Multianalyte Serum Biomarker Panel for Early Detection of Pancreatic Adenocarcinoma.

PURPOSE: We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC). We used machine learning to develop classification algorithms using the relationship between subjects on the basis of their changes across the predictors. Model performance was subsequently evaluated in an independent validation data set from 186 additional subjects. RESULTS: A classification model was trained on 669 subjects (358 healthy, 159 benign, and 152 early-stage PDAC). Model evaluation on a hold-out test set of 168 subjects (103 healthy, 35 benign, and 30 early-stage PDAC) yielded an area under the receiver operating characteristic curve (AUC) of 0.920 for classification of PDAC from non-PDAC (benign and healthy controls) and an AUC of 0.944 for PDAC versus healthy controls. The algorithm was then validated in 146 subsequent cases presenting with pancreatic disease (73 benign pancreatic disease and 73 early- and late-stage PDAC cases) and 40 healthy control subjects. The validation set yielded an AUC of 0.919 for classification of PDAC from non-PDAC and an AUC of 0.925 for PDAC versus healthy controls. CONCLUSION: Individually weak serum biomarkers can be combined into a strong classification algorithm to develop a blood test to identify patients who may benefit from further testing.

Surgical resection for intraductal papillary mucinous neoplasm in the older population.

BACKGROUND: Surgery for intraductal papillary mucinous neoplasm (IPMN) in older adults requires a careful balance of risk and benefit. We sought to analyze patient outcomes in the older individuals after pancreatic resection for IPMN. METHODS: Retrospective analysis of a prospectively maintained database was performed for patients 65 years or older undergoing IPMN resection between January 1, 2012 and December 31, 2017. Statistical analysis was performed based on age and Memorial Sloan Kettering Frailty Index (MSKFI) score. RESULTS: 148 patients underwent resection of an IPMN, including five patients who required two operations for recurrent disease. Median age at surgery was 74 (range, 65-90 years), and 52% were male. Most patients underwent pancreaticoduodenectomy (53%) or distal pancreatectomy/splenectomy (35%). An associated adenocarcinoma was seen on pathology for 56 patients (37%). Median hospital length of stay was 7 days (range, 4-46 days). Grade 3 or higher post-operative complications on the Clavien-Dindo classification scale were seen in 20%. No patient died within 30-days. Patient outcomes were evaluated by age, split at age ≥75 (considered "elderly"), and separately by MSKFI score. No differences in post-operative morbidity or mortality was seen when stratified by age (65 - 74 vs > 75 years) or by MSKFI frailty score. CONCLUSION: Pancreatic resection can be safely performed in selected patients 65 years and older with low morbidity and mortality. More analysis is needed to determine if MSKFI score is a useful predictor of complications in older individuals.

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.

Blood Type as a Predictor of High-Grade Dysplasia and Associated Malignancy in Patients with Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to the development of pancreatic adenocarcinoma. We determined if non-O blood groups are more common in patients with IPMN and if blood group is a risk factor for progression to invasive pancreatic cancer among patients with IPMN. METHODS: The medical records were reviewed of all patients undergoing resection of an IPMN at Johns Hopkins Hospital from June 1997 to August 2016. Potential risk factors of high-grade dysplasia and associated adenocarcinoma were identified through a multivariate logistic regression model. RESULTS: Seven hundred and seventy-seven patients underwent surgical resection of an IPMN in which preoperative blood type was known. Sixty-two percent of IPMN patients had non-O blood groups (vs. 57% in two large US reference cohorts, P = 0.002). The association between non-O blood group was significant for patients with IPMN with low- or intermediate-grade dysplasia (P < 0.001), not for those with high-grade dysplasia (P = 0.68). Low- and intermediate-grade IPMNs were more likely to have non-type O blood compared to those with high-grade IPMN and/or associated invasive adenocarcinoma (P = 0.045). Blood type O was an independent predictor of having high-grade dysplasia without associated adenocarcinoma (P = 0.02), but not having associated invasive cancer (P = 0.72). The main risk factor for progression to invasive cancer after surgical resection was IPMN with high-grade dysplasia (P = 0.002). CONCLUSION: IPMN patients are more likely to have non-O blood groups than controls, but type O blood group carriers had higher odds of having high-grade dysplasia in their IPMN. These results indicate blood group status may have different effects on the risk and progression of IPMNs.

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.

Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and Cystic Pancreatic Lesions.

