Predictors for Long-Term Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Improved systemic therapy has made long term (≥ 5 years) overall survival (LTS) after resection of pancreatic ductal adenocarcinoma (PDAC) increasingly common. However, a systematic review on predictors of LTS following resection of PDAC is lacking. METHODS: The PubMed, Embase, Scopus, and Cochrane CENTRAL databases were systematically searched from inception until March 2023. Studies reporting actual survival data (based on follow-up and not survival analysis estimates) on factors associated with LTS were included. Meta-analyses were conducted by using a random effects model, and study quality was gauged by using the Newcastle-Ottawa Scale (NOS). RESULTS: Twenty-five studies with 27,091 patients (LTS: 2,132, non-LTS: 24,959) who underwent surgical resection for PDAC were meta-analyzed. The median proportion of LTS patients was 18.32% (IQR 12.97-21.18%) based on 20 studies. Predictors for LTS included sex, body mass index (BMI), preoperative levels of CA19-9, CEA, and albumin, neutrophil-lymphocyte ratio, tumor grade, AJCC stage, lymphovascular and perineural invasion, pathologic T-stage, nodal disease, metastatic disease, margin status, adjuvant therapy, vascular resection, operative time, operative blood loss, and perioperative blood transfusion. Most articles received a "good" NOS assessment, indicating an acceptable risk of bias. CONCLUSIONS: Our meta-analysis pools all true follow up data in the literature to quantify associations between prognostic factors and LTS after resection of PDAC. While there appears to be evidence of a complex interplay between risk, tumor biology, patient characteristics, and management related factors, no single parameter can predict LTS after the resection of PDAC.

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries.

BACKGROUND: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. METHODS: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. RESULTS: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. CONCLUSION: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).

Pancreatic surgery can sometimes lead to health problems afterwards. Although some top hospitals report good results, it is not clear how patients are doing all over the world. The aim was to find out how people are recovering after pancreatic surgery in different countries, and to see whether where they live affects their health outcomes after pancreatic surgery. The health records of 4223 patients from 67 countries who had pancreatic surgery in a 3-month interval in 2021 were studied, especially looking at how many people faced serious complications or passed away within 90 days of the surgery. Almost 7 in 10 patients faced some health problems after operation. The chance of having a major health issue or dying after the surgery was higher in countries with fewer resources and less developed healthcare. For example, 10 of 100 patients died after the surgery in these countries, but only 5 of 100 patients did in richer countries. What stands out is that countries with fewer resources have a tougher time getting patients back to health when things go wrong after surgery. It is hoped that doctors and medical groups worldwide can work together to improve these outcomes and give everyone the best chance of recovering well after pancreatic surgery.

Assessing quality of hepato-pancreato-biliary surgery: nationwide benchmarking.

BACKGROUND: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified. METHODS: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020-2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). RESULTS: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 -3.2%) and 3.3% (0-16.7%) for minor and major LR, and 2.7% (0-7.0%) and 0.6% (0-4.2%) for PD and DP respectively. FTR rates were 5.4% (0-33.3%), 14.2% (0-100%), 7.5% (1.6%-28.5%) and 3.1% (0-14.9%). For major morbidity rate, corresponding rates were 9.8% (0-20.5%), 28.1% (0-47.1%), 36% (15.8%-58.3%) and 22.3% (5.2%-46.1%). For TO, corresponding rates were 73.6% (61.3%-94.4%), 54.1% (35.3-100), 46.8% (25.3%-59.4%) and 63.3% (30.7%-84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers. CONCLUSION: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking.

Contemporary report of surgical outcomes after single-stage total pancreatectomy: A 10-year experience.

BACKGROUND: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients. METHODS: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed. RESULTS: SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6). CONCLUSION: Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.

Addressing long-term mortality risk in patients undergoing total pancreatectomy with islet autotransplant (TPIAT): causes of death and risk factors.

BACKGROUND: Total pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. METHODS: We studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. RESULTS: Mean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. CONCLUSIONS: For patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.

Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma.

OBJECTIVE: To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). METHODS: The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. RESULTS: High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. CONCLUSIONS: The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.

Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS). METHODS: Between 2000 and 2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed and histological findings were evaluated applying international guidelines. RESULTS: DSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI) 26.0-57.6 vs. 20.6 months, 95% CI 10.3-30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19-9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02-2.16], lymph node metastases N1-2 (HR 1.71, 95% CI 1.16-2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04-2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27-2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03-2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453). CONCLUSIONS: Our results indicate that the pancreatic stroma is associated with PDAC patients' DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.

Associations of gender, race, and ethnicity with disparities in short-term adverse outcomes after pancreatic resection for cancer.

BACKGROUND: Several studies have identified disparities in pancreatic cancer treatment associated with gender, race, and ethnicity. There are limited data examining disparities in short-term adverse outcomes after pancreatic resection for cancer. The aim of this study is to evaluate associations of gender, race, and ethnicity with morbidity and mortality after pancreatic resection for malignancy. METHODS: The American College of Surgeons National Surgical Quality Improvement database was retrospectively reviewed. The χ2 test and Student's t-test were used for univariable analysis and hierarchical logistic regression for multivariable analysis. RESULTS: Morbidity and major morbidity after pancreaticoduodenectomy are associated with male gender, Asian race, and Hispanic ethnicity, whereas 30-day mortality is associated with the male gender. Morbidity and major morbidity after distal pancreatectomy are associated with the male gender. Morbidity after pancreaticoduodenectomy is independently associated with male gender, Asian race, and Hispanic ethnicity; major morbidity is independently associated with male gender and Asian race, and mortality is independently associated with Hispanic ethnicity. CONCLUSIONS: Gender, race, and ethnicity are independently associated with morbidity after pancreaticoduodenectomy for cancer; gender and race are independently associated with major morbidity; and ethnicity is independently associated with mortality. Further studies are warranted to determine the basis of these associations.

A Nationwide Population-based Study From Taiwan Assessing the Influence of Preventable Hospitalization Rate on Mortality After Oncologic Surgery.

OBJECTIVE: To determine the effect of a previously unassessed measure of quality-preventable hospitalization rate-on mortality after oncologic surgery for 4 procedures with established volume-outcome relationships. We hypothesize that hospitals with higher preventable hospitalization rates (indicating poor quality of primary care) have increased hospital mortality. Additionally, patients having surgery at hospitals with higher preventable hospitalization rates have increased mortality. SUMMARY BACKGROUND DATA: Although different factors have been used to measure healthcare quality, most have not resulted in long-term hospital-based improvements in patient outcomes. METHODS: We retrieved data from Taiwan's National Health Insurance database for patients who underwent surgery during 2001 to 2014 for esophagectomy, pancreatectomy, lung resection, or cystectomy. Preventable hospitalization rates assess hospitalizations for 11 chronic conditions that are deemed to be preventable with effective primary care. The outcome was 30-day surgical mortality. Identifiable factors potentially related to surgical mortality, including surgeon and hospital volume, were controlled for in the models. RESULTS: Our dataset contained 35,081 patients who had surgery for one of the procedures. For all procedures, hospitals with high preventable hospitalization rates were associated with higher mortality rates (all P < 0.01). For esophagectomy, lung resection, and cystectomy, the adjusted odds of individual mortality increased by 8% to 10% (P < 0.01) for every 1% increase in the preventable hospitalization rate. For pancreatectomy, the adjusted odds of individual mortality increased by 21% for every 1% increase in preventable hospitalization rate when the rate was ≥8% (P < 0.01). CONCLUSIONS: Preventable hospitalization rates could serve as warning signs of low quality of care and be a publically-reported quality measure.

Root-cause Analysis of Mortality After Pancreatic Resection (CARE Study): A Multicenter Cohort Study.

