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Objective: To evaluate the safety and efficacy of neoadjuvant therapy (NAT), followed by surgical resection in patients with pancreatic ductal adenocarcinoma (PDAC) aged ≥75 years. Background: Whether administration of NAT, followed by surgical resection in elderly patients with PDAC is safe and effective is unknown. Methods: The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with nonmetastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older versus younger patients who underwent NAT, followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT, followed by surgical resection versus upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR) were compared. Propensity score matching (PSM) analysis was performed to adjust for potential confounders. Results: In the first analysis, a lower proportion of older patients (n = 40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared with younger patients (n = 214; 65.0% vs 81.4%, P = 0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P = 0.89), as well as surgical resection (57.5% vs 55.6%, P = 0.70). In the second analysis, PSM was conducted to compare older (n = 54) versus younger patients (n = 54) who underwent NAT, followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in OS between older and younger patients (median OS: 16.43 vs 30.83 months, P = 0.002), importantly, there was no significant difference in TTR (median: 7.65 vs 11.83 months, P = 0.215). In the third analysis, older patients who underwent NAT, followed by surgical resection (n = 48) were compared with similar older patients who underwent upfront surgical resection (n = 48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs 11.51 months, P = 0.037), as well as TTR (median TTR: 8.81 vs 7.10 months, P = 0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. Conclusions: This comprehensive three-part study showed that administration of NAT, followed by surgical resection, seems to be safe and effective among patients ≥75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of clinical significance reporting in contemporary comparative effectiveness research (CER). Background: In CER, a statistically significant difference between study groups may or may not be clinically significant. Misinterpreting statistically significant results could lead to inappropriate recommendations that increase health care costs and treatment toxicity. Methods: CER studies from 2022 issues of the Annals of Surgery, Journal of the American Medical Association, Journal of Clinical Oncology, Journal of Surgical Research, and Journal of the American College of Surgeons were systematically reviewed by 2 different investigators. The primary outcome of interest was whether the authors specified what they considered to be a clinically significant difference in the “Methods.” Results: Of 307 reviewed studies, 162 were clinical trials and 145 were observational studies. Authors specified what they considered to be a clinically significant difference in 26 studies (8.5%). Clinical significance was defined using clinically validated standards in 25 studies and subjectively in 1 study. Seven studies (2.3%) recommended a change in clinical decision-making, all with primary outcomes achieving statistical significance. Five (71.4%) of these studies did not have clinical significance defined in their methods. In randomized controlled trials with statistically significant results, sample size was inversely correlated with effect size (r = −0.30, P = 0.038). Conclusions: In contemporary CER, most authors do not specify what they consider to be a clinically significant difference in study outcome. Most studies recommending a change in clinical decision-making did so based on statistical significance alone, and clinical significance was usually defined with clinically validated standards. [ABSTRACT FROM AUTHOR]

BACKGROUND: The authors aimed to assess the safety of an enhanced recovery after surgery (ERAS) and early discharge pathway in a robotic pancreatoduodenectomy (PD) program and compared outcomes with an open PD control cohort to identify the synergistic effects of robotic surgery and an ERAS pathway on lengths of stay (LOS). STUDY DESIGN: Consecutive patients undergoing open or robotic PD from a single surgeon between March 2020 and July 2022 were identified. Logistic regression models were used for adjusted analyses of postoperative outcomes. RESULTS: There were 134 consecutive PD patients, of which 40 (30%) were performed robotically. Pancreatic adenocarcinoma was the most common indication in both open (56%) and robotic (55%, p = 0.51) groups, with a similar proportion of them being borderline resectable or locally advanced tumors (78% vs 82% in robotic group, p = 0.82). The LOS was significantly shorter in the robotic PD group (median, 5 [IQR 4 to 7] days) when compared with the open PD group (median, 6 [IQR 5 to 8] days, p < 0.001). LOS of 4 days or fewer were observed in 40% of the robotic PD group compared with only 3% of patients in the open PD group (p < 0.001). There was no difference in the overall readmission rate (10% vs 12% in the robotic PD group, p = 0.61). On multivariable logistic regression, robotic PD was independently associated with higher odds of LOS of 4 days or fewer (odds ratio 22.4, p = 0.001) when compared with open PD. CONCLUSIONS: An ERAS and early discharge pathway could be safely implemented in a robotic PD program. Patients undergoing robotic PD have significantly shorter length of stay without increased complication or readmission rate compared with open PD, with 40% of patients undergoing robotic PD achieving a LOS of 4 days or fewer. [ABSTRACT FROM AUTHOR]

