Faculty Bibliography

OBJECTIVE:Although pancreatic ductal adenocarcinoma is considered a rapidly progressive disease, mathematical models estimate that it takes many years for an initiating pancreatic cancer cell to grow into an advanced stage cancer. In order to estimate the time it takes for a pancreatic cancer to progress through different tumor, node, metastasis (TNM) stages, we compared the mean age of patients with pancreatic cancers of different sizes and stages. DESIGN/METHODS:Patient age, tumour size, stage and demographic information were analysed for 13,131 patients with pancreatic ductal adenocarcinoma entered into the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. Multiple linear regression models for age were generated, adjusting for patient ethnicity, gender, tumour location and neoplastic grades. RESULTS:African-American ethnicity and male gender were associated with an earlier age at diagnosis. Patients with stage I cancers (mean age 64.8 years) were on average 1.3 adjusted years younger at diagnosis than those with stage IV cancers (p=0.001). Among patients without distant metastases, those with T1 stage cancers were on average 1.06 and 1.19 adjusted years younger, respectively, than patients with T3 or T4 cancers (p=0.03 for both). Among patients with stage IIB cancers, those with T1/T2 cancers were 0.79 adjusted years younger than those with T3 cancers (p=0.06). There was no significant difference in the mean adjusted age of patients with stage IA versus stage IB cancers. CONCLUSIONS:These results are consistent with the hypothesis that once pancreatic ductal adenocarcinomas become detectable clinically progression from low-stage to advanced-stage disease is rapid.

BACKGROUND & AIMS/OBJECTIVE:The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. METHODS:We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. RESULTS:We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. CONCLUSIONS:We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.

INTRODUCTION/BACKGROUND:The clinico-radiological characteristics and the natural history of postoperative omental infarct (OI) in patients who underwent distal pancreatectomy (DP) and splenectomy have not been defined. MATERIALS AND METHODS/METHODS:Twelve patients who underwent DP over a period of 2 years and were postoperatively diagnosed with OI based on computed tomography (CT) findings were identified. RESULTS:A total of 12 patients were diagnosed with an OI based on their postoperative imaging. Seven (58.3 %) patients had previously undergone laparoscopic DP, one (8.3 %) had undergone a robotic DP, and in one (8.3 %), a laparoscopic DP was converted to an open procedure. The remaining three (25.1 %) were treated with open DP. In five (41.6 %) patients, the diagnosis of OI was made during routine follow-up. One patient underwent surgical resection of OI, and two had drains placed in the mass. Nine patients were managed conservatively. During the study period, on review of CT imaging, the minimum prevalence of postoperative OI after DP was found to be 22.8 %. A review of literature identified nine articles that reported a total of 34 patients who were diagnosed with OI after abdominal surgery. CONCLUSION/CONCLUSIONS:The management of an asymptomatic postoperative OI should be conservative while an early invasive intervention should be performed in patients who are symptomatic or have infected OI.

BACKGROUND:Interest in laparoscopic liver resection (LLR) has grown since the International 'Louisville Statement' regarding laparoscopic liver surgery was published in 2009. However, limited population-based data on LLR utilization patterns and outcomes are available. METHODS:LLR data from the Nationwide Inpatient Sample (NIS, 2000-2012) and the National Surgical Quality Improvement Project (NSQIP, 2005-2012) were compared before and after the Louisville Statement in 2009. RESULTS:In total, 1131 and 642 LLR were identified from NIS and NSQIP, respectively. Three-quarters of patients underwent LLR for a malignant indication (NIS primary malignancy, 29.6% versus metastasis, 45.1%; NSQIP primary malignancy, 35.5% versus metastasis, 46.1%). The annual volume of LLR increased from 2000-2008 versus 2009-2012 (NIS: 63 versus 168, P < 0.001; NSQIP: 52 versus 127; both P = 0.001). The peri-operative mortality associated with LLR was 2.8% in NIS and 2.2% in NSQIP. The morbidity was 38.1% in NIS and 30.7% in NSQIP. Mortality and morbidity did not change over time (both P > 0.050). After 2009, LLR was associated with a shorter length of stay (LOS) (NIS: 5 versus 6 days, P = 0.007). CONCLUSION/CONCLUSIONS:Since the Louisville Statement in 2009, utilization of LLR has increased. LLR is associated with a modest decrease in LOS and appears to be safe with mortality and morbidity similar to open surgery.