OBJECTIVES: Analyze a multicenter cohort of deceased patients after pancreatectomy in high-volume centers in France by performing a root-cause analysis (RCA) to define the avoidable mortality rate. BACKGROUND: Despite undeniable progress in pancreatic surgery for over a century, postoperative outcome remains particularly worse and could be further improved. METHODS: All patients undergoing pancreatectomy between January 2015 and December 2018 and died postoperatively within 90 days after were included. RCA was performed in 2 stages: the first being the exhaustive collection of data concerning each patient from preoperative to death and the second being blind analysis of files by an independent expert committee. A typical root cause of death was defined with the identification of avoidable death. RESULTS: Among the 3195 patients operated on in 9 participating centers, 140 (4.4%) died within 90 days after surgery. After the exclusion of 39 patients, 101 patients were analyzed. The cause of death was identified in 90% of cases. After RCA, mortality was preventable in 30% of cases, mostly consequently to a preoperative assessment (disease evaluation) or a deficient postoperative management (notably pancreatic fistula and hemorrhage). An inappropriate intraoperative decision was incriminated in 10% of cases. The comparative analysis showed that young age and arterial resection, especially unplanned, were often associated with avoidable mortality. CONCLUSIONS: One-third of postoperative mortality after pancreatectomy seems to be avoidable, even if the surgery is performed in high volume centers. These data suggest that improving postoperative pancreatectomy outcome requires a multidisciplinary, rigorous, and personalized management.

Patient Social Vulnerability and Hospital Community Racial/Ethnic Integration: Do All Patients Undergoing Pancreatectomy Receive the Same Care Across Hospitals?

OBJECTIVE: The objective of the current study was to characterize the role of patient social vulnerability relative to hospital racial/ethnic integration on postoperative outcomes among patients undergoing pancreatectomy. BACKGROUND: The interplay between patient- and community-level factors on outcomes after complex surgery has not been well-examined. METHODS: Medicare beneficiaries who underwent a pancreatectomy between 2013 and 2017 were identified utilizing 100% Medicare inpatient files. P-SVI was determined using the Centers for Disease Control and Prevention criteria, whereas H-REI was estimated using Shannon Diversity Index. Impact of P-SVI and H-REI on "TO" [ie, no surgical complication/extended length-of-stay (LOS)/90-day mortality/90-day readmission] was assessed. RESULTS: Among 24,500 beneficiaries who underwent pancreatectomy, 12,890 (52.6%) were male and median age was 72 years (Interquartile range: 68-77); 10,619 (43.3%) patients achieved a TO. The most common adverse postoperative outcome was 90-day readmission (n = 8,066, 32.9%), whereas the least common was 90-day mortality (n = 2282, 9.3%). Complications and extended LOS occurred in 30.4% (n = 7450) and 23.3% (n = 5699) of the cohort, respectively. Patients from an above average SVI county who underwent surgery at a below average REI hospital had 18% lower odds [95% confidence interval (CI): 0.74-0.95] of achieving a TO compared with patients from a below average SVI county who underwent surgery at a hospital with above average REI. Of note, patients from the highest SVI areas who underwent pancreatectomy at hospitals with the lowest REI had 30% lower odds (95% CI: 0.54-0.91) of achieving a TO compared with patients from very low SVI areas who underwent surgery at a hospital with high REI. Further comparisons of these 2 patient groups indicated 76% increased odds of 90-day mortality (95% CI: 1.10-2.82) and 50% increased odds of an extended LOS (95% CI: 1.07-2.11). CONCLUSION: Patients with high social vulnerability who underwent pancreatectomy in hospitals located in communities with low racial/ethnic integration had the lowest chance to achieve an "optimal" TO. A focus on both patient- and community-level factors is needed to ensure optimal and equitable patient outcomes.

Effect of centralization and regionalization of pancreatic surgery on resection rates and survival.

