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Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression. [Display omitted] Analysis of serum immune markers in a large cohort of pancreatitis allowed the identification of distinct immune markers that could serve as potential biomarkers providing mechanistic insights into pancreatitis progression. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of intraoperative estimated blood loss (EBL) on development of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). Background: Minimizing EBL has been shown to decrease transfusions and provide better perioperative outcomes in PD. EBL is also felt to be influential on CR-POPF development. Methods: This study consists of 5534 PDs from a 17-institution collaborative (2003–2018). EBL was progressively categorized (≤150mL; 151–400mL; 401–1,000 mL; > 1,000 mL). Impact of additive EBL was assessed using 20 3– factor fistula risk score (FRS) scenarios reflective of endogenous CR-POPF risk. Results: CR-POPF developed in 13.6% of patients (N = 753) and median EBL was 400 mL (interquartile range 250-600 mL). CR-POPF and Grade C POPF were associated with elevated EBL (median 350 vs 400 mL, P = 0.002; 372 vs 500 mL, P < 0.001, respectively). Progressive EBL cohorts displayed incremental CR-POPF rates (8.5%, 13.4%, 15.2%, 16.9%; P < 0.001). EBL >400mL was associated with increased CR-POPF occurrence in 13/20 endogenous risk scenarios. Moreover, 8 of 10 scenarios predicated on a soft gland demonstrated increased CR-POPF incidence. Hypothetical projections demonstrate significant reductions in CR-POPF can be obtained with 1–, 2–, and 3-point decreases in FRS points attributed to EBL risk (12.2%, 17.4%, and 20.0%; P < 0.001). This is especially pronounced in high-risk (FRS7–10) patients, who demonstrate up to a 31% reduction (P < 0.001). Surgeons in the lowest-quartile of median EBL demonstrated CR-POPF rates less than half those in the upper-quartile (7.9% vs 18.8%; P < 0.001). Conclusion: EBL independently contributes significant biological risk to CR-POPF. Substantial reductions in CR-POPF occurrence are projected and obtainable by minimizing EBL. Decreased individual surgeon EBL is associated with improvements in CR-POPF. [ABSTRACT FROM AUTHOR]

Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort. This is a cross-sectional analysis of data from PROCEED, a multicenter U.S. cohort study of chronic pancreatitis. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after completion of the last course. Multivariable logistic regression identified predictive factors for receiving PET, and proportional rates model assessed risk factors for repeat PET. Of 681 subjects, 238 (34.9%) received PET. Factors associated with receiving PET included female sex (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.03-1.53), lower education (OR, 1.30; 95% CI, 1.04-1.62), income ≤$50,000 per year (OR, 1.35; 95% CI, 1.07-1.71), and prior acute pancreatitis (OR, 1.74; 95% CI, 1.31-2.32). Of 238 subjects, 103 (43.3%) underwent repeat PET at a median duration of 2 years, with 23.1% receiving 2 courses, 9.7% receiving 3 courses, and 10.4% receiving ≥4 courses. Nearly half of patients with chronic pancreatitis who undergo PET received 1 or more repeat courses within 2 to 3 years. In addition to a prior history of acute pancreatitis, demographic and socioeconomic factors were associated with receiving PET. [Display omitted] [ABSTRACT FROM AUTHOR]

Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF. The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach. A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P <.001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone. In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes. [ABSTRACT FROM AUTHOR]

The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored. In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003–2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with α = 0.05 and β = 0.2. The propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P <.001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P <.001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37–2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46–2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74–5.57; all P <.001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32–2.44; P <.001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34–1.88; P =.156). This study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal. [ABSTRACT FROM AUTHOR]

Pancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood. The fistula risk score was applied to identify high-risk patients (fistula risk score 7–10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003–2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models. Eight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (–49.7%) and career length (–41.2%; both P <.001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35–0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22–0.74). Surgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss. [ABSTRACT FROM AUTHOR]

Abstract Background Although current guidelines recommend multimodal therapy for all patients with pancreatic ductal adenocarcinoma, it is unclear the extent to which clinical stage I patients are accurately staged and how this may affect management. Methods In this retrospective cohort study of 4,404 patients aged 18–79 years with clinical stage 1 (ie, T1N0 or T2N0) pancreatic ductal adenocarcinoma treated with upfront resection in the National Cancer Database (2004–2014), understaging was ascertained by comparing pretreatment clinical stage with pathologic stage. The association between adjuvant treatment and overall risk of death among true stage I and understaged patients was evaluated using multivariable Cox regression. Results Upstaging was identified in 72.6% of patients (62.8% T3/4, 53.9% N1) of whom 69.7% received adjuvant therapy compared with 47.0% with true stage I disease. Overall survival at 5 years among those with true stage I disease was significantly higher than those who had been clinically understaged (42.9% vs 16.6%; log-rank, p < 0.001). For true stage I patients, adjuvant therapy was not associated with risk of death (hazard ratio: 1.07, 95% confidence interval: 0.89–1.29). For understaged patients, adjuvant therapy significantly decreased risk of death (hazard ratio: 0.64, 95% confidence interval: 0.55–0.74). Conclusion The majority of clinical stage I pancreatic ductal adenocarcinoma patients actually have higher-stage disease and benefit from multimodal therapy; however, one third of understaged patients do not receive any adjuvant treatment. Clinicians should discuss all potential treatment strategies with patients (in the context of the acknowledged risks and benefits), including the utilization of neoadjuvant approaches in those presenting with potentially resectable disease. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate a new academic relative-value unit (aRVU) scoring system linked to faculty compensation and analyze its association with overall departmental academic productivity. Summary Background Data: Faculty are often not incentivized or financially compensated for educational and research activities crucial to the academic mission. Methods: We launched an online, self-reporting aRVU system in 2015 to document and incentivize the academic productivity of our faculty. The system captured 65 specific weighted scores in 5 major categories of research, education, innovation, academic service, and peer review activities. The aRVU scores were rank-aggregated annually, and bonuses were distributed to faculty members in 3 tiers: top 10%, top third, and top half. We compared pre-aRVU (academic year 2015) to post-aRVU (academic year 2017) departmental achievement metrics. Results: Since 2015, annual aRVU bonuses totaling $493,900 were awarded to 59 faculty members (58% of eligible department faculty). Implementing aRVUs was associated with significant increases in several key departmental academic achievement metrics: presentations (579 to 862; P = 0.02; 49% increase), publications (390 to 446; P = 0.02; 14%), total research funding ($4.6M to $8.4M; P < 0.001; 83%), NIH funding ($0.6M to $3.4M; P < 0.001; 467%), industry-sponsored clinical trials (8 to 23; P = 0.002; 188%), academic society committee positions (226 to 298; P < 0.001; 32%), and editorial leadership positions (50 to 74; P = 0.01; 48%). Conclusions: Implementing an aRVU system was associated with increases in departmental academic productivity. Although other factors undoubtedly contributed to these increases, an aRVU program may represent an important mechanism for tracking and rewarding academic productivity in surgery departments. [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]

