Vicente Valero

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.

Management of perihilar cholangiocarcinoma in the era of multimodal therapy

Perihilar cholangiocarcinoma (CCA) is the second most common primary malignant tumor of the liver. In the USA, there are approximately 3000 cases of CCA diagnosed annually, with approximately 50–70% of these tumors arising at the hilar plate of the biliary tree. Risk factors include advanced age, male gender, primary sclerosing cholangitis, choledochal cysts, cholelithiasis, parasitic infection, inflammatory bowel disease, cirrhosis and chronic pancreatitis. Patients typically present with jaundice, abdominal pain, pruritus and weight loss. The mainstays of treatment include surgery, chemotherapy, radiation therapy and photodynamic therapy. Specific preoperative interventions for patients with perihilar CCA include endoscopic retrograde cholangiopancreatography, percutanteous transhepatic cholangiography and portal vein embolization. Surgical resection offers the only chance for curative therapy in perihilar CCA. R0 resection is of utmost importance and has been linked to improved survival. Major hepatic resection is needed to achieve both longitudinal and radial margins negative for tumor. Fractionated stereotactic body radiotherapy has shown promising results in CCA. Perihilar CCA typically presents with advanced disease, and many patients receive systemic therapy; however, the response to current regimens is limited. Orthotopic liver transplantation offers complete resection of locally advanced tumors in select patient groups.

Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma

Objective: We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC). Background: PDAC is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification. Methods: Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45. Results: Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P < 0.01), but not mesenchymal-like CTCs (P = 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P < 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P = 0.02). Conclusions: CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers.

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 Programs (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.

Tracking early readmission after pancreatectomy to index and nonindex institutions: a more accurate assessment of readmission.

IMPORTANCE Readmission after pancreatectomy is common, but few data compare patterns of readmission to index and nonindex hospitals. OBJECTIVES To evaluate the rate of readmission to index and nonindex institutions following pancreatectomy at a tertiary high-volume institution and to identify patient-level factors predictive of those readmissions. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of a prospectively collected institutional database linked to statewide data of patients who underwent pancreatectomy at a tertiary care referral center between January 1, 2005, and December 2, 2010. EXPOSURE Pancreatectomy. MAIN OUTCOMES AND MEASURES The primary outcome was unplanned 30-day readmission to index or nonindex hospitals. Risk factors and reasons for readmission were measured and compared by site using univariable and multivariable analyses. RESULTS Among all 623 patients who underwent pancreatectomy during the study period, 134 (21.5%) were readmitted to our institution (105 [78.4%]) or to an outside institution (29 [21.6%]). Fifty-six patients (41.8%) were readmitted because of a gastrointestinal or nutritional problem related to surgery and 42 patients (31.3%) because of a postoperative infection. On multivariable analysis, factors independently associated with readmission included age 65 years or older (odds ratio [OR], 1.80; 95% CI, 1.19-2.71), preexisting liver disease (OR, 2.28; 95% CI, 1.23-4.24), distal pancreatectomy (OR, 1.77; 95% CI, 1.11-2.84), and postoperative drain placement (OR, 2.81; 95% CI, 1.00-7.14). CONCLUSIONS AND RELEVANCE In total, 21.5% of patients required early readmission after pancreatectomy. Even in the setting of a tertiary care referral center, 21.6% of these readmissions were to nonindex institutions. Specific patient-level factors were associated with an increased risk of readmission.

Reliable detection of somatic mutations in fine needle aspirates of pancreatic cancer with next-generation sequencing: Implications for surgical management

OBJECTIVE To determine the feasibility of genotyping pancreatic tumors via fine needle aspirates (FNAs). BACKGROUND FNA is a common method of diagnosis for pancreatic cancer, yet it has traditionally been considered inadequate for molecular studies due to the limited quantity of DNA derived from FNA specimens and tumor heterogeneity. METHODS In vitro mixing studies were performed to deduce the minimum cellularity needed for genetic analysis. DNA from both simulated FNAs and clinical FNAs was sequenced. Mutational concordance was determined between simulated FNAs and that of the resected specimen. RESULTS Limiting dilution studies indicated that mutations present at allele frequencies as low as 0.12% are detectable. Comparison of simulated FNAs and matched tumor tissue exhibited a concordance frequency of 100% for all driver genes present. In FNAs obtained from 17 patients with unresectable disease, we identified at least 1 driver gene mutation in all patients including actionable somatic mutations in ATM and MTOR. The constellation of mutations identified in these patients was different than that reported for resectable pancreatic cancers, implying a biologic basis for presentation with locally advanced pancreatic cancer. CONCLUSIONS FNA sequencing is feasible and subsets of patients may harbor actionable mutations that could potentially impact therapy. Moreover, preoperative FNA sequencing has the potential to influence the timing of surgery relative to systemic therapy. FNA sequencing opens the door to clinical trials in which patients undergo neoadjuvant or a surgery-first approach based on their tumor genetics with the goal of utilizing cancer genomics in the clinical management of pancreatic cancer.

