The Fistula Risk Score Catalog: Toward Precision Medicine for Pancreatic Fistula After Pancreatoduodenectomy.

OBJECTIVE: This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter. BACKGROUND: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes. METHODS: FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003-2019). The FRS was used to derive 80 unique combinations of patient "scenarios." Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches. RESULTS: The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) - the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33). CONCLUSION: Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.

Decoding Grade B Pancreatic Fistula: A Clinical and Economical Analysis and Subclassification Proposal.

OBJECTIVE: The aim of this study was to describe characteristics and management approaches for grade B pancreatic fistula (B-POPF) and investigate whether it segregates into distinct subclasses. BACKGROUND: The 2016 ISGPS refined definition of B-POPF is predicated on various postoperative management approaches, ranging from prolonged drainage to interventional procedures, but the spectrum of clinical severity within this entity is yet undefined. METHODS: Pancreatectomies performed at 2 institutions from 2007 to 2016 were reviewed to identify B-POPFs and their treatment strategies. Subclassification of B-POPFs into 3 classes was modeled after the Fistula Accordion Severity Grading System (B1: prolonged drainage only; B2: pharmacologic management; B3: interventional procedures). Clinical and economic outcomes, unique from the ISGPS definition qualifiers, were analyzed across subclasses. RESULTS: B-POPF developed in 320 of 1949 patients (16.4%), and commonly required antibiotics (70.3%), prolonged drainage (67.8%), and enteral/parenteral nutrition (54.7%). Percutaneous drainage occurred in 79 patients (24.7%), always in combination with other strategies. Management of B-POPFs was widely heterogeneous with a median of 2 approaches/patient (range 1 to 6) and 38 various strategy combinations used. Subclasses B1-3 comprised 19.1%, 52.2%, and 28.8% of B-POPFs, respectively, and were associated with progressively worse clinical and economic outcomes. These results were confirmed by multivariable analysis adjusted for clinical and operative factors. Notably, distribution of the B-POPF subclasses was influenced by institution and type of resection (P < 0.001), while clinical/demographic predictors proved elusive. CONCLUSION: B-POPF is a heterogeneous entity, where 3 distinct subclasses with increasing clinical and economic burden can be identified. This classification framework has potential implications for accurate reporting, comparative research, and performance evaluation.

The Beneficial Effects of Minimizing Blood Loss in Pancreatoduodenectomy.

OBJECTIVE: The aim of this study was to elucidate the impact of intraoperative blood loss on outcomes following pancreatoduodenectomy (PD). BACKGROUND: The negative impact of intraoperative blood loss on outcomes in PD has long been suspected but not well characterized, particularly those factors that may be within surgeons' control. METHODS: From 2001 to 2015, 5323 PDs were performed by 62 surgeons from 17 institutions. Estimated blood loss (EBL) was discretized (0 to 300, 301 to 750, 751 to 1300, and >1300 mL) using optimal scaling methodology. Multivariable regression, adjusted for patient, surgeon, and institutional variables, was used to identify associations between EBL and perioperative outcomes. Factors associated with both increased and decreased EBL were elucidated. The relative impact of surgeon-modifiable contributors was estimated through beta coefficient standardization. RESULTS: The median EBL of the series was 400 mL [interquartile range (IQR) 250 to 600]. Intra-, post-, and perioperative transfusion rates were 15.8%, 24.8%, and 37.2%, respectively. Progressive EBL zones correlated with intra- but not postoperative transfusion in a dose-dependent fashion (P < 0.001), with a key threshold of 750 mL EBL (8.14% vs 40.9%; P < 0.001). Increasing blood loss significantly correlated with poor perioperative outcomes. Factors associated with increased EBL were trans-anastomotic stent placement, neoadjuvant chemotherapy, pancreaticogastrostomy reconstruction, multiorgan or vascular resection, and elevated operative time, of which 38.7% of the relative impact was "potentially modifiable" by the surgeon. Conversely, female sex, small duct, soft gland, minimally invasive approach, pylorus-preservation, biological sealant use, and institutional volume (≥67/year) were associated with decreased EBL, of which 13.6% was potentially under the surgeon's influence. CONCLUSION: Minimizing blood loss contributes to fewer intraoperative transfusions and better perioperative outcomes for PD. Improvements might be achieved by targeting modifiable factors that influence EBL.

Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy: A Multi-institutional Analysis and External Validation.