Background Multimodal therapy is recommended for early stage pancreatic cancer, although whether all patients benefit and the optimal timing of chemotherapy remain unclear. Methods Retrospective cohort study of patients aged 18–79 years with stage I-II pancreatic ductal adenocarcinoma in the National Cancer Database (2004–2012). Patients were grouped based on treatment strategy as surgery only, adjuvant, and preoperative. Accuracy of nodal staging and rate of nodal downstaging were ascertained using pretreatment clinical and postresection pathologic nodal status data. Association between overall risk of death and treatment strategy was evaluated with multivariable Cox regression. Results Among 19,031 patients, 31.1% underwent surgery only, 59.6% received adjuvant, and 9.3% preoperative therapy. Based on patients receiving upfront surgery, clinical nodal staging bore sensitivity, specificity, positive predictive value, and negative predictive value of 46.2%, 95.7%, 95.1%, and 49.8%, respectively. Preoperative therapy downstaged 38% of cN1 patients to ypN0; 5-year overall survival for this group was 27.2% vs 12.3% for ypN1 patients ( P < .001). Relative to surgery only, adjuvant (HR 0.75, 95% CI [0.71–0.78]) and preoperative therapy (HR 0.66 [0.60–0.73]) were associated with lower risk of death among patients with pN1, but not pN0 (adjuvant—HR 1.01 [0.94–1.09]; preoperative—HR 1.10 [0.99–1.22]), disease. Conclusion Our data provide strong support for preoperative chemotherapy for patients with node-positive pancreatic cancer, one third of whom may be downstaged. Among those with seemingly node-negative disease, half will be understaged with current clinical staging modalities. These results should be considered when planning treatment for patients with early stage pancreatic cancer. [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]

Introduction: Perioperative transfusion of packed red blood cells (PRBC) has been associated with negative side effects. We hypothesized that a majority of transfusions in our series of patients who underwent pancreaticoduodenectomy (PD) were unnecessary. A retrospective analysis was performed to determine whether transfusions were indicated based on pre-determined criteria, and the impact of perioperative transfusions on postoperative outcomes was assessed. Methods: Our prospectively maintained database was queried for patients who underwent PD between 2004 and 2011. 200 patients were divided into Cohort 1 (no transfusion) and Cohort 2 (transfusion). Rates of various graded 90-day postoperative complications were compared. Categorical values were compared according to the Common Terminology Criteria for Adverse Events. All cases involving intraoperative blood transfusion were reviewed for associated blood loss, intraoperative vital signs, urine output, hemoglobin values, and presence or absence of EKG changes to determine whether the transfusion was indicated based on these criteria. Results: There were 164 patients (82%) in Cohort 1 (no transfusion) and 36 patients (18%) in Cohort 2 (transfused). Both groups had similar demographics. Patients in Cohort 2 had lesser median preoperative values of hemoglobin (12.3 vs 13.1, P = .002), a greater incidence of vein resection (33% vs 16%, P = .021), longer operative times (518 vs 440 minutes, P < .0001), a greater estimated blood loss (850 vs 300 mL, P < .001), and greater intraoperative fluid resuscitation (6,550 vs 5,300 mL, P = .002). Ninety-day mortality was similar between the 2 groups (3% vs 1%, P = .328). Patients in Cohort 2 (transfused) had increased rates of delayed gastric emptying (36% vs 20%, P = .031), wound infection (28% vs 7%, P = .031), pulmonary complications (6% vs 0%, P = .032), and urinary retention (6% vs 0%, P = .032). A greater incidence of any complication of grade II severity (67% vs 35%, P = .0005) or grade III severity (36% vs 17%, P = .010) was also noted in Cohort 2. Of the 33 intraoperative transfusions, 15 (46%) did not meet any of the predetermined criteria: intraoperative hypotension (<90/60 mmHg), tachycardia (>110 beats per minute), low urine output (<10 mL/hour), decreased oxygen saturation (<95%), excessive blood loss (>1,000 mL), EKG changes, and low hemoglobin (<7.0 g/dL). Conclusion: Perioperative transfusions among patients with PD were associated with increased rates of various postoperative complications. A substantive portion (∼46%) of perioperative transfusions in this patient population did not meet predetermined criteria, indicating a potential opportunity for improved blood product use. Further prospective studies are required to determine whether the implementation of these criteria may a positive impact on perioperative outcomes. [Copyright &y& Elsevier]