Association Between Prolonged Graft Ischemia and Primary Graft Failure or Survival Following Lung Transplantation

IMPORTANCE The effect of prolonged graft ischemia (≥6 hours) on outcomes following lung transplantation is controversial. OBJECTIVE To evaluate the effect of prolonged total graft ischemia times on long-term survival rates and the development of primary graft failure (PGF) following lung transplantation. DESIGN, SETTING, AND PARTICIPANTS In this retrospective study, the United Network for Organ Sharing database was queried for adult patients who underwent lung transplantation from May 1, 2005, through December 31, 2011. Primary stratification by the presence of prolonged graft ischemia was performed. Kaplan-Meier estimates at 1 and 5 years were used to compare survival in the 2 cohorts. A multivariable Cox proportional hazards regression model was constructed to identify predictors of 1- and 5-year mortality. A risk-adjusted predictive model for the development of PGF was formulated in a similar fashion. MAIN OUTCOMES AND MEASURES The primary outcome of interest was 1- and 5-year survival. Secondary outcomes included PGF and other postoperative events, such as renal failure, biopsy-proven rejection, and stroke. RESULTS Of the 10,225 patients who underwent lung transplantation, 3127 (30.6%) had allografts exposed to prolonged ischemia. There was no difference in survival at 1 (83.6% [95% CI, 82.3%-84.9%] vs 84.1% [95% CI, 83.3%-85.0%]; P = .41) or 5 (52.5% [95% CI, 51.0%-54.0%] vs 53.5% [95% CI, 51.3%-55.6%]; P = .82) years between patients who received grafts that were or were not exposed to ischemia that lasted 6 hours or more, respectively. Prolonged graft ischemia did not independently predict 1- or 5-year mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P = .37). Furthermore, prolonged ischemia did not independently predict 1-year (hazard ratio, 1.09; 95% CI, 0.97-1.22; P =.15) or 5-year (hazard ratio, 1.05; 95% CI, 0.98-1.14; P =.18) mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P =.37). CONCLUSIONS AND RELEVANCE No association was found between prolonged total graft ischemia times and primary graft failure or survival following lung transplantation. Given the scarcity of organs and the paucity of suitable recipients, prolonged ischemia time should not preclude transplantation. It is, therefore, reasonable to consider extending the accepted period of ischemia to more than 6 hours in certain patient populations to improve organ use.

A Novel Risk Scoring System Reliably Predicts Readmission after Pancreatectomy

BACKGROUND Postoperative readmissions have been proposed by Medicare as a quality metric and can impact provider reimbursement. Because readmission after pancreatectomy is common, we sought to identify factors associated with readmission to establish a predictive risk scoring system. STUDY DESIGN A retrospective analysis of 2,360 pancreatectomies performed at 9 high-volume pancreatic centers between 2005 and 2011 was performed. Forty-five factors strongly associated with readmission were identified. To derive and validate a risk scoring system, the population was randomly divided into 2 cohorts in a 4:1 fashion. A multivariable logistic regression model was constructed and scores were assigned based on the relative odds ratio (OR) of each independent predictor. A composite Readmission after Pancreatectomy (RAP) score was generated and then stratified to create risk groups. RESULTS Overall, 464 (19.7%) patients were readmitted within 90 days. Eight pre- and postoperative factors, including earlier MI (OR = 2.03), American Society of Anesthesiologists class ≥ 3 (OR = 1.34), dementia (OR = 6.22), hemorrhage (OR = 1.81), delayed gastric emptying (OR = 1.78), surgical site infection (OR = 3.31), sepsis (OR = 3.10), and short length of stay (OR = 1.51) were independently predictive of readmission. The 32-point RAP score generated from the derivation cohort was highly predictive of readmission in the validation cohort (area under the receiver operating curve = 0.72). The low-risk (0 to 3), intermediate-risk (4 to 7), and high-risk (>7) groups correlated with 11.7%, 17.5%, and 45.4% observed readmission rates, respectively (p < 0.001). CONCLUSIONS The RAP score is a novel and clinically useful risk scoring system for readmission after pancreatectomy. Identification of patients with increased risk of readmission using the RAP score will allow efficient resource allocation aimed to attenuate readmission rates. It also has potential to serve as a new metric for comparative research and quality assessment.