OBJECTIVE: The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction. BACKGROUND: DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored. METHODS: DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables. RESULTS: In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts. CONCLUSION: A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.

Risk Factors and Mitigation Strategies for Pancreatic Fistula After Distal Pancreatectomy: Analysis of 2026 Resections From the International, Multi-institutional Distal Pancreatectomy Study Group.

OBJECTIVE: To identify a clinical fistula risk score following distal pancreatectomy. BACKGROUND: Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive. METHODS: This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution. RESULTS: CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (<60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P < 0.001). CONCLUSIONS: From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

Characterization and Optimal Management of High-risk Pancreatic Anastomoses During Pancreatoduodenectomy.

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.

Adjuvant chemotherapy versus chemoradiotherapy in the management of patients with surgically resected duodenal adenocarcinoma: A propensity score-matched analysis of a nationwide clinical oncology database.

BACKGROUND: To the authors' knowledge, optimal adjuvant approaches for resected duodenal adenocarcinoma are not well established. Given the significant risk of locoregional disease recurrence, there may be a subset of patients who demonstrate an improvement in overall survival (OS) from the addition of radiotherapy (chemoradiotherapy [CRT]) to an adjuvant chemotherapy regimen. METHODS: Patients with resected, nonmetastatic duodenal adenocarcinoma who received chemotherapy (694 patients) or CRT (550 patients) were identified in the National Cancer Data Base (1998-2012). Cox regression identified covariates associated with OS. The chemotherapy and CRT cohorts were matched (1:1) by propensity scores based on the likelihood of receiving CRT or the survival hazard from Cox modeling. OS was compared using Kaplan-Meier estimates. RESULTS: CRT was more frequently used for patients who underwent positive-margin surgical resection (15.9% vs 9.1%; P<.001). At a median follow-up of 79.2 months (interquartile range, 52.9-114.9 months), the median OS of the propensity score-matched cohort was 46.7 months (interquartile range, 18.9 months to not reached). No survival advantage was observed for patients who were treated with adjuvant CRT compared with those treated with adjuvant chemotherapy (median OS: 48.9 months vs 43.5 months [HR, 1.04; 95% confidence interval, 0.88-1.22 (P = .669)]). CRT was not found to be associated with a significant improvement in the median OS after positive-margin surgical resection (133 patients; 27.6 months vs 18.5 months [P = .210]) or in the presence of T4 classification (461 patients; 30.6 months vs 30.4 months [P = .844]) inadequate lymph node staging (584 patients; 40.5 months vs 43.2 months [P = .707]), lymph node positivity (647 patients; 38.3 months vs 34.1 months [P = .622]), or poorly differentiated histology (429 patients; 46.6 months vs 35.7 months [P = .434]). CONCLUSIONS: The addition of radiation to adjuvant therapy does not appear to significantly improve survival, even in high-risk cases. Cancer 2017;123:967-76. © 2016 American Cancer Society.

Multicenter, Prospective Trial of Selective Drain Management for Pancreatoduodenectomy Using Risk Stratification.

OBJECTIVE: This multicenter study sought to prospectively evaluate a drain management protocol for pancreatoduodenectomy (PD). BACKGROUND: Recent evidence suggests value for both selective drain placement and early drain removal for PD. Both strategies have been associated with reduced rates of clinically relevant pancreatic fistula (CR-POPF)-the most common and morbid complication after PD. METHODS: The protocol was applied to 260 consecutive PDs performed at two institutions over 17 months. Risk for ISGPF CR-POPF was determined intraoperatively using the Fistula Risk Score (FRS); drains were omitted in negligible/low risk patients and drain fluid amylase (DFA) was measured on postoperative day 1 (POD 1) for moderate/high risk patients. Drains were removed early (POD 3) in patients with POD 1 DFA ≤5,000 U/L, whereas patients with POD 1 DFA >5,000 U/L were managed by clinical discretion. Outcomes were compared with a historical cohort (N = 557; 2011-2014). RESULTS: Fistula risk did not differ between cohorts (median FRS: 4 vs 4; P = 0.933). No CR-POPFs developed in the 70 (26.9%) negligible/low risk patients. Overall CR-POPF rates were significantly lower after protocol implementation (11.2 vs 20.6%, P = 0.001). The protocol cohort also demonstrated lower rates of severe complication, any complication, reoperation, and percutaneous drainage (all P < 0.05). These patients also experienced reduced hospital stay (median: 8 days vs 9 days, P = 0.001). There were no differences between cohorts in the frequency of bile or chyle leaks. CONCLUSIONS: Drains can be safely omitted for one-quarter of PDs. Drain amylase analysis identifies which moderate/high risk patients benefit from early drain removal. This data-driven, risk-stratified approach significantly decreases the occurrence of clinically relevant pancreatic fistula.