BACKGROUND: FOLFIRINOX is increasingly used in the management of pancreatic ductal adenocarcinoma (PDAC). However, neoadjuvant therapy is associated with toxicity, possible disease progression, and biopsy-related and biliary complications that may preclude operative exploration. Data on the true attrition rate outside of clinical trials or resected surgical series are lacking. STUDY DESIGN: Patients with nonmetastatic PDAC who initiated FOLFIRINOX from 2015 to 2020 were identified from our institution’s pharmacy records. Multivariable regression and Cox proportional hazard models were used for adjusted analyses of categorical and survival outcomes, respectively. RESULTS: Of 254 patients who initiated first-line neoadjuvant FOLFIRINOX, 199 (78.3%) underwent exploration, and 54 (21.3%) did not complete their chemotherapy cycles due to poor tolerability (46.3%), poor response (31.5%), or disease progression (14.8%), among other causes (7.4%). A total of 109 (42.9%) patients experienced grade 3/4 FOLFIRINOX-related toxicity, of whom 73 (28.7%) and 100 (39.4%) required an emergency department visit or inpatient admission, respectively. Finally, not undergoing surgical exploration was associated with impaired overall survival (hazard ratio 7.0; 95% CI 3.8 to 12.8; p < 0.001). Independent predictors of not undergoing exploration were remote history of chemotherapy receipt (odds ratio [OR] 0.06; p = 0.02), inability to complete FOLFIRINOX cycles (OR 0.2, p = 0.003), increase in ECOG score (OR 0.2, p < 0.001), and being single or divorced (OR 0.3, p = 0.018). CONCLUSIONS: Among 254 patients with nonmetastatic PDAC initiated on FOLFIRINOX, of whom 52% were locally advanced, a total of 199 (78.3%) were explored, 142 (71.4%) underwent successful resection, and 129 (90.8%) were resected with negative margins. Despite 109 (42.9)% of patients experiencing significant toxicity, most patients could be managed through treatment- related complications to complete planned neoadjuvant chemotherapy and undergo planned surgical exploration. [ABSTRACT FROM AUTHOR]