BACKGROUND: Centralization of pancreatic surgery in the Netherlands has been ongoing since 2011. The aim of this study was to assess how centralization has affected the likelihood of resection and survival of patients with non-metastatic pancreatic head and periampullary cancer, diagnosed in hospitals with and without pancreatic surgery services. METHODS: An observational cohort study was performed on nationwide data from the Netherlands Cancer Registry (2009-2017), including patients diagnosed with non-metastatic pancreatic head or periampullary cancer. The period of diagnosis was divided into three time intervals: 2009-2011, 2012-2014 and 2015-2017. Hospital of diagnosis was classified as a pancreatic or non-pancreatic surgery centre. Analyses were performed using multivariable logistic and Cox regression models. RESULTS: In total, 10 079 patients were included, of whom 3114 (30.9 per cent) were diagnosed in pancreatic surgery centres. Between 2009-2011 and 2015-2017, the number of patients undergoing resection increased from 1267 of 3169 (40.0 per cent) to 1705 of 3566 (47.8 per cent) (P for trend < 0.001). In multivariable analysis, in 2015-2017, unlike the previous periods, patients diagnosed in pancreatic and non-pancreatic surgery centres had a similar likelihood of resection (odds ratio 1.08, 95 per cent c.i. 0.90 to 1.28; P = 0.422). In this period, however, overall survival was higher in patients diagnosed in pancreatic surgery than in those diagnosed in non-pancreatic surgery centres (hazard ratio 0.92, 95 per cent c.i. 0.85 to 0.99; P = 0.047). CONCLUSION: After centralization of pancreatic surgery, the resection rate for patients with pancreatic head and periampullary cancer diagnosed in non-pancreatic surgery centres increased and became similar to that in pancreatic surgery centres. Overall survival remained higher in patients diagnosed in pancreatic surgery centres.

Robotic versus laparoscopic distal pancreatectomy: multicentre analysis.

BACKGROUND: The role of minimally invasive distal pancreatectomy is still unclear, and whether robotic distal pancreatectomy (RDP) offers benefits over laparoscopic distal pancreatectomy (LDP) is unknown because large multicentre studies are lacking. This study compared perioperative outcomes between RDP and LDP. METHODS: A multicentre international propensity score-matched study included patients who underwent RDP or LDP for any indication in 21 European centres from six countries that performed at least 15 distal pancreatectomies annually (January 2011 to June 2019). Propensity score matching was based on preoperative characteristics in a 1 : 1 ratio. The primary outcome was the major morbidity rate (Clavien-Dindo grade IIIa or above). RESULTS: A total of 1551 patients (407 RDP and 1144 LDP) were included in the study. Some 402 patients who had RDP were matched with 402 who underwent LDP. After matching, there was no difference between RDP and LDP groups in rates of major morbidity (14.2 versus 16.5 per cent respectively; P = 0.378), postoperative pancreatic fistula grade B/C (24.6 versus 26.5 per cent; P = 0.543) or 90-day mortality (0.5 versus 1.3 per cent; P = 0.268). RDP was associated with a longer duration of surgery than LDP (median 285 (i.q.r. 225-350) versus 240 (195-300) min respectively; P < 0.001), lower conversion rate (6.7 versus 15.2 per cent; P < 0.001), higher spleen preservation rate (81.4 versus 62.9 per cent; P = 0.001), longer hospital stay (median 8.5 (i.q.r. 7-12) versus 7 (6-10) days; P < 0.001) and lower readmission rate (11.0 versus 18.2 per cent; P = 0.004). CONCLUSION: The major morbidity rate was comparable between RDP and LDP. RDP was associated with improved rates of conversion, spleen preservation and readmission, to the detriment of longer duration of surgery and hospital stay.

Radiological tumour invasion of splenic artery or vein in patients with pancreatic body or tail adenocarcinoma and effect on recurrence and survival.

BACKGROUND: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. METHODS: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. RESULTS: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9 cm, P = 0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P = 0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P < 0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P = 0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. CONCLUSION: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach.