Incorporation of Procedure-specific Risk Into the ACS-NSQIP Surgical Risk Calculator Improves the Prediction of Morbidity and Mortality After Pancreatoduodenectomy.

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.

Implications of Lymph Node Evaluation in the Management of Resectable Soft Tissue Sarcoma.

BACKGROUND: The rate of lymph node (LN) metastasis is rare in soft tissue sarcoma, but there are histologic subtypes that metastasize via the lymphatics. The prognostic value of LN evaluation in these high-risk histologies is unknown. METHODS: Resected soft-tissue sarcoma patients with clear cell sarcoma, epithelioid sarcoma, rhabdomyosarcoma, or angiosarcoma (n = 2993) were identified in the National Cancer Data Base (2004-2013). Cox regression evaluated the association of omission of LN assessment (NX) and overall survival (OS). Subjects who underwent surgical resection with or without regional LN evaluation were matched (1:1) by propensity scores based on the likelihood of NX or survival hazard on Cox modeling. OS was compared by Kaplan-Meier estimates. RESULTS: A total of 637 (21.3%) underwent LN evaluation and 176 (5.9%) were found to have nodal metastasis. Omission of nodal evaluation was significantly associated with risk of death (reference: N0; N+: hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.11-1.91; NX: OR 1.18, 95% CI 1.00-1.40). After propensity score matching, there was a significant difference in median OS following pathologic identification of nodal disease for epithelioid sarcoma (N0: not reached vs. N+: 55.9 months vs. NX: not reached, p = 0.001) and clear cell sarcoma (N0: not reached vs. N+: 20.0 months vs. NX: 95.0 months, p < 0.001). CONCLUSIONS: These data support more standardized approaches to regional lymph node examination for patients with epithelioid and possibly clear cell sarcoma and provide compelling evidence that nodal evaluation can be considered a quality measure in the delivery of cancer care for certain sarcoma subtypes.

Pancreatic fistula risk for pancreatoduodenectomy: an international survey of surgeon perception.

INTRODUCTION: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a morbid complication following pancreatoduodenectomy (PD). It is unclear how pancreatic surgeons perceive risk for this complication, and the implications thereof. METHODS: A web-based survey was distributed to members of 22 international GI surgical societies. CR-POPF risk factors were categorized as follows: (i) patient factors, (ii) pancreatic gland characteristics, (iii) intraoperative variables, (iv) perioperative mitigation techniques, or (v) institutional features. RESULTS: Surveys were completed by 897 surgeons worldwide. The most commonly cited contributors to CR-POPF risk were gland characteristics (90.7%), while patient and intraoperative factors were selected 71.2 and 69.3% of the time, respectively. Conversely, institutional features (31.7%) and perioperative mitigation techniques (21.3%) were rarely recognized. Eighty percent of surgeons use drain amylase concentration to guide drain removal decision-making; however, only 45.2% of surgeon remove drains early based upon drain amylase values. When evaluating clinical scenarios, surgeons were able to identify both negligible and high risk scenarios but struggled to differentiate between low and moderate CR-POPF risk. CONCLUSION: This international study analyzed how surgeons discern CR-POPF risk for PD. There was considerable variability in surgeons' perceptions of risk, which may have an adverse effect on the clinical use of risk adjustment measures.

Pancreas fistula risk prediction: implications for hospital costs and payments.

BACKGROUND: As payment models evolve, disease-specific risk stratification may impact patient selection and financial outcomes. This study sought to determine whether a validated clinical risk score for post-operative pancreatic fistula (POPF) could predict hospital costs, payments, and profit margins. METHODS: A multi-institutional cohort of 1193 patients undergoing pancreaticoduodenectomy (PD) were matched to an independent hospital where cost, in US$, and payment data existed. An analytic model detailed POPF risk and post-operative sequelae, and their relationship with hospital cost and payment. RESULTS: Per-patient hospital cost for negligible-risk patients was $37,855. Low-, moderate-, and high- risk patients had incrementally higher hospital costs of $38,125 ($270; 0.7% above negligible-risk), $41,128 ($3273; +8.6%), and $41,983 ($3858; +10.9%), respectively. Similarly, hospital payment for negligible-risk patients was $42,685/patient, with incrementally higher payments for low-risk ($43,265; +1.4%), moderate-risk ($45,439; +6.5%) and high-risk ($46,564; +9.1%) patients. The lowest 30-day readmission rates - with highest net profit - were found for negligible/low-risk patients (10.5%/11.1%), respectively, compared with readmission rates of moderate/high-risk patients (15%/15.7%). CONCLUSION: Financial outcomes following PD can be predicted using the FRS. Such prediction may help hospitals and payers plan for resource allocation and payment matched to patient risk, while providing a benchmark for quality improvement initiatives.

