Faculty Bibliography

BACKGROUND:The role of EUS for detection of pancreatic neuroendocrine tumors (PNETs) is not clearly defined in institutions that use multidetector CT for pancreatic imaging. OBJECTIVE:The aims of this study were to (1) compare the detection rates of EUS and CT by type and size of PNET and calculate the incremental benefit of EUS over CT, (2) evaluate the CT detection rate for PNETs adjusted for improved CT technology over time, and (3) determine the factors associated with CT-negative PNETs. DESIGN/METHODS:Retrospective single-center cohort study. SETTING/METHODS:Johns Hopkins Hospital. PATIENTS/METHODS:Patients with pathologically proven PNETs with preoperative CT. Incidentally found PNETs (resection specimens) and those without Johns Hopkins Hospital CT imaging were excluded. MAIN OUTCOME MEASUREMENT/METHODS:Detection rates of CT and EUS were compared by using pathology as the reference standard. RESULTS:In 217 patients (with 231 PNETs) studied, CT detected 84% of tumors (54.3% of insulinomas). The sensitivity of CT for the detection of PNETs significantly increased with improvement in CT technology (P = .02; χ(2) for trend). CT was more likely to miss lesions <2 cm (P = .005) and insulinomas (P < .0001). In 56 patients who had both CT and EUS, the sensitivity of EUS was greater than CT (91.7% vs 63.3%; P = .0002), particularly for insulinomas (84.2% vs 31.6%; P = .001). EUS detected 20 of 22 CT-negative tumors (91%). LIMITATIONS/CONCLUSIONS:Retrospective nonrandomized design and referral bias. CONCLUSIONS:The detection rate of CT has significantly improved over time. CT-negative tumors are small and more likely to be insulinomas. A sequential approach of CT followed by EUS can detect most PNETs. EUS is a more sensitive initial test for the detection of suspected insulinomas.

PURPOSE/OBJECTIVE:The choice between liver transplantation (LT), liver resection (LR), and radiofrequency ablation (RFA) as initial therapy for early hepatocellular carcinoma (HCC) is controversial, yet little is known about how surgeons choose therapy for individual patients. We sought to quantify the impact of both clinical factors and surgeon specialty on surgical decision making in early HCC by using conjoint analysis. METHODS:Surgeons with an interest in liver surgery were invited to complete a Web-based survey including 10 case scenarios. Choice of therapy was then analyzed by using regression models that included both clinical factors and surgeon specialty (non-LT v LT). RESULTS:When assessing early HCC occurrences, non-LT surgeons (50% LR; 41% LT; 9% RFA) made significantly different recommendations compared with LT surgeons (63% LT; 31% LR; 6% RFA; P < .001). Clinical factors, including tumor number and size, type of resection required, and platelet count, had significant effects on the choice between LR, LT, and RFA. After adjusting for clinical factors, non-LT surgeons remained more likely than LT surgeons to choose LR compared with LT (relative risk ratio [RRR], 2.67). When the weight of each clinical factor was allowed to vary by surgeon specialty, the residual independent effect of surgeon specialty on the decision between LR and LT was negligible (RRR, 0.93). CONCLUSION/CONCLUSIONS:The impact of surgeon specialty on choice of therapy for early HCC is stronger than that of some clinical factors. However, the influence of surgeon specialty does not merely reflect an across-the-board preference for one therapy over another. Rather, certain clinical factors are weighed differently by surgeons in different specialties.

Solid-pseudopapillary neoplasms of the pancreas are uncommon and usually occur in young women. They are generally large, encapsulated masses with mixture of solid, cystic, and hemorrhagic components. Some cases have atypical features; for example, they can form a small predominantly solid mass and produce dilatation of the main pancreatic duct. In this article we discuss and illustrate the spectrum of the appearances of this distinctive neoplasm on multidetector CT.

Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1, which encodes menin, a component of a histone methyltransferase complex, and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX (α thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Following resection of pancreatic adenocarcinoma, tumor size has been considered a key prognostic feature; however, this remains controversial. We sought to examine the association of size with outcomes following resection of pancreatic adenocarcinoma. METHODS:Between 1970 and 2010, 1,697 patients with pancreatic adenocarcinoma at the Johns Hopkins Hospital underwent curative intent pancreaticoduodenectomy. Prognostic factors were identified by univariate and multivariate analyses. RESULTS:Of 1,697 patients, tumor size was ≤ 2 cm in 418 (24.6%) patients, 2-5 cm in 1,070 (63.1%) patients, and ≥ 5 cm in 209 (12.3%) patients. On univariate analyses, 5-year survival was inversely proportional to tumor size (≤ 2 cm: 28.8% vs. 2-5 cm: 19.4% vs. ≥ 5 cm: 14.2%; P < 0.001). Size correlated with the risk of other adverse factors, with larger tumors being more likely to be associated with nodal disease and poor differentiation (both P < 0.05). On multivariate analysis, the 2 cm cut-off was not associated with survival, while nodal disease (HR = 1.59; P = 0.006) and poor differentiation (HR = 1.59; P = 0.04) remained predictive of outcome, regardless of size. CONCLUSION/CONCLUSIONS:The cut-off value of 2 cm is not independently associated with outcome, however, tumor size was strongly associated with the risk of other adverse prognostic factors. The effect of size on prognosis was largely attributable to these other biologic factors rather than tumor size itself.