Short- and long-term surgical outcomes of total pancreatectomy with islet autotransplantation: A comparative analysis of surgical technique and intraoperative heparin dosing to optimize outcomes.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TP-IAT) is an uncommon surgical procedure with unique perioperative management. We evaluated the short- and long-term morbidity and mortality of TP-IAT to optimize surgical technique and heparin dosing during islet autotransplantation. METHODS: Eighty patients with chronic pancreatitis undergoing TP-IAT were reviewed. Primary outcome was to evaluate morbidity and mortality based on operative technique: classic (resection of antrum) vs pylorus-preserving. Secondary outcome was to evaluate the effect of heparin dosing (<60 vs ≥ 60 units/kg) during islet autotransplantation on postoperative hemorrhage and portal vein thrombosis (PVT) rates. RESULTS: There was no 90-day mortality, and median length of stay was 9 days. All patients underwent an open operation with 53 (66%) pylorus-preserving resections. The 30-day morbidity rate was 39%, with no difference between operative technique (p = 0.82). The median dose was different for each heparin group (<60: 52 units/kg vs ≥ 60: 66 units/kg, p < 0.0001). No difference was observed in postoperative hemorrhage rates between heparin groups (<60: 9% vs ≥ 60: 9%, p = 0.97), with no known incidence of PVT. Median follow-up was 36 months (IQR, 14-71). Morbidity >30 days after TP-IAT was 43% with a higher rate in the pylorus-preserving group (55% vs 15%, p < 0.0001), mainly attributed to marginal ulcer formation (15% vs 0%, p = 0.03). CONCLUSIONS: A classic TP-IAT technique should be universally adopted to achieve optimal outcomes, particularly to prevent the formation of marginal ulcers. When considering PVT versus postoperative hemorrhage risk, a lower heparin dose nearing 50 units/kg is optimal. These findings highlight potential areas for future improvement.

Hepatopancreatic Surgery in the Rural United States: Variation in Outcomes at Critical Access Hospitals.

BACKGROUND: Sixty million Americans live in rural America, with roughly 17.5% of the rural population being 65 y or older. Outcomes and costs of Medicare beneficiaries undergoing hepatopancreatic surgery at critical access hospitals (CAHs) are not known. MATERIALS AND METHODS: Medicare files were used to identify patients who underwent hepatopancreatic resection. Outcomes were compared (CAHs versus non-CAHs). RESULTS: Patients undergoing hepatopancreatic surgery at non-CAHs versus CAHs had a similar comorbidity score (4 versus 5, P = 0.53). After adjusting for patient-level factors and procedure-specific volume, there was no difference in complication rate (adjusted odds ratio (aOR) 0.80, 95% confidence interval (CI) 0.52-1.24). The median cost of hospitalization was roughly $4000 less at CAHs than that at non-CAHs (P < 0.001). However, compared with patients undergoing surgery at non-CAHs, beneficiaries operated at CAHs had more than two times the odds of dying within 30 (aOR 2.45, 95% CI 1.42-4.2) and 90 d (aOR 2.28, 95% CI 1.4-3.71). CONCLUSIONS: Only a small subset of Medicare beneficiaries underwent hepatic or pancreatic resection at a CAH. Despite similar complication rate, Medicare beneficiaries undergoing surgery at a CAH had more than two times the odds of dying within 30 and 90 d after surgery.

Sex-based differences in time to surgical care among pancreatic cancer patients: A national study of Medicare beneficiaries.

