Faculty Bibliography

BACKGROUND: Sarcopenia is a surrogate marker of patient frailty that estimates the physiologic reserve of an individual patient. We sought to investigate the impact of sarcopenia on short- and long-term outcomes in patients having undergone surgical intervention for primary hepatic malignancies. METHODS: Ninety-six patients who underwent hepatic resection or liver transplantation for HCC or ICC at the John Hopkins Hospital between 2000 and 2013 met inclusion criteria. Sarcopenia was assessed by the measurement of total psoas major volume (TPV) and total psoas area (TPA). The impact of sarcopenia on perioperative complications and survival was assessed. RESULTS: Mean age was 61.9 years and most patients were men (61.4 %). Mean adjusted TPV was lower in women (23.3 cm(3)/m) versus men (34.9 cm(3)/m) (P < 0.01); 47 patients (48.9 %) had sarcopenia. The incidence of a postoperative complication was 40.4 % among patients with sarcopenia versus 18.4 % among patients who did not have sarcopenia (P = 0.01). Of note, all Clavien grade >/=3 complications (n = 11, 23.4 %) occurred in the sarcopenic group. On multivariable analysis, the presence of sarcopenia was an independent predictive factor of postoperative complications (OR = 3.06). Sarcopenia was not associated with long-term survival (HR = 1.23; P = 0.51). CONCLUSIONS: Sarcopenia, as assessed by TPV, was an independent factor predictive of postoperative complications following surgical intervention for primary hepatic malignancies.

OBJECTIVE:This study was carried out to determine relative survival rates and trends in outcomes in patients who underwent resection of periampullary adenocarcinomas (PACs) with curative intent at a single institution over the last three decades. METHODS:From 1980 to 2011, 2564 pancreaticoduodenectomies (PDs) were performed for PACs. Pathological diagnosis, therapy and survival were retrospectively analysed. RESULTS:The primary sites included the pancreas (66%), ampulla (16%), bile duct (12%) and duodenum (6%). Operation volume increased from 11 per year in the 1980s to 135 per year in the 2000s (P < 0.001). Patients in the 1980s were younger (median age: 64 years; range: 33-90 years) than those in the 1990s (median age: 68 years; range: 31-103 years) and 2000s (median age: 68 years; range: 24-93 years) (P < 0.001). Over time, the frequency of a diagnosis of pancreatic cancer arising from intraductal papillary mucinous neoplasm increased from 2% in the 1980s to 8% in the 2000s (P < 0.001). The rate of 30-day mortality after surgery in the 1980s was 2%, which was similar to rates in the 1990s (1%) and 2000s (1%). Survival in each type of PAC did not change over time. Pancreatic cancer was associated with the worst survival (median survival: 19 months) compared with adenocarcinomas of the ampulla (median survival: 47 months), bile duct (median survival: 23 months) and duodenum (median survival: 54 months) (P < 0.001). CONCLUSIONS:There are significant differences among PACs in longterm survival following PD. Although the numbers of patients undergoing safe resection have increased, overall longterm outcomes have not improved significantly.

OBJECTIVE:To validate the 2010 American Joint Committee on Cancer (AJCC) and 2006 European Neuroendocrine Tumor Society (ENETS) tumor staging systems for pancreatic neuroendocrine tumors (PanNETs) using the largest, single-institution series of surgically resected patients in the literature. BACKGROUND:The natural history and prognosis of PanNETs have been poorly defined because of the rarity and heterogeneity of these neoplasms. Currently, there are 2 main staging systems for PanNETs, which can complicate comparisons of reports in the literature and thereby hinder progress against this disease. METHODS:Univariate and multivariate analyses were conducted on the prognostic factors of survival using 326 sporadic, nonfunctional, surgically resected PanNET patients who were cared for at our institution between 1984 and 2011. Current and proposed models were tested for survival prognostication validity as measured by discrimination (Harrel's c-index, HCI) and calibration. RESULTS:Five-year overall-survival rates for AJCC stages I, II, and IV are 93% (88%-99%), 74% (65%-83%), and 56% (42%-73%), respectively, whereas ENETS stages I, II, III, and IV are 97% (92%-100%), 87% (80%-95%), 73% (63%-84%), and 56% (42%-73%), respectively. Each model has an HCI of 0.68, and they are no different in their ability to predict survival. We developed a simple prognostic tool just using grade, as measured by continuous Ki-67 labeling, sex, and binary age that has an HCI of 0.74. CONCLUSIONS:Both the AJCC and ENETS staging systems are valid and indistinguishable in their survival prognostication. A new, simpler prognostic tool can be used to predict survival and decrease interinstitutional mistakes and uncertainties regarding these neoplasms.