BACKGROUND:The management of patients with liver metastasis from a gynecologic carcinoma remains controversial, as there is currently little data available. We sought to determine the safety and efficacy of liver-directed surgery for hepatic metastasis from gynecologic primaries. METHODS:Between 1990 and 2010, 87 patients with biopsy-proven liver metastasis from a gynecologic carcinoma were identified from an institutional hepatobiliary database. Fifty-two (60%) patients who underwent hepatic surgery for their liver disease and 35 (40%) patients who underwent biopsy only were matched for age, primary tumor characteristics, and hepatic tumor burden. Clinicopathologic, operative, and outcome data were collected and analyzed. RESULTS:Of the 87 patients, 30 (34%) presented with synchronous metastasis. The majority of patients had multiple hepatic tumors (63%), with a median size of the largest lesion being 2.5 cm. Of those patients who underwent liver surgery (n=52), most underwent a minor hepatic resection (n=44; 85%), while 29 (56%) patients underwent concurrent lymphadenectomy and 45 (87%) patients underwent simultaneous peritoneal debulking. Postoperative morbidity and mortality were 37% and 0%, respectively. Median survival from time of diagnosis was 53 months for patients who underwent liver-directed surgery compared with 21 months for patients who underwent biopsy alone (n=35) (p=0.01). Among those patients who underwent liver-directed surgery, 5-year survival following hepatic resection was 41%. CONCLUSIONS:Hepatic surgery for liver metastasis from gynecologic cancer can be performed safely. Liver surgery may be associated with prolonged survival in a subset of patients with hepatic metastasis from gynecologic primaries and therefore should be considered in carefully selected patients.

OBJECTIVES/OBJECTIVE:The majority of pancreatic serous cystic neoplasms (SCNs) are benign. However, these neoplasms can cause symptoms and rarely can be aggressive. Identification of factors associated with symptomatic or aggressive SCNs may aid management decisions. The aim of this study was to identify variables that predict aggressive SCNs. METHODS:Prospective pathology database was queried for SCNs that were surgically resected at Johns Hopkins Hospital. Tumors were considered aggressive if they invaded surrounding structures and/or vessels or if they metastasized to lymph nodes or distant organs. The associations of gender, tumor size, and tumor location, with the presence or absence of symptoms and tumor behavior were examined using Fisher's exact test, logistic regression, and multivariate analyses. RESULTS:A total of 257 patients with SCNs underwent surgical resection. Mean tumor diameter was 4.9 cm. Tumor location in the head of pancreas (HOP) was associated with symptoms (odds ratio (OR) 1.87, 95% confidence interval (CI) 1.1-3.3). Computed tomography (CT) predicted the diagnosis of SCN in approximately a quarter of patients. Thirteen tumors (mean 10.5 cm) were considered aggressive. Multivariate analysis showed that tumor diameter (OR 1.53, 95% CI 1.24-1.89) and location of tumor in pancreatic head (OR 10.44, 95% CI 1.73-63.04) were independently associated with aggressive behavior. CONCLUSIONS:We describe the largest case series of patients with pathologically proven SCNs. CT performed poorly in preoperative diagnosis of SCNs. Large tumor size and head location predicted aggressive behavior. These factors should be considered in the management of patients with SCN.

BACKGROUND:Margin status is one of the strongest prognosticators after resection of pancreatic ductal adenocarcinoma (PDAC). The clinical significance of pancreatic intraepithelial neoplasia (PanIN) at a surgical margin has not been established. METHODS:A total of 208 patients who underwent R0 resection for PDAC between 2004 and 2008 were selected. Intraoperative frozen section slides containing the final pancreatic parenchymal transection margin were evaluated for presence or absence, number, and grade of PanINs. Data were compared to clinicopathologic factors, including patient survival. RESULTS:PanIN lesions were present in margins in 107 of 208 patients (51.4%). Median number of PanINs per pancreatic resection margin was 1 (range, 1-11). A total of 72 patients had PanIN-1 (34.6%), 44 had PanIN-2 (21.1%), and 16 had PanIN-3 (7.2%) at their margin. Overall median survival was 17.9 (95% confidence interval, 14-21.9) months. Neither the presence nor absence of PanIN nor histological grade had any significant correlation with important clinicopathologic characteristics. There were no significant survival differences between patients with or without PanIN lesions at the resection margin or among patients with PanIN-3 (carcinoma in situ) versus lower PanIN grades. However, patients with R1 resection had a significantly worse outcome compared with patients without invasive cancer at a margin irrespective of the presence of PanIN (P = 0.02). CONCLUSIONS:The presence of PanINs at a resection margin does not affect survival in patients who undergo R0 resection for PDAC. These results have significant clinical implications for surgeons, because no additional resection seems to be indicated when intraoperative frozen sections reveal even high-grade PanIN lesions.

PURPOSE/OBJECTIVE:Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma. METHODS AND MATERIALS/METHODS:Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes, including median survival, overall survival, and complication rates were assessed for both groups. RESULTS:Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-oclusive disease or graft failure/leakage. CONCLUSION/CONCLUSIONS:In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.

PURPOSE/OBJECTIVE:Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. METHODS AND MATERIALS/METHODS:Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. RESULTS:The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. CONCLUSION/CONCLUSIONS:Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.