The efficacy of adjuvant therapy for pancreatic invasive intraductal papillary mucinous neoplasm (IPMN).

BACKGROUND: The literature investigating pancreatic invasive intraductal papillary mucinous neoplasm (IPMN) has largely come from small institutional studies, preventing adequately powered comparisons of adjuvant therapy versus surgery alone (SA) within specific patient subgroups. METHODS: Patients with resected, stage I through IV, invasive IPMN and conventional pancreatic ductal adenocarcinoma (PDAC) were identified in the National Cancer Data Base (1998-2010). Cox modeling of patients with invasive IPMN was used to compare overall survival (OS) between patients who received adjuvant therapy and those who underwent SA. A second model was used to compare OS between patients with invasive IPMN and those with PDAC. RESULTS: For the 1220 patients with invasive IPMN, the median OS was 28.9 months; the 1-year and 5-year actuarial survival rates were 76% and 17%, respectively; and 47% received adjuvant therapy. Cox modeling associated SA with worse OS (hazard ratio, 1.36; 95% confidence interval, 1.17-1.58; P = .00005) as well as American Joint Committee on Cancer (AJCC) TNM stage III/IV disease, positive lymph node status, positive margins, and poor tumor differentiation (all P ≤ .05). In addition, Cox modeling stratified by the following characteristics demonstrated improved OS with adjuvant therapy: AJCC TNM stage II or III/IV, positive lymph node status, positive margins, and poorly differentiated tumors. There was no survival advantage from adjuvant therapy for patients who had AJCC TNM stage I or lymph node-negative disease. Patients who had invasive IPMN had improved risk-adjusted OS compared with those who had PDAC (hazard ratio, 0.73; 95% confidence interval, 0.68-0.78; P < .00001). CONCLUSIONS: Invasive IPMN appears to be more indolent than conventional PDAC. Adjuvant therapy is associated with improved OS compared with SA in patients with invasive IPMN, especially for those with higher stage disease, positive lymph nodes, positive margins, or poorly differentiated tumors. Conversely, this benefit does not extend to patients with stage I or lymph node-negative disease.

Efficacy of adjuvant chemotherapy for small bowel adenocarcinoma: A propensity score-matched analysis.

BACKGROUND: The role of adjuvant chemotherapy (AC) in the treatment of small bowel adenocarcinoma is poorly defined. Previous analyses have been limited by small sample sizes and have failed to demonstrate a survival advantage. METHODS: Patients with resected small bowel adenocarcinoma (American Joint Committee on Cancer [AJCC] pathologic stage I-III) who were receiving AC (n = 1674) or surgery alone (SA; n = 3072) were identified in the NCDB (1998-2011). Cox regression identified covariates associated with overall survival (OS). AC and SA cohorts were matched (1:1) by propensity scores based on the likelihood of receiving AC or the survival hazard from Cox modeling. OS was compared with Kaplan-Meier estimates. RESULTS: The omission of AC conferred an increased risk of death (hazard ratio, 1.36; 95% confidence interval, 1.24-1.50; P < .001). After propensity score matching, there was a nonsignificant trend toward improved OS with AC in AJCC stage I patients (158.8 vs 110.7 months; P = .226) and AJCC stage II patients (104.0 vs 79.6 months; P = .185), including the subset with a T4 tumor classification (64.0 vs 47.4 months; P = .130) or a positive resection margin (44.4 vs 31.0 months; P = .333). Median OS was superior for patients with AJCC stage III disease who were receiving AC versus SA (42.4 vs 26.1 months; P < .001). CONCLUSIONS: These data support the use of AC for resected stage III small bowel adenocarcinoma. The trend toward improved OS for patients without nodal metastasis, including those who have T4 tumors or have undergone positive-margin resection, may justify the use of AC in select patients with earlier stage disease. Cancer 2016;122:693-701. © 2015 American Cancer Society.