Objective: This study simulates the regionalization of pancreatectomies to assess its impact on spatial access in terms of patient driving times. Background: Although policies to regionalize complex procedures to high-volume centers may improve outcomes, the impact on patient access is unknown. Methods: Patients who underwent pancreatectomies from 2005 to 2014 were identified from California's statewide database. Round-trip driving times between patients' home ZIP code and hospital addresses were calculated via Google Maps. Regionalization was simulated by eliminating hospitals performing <20 pancreatectomies/yr, and reassigning patients to the next closest hospital that satisfied the volume threshold. Sensitivity analyses were performed for New York and Medicare patients to assess for influence of geography and insurance coverage, respectively. Results: Of 13,317 pancreatectomies, 6335 (47.6%) were performed by hospitals with <20 cases/yr. Patients traveled a median of 49.8 minutes [interquartile range (IQR) 30.8-96.2] per round-trip. A volume-restriction policy would increase median round-trip driving time by 24.1 minutes (IQR 4.5-53.5). Population in-hospital mortality rates were estimated to decrease from 6.7% to 2.8% (P < 0.001). Affected patients were more likely to be racial minorities (44.6% vs 36.5% of unaffected group, P < 0.001) and covered by Medicaid or uninsured (16.3% vs 9.8% of unaffected group, P < 0.001). Sensitivity analyses revealed a 17.8 minutes increment for patients in NY (IQR 0.8-47.4), and 27.0 minutes increment for Medicare patients (IQR 6.2-57.1). Conclusions: A policy that limits access to low-volume pancreatectomy hospitals will increase round-trip driving time by 24 minutes, but up to 54 minutes for 25% of patients. Population mortality rates may improve by 1.5%. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that complete, tumor-free resection at the pancreatic neck, achieved either en-bloc or non-en-bloc (ie, revision based on intraoperative frozen section [FS] analysis), is associated with improved survival as compared with incomplete resection (IR) in pancreatic ductal adenocarcinoma. Summary background data: Given the likely systemic nature of pancreatic ductal adenocarcinoma, the oncologic benefit of achieving a histologically complete local resection, particularly through revision of a positive intraoperative FS at the pancreatic neck, remains controversial. Methods: Clinicopathologic and treatment data were reviewed for 986 consecutive patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas who underwent open pancreatectomy as well as intraoperative FS analysis between 1998 and 2012 at Massachusetts General Hospital and between 1998 and 2013 at the University of Verona. Overall survival (OS) and perioperative morbidity and mortality were compared across 3 groups: complete resection achieved en-bloc (CR-EB), complete resection achieved non-en-bloc (CR-NEB), and IR. Results: The CR-EB cohort comprised 749 (76%) patients, CR-NEB 159 patients (16%), and IR 78 patients (8%). Other than a higher incidence of vascular resection among CR-NEB and IR patients, no demographic, pathologic (eg, tumor grade, lymph node positivity, superior mesenteric artery involvement), or treatment factors (eg, neoadjuvant and adjuvant therapy use) differed between the groups. Median OS was significantly higher in patients with CR-EB (28 mo, P = 0.01) and CR-NEB resections (24 mo, P = 0.02) as compared with patients with IR resections (19 mo). After adjusting for clinicopathologic and treatment characteristics, CR-EB and CR-NEB margin status were found to be independent predictors of improved OS (relative to IR, CR-EB hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.49-0.86; CR-NEB HR 0.69, 95% CI 0.50-0.96). There were no intergroup differences in perioperative morbidity and mortality, including rates of pancreatic fistula. Conclusions: For patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas undergoing pancreatectomy, complete tumor extirpation via either en-bloc or non-en-bloc complete resection based on FS analysis is associated with improved OS, without an associated increased perioperative morbidity or mortality. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. Background: The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. Methods: This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. Results: A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25–0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30–0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an “optimal” mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). Conclusions: The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to assess quality of life (QOL) and functionality in a large cohort of patients ≥5-years after pancreaticoduodenectomy (PD). Background: Long-term QOL outcomes after PD for benign or malignant disease are largely undocumented. Methods: We administered the EORTC QLQ-C30 questionnaire to patients who underwent PD for neoplasms from 1998 to 2011 and compared their scores with an age- and sex-matched normal population. Clinical relevance (CR) of differences was scored as small (5-10), moderate (10-20), or large (>20) based on validated interpretation of clinically important differences. Results: Of 305 PD survivors, 245 (80.3%) responded, of whom 157 (64.1%) underwent PD for nonmalignant lesions. Median follow-up was 9.1 years (range 5.1-21.2 yrs). New-onset diabetes developed in 10.6%; 50.4% reported taking pancreatic enzymes; 54.6% reported needing antacids. Compared with the age- and sex-adjusted controls, PD survivors demonstrated higher global QOL (78.7 vs 69.7, CR small, P < 0.001), physical (86.7 vs 77.9, CR small, P < 0.001) and role-functioning scores (86.3 vs 74.1, CR medium, P < 0.001). Using linear regression and adjusting for socioeconomic variables, there were no differences in QOL or functional scores in the benign versus malignant subgroups. Older age at operation was associated with worse physical-functioning (-0.4/yr, P = 0.008). Taking pancrelipase (-6.8, P = 0.035) or antacids (-6.3, P = 0.044) were both associated with lower socialfunctioning scores. Conclusions: Patients who had a PD demonstrated better global QOL, physical- and role-functioning scores at 5-years when compared with ageand sex-matched controls. Approximately half of the patients required pancreatic enzyme replacement, while only 11% developed new-onset diabetes. [ABSTRACT FROM AUTHOR]

Objective: This multicenter study sought to evaluate the accuracy of the American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) surgical risk calculator for predicting outcomes after pancreatoduodenectomy (PD) and to determine whether incorporating other factors improves its predictive capacity. Background: The ACS-NSQIP surgical risk calculator has been proposed as a decision-support tool to predict complication risk after various operations. Although it considers 21 preoperative factors, it does not include procedure-specific variables, which have demonstrated a strong predictive capacity for the most common and morbid complication after PD -- clinically relevant pancreatic fistula (CR-POPF). The validated Fistula Risk Score (FRS) intraoperatively predicts the occurrence of CR-POPF and serious complications after PD. Methods: This study of 1480 PDs involved 47 surgeons at 17 high-volume institutions. Patient complication risk was calculated using both the universal calculator and a procedure-specific model that incorporated the FRS and surgeon/institutional factors. The performance of each model was compared using the c-statistic and Brier score. Results: The FRS was significantly associated with 30-day mortality, 90-day mortality, serious complications, and reoperation (all P < 0.0001). The procedure-specific model outperformed the universal calculator for 30-day mortality (c-statistic: 0.79 vs 0.68; Brier score: 0.020 vs 0.021), 90-day mortality, serious complications, and reoperation. Neither surgeon experience nor institutional volume significantly predicted mortality; however, surgeons with a career PD volume >450 were less likely to have serious complications (P < 0.001) or perform reoperations (P < 0.001). Conclusions: Procedure-specific complication risk influences outcomes after pancreatoduodenectomy; therefore, risk adjustment for performance assessment and comparative research should consider these preoperative and intraoperative factors along with conventional ACS-NSQIP preoperative variables. [ABSTRACT FROM AUTHOR]

