeons familiar with advanced techniques. When indicated, venous reconstruction should be offered as standard of care because it has acceptable morbidity. Morbidity and mortality of pancreas surgery may be mitigated when surgery is performed at high-volume centers.

Impact of a non-therapeutic laparotomy in patients with locally advanced pancreatic cancer treated with induction (m)FOLFIRINOX: Trans-Atlantic Pancreatic Surgery (TAPS) Consortium study.

BACKGROUND: Surgery in selected patients with locally advanced pancreatic cancer after induction chemotherapy may have drawbacks related to surgical risks and breaks or delays in oncological treatment, in particular when curative intent resection is not possible (that is non-therapeutic laparotomy). The aim of this study was to assess the incidence and oncological impact of a non-therapeutic laparotomy in patients with locally advanced pancreatic cancer treated with induction (m)FOLFIRINOX chemotherapy. METHODS: This was a retrospective international multicentre study including patients diagnosed with pathology-proven locally advanced pancreatic cancer treated with at least one cycle of (m)FOLFIRINOX (2012-2019). Patients undergoing a non-therapeutic laparotomy (group A) were compared with those not undergoing surgery (group B) and those undergoing resection (group C). RESULTS: Overall, 663 patients with locally advanced pancreatic cancer were included (67 patients (10.1%) in group A, 425 patients (64.1%) in group B, and 171 patients (25.8%) in group C). A non-therapeutic laparotomy occurred in 28.2% of all explorations (67 of 238), with occult metastases in 30 patients (30 of 67, 44.8%) and a 90-day mortality rate of 3.0% (2 of 67). Administration of palliative therapy (65.9% versus 73.1%; P = 0.307) and median overall survival (20.4 [95% c.i. 15.9 to 27.3] versus 20.2 [95% c.i. 19.1 to 22.7] months; P = 0.752) did not differ between group A and group B respectively. The median overall survival in group C was 36.1 (95% c.i. 30.5 to 41.2) months. The 5-year overall survival rates were 11.4%, 8.7%, and 24.7% in group A, group B, and group C, respectively. Compared with group B, non-therapeutic laparotomy (group A) was not associated with reduced overall survival (HR = 0.88 [95% c.i. 0.61 to 1.27]). CONCLUSION: More than a quarter of surgically explored patients with locally advanced pancreatic cancer after induction (m)FOLFIRINOX did not undergo a resection. Such non-therapeutic laparotomy does not appear to substantially impact oncological outcomes.

Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study.

PURPOSE: Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated. METHODS: In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS). RESULTS: Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively. CONCLUSION: The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.

Serum CEA as a Prognostic Marker for Overall Survival in Patients with Localized Pancreatic Adenocarcinoma and Non-Elevated CA19-9 Levels Treated with FOLFIRINOX as Initial Treatment: A TAPS Consortium Study.

INTRODUCTION: About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative. METHODS: This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics. RESULTS: Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not. CONCLUSIONS: Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9.

Risk Factors for Progression in Patients Undergoing Surveillance for Pancreatic Cysts.

OBJECTIVE: To identify risk factors associated with the progression of pancreatic cysts in patients undergoing surveillance. BACKGROUND: Previous studies of intraductal papillary mucinous neoplasms (IPMNs) rely on surgical series to determine malignancy risk and have inconsistently identified characteristics associated with IPMN progression. METHODS: We conducted a retrospective review of 2197 patients presenting with imaging concerning for IPMN from 2010 to 2019 at a single institution. Cyst progression was defined as resection or pancreatic cancer development. RESULTS: The median follow-up time was 84 months from the presentation. The median age was 66 years, and 62% were female. Ten percent had a first-degree relative with pancreatic cancer, and 3.2% had a germline mutation or genetic syndrome associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). Cumulative incidence of progression was 17.8% and 20.0% at 12 and 60 months postpresentation, respectively. Surgical pathology for 417 resected cases showed noninvasive IPMN in 39% of cases and PDAC with or without associated IPMN in 20%. Only 18 patients developed PDAC after 6 months of surveillance (0.8%). On multivariable analysis, symptomatic disease [hazard ratio (HR)=1.58; 95% CI: 1.25-2.01], current smoker status (HR=1.58; 95% CI: 1.16-2.15), cyst size (HR=1.26; 95% CI: 1.20-1.33), main duct dilation (HR=3.17; 95% CI: 2.44-4.11), and solid components (HR=1.89; 95% CI: 1.34-2.66) were associated with progression. CONCLUSIONS: Worrisome features on imaging at presentation, current smoker status, and symptomatic presentation are associated with IPMN progression. Most patients progressed within the first year of presentation to Memorial Sloan Kettering Cancer Center (MSKCC). Further investigation is necessary to develop personalized cyst surveillance strategies.