Implications of Lymph Node Staging on Selection of Adjuvant Therapy for Gastric Cancer in the United States: A Propensity Score-matched Analysis.

OBJECTIVE: To compare the efficacy of adjuvant chemoradiotherapy (CRT) and chemotherapy alone (CA) in gastric adenocarcinoma patients undergoing gastrectomy in the United States (US). BACKGROUND: A majority of US gastric adenocarcinoma patients are inadequately staged (<15 nodes examined). Despite this, and limited data comparing adjuvant CRT with CA in US patients, national guidelines endorse CA in selected patients undergoing D2 lymphadenectomy. METHODS: Resected stage IB-III gastric adenocarcinoma patients receiving adjuvant CRT or CA (n = 3008) were identified in the National Cancer Database (1998-2006). Cox regression identified covariates associated with overall survival (OS). CRT and CA cohorts were matched (3:1) by propensity scores based on the likelihood of receiving CA. OS was compared by Kaplan-Meier estimates. RESULTS: Adjuvant CA was associated with an increased risk of death (HR 1.29, P < 0.001) relative to CRT. Inadequate lymph node staging (LNS) and nodal positivity were strong predictors of risk-adjusted mortality (P < 0.001). After propensity score-matching, CRT demonstrated superior median OS compared with CA (36.1 vs 28.9 m; P < 0.0001), regardless of stage. CRT was superior to CA in inadequately staged patients (33.1 m vs 24.5 m; P < 0.001); this benefit was less pronounced with increasing nodal examination. CRT improved OS in node-positive disease (29.8 vs 22.2 m; P < 0.001), regardless of LNS adequacy. In node-negative disease, OS did not differ significantly between CRT and CA cohorts; however, node-negative patients undergoing inadequate LNS benefited from CRT. CONCLUSIONS: CRT is associated with improved stage-stratified OS compared with CA. Lymph node status and adequacy of surgical staging should influence adjuvant therapy selection in the United States.

Risk-adjusted Outcomes of Clinically Relevant Pancreatic Fistula Following Pancreatoduodenectomy: A Model for Performance Evaluation.

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.

Multimodality Therapy Improves Survival in Resected Early Stage Gastric Cancer in the United States.

BACKGROUND: National guidelines endorse adjuvant chemotherapy ± radiotherapy (C ± RT) for early-stage gastric cancer (ESGC). Compliance with these guidelines and the specific impact of adjuvant C ± RT on overall survival (OS) in ESGC have not been extensively explored. METHODS: The National Cancer Data Base was queried for stage IB-II gastric adenocarcinoma patients undergoing gastrectomy (1998-2011). Multivariable modeling identified factors associated with adjuvant C ± RT receipt and compared risk-adjusted OS by treatment type (i.e., adjuvant therapy versus surgery alone). RESULTS: Of 23,461 ESGC patients (1998-2011), 79.4 % and 20.6 % received surgery alone and adjuvant C ± RT (chemoradiotherapy 17.7 %; chemotherapy alone 2.9 %), respectively. Predictors of adjuvant C ± RT receipt included age <67 years, pathologic nodal positivity, and adequate lymph node staging (LNS; ≥15 nodes examined; all p < 0.001). Survival analyses included 15,748 patients (1998-2006); median, 1-, and 5-year survival were 63.5 months, 86.0 %, and 27.0 % respectively. Omission of adjuvant C ± RT conferred an increased hazard of risk-adjusted mortality in the overall cohort, and stage IB and II subgroups (all p ≤ 0.001). The benefit of adjuvant C ± RT was most pronounced in stage II and node-positive patients-regardless of LNS adequacy (all p < 0.001)-and inadequately staged IB patients (p = 0.003). While associated with a trend toward improved OS in node-negative patients overall (p = 0.051), adjuvant C ± RT did not improve OS if surgical LNS was adequate in this subgroup (p = 0.960). CONCLUSIONS: Adoption of adjuvant C ± RT in ESGC remains incomplete nationally. Receipt of adjuvant therapy is associated with improved risk-adjusted survival relative to surgery alone; however, in adequately staged patients without lymph node metastasis, this benefit is less certain.

A prognostic model for resectable soft tissue and cutaneous angiosarcoma.