BACKGROUND:We sought to define the utilization and effect of adjuvant external-beam radiotherapy (XRT) on patients having undergone curative-intent resection for gallbladder cancer (GBC). METHODS:Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 5,011 patients with GBC who underwent resection between 1988 and 2009. The impact of XRT on survival was analyzed by the use of propensity-score matching by comparing clinicopathologic factors between patients who received resection only versus resection plus XRT. RESULTS:Median age was 72 years, and most patients were female (73.4%); 66.2% patients had intermediate to poorly differentiated tumors, and 19.1% had lymph node metastasis. The majority (75.0%) had "localized" disease by Surveillance, Epidemiology, and End Results classification. A total of 899 patients (17.9%) received XRT whereas 4,112 patients did not. Factors associated with receipt of XRT were younger age (odds ratio [OR] 5.33), tumor extension beyond the serosa (OR 1.55), intermediate- to poorly differentiated tumors (OR 1.56), and lymph node metastasis (OR 2.59) (all P < .05). Median and 1-year survival were 15 months and 59.0%, respectively. On propensity-matched multivariate model, despite having more advanced tumors, XRT was independently associated with better long-term survival at 1 year (hazard ratio 0.45; P < .001), but not 5 years (hazard ratio 1.06; P = .50). CONCLUSION/CONCLUSIONS:A total of 18% of patients with GBC received XRT after curative intent surgery. The use of adjuvant XRT was associated with a short-term survival benefit, but the benefit dissipated over time.

BACKGROUND:Hepatocellular carcinoma (HCC) primarily affects patients with a cirrhotic liver. Reports on the characteristics of patients with HCC in noncirrhotic liver, as well as predictors of recurrence and survival, are scarce. METHODS:Between 1992 and 2011, 334 patients treated for HCC in noncirrhotic liver were identified from three major hepatobiliary centers. Clinicopathological characteristics were analyzed and independent predictors of recurrence and overall survival were identified using Cox proportional hazards models. RESULTS:Median patient age was 58 years and 77 % were male. Most patients had a solitary (81 %) and poorly or undifferentiated tumor (56 %); median size was 6.5 cm. The majority of patients (96 %) underwent liver resection (microscopically negative margins in 94 %), whereas a few had transarterial chemoembolization or transplantation (4 %). Median recurrence-free survival (RFS) was 2.5 years, and 1- and 5-year RFS was 71.1, and 35 %, respectively. Elevated alkaline phosphatase levels [hazards ratio (HR) = 1.82], poor tumor differentiation (HR = 1.4), macrovascular invasion (HR = 2.18), and the presence of satellite lesions (HR = 1.9), or intrahepatic metastases (HR = 2.59) were independently associated with shorter RFS; in contrast, an intact tumor capsule independently prolonged RFS (HR = 0.46). Median overall survival was 5.9 years, and 1- and 5-year overall survival was 86.9, and 54.5 %, respectively. Tumor size ≥5 cm (HR = 2.27), macrovascular (HR = 2.72) or adjacent organ invasion (HR = 3.34), and satellite lesions (HR = 2.18) were independently associated with shorter overall survival, whereas an intact tumor capsule showed a protective effect (HR = 0.51). CONCLUSIONS:Following resection of HCC in the setting of no cirrhosis, more than one-half of patients were alive after 5 years. However, even among patients with no cirrhosis, recurrence was common. Factors associated with RFS and overall survival included tumor characteristics, such as tumor capsule, satellite lesions, and vascular invasion.