OBJECTIVES: Circulating epithelial cells (CECs) are identified in the blood of patients with intraductal papillary mucinous neoplasms (IPMNs) despite the absence of malignancy. We assessed the blood of patients undergoing resection for IPMN or other benign pancreatic lesions for CECs. METHODS: Peripheral blood was collected from 26 patients prior to pancreatic resection and filtered by the ISET (Isolation by Size of Epithelial Tumor Cells) method. Circulating epithelial cells were identified with antibodies to cytokeratin and Pdx1 (pancreas and duodenal homeobox protein 1), a pancreas marker. RESULTS: Nineteen patients underwent resection of an IPMN without associated malignancy. Eleven patients (58%) had cytokeratin-positive CECs. Circulating epithelial cells were significantly more likely to be found in patients with IPMNs with high-grade dysplasia (P = 0.04). In addition, 10 of the 11 patients with cytokeratin-positive CECs also had separate populations of cytokeratin-positive, Pdx1-positive CECs, suggesting a pancreatic source. Dual-staining CECs were more frequently found in patients with high-grade dysplasia (P = 0.04). Patients with IPMNs were significantly more likely to have pan-cytokeratin CECs in the blood compared with those without IPMNs (P = 0.01). CONCLUSIONS: Circulating epithelial cells staining with potential pancreas-specific markers have been found in patients with IPMNs, even without malignancy. Circulating epithelial cells may help to differentiate patients with high-grade IPMN from lower grades of dysplasia and other pancreatic cysts.

The use of negative pressure wound therapy to prevent post-operative surgical site infections following pancreaticoduodenectomy.

BACKGROUND: Rates of superficial surgical site infection (SSI) following pancreaticoduodenectomy remain high. Following resection for cancer, complications such as SSI impact adjuvant therapy delivery and portend worse survival. An incisional negative pressure dressing (iVAC) has been demonstrated to reduce SSI in other high-risk cohorts. METHODS: Following a comprehensive effort to identify patients at high risk for SSI, the practice patterns at a single academic center shifted and iVAC use increased. SSI rates were tracked in a prospectively maintained database and are reported. RESULTS: 394 patients underwent pancreaticoduodenectomy over 21 months. 120 patients (30.5%) had an iVAC applied. The overall rate of SSI was 19.8%. On multivariate analysis, increased risk for SSI was associated with neoadjuvant therapy, preoperative biliary interventions and prior abdominal surgery. iVAC use decreased the rate of SSI (OR 0.45, p = 0.015). In the highest-risk patients, SSI rate declined from 50% in patients without an iVAC to 19.1% with iVAC use (p = 0.015). CONCLUSION: The use of an iVAC following pancreaticoduodenectomy is associated with decreased SSI rates. This is particularly true for patients at highest risk as defined by a previously established risk scoring system in patients undergoing open pancreaticoduodenectomy.

Circulating Tumor Cells Expressing Markers of Tumor-Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma.

Purpose: Circulating tumor cells (CTCs) have been identified in the blood of patients with pancreatic adenocarcinoma (PDAC), but little is known about the exact phenotype of these cells. We assessed expression of aldehyde dehydrogenase (ALDH), CD133, and CD44 as markers of CTCs with a tumor-initiating cell (TIC) phenotype in patients with PDAC and the relationship of this expression to patient outcomes.Experimental Design: Peripheral blood from 60 consecutive patients with PDAC undergoing surgical resection was obtained and processed using the Isolation by Size of Epithelial Tumor (ISET) method. Immunofluorescence was used to identify CTCs expressing cytokeratin, CD133, CD44, and ALDH.Results: Forty-seven patients (78%) had epithelial CTCs staining positive for pan-cytokeratin and at least one TIC marker. Forty-six patients (77%) had epithelial CTCs that labeled with antibodies to cytokeratin and ALDH. By separate analysis, 34 (57%) had cytokeratin-positive, CD133-positive, and CD44-positive (triple-positive) CTCs, whereas 40 (67%) had cytokeratin-positive, CD133-positive, CD44-negative CTCs. The remaining 13 patients did not have CTCs, as defined by cytokeratin expression. ALDH-positive CTCs and triple-positive CTCs were significantly associated with worse survival by univariate analysis, even when accounting for other significant prognostic factors (all, P ≤ 0.01). ALDH-positive CTCs, triple-positive CTCs, and dual cytokeratin- and CD133-positive CTCs were independent predictors of tumor recurrence by logistic regression analysis and associated with decreased disease-free survival (all, P ≤ 0.03).Conclusions: CTCs labeling with one or more markers of TICs are found in a majority of patients with PDAC and are independently predictive of decreased disease-free and overall survival. Clin Cancer Res; 23(11); 2681-90. ©2016 AACR.

Primary Tumor Resection Following Favorable Response to Systemic Chemotherapy in Stage IV Pancreatic Adenocarcinoma with Synchronous Metastases: a Bi-institutional Analysis.