INTRODUCTION: The objective of this study was to characterize time from cancer symptoms to diagnosis and time from diagnosis to surgical treatment among patients undergoing pancreatectomy for cancer. METHODS: Medicare beneficiaries who underwent pancreatectomy for cancer between 2013 and 2017 were identified using the 100% Medicare Inpatient Standard Analytic Files. Mixed effects negative binomial regression models were utilized to determine which factors were associated with the number of weeks to diagnosis and pancreatic resection. RESULTS: Among 7647 Medicare beneficiaries, two-thirds (n = 5127, 67%) had symptoms associated with a pancreatic cancer diagnosis before surgery. Median time from the first symptom to diagnosis was 6 weeks (IQR: 1-25) and the median time from diagnosis to surgery was 4 weeks (IQR: 2-15). In risk-adjusted models, female patients had 13% longer waiting times from identification of a related symptom to pancreatic cancer diagnosis (OR = 1.13, 95% CI: 1.05-1.21) and 12% longer waiting times from diagnosis to surgery (OR = 1.12, 95% CI: 1.07-1.18). Older age was associated with 10% longer waiting times from symptom identification to diagnosis (p < .0001). CONCLUSIONS: Female and older patients had longer wait times between symptom presentation and pancreatic cancer diagnosis. Sex-based disparities in cancer care need to be recognized and addressed by policymakers and health care institutions.

Surgical resection of high-grade nonfunctional pancreatic neuroendocrine carcinoma is associated with improved survival.

BACKGROUND AND OBJECTIVES: The role of surgery in the treatment of nonfunctional pancreatic neuroendocrine carcinomas (PNEC) is not well defined. This study investigated the effect of surgical resection on cause-specific survival compared with nonoperative management. METHODS: The Surveillance, Epidemiology, and End Results Program (SEER) database was utilized to identify patients with nonfunctional pancreatic neuroendocrine carcinoma diagnosed between January 1, 2004 and December 31, 2015. Survival was modeled using Kaplan-Meier analysis and multivariable Cox proportional hazards models. RESULTS: Of the 488 patients identified, 137 (29%) underwent surgical resection of the primary site. Patients who underwent surgery had a median CSS of 31 months compared with 5 months in those who did not (p < 0.01). A survival benefit was observed when the cohort was stratified into local, nodal, and metastatic disease. CONCLUSION: Resection of the primary site in the cohort of PNEC patients compiled by SEER is associated with improved survival. Further consideration be placed on primary surgical resection for PNEC while additional studies that can select specifically for high-grade, poorly differentiated carcinomas need to be undertaken.

Optimal management of patients with operable pancreatic head cancer: A Markov decision analysis.

INTRODUCTION: Neoadjuvant therapy (NAT) is an emerging strategy for operable pancreatic ductal adenocarcinoma (PDAC). While NAT increases multimodal therapy completion, it risks functional decline and treatment dropout. We used decision analysis to determine optimal management of localized PDAC and consider risks faced by elderly patients. METHODS: A Markov cohort decision analysis model evaluated treatment options for a 60-year-old patient with resectable PDAC: (1) upfront pancreaticoduodenectomy or (2) NAT. One-way and probabilistic sensitivity analyses were performed. A subanalysis considered the scenario of a 75-year-old patient. RESULTS: For the base case, NAT offered an incremental survival gain of 4.6 months compared with SF (overall survival: 26.3 vs. 21.7 months). In one-way sensitivity analyses, findings were sensitive to recurrence-free survival for NAT patients undergoing adjuvant, probability of completing NAT, and probability of being resectable at exploration after NAT. On probabilistic analysis, NAT was favored in a majority of trials (97%) with a median survival benefit of 5.1 months. In altering the base case for the 75-year-old scenario, NAT had a survival benefit of 3.8 months. CONCLUSIONS: This analysis demonstrates a significant benefit to NAT in patients with localized PDAC. This benefit persists even in the elderly cohort.

Predicting overall survival and resection in patients with locally advanced pancreatic cancer treated with FOLFIRINOX: Development and internal validation of two nomograms.

BACKGROUND AND OBJECTIVES: Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC. METHODS: From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first-line FOLFIRINOX (April 2015-December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated. RESULTS: A total of 252 patients were included, with a median OS of 14 months. Thirty-two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index ≤1, and CA 19.9 < 274 were independent factors predicting a better OS (c-index: 0.61). WHO ps >1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein ≥ 270° were independent factors decreasing the probability of resection (c-index: 0.79). CONCLUSIONS: Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision-making process and counseling of these patients.