BACKGROUND: Angiosarcoma is an aggressive tumor rising in incidence from use of therapeutic radiation. Because of its relative rarity, prognostic factors have not been clearly delineated. METHODS: Patients who underwent resection of localized angiosarcoma from 2002 to 2012 were identified using the National Cancer Data Base. Factors associated with poor overall survival (OS) were identified using Cox proportional hazards modeling and internally validated with bootstrap resampling. These were used to construct a risk model to identify low-, intermediate-, or high-risk groups. RESULTS: Median OS among 821 patients undergoing resection was 3.4 years. On multivariable analysis of factors known preoperatively, those associated with worse OS included: age >70 years (HR 2.02, P < 0.0001), black race (HR 1.92, P < 0.0001), head and neck primary (HR 1.44, P = 0.003), grade 3 tumor (HR 1.53, P = 0.013), size 3-7 cm (HR 1.64, P < 0.0001), size >7 cm (HR 2.37, P < 0.0001). After including postoperative variables, positive resection margins were associated with worse OS (microscopic, HR 1.59, P = 0.002; macroscopic, HR 3.38, P = 0.008). Stratification by risk group was superior to AJCC stage in discriminating OS. CONCLUSIONS: In the largest study to date of patients with angiosarcoma, risk factors for poor OS were identified to create a clinically useful risk model that can prognosticate patients with localized disease following surgical resection. J. Surg. Oncol. 2016;114:557-563. © 2016 Wiley Periodicals, Inc.

The influence of fellowship training on the practice of pancreatoduodenectomy.

BACKGROUND: There has been a proliferation of gastrointestinal surgical fellowships; however, little is known regarding their association with surgical volume and management approaches. METHODS: Surveys were distributed to members of GI surgical societies. Responses were evaluated to define relationships between fellowship training and surgical practice with pancreatoduodenectomy (PD). RESULTS: Surveys were completed by 889 surgeons, 84.1% of whom had completed fellowship training. Fellowship completion was associated with a primarily HPB or surgical oncology-focused practice (p < 0.001), and greater median annual PD volume (p = 0.030). Transplant and HPB fellowship-trained respondents were more likely to have high-volume (≥20) annual practice (p = 0.005 and 0.029, respectively). Regarding putative fistula mitigation strategies, HPB-trained surgeons were more likely to use stents, biologic sealants, and autologous tissue patches (p = 0.007, <0.001 and 0.001, respectively). Surgical oncology trainees reported greater autologous patch use (p = 0.003). HPB fellowship-trained surgeons were less likely to routinely use intraperitoneal drainage (p = 0.036) but more likely to utilize early (POD ≤ 3) drain amylase values to guide removal (p < 0.001). Finally, HPB fellowship-trained surgeons were more likely to use the Fistula Risk Score in their practice (29 vs. 21%, p = 0.008). CONCLUSION: Fellowship training correlated with significant differences in surgeon experience, operative approach, and use of available fistula mitigation strategies for PD.

Multimodality Treatment of T4 Gastric Cancer in the United States: Utilization Trends and Impact on Survival.

BACKGROUND: National guidelines advocate use of multimodality therapy (MMT) for treatment of T4 gastric cancer (T4GC). Prior studies demonstrate poor compliance with these guidelines. We sought to assess treatment trends and association between different treatment approaches and overall survival (OS) in a large cohort of U.S. METHODS: Patients diagnosed with clinical T4 gastric adenocarcinoma were selected from the National Cancer Data Base (1998-2011). Temporal trends, risk factors associated with failure to receive treatment, and effect of treatments on OS were assessed. RESULTS: Of 4369 patients with T4GC, only 15 % (n = 652) received MMT. Treatment with MMT increased over time, and was utilized in 25 % of patients after 2006. Older age, African American race, nonprivate insurance, proximal tumor location, and clinical node-negative disease were associated with failure to receive surgery; older age, female sex, poorly differentiated tumor grade, clinical node-negative disease, and prolonged postoperative length of stay were associated with failure to complete MMT in patients who underwent surgical resection. Median OS was longest in patients receiving MMT (19.2 months), and was similarly poor in patients undergoing surgical resection (9.0 months) or nonsurgical therapy (8.3 months; p < 0.001). Median OS was longer in patients receiving neoadjuvant therapy compared to patients receiving adjuvant therapy (27.8 vs. 16.6 months; p = 0.004). CONCLUSIONS: Treatment with neoadjuvant MMT is increasing and is associated with prolonged survival. Surgery alone and chemotherapy with or without radiotherapy without resection are associated with similarly poor outcomes. Appropriate treatment sequencing may facilitate delivery of MMT and improve outcomes in patients with T4GC.