INTRODUCTION/BACKGROUND:Obesity is an epidemic in the U.S.A., with approximately 7% of the population considered morbidly obese (BMI > 40 or >35 with significant comorbidities). DISCUSSION/CONCLUSIONS:Weight loss surgery is recognized as a durable solution to both obesity and obesity-associated morbidities. With an increasing number of pancreatic lesions being discovered on cross-sectional imaging, the pancreatic surgeon is increasingly likely to encounter patients with prior bariatric surgery who are in need of pancreaticoduodenectomy. As such, surgeons need to be familiar with the various bariatric operations, as well as the manner in which to handle prior bariatric reconstructions at the time of pancreatic surgery. Literature on this topic, however, is scarce with only a handful of small case series. CONCLUSION/CONCLUSIONS:We herein review the different operations performed for weight loss, as well as provide an overview of the available operative approaches for reconstruction after pancreaticoduodenectomy in postbariatric surgical patients.

Pancreatic carcinomas with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma and carcinomas with mixed differentiation, are distinct pancreatic neoplasms with poor prognosis. Although recent whole-exome sequencing analyses have defined the somatic mutations that characterize the other major neoplasms of the pancreas, the molecular alterations underlying pancreatic carcinomas with acinar differentiation remain largely unknown. In the current study, we sequenced the exomes of 23 surgically resected pancreatic carcinomas with acinar differentiation. These analyses revealed a relatively large number of genetic alterations at both the individual base pair and chromosomal levels. There was an average of 119 somatic mutations/carcinoma. When three outliers were excluded, there was an average of 64 somatic mutations/tumour (range 12-189). The mean fractional allelic loss (FAL) was 0.27 (range 0-0.89) and heterogeneity at the chromosome level was confirmed in selected cases using fluorescence in situ hybridization (FISH). No gene was mutated in >30% of the cancers. Genes altered in other neoplasms of the pancreas were occasionally targeted in carcinomas with acinar differentiation; SMAD4 was mutated in six tumours (26%), TP53 in three (13%), GNAS in two (9%), RNF43 in one (4%) and MEN1 in one (4%). Somatic mutations were identified in genes in which constitutional alterations are associated with familial pancreatic ductal adenocarcinoma, such as ATM, BRCA2 and PALB2 (one tumour each), as well as in genes altered in extra-pancreatic neoplasms, such as JAK1 in four tumours (17%), BRAF in three (13%), RB1 in three (13%), APC in two (9%), PTEN in two (9%), ARID1A in two (9%), MLL3 in two (9%) and BAP1 in one (4%). Perhaps most importantly, we found that more than one-third of these carcinomas have potentially targetable genetic alterations, including mutations in BRCA2, PALB2, ATM, BAP1, BRAF and JAK1.

INTRODUCTION/BACKGROUND:Patient-specific factors impacting the need for possible perioperative blood transfusions have not been examined in patients undergoing hepatopancreatobiliary (HPB) procedures. We sought to define the overall utilization of blood transfusions for HPB surgery stratified by procedure type, as well as identify patient-level risk factors for transfusion. METHODS:Hepatic and pancreatic resections were selected from the 2005-2011 American College of Surgeons National Surgical Quality Improvement Program's public use files. Transfusion utilization, risk factors, temporal trends, and outcomes were assessed using regression models. Missing data were addressed using multiple imputation. RESULTS:Twenty-six thousand eight hundred twenty-seven patients met the inclusion criteria. There were 16,953 pancreas cases (distal pancreatectomy (31.2%), pancreaticoduodenectomy (65.8%), total pancreatectomy (3.0%)), and 9,874 liver cases (wedge resection (60.0%), hemi-hepatectomy (30.1%), trisegmentectomy (9.9%)). Overall, 25.7% patients received a perioperative transfusion. Transfusion rates varied by operation type (hepatic wedge resection 18.7%, lobectomy 31.3%, trisegmentectomy 39.8%, distal pancreatectomy 19.8%, Whipple 28.7%, total pancreatectomy 43.6%, p < 0.001). On multivariate analysis, several patient-level factors were strongly associated with the risk of transfusion: preoperative hematocrit <36% (risk ratios (RR) 1.99, 95% CI 1.91-2.08), preoperative albumin <3.0 g/dL (RR 1.25, 95% CI 1.19-1.31), American Society of Anesthesiologists (ASA) class IV (RR 1.24, 95% CI 1.16-1.33), and anticoagulation/bleeding disorder (RR 1.26, 95% CI 1.15-1.38) (all p < 0.001). Patients with any one of these high-risk factors had an over twofold increased risk of perioperative transfusion (RR 2.31, 95% CI 2.21-2.40, p < 0.001). CONCLUSION/CONCLUSIONS:There are large differences in the incidence of transfusion among patients undergoing HPB procedures. While the type of HPB procedure was associated with the risk of transfusion, patient-level factors-including preoperative hematocrit and albumin, ASA classification, and history of anticoagulation/bleeding disorder-were as important.