Early-Onset Pancreatic Neuroendocrine Tumors: Clinical Presentation, Pathology Features, and Oncological Outcomes.

BACKGROUND: Early-Onset (EO) pancreatic neuroendocrine tumor (PanNET) is a rare disease, but whether it is clinically different from late-onset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO-PanNET and LO-PanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome. METHODS: Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000 and 2017 were identified. Those with metastatic disease and poorly differentiated tumors were excluded. EO-PanNET was defined as <50 and LO-PanNET >50 years of age at the time of diagnosis. Family history and clinical and pathology characteristics were recorded. RESULTS: Overall 383 patients were included, 107 (27.9%) with EO-PanNET. Compared with LO-PanNET, EO-PanNET were more likely to have a hereditary syndrome (2.2% vs. 16%, P <0.001) but had similar pathology features such as tumor grade ( P =0.6), size (2.2 Vs. 2.3 cm, P =0.5) and stageof disease ( P =0.8). Among patients with EO-PanNET, those with hereditary syndrome had more frequently a multifocal disease (65% vs. 3.3%, P <0.001). With a median follow-up of 70 months (range 0-238), the 5-year cumulative incidence of recurrence after curative surgery was 19% (95% CI 12%-28%) and 17% (95% CI 13%-23%), in EO-PanNET and LO-PanNET ( P =0.3). Five-year disease-specific survival was 99% (95% CI 98%-100%) with no difference with respect to PanNET onset time ( P =0.26). CONCLUSIONS: In this surgical cohort, we found that EO-PanNET is associated with hereditary syndromes but has pathologic characteristics and oncological outcomes similar to LO-PanNET. These findings suggest that patients with EO-PanNET can be managed similarly to those with LO-PanNET.

Defining Standards for Hepatopancreatobiliary Cancer Surgery in Ontario, Canada: A Population-Based Cohort Study of Clinical Outcomes.

BACKGROUND: In 2006, Cancer Care Ontario created Surgical Oncology Standards for the delivery of hepatopancreatobiliary (HPB) surgery including hepatectomy and pancreaticoduodenectomy (PD). Our objective was to identify the impact of standardization on outcomes after HPB surgery in Ontario, Canada. STUDY DESIGN: This study was a population-level analysis of patients undergoing hepatectomy or PD (2003 to 2019). Logistic regression models were used to compare 30- and 90-day mortality and length of stay (LOS) before (2003 to 2006), during (2007 to 2011), and after (2012 to 2019) standardization. Interrupted time series models were used to co-analyze secular trends. RESULTS: A total of 7,904 hepatectomies and 5,238 PDs were performed. More than 80% of all cases were performed at a designated center (DC) before standardization. This increased to >98% in the poststandardization era. Median volumes at DCs increased from 55 to 67 hepatectomies/year and from 22 to 50 PDs/year over time. In addition, 30-day mortality after hepatectomy was 2.6% before standardization and 2.3% after standardization (p = 0.9); 30-day mortality after PD was 3.6% before standardization and 2.4% after standardization (p = 0.1). Multivariable analyses revealed a significant difference in 90-day mortality following PD poststandardization (4.3% vs 6.3%; adjusted odds ratio, 0.7; p = 0.03). Median LOS was shorter for hepatectomy (6 days vs 8 days) and PD (9 days vs 14 days; p < 0.0001) after standardization. Immediate and late effects on mortality and LOS were likely attributable to secular trends, which predated standardization. CONCLUSIONS: Standardization was associated with a higher volume of hepatectomy and PDs with further concentration of care at DCs. Pre-existing quality initiatives may have attenuated the effect of standardization on quality outcomes. Our data highlight the merits of a multifaceted provincial system for enabling consistent access to high quality HPB care throughout a region of 15 million people over a 16-year period.