Objective: To evaluate surgical performance in pancreatoduodenectomy using clinically relevant postoperative pancreatic fistula (CR-POPF) occurrence as a quality indicator. Background: Accurate assessment of surgeon and institutional performance requires (1) standardized definitions for the outcome of interest and (2) a comprehensive risk-adjustment process to control for differences in patient risk. Methods: This multinational, retrospective study of 4301 pancreatoduodenectomies involved 55 surgeons at 15 institutions. Risk for CR-POPF was assessed using the previously validated Fistula Risk Score, and pancreatic fistulas were stratified by International Study Group criteria. CR-POPF variability was evaluated and hierarchical regression analysis assessed individual surgeon and institutional performance. Results: There was considerable variability in both CR-POPF risk and occurrence. Factors increasing the risk for CR-POPF development included increasing Fistula Risk Score (odds ratio 1.49 per point, P < 0.00001) and octreotide (odds ratio 3.30, P < 0.00001). When adjusting for risk, performance outliers were identified at the surgeon and institutional levels. Of the top 10 surgeons (=15 cases) for nonrisk-adjusted performance, only 6 remained in this high-performing category following risk adjustment. Conclusions: This analysis of pancreatic fistulas following pancreatoduodenectomy demonstrates considerable variability in both the risk and occurrence of CR-POPF among surgeons and institutions. Disparities in patient risk between providers reinforce the need for comprehensive, risk-adjusted modeling when assessing performance based on procedure-specific complications. Furthermore, beyond inherent patient risk factors, surgical decision-making influences fistula outcomes. [ABSTRACT FROM AUTHOR]

With the widespread use and advances in radiographic imaging, Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are identified with increasing frequency. Although many studies have addressed its biology and treatment, true understanding of its natural history continues to elude us. Its malignant potential places careproviders in a clinical dilemma of balancing the morbidity of pancreatectomy against the risk of malignant transformation while under continuous surveillance. Recently, there have been conflicting data published in the literature, generating more uncertainty in the field. In this article, we critically analyze the contrasting consensus guidelines from the International Association of Pancreatology and the American Gastroenterology Association, and address lingering questions and controversies. We also synthesize newly published data in the context of current standard of care, and provide a comprehensive review and recommendations for the clinical diagnosis, treatment, and follow-up strategy in the management of patients with Intraductal Papillary Mucinous Neoplasms. [ABSTRACT FROM AUTHOR]

Background: Early invasive carcinoma may be encountered in association with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The natural history of these early invasive lesions is unknown. Methods: Pancreatic surgical databases from 4 high-volume centers were queried for IPMNs, with invasive components measuring 20mm or less. All cases were reviewed by GI gastrointestinal pathologists, and pathologic features were analyzed to identify predictors of recurrence and survival. Results: A total of 70 small IPMN-associated invasive carcinomas (20-mm invasion) were identified, comprising 25% of resected IPMN-associated carcinomas (n 280). Most of these small invasive cancers were multifocal (66%), less than 10mm in size (73%), and arose in the setting of a main duct IPMN (96%). The most common adenocarcinoma subtypes were tubular (57%) and colloid (29%). Lymph node metastases were present in 19% of cases and 23% were T3 lesions. The overall recurrence rate was 24% (n=17), and the median time to recurrence was 16 months (range: 4-132 months). Median and 5-year survival rates were 99 months and 59%. Recurrence patterns of invasive disease were local in 35%, distant in 47%, and both in 18%. Lymphatic spread and T3 stage were predictive of recurrence (univariate, P=0.006), whereas tubular carcinoma type was the most predictive of poor overall survival (multivariate hazard ratio=3.7, P=0.04). Conclusions: This study represents the largest multi-institutional experience of resected small IPMN-associated carcinoma. Although these malignancies may frequently be cured with resection, recurrence risk is significant. Lymphatic spread, increased T stage, and tubular type carcinoma were associated with the poorest outcome. [ABSTRACT FROM AUTHOR]