BACKGROUND:The purpose of this study was to investigate the prognostic significance of early (30-day) hospital readmission (EHR) on mortality after pancreatectomy. METHODS:Using a prospectively collected institutional database linked with a statewide dataset, we evaluated the association between EHR and overall mortality in all patients undergoing pancreatectomy at our tertiary institution (2005 to 2010). RESULTS:Of 595 pancreatectomy patients, EHR occurred in 21.5%. Overall mortality was 29.4% (median follow-up 22.7 months). Patients with EHR had decreased survival compared with those who were not readmitted (P = .011). On multivariate analysis adjusting for baseline group differences, EHR for gastrointestinal-related complications was a significant independent predictor of mortality (hazard ratio 2.30, P = .001). CONCLUSIONS:In addition to known risk factors, 30-day readmission for gastrointestinal-related complications following pancreatectomy independently predicts increased mortality. Additional studies are necessary to identify surgical, medical, and social factors contributing to EHR, as well as interventions aimed at decreasing postpancreatectomy morbidity and mortality.

Pancreatic resection has become a feasible treatment of pancreatic neoplasms, and with improvements in surgical techniques and perioperative management, mortality associated with pancreatic surgery has decreased considerably. Despite this improvement, a high rate of complications is still associated with these procedures. Among these complications, delayed gastric emptying (DGE) and postoperative pancreatic fistula (POPF) have a substantial impact on patient outcomes and burden our healthcare system. Technical modifications and postoperative approaches have been proposed to reduce rates of both POPF and DGE in patients undergoing pancreatectomy; however, to date, their rates have remained unchanged. In the present study, we summarize the findings of the most significant studies that have investigated these complications. In particular, several studies focused on technical modifications including extent of dissection, stent placement, nature of anastomosis, type of reconstruction, and application of biological or non-biological agents to site of anastomosis. Moreover, postoperatively, drain placement, duration of drain usage, postoperative feeding, and use of pharmacological agents were studied to reduce rates of POPF and DGE. In this review, we summarize the most relevant literature on this fundamental aspect of pancreatic surgery. Despite studies identifying the potential benefit of technical modifications and postoperative approaches, these findings remain controversial and suggest need for further extensive investigation. Most importantly, we recommend that all surgeons performing these procedures base their practice on the most updated and highest available level of evidence.

BACKGROUND:Choledochal cysts (CC) are a cystic dilation of the intra- or extrahepatic biliary tree. They are rare, and are associated with a risk of malignant transformation. Due to the close proximity to the pancreas, Type II CC, in which a diverticular outpouching is connected to the extrahepatic bile duct via a narrow stalk, can be difficult to differentiate from pancreatic cysts. The aim of this study was to determine the role of endoscopic ultrasound (EUS) in the diagnosis of Type II CC. METHODS:A retrospective review of all patients seen in the Multidisciplinary Pancreatic Cyst Clinic at Johns Hopkins Hospital from November 2010 to March 2014 was performed to identify patients classified as having Type II CC on computed tomography (CT) or magnetic resonance imaging (MRI) who also underwent EUS. Patient demographics, clinical presentation, imaging, and follow-up were recorded. RESULTS:Four female patients with median age of 52 years, three of whom were identified as having Type II CC and one as equivocal for CC on MRI, and two as having Type II CC, one equivocal for CC and one as branch-duct intraductal papillary mucinous neoplasm on CT. On EUS, no communication was seen in any cases between the CC and common bile duct. EUS-guided fluid aspiration from each cyst demonstrated clear fluid with undetectable bilirubin and either elevated CEA or amylase confirming the diagnosis of pancreatic cyst. CONCLUSIONS:EUS is a useful tool for the differentiation of equivocal cases of CC. It can show a very small separation as little as 1 mm between two structures, and cyst fluid analysis can be performed and used to further differentiate between biliary cysts and other cystic structures.

BACKGROUND:While sarcopenia is typically defined using total psoas area (TPA), characterizing sarcopenia using only a single axial cross-sectional image may be inadequate. We sought to evaluate total psoas volume (TPV) as a new tool to define sarcopenia and compare patient outcomes relative to TPA and TPV. METHOD/METHODS:Sarcopenia was assessed in 763 patients who underwent pancreatectomy for pancreatic adenocarcinoma between 1996 and 2014. It was defined as the TPA and TPV in the lowest sex-specific quartile. The impact of sarcopenia defined by TPA and TPV on overall morbidity and mortality was assessed using multivariable analysis. RESULT/RESULTS:Median TPA and TPV were both lower in women versus men (both P < 0.001). TPA identified 192 (25.1%) patients as sarcopenic, while TPV identified 152 patients (19.9%). Three hundred sixty-nine (48.4%) patients experienced a postoperative complication. While TPA-sarcopenia was not associated with higher risk of postoperative complications (OR 1.06; P = 0.72), sarcopenia defined by TPV was associated with morbidity (OR 1.79; P = 0.002). On multivariable analysis, TPV-sarcopenia remained independently associated with an increased risk of postoperative complications (OR 1.69; P = 0.006), as well as long-term survival (HR 1.46; P = 0.006). CONCLUSION/CONCLUSIONS:The use of TPV to define sarcopenia was associated with both short- and long-term outcomes following resection of pancreatic cancer. Assessment of the entire volume of the psoas muscle (TPV) may be a better means to define sarcopenia rather than a single axial image.