MELD-XI Score Predicts Early Mortality in Patients After Heart Transplantation

BACKGROUND The aim of this study was to determine the utility of the Model for End-Stage Liver Disease Excluding INR (MELD-XI) in predicting early outcomes (30 days and 1 year) and late outcomes (5 years) in patients after orthotopic heart transplantation (OHT). METHODS The United Network for Organ Sharing database was queried for all adult patients (aged ≥ 18 years) undergoing OHT from 2000 to 2012. A MELD-XI was calculated and the population stratified into score quartiles. Early and late survivals were compared among the MELD-XI cohorts. Multivariable Cox proportional hazards models were constructed to determine the capacity of MELD-XI (when modeled both as a categoric and a continuous variable) to predict 30-day, 1-year, and 5-year mortality. Conditional models were also designed to determine the effect of early mortality on long-term survival. RESULTS A total of 22,597 patients were included for analysis. The MELD-XI cutoff scores were established as follows: low (≤ 10.5), low-intermediate (10.6 to 12.6), intermediate-high (12.7 to 16.4), and high (>16.4). The high MELD-XI cohort experienced statistically worse 30-day, 1-year, and 5-year unconditional survivals when compared with patients with low scores (p < 0.001). Similarly, a high MELD-XI score was also predictive of early and late mortality (p < 0.001) after risk adjustment. There was, however, no difference in 5-year survival between the high score and low score cohorts after accounting for 1-year deaths. Subanalysis of patients bridged to transplant with a continuous-flow left ventricular assist device demonstrated similar findings. CONCLUSIONS This is the first known study to examine the relationship between a high MELD-XI score and outcomes in patients after OHT. Patients with hepatic or renal dysfunction before OHT should be closely monitored and aggressively optimized as early mortality appears to drive long-term outcomes.

Southern surgical association articleA Novel Risk Scoring System Reliably Predicts Readmission after Pancreatectomy

BACKGROUND Postoperative readmissions have been proposed by Medicare as a quality metric and can impact provider reimbursement. Because readmission after pancreatectomy is common, we sought to identify factors associated with readmission to establish a predictive risk scoring system. STUDY DESIGN A retrospective analysis of 2,360 pancreatectomies performed at 9 high-volume pancreatic centers between 2005 and 2011 was performed. Forty-five factors strongly associated with readmission were identified. To derive and validate a risk scoring system, the population was randomly divided into 2 cohorts in a 4:1 fashion. A multivariable logistic regression model was constructed and scores were assigned based on the relative odds ratio (OR) of each independent predictor. A composite Readmission after Pancreatectomy (RAP) score was generated and then stratified to create risk groups. RESULTS Overall, 464 (19.7%) patients were readmitted within 90 days. Eight pre- and postoperative factors, including earlier MI (OR = 2.03), American Society of Anesthesiologists class ≥ 3 (OR = 1.34), dementia (OR = 6.22), hemorrhage (OR = 1.81), delayed gastric emptying (OR = 1.78), surgical site infection (OR = 3.31), sepsis (OR = 3.10), and short length of stay (OR = 1.51) were independently predictive of readmission. The 32-point RAP score generated from the derivation cohort was highly predictive of readmission in the validation cohort (area under the receiver operating curve = 0.72). The low-risk (0 to 3), intermediate-risk (4 to 7), and high-risk (>7) groups correlated with 11.7%, 17.5%, and 45.4% observed readmission rates, respectively (p < 0.001). CONCLUSIONS The RAP score is a novel and clinically useful risk scoring system for readmission after pancreatectomy. Identification of patients with increased risk of readmission using the RAP score will allow efficient resource allocation aimed to attenuate readmission rates. It also has potential to serve as a new metric for comparative research and quality assessment.