BACKGROUND:The incidence of venous thromboembolism (VTE) among patients undergoing hepatic surgery is poorly defined, leading to varied use of VTE prophylaxis among surgeons. We sought to define the incidence of VTE after liver surgery and identify risk factors associated with VTE. METHODS:Incidence of VTE and associated risk factors within 90 days of hepatic resection between 2006 and 2012 at a major academic center was analyzed. Risk factors for VTE were identified using univariate and multivariate analyses. RESULTS:A total of 599 patients were included in the study cohort; 30 (5.0 %) had a prior history of VTE. The indications for surgery were malignant (90.8 %) and benign lesions (9.2 %). The majority of patients underwent a minor hepatectomy (<3 Couinaud segments; n = 402, 67.1 %) while 195 (32.6 %) patients underwent a major hepatectomy (≥3 Couinaud segments). Three hundred seven (51.3 %) patients were started on VTE chemoprophylaxis preoperatively with 407 (67.8 %) patients receiving VTE chemoprophylaxis within 24 h of surgery. Twenty-eight (4.7 %) patients developed VTE; 20 (3.3 %) had deep venous thrombosis (DVT), 11 (1.8 %) had pulmonary embolism (PE), and three (0.5 %) developed both DVT and PE. Among the VTE patients, 23 (82.1 %) had received VTE chemoprophylaxis. On multivariate analyses, history of VTE (odds ratio [OR] 4.51, 95 % confidence interval [CI] 1.81-17.22, P = 0.03), prolonged operative time (OR 1.17 per additional hour, 95 % CI 1.04-1.32, P = 0.009), and increased length of stay (LOS) (OR 1.07, 95 % CI 1.02-1.12, P = 0.01) were independent risk factors for VTE. CONCLUSION/CONCLUSIONS:VTE within 90 days of hepatic resection is common, occurring in nearly one in 20 patients. Most VTE events occurred among patients who received current best practice prophylaxis for VTE. More aggressive strategies to identify and reduce the risk of VTE in patients at highest risk of VTE, including those with a history of VTE, extended operative time, and prolonged LOS, are warranted.

BACKGROUND:Left ventricular assist devices (LVADs) have become common as a bridge to heart transplant as well as destination therapy. Acute care surgical (ACS) problems in this population are prevalent but remain ill-defined. Therefore, we reviewed our experience with ACS interventions in LVAD patients. METHODS:A total of 173 patients who received HeartMate(®) XVE or HeartMate(®) II (HMII) LVADs between December 2001 and March 2010 were studied. Patient demographics, presentation of ACS problem, operative intervention, co-morbidities, transplantation, complications, and survival were analyzed. RESULTS:A total of 47 (27 %) patients underwent 67 ACS procedures at a median of 38 days after device implant (interquartile range 15-110), with a peri-operative mortality rate of 5 % (N = 3). Demographics, device type, and acuity were comparable between the ACS and non-ACS groups. A total of 21 ACS procedures were performed emergently, eight were urgent, and 38 were elective. Of 29 urgent and emergent procedures, 28 were for abdominal pathology. In eight patients, the cause of the ACS problem was related to LVADs or anticoagulation. Cumulative survival estimates revealed no survival differences if patients underwent ACS procedures (p = 0.17). Among HMII patients, transplantation rates were unaffected by an ACS intervention (p = 0.2). CONCLUSIONS:ACS problems occur frequently in LVAD patients and are not associated with adverse outcomes in HMII patients. The acute care surgeon is an integral member of a comprehensive approach to effective LVAD management.