INTRODUCTION: Patients with metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone, and the role of surgery in these patients remains unknown. METHODS: A bi-institutional retrospective review was performed for patients with metastatic pancreatic adenocarcinoma who underwent resection of the primary tumor from 2008 to 2013. The primary outcome measured was postoperative overall survival. Secondary outcomes included postoperative disease-free survival and overall survival from the time of diagnosis. RESULTS: Twenty-three patients were identified who met the study criteria with a median follow-up of 30 months. Metastatic sites included the liver (n = 16), the lung (n = 6), and the peritoneum (n = 2). Chemotherapy included FOLFIRINOX (n = 14) and gemcitabine-based regimens (n = 9), with a median of 9 cycles (range 2-31) prior to surgical treatment. Median time from diagnosis to surgery was 9.7 months (IQR 5.8-12.8). Median overall survival (OS) from surgery, disease-free survival, and OS from diagnosis were 18.2 months (95 % CI 11.8-35.5), 8.6 months (95 % CI 5.2-16.8), and 34.1 months (95 % CI 22.5-46.2), respectively. The 1- and 3-year OS from surgery were 72.7 % (95 % CI 49.1-86.7) and 21.5 % (95 % CI 4.3-47.2), respectively. CONCLUSION: Resection of the primary tumor in patients with metastatic pancreatic adenocarcinoma may be considered in highly selected patients with favorable imaging and CA 19-9 response following chemotherapy at high-volume centers providing multidisciplinary care. These patients should be enrolled in prospective clinical trials or institutional registries to better quantify the potential benefits of such a strategy.

A novel, validated risk score to predict surgical site infection after pancreaticoduodenectomy.

BACKGROUND: Although pancreaticoduodenectomy (PD) outcomes have improved, complications including surgical site infection (SSI) remain common. We present a stratification tool to predict risk for SSI after PD. METHODS: Data was retrospectively reviewed on all patients undergoing PD at a tertiary hospital (9/2011-8/2014). Potential SSI risk factors identified by univariate analysis were incorporated into a multivariate logistic regression model. The resulting odds ratios were converted into a point system to create an SSI risk score with internal validation. RESULTS: Six hundred seventy nine patients underwent PD and were chronologically split into derivation (443 patients) and validation (236 patients) groups. There was no difference in demographics or perioperative outcomes between groups. Overall thirty-day SSI was observed in 17.2% (n = 117). Neoadjuvant chemotherapy and/or radiation, intraoperative red blood cell transfusion, operative time greater than 7 h, preoperative bile stent/drain, and vascular resection were associated with SSI in univariate analysis (all p < 0.05). On multivariate analysis, preoperative bile stent/drain and neoadjuvant chemotherapy were independent predictors of SSI, each assigned 1 point (both p < 0.001). Patients with 0, 1, and 2 points, respectively, had 0%, 32%, and 64% predicted risk of SSI (AUC = 0.73, R2 = 0.93). The model performed equivalently in the validation group (AUC = 0.77, R2 = 0.99). CONCLUSION: This novel, validated risk score accurately predicts SSI risk after pancreaticoduodenectomy. Identifying the highest risk patients can help target interventions to reduce SSI.

Long-term outcomes of sandwich ventral hernia repair paired with hybrid vacuum-assisted closure.

BACKGROUND: Sandwich ventral hernia repair (SVHR) may reduce ventral hernia recurrence rates, although with an increased risk of surgical site occurrences (SSOs) and surgical site infections (SSIs). Previously, we found that a modified negative pressure wound therapy (hybrid vacuum-assisted closure [HVAC]) system reduced SSOs and SSIs after ventral hernia repair. We aimed to describe our outcomes after SVHR paired with HVAC closure. METHODS: We conducted a 4-y retrospective review of all complex SVHRs (biologic mesh underlay and synthetic mesh overlay) with HVAC closure performed at our institution by a single surgeon. All patients had fascial defects that could not be reapproximated primarily using anterior component separation. Descriptive statistics were used to report the incidence of postoperative complications and hernia recurrence. RESULTS: A total of 60 patients (59.3 ± 11.4 y, 58.3% male, 75% American Society of Anesthesiologists class ≥3) with complex ventral hernias being underwent sandwich repair with HVAC closure. Major postoperative morbidity (Dindo-Clavien class ≥3) occurred in 14 (23.3%) patients, but incidence of SSO (n = 13, 21.7%) and SSI (n = 4, 6.7%) was low compared with historical reports. Median follow-up time for all patients was 12 mo (interquartile range 5.8-26.5 mo). Hernia recurrence occurred in eight patients (13.3%) after a median time of 20.6 months (interquartile range 16.4- 25.4 months). CONCLUSIONS: Use of a dual layer sandwich repair for complex abdominal wall reconstruction is associated with low rates of hernia recurrence at 1 year postoperatively. The addition of the HVAC closure system may reduce the risk of SSOs and SSIs previously reported with this technique and deserves consideration in future prospective studies assessing optimization of ventral hernia repair approaches.

Aberrant Menin expression is an early event in pancreatic neuroendocrine tumorigenesis.

Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic malignancy and cause significant morbidity and mortality. Neuroendocrine microadenomas have been proposed as a potential precursor lesion for sporadic PanNETs. In this study, we applied telomere-specific fluorescent in situ hybridization (FISH) to a series of well-characterized sporadic neuroendocrine microadenomas and investigated the prevalence of alterations in known PanNET driver genes (MEN1 and ATRX/DAXX) in these same tumors using immunohistochemistry for the encoded proteins. We identified aberrant Menin expression in 14 of 19 (74%) microadenomas, suggesting that alterations in Menin, at least a subset of which was likely due to somatic mutation, are early events in pancreatic neuroendocrine tumorigenesis. In contrast, none of the microadenomas met criteria for the alternative lengthening of telomeres phenotype (ALT) based on telomere FISH, a phenotype that is strongly correlated to ATRX or DAXX mutations. Two of 13 microadenomas (15%) were noted to have very rare abnormal bright telomere foci on FISH, suggestive of early ALT, but these lesions did not show loss of ATRX or DAXX protein expression by immunohistochemistry. Overall, these data suggest that loss of Menin is an early event in pancreatic neuroendocrine tumorigenesis and that ATRX/DAXX loss and ALT are relatively late events.

Is It Time to Expand the Role of Total Pancreatectomy for IPMN?

Intraductal papillary mucinous neoplasms (IPMN) are cystic precursors to pancreatic cancer believed to arise within a widespread neoplastic field defect. The tendency for some patients to present with multifocal disease and/or develop additional lesions over time argues in favor of a field defect and complicates surgical management decisions. Surgery usually consists of partial pancreatic resection, which leaves behind a pancreatic remnant at risk for recurrent disease and progression to cancer. As an alternative, total pancreatectomy (TP) provides the most complete oncologic resection, but postoperative morbidity and quality of life (QoL) issues have generally limited its use to only the highest risk patients. Significant progress has been made in the management of the post-TP apancreatic state and studies now show less morbidity with acceptable QoL comparable to type 1 diabetic and post-pancreaticoduodenectomy patients. These improvements do not yet justify the routine use of TP, but they have opened the door for expansion to additional subsets of non-invasive IPMN. Here, we have identified several groups of patients that we believe would benefit from TP over partial resection based on the most current literature.

Palliative Management of Unresectable Pancreas Cancer.

Pancreatic adenocarcinoma is the fourth leading cause of cancer death in the United States. Surgical resection offers the best opportunity for prolonged survival but is limited to patients with locally resectable disease without distant metastases. Regrettably, most patients are diagnosed at a point in which curative surgery is no longer a treatment option. In these patients, management of symptoms becomes paramount to improve quality of life and potentially increase survival. This article reviews the palliative management of unresectable pancreatic cancer, including potential palliative resection, surgical and endoscopic biliary and gastric decompression, and pain control with celiac plexus block.

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.

Individualized Performance Feedback to Surgical Residents Improves Appropriate Venous Thromboembolism Prophylaxis Prescription and Reduces Potentially Preventable VTE: A Prospective Cohort Study.

OBJECTIVE: To investigate the effect of providing personal clinical effectiveness performance feedback to general surgery residents regarding prescription of appropriate venous thromboembolism (VTE) prophylaxis. BACKGROUND: Residents are frequently charged with prescribing medications for patients, including VTE prophylaxis, but rarely receive individual performance feedback regarding these practice habits. METHODS: This prospective cohort study at the Johns Hopkins Hospital compared outcomes across 3 study periods: (1) baseline, (2) scorecard alone, and (3) scorecard plus coaching. All general surgery residents (n = 49) and surgical patients (n = 2420) for whom residents wrote admission orders during the first 9 months of the 2013-2014 academic year were included. Outcomes included the proportions of patients prescribed appropriate VTE prophylaxis, patients with preventable VTE, and residents prescribing appropriate VTE prophylaxis for every patient, and results from the Accreditation Council for Graduate Medical Education resident survey. RESULTS: At baseline, 89.4% of patients were prescribed appropriate VTE prophylaxis and only 45% of residents prescribed appropriate prophylaxis for every patient. During the scorecard period, appropriate VTE prophylaxis prescription significantly increased to 95.4% (P < 0.001). For the scorecard plus coaching period, significantly more residents prescribed appropriate prophylaxis for every patient (78% vs 45%, P = 0.0017). Preventable VTE was eliminated in both intervention periods (0% vs 0.35%, P = 0.046). After providing feedback, significantly more residents reported receiving data about practice habits on the Accreditation Council for Graduate Medical Education resident survey (87% vs 38%, P < 0.001). CONCLUSIONS: Providing personal clinical effectiveness feedback including data and peer-to-peer coaching improves resident performance, and results in a significant reduction in harm for patients.

Pancreatic cancer surgery: past, present, and future.

The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.

Surgery for oligometastasis of pancreatic cancer.

The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.