Faculty Bibliography

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts. As the cysts increase in size, they fuse forming larger cysts. Later lesions demonstrate a unilocular cyst lined by predominantly acinar epithelium with scattered ductal cells. The term cystadenoma, with its neoplastic connotation, does not seem to accurately reflect the histologic, immunohistochemical, or molecular features of these lesions. We suggest readopting the term "acinar cystic transformation" until the non-neoplastic versus neoplastic origin of these lesions can be resolved.

BACKGROUND: The purpose of this study was to evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer. METHODS: Eligibility included confirmation of adenocarcinoma, resectable or borderline resectable disease, a performance status /=3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months). CONCLUSIONS: Preoperative therapy with full-dose gemcitabine, oxaliplatin, and RT was feasible and resulted in a high percentage of R0 resections. The current results are particularly encouraging, because the majority of patients had borderline resectable disease.

BACKGROUND:Studies reporting perioperative outcomes after pancreaticoduodenectomy (PD) have focused on morbidity and mortality. Understanding factors that impact hospital duration of stay may have cost-saving implications. We sought to examine variation in duration of stay after PD occurring at the patient, surgeon, and hospital levels. METHODS:Year-specific PD volumes for both surgeons and hospitals were determined from the 2003-2009 Nationwide Inpatient Sample and grouped into terciles. Patient age, gender, and comorbidities were examined. Median duration of stay was calculated and modified Poisson regression examined factors associated with duration of stay. RESULTS:Among 5,190 individuals undergoing PD, median age was 65 years and 49.3% were female. Median duration of stay was 13 days (range, 0-234). Older patients and those with comorbid illness were more likely to have duration of stay of ≥ 14 days (P < .001). Median annual surgeon volume was 8 (interquartile range [IQR], 2-19; range, 1-54). Annual hospital volume ranged from 1 to 129 (median, 18; IQR, 6-52). Both low surgeon and hospital PD volume were associated with longer durations of stay (P < .001). In multivariable modeling, age remained associated with duration of stay (relative risk [RR], 1.007 per year; P < .001); however, comorbidity did not. Patients operated on by high-volume surgeons (RR, 0.67) or at high-volume hospitals (RR, 0.75) had a reduced risk of a prolonged duration of stay of ≥ 14 days (both P < .001). CONCLUSION/CONCLUSIONS:PD patients treated by higher volume surgeons and at higher volume hospitals had a shorter duration of stay. Although some patient-level factors impact duration of stay after PD, nonclinical factors such as surgeon and hospital volume were also important contributors to duration of stay.

BACKGROUND:Little is known about current surveillance patterns after treatment of colorectal liver metastasis (CRLM) or whether the intensity of surveillance correlates with outcome. We sought to define current population-based patterns of surveillance and investigate whether intensity of surveillance impacted outcome. METHODS:We queried the Surveillance, Epidemiology, and End Results-linked Medicare database for patients with CRLM diagnosed between 1991 and 2005 who underwent liver resection and/or tumor ablation. Frequency of post-treatment abdominal computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) was recorded for ≤ 5 years after treatment. The association between frequency of imaging with secondary interventions and long-term survival were analyzed. RESULTS:We identified 1,739 patients with CRLM treated with surgery; median age was 73 years, and the majority were male (52.6%). CRLM treatment consisted of liver resection (61%), ablation (32%), or both simultaneously (6%). CT (97%) was utilized more often for post-treatment surveillance compared with MRI (7%) and PET (18%). A temporal trend was noted with more frequent surveillance imaging obtained in post-treatment year 1 (2.4 scans/year) versus year 5 (0.6 scans/year; P = .01); 66% of living patients had no imaging after 2 years. Frequency of surveillance imaging correlated with procedure type (total number of scans/5 years: resection, 5.0; ablation, 4.6; resection and ablation, 6.2; P = .01). Other factors associated with a greater frequency of surveillance included younger age at diagnosis, geographic location in the South, and CRLM directed surgery in 2000 through 2005 (all P < .05). Overall survival did not differ by intensity of surveillance imaging (3-4 scans/yr, 43 months vs 2 scans/yr, 57 months vs 1 scan/yr, 54 months; P = .08). CONCLUSION/CONCLUSIONS:Marked heterogeneity exists in how often surveillance imaging is obtained after treatment of CRLM. Intensity of imaging does not affect time to second procedure or median survival duration. Surveillance guidelines for CRLM need to be refocused to provide the best value for healthcare resources.

OBJECTIVE:Solid pseudopapillary neoplasms (SPNs) are low-grade malignancies with an excellent prognosis, albeit with the potential for metastatic disease. This study details our institution's experience with the diagnosis and treatment of SPN, including clinical presentation, multimodality imaging findings, and potential predictors of aggressive tumor behavior. MATERIALS AND METHODS/METHODS:The institutional pathology database was searched through for all cases of SPN since 1988, yielding 51 patients. The electronic medical record was searched for clinical and demographic information regarding these patients, including age, sex, presenting symptoms, type of surgery, postoperative length of stay, tumor markers, and postsurgical follow-up. All available imaging data were reviewed, including those of 30 patients who underwent multidetector computed tomography, those of 9 patients who underwent magnetic resonance imaging (MRI), those of 3 patients who underwent conventional ultrasound, and those of 11 patients who underwent endoscopic ultrasound. RESULTS:A total of 84% of patients were females, with a mean age of only 33 years. Prognosis was excellent, with a mean follow-up of 3 years without recurrence. Only 1 of the 51 patients developed metastatic disease to the liver 8 years after the surgery. On computed tomography, lesions tended to be large (5.3 cm), well circumscribed (29/30), round/oval (20/30), and encapsulated (23/30). The lesions often demonstrated calcification (14/30) and typically resulted in no biliary or pancreatic ductal dilatation. The lesions ranged from completely cystic to completely solid. On MRI, the lesions often demonstrated a T2 hypointense or enhancing capsule (6/9) and demonstrated internal blood products (5/9). The lesions tended to be devoid of vascularity on conventional ultrasound. Ten patients were found to have "aggressive" histology at presentation (T3 tumor, nodal involvement, perineural invasion, or vascular invasion). No demographic, clinical, or multidetector computed tomographic imaging features were found to correlate with aggressive histology. CONCLUSIONS:Certain imaging features (eg, well-circumscribed mass with calcification, peripheral capsule, internal blood products, and lack of biliary/pancreatic ductal obstruction) on computed tomography and MRI are highly suggestive of the diagnosis of SPN, particularly when visualized in young female patients. However, it is not possible to predict aggressive histology on the basis of imaging findings, clinical presentation, or patient demographic features.

PURPOSE/OBJECTIVE:Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. METHODS AND MATERIALS/METHODS:Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m(2) twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). RESULTS:The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. CONCLUSION/CONCLUSIONS:Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

PURPOSE/OBJECTIVE:Our goal was to identify circulating micro RNA (miRNA) levels that could distinguish patients with low-stage pancreatic cancer from healthy and disease controls. EXPERIMENTAL DESIGN/METHODS:We measured 735 miRNAs in pancreatic cancer case and control sera by QRTPCR using TaqMan MicroRNA Arrays. After array analysis, we selected 18 miRNA candidates for validation in an independent set of cases and control samples. RESULTS:Of the significantly elevated circulating miRNAs in patients with pancreatic cancer compared with controls, miR-1290 had the best diagnostic performance: receiver operating characteristic (ROC) analysis on miR-1290 serum level yielded curve areas (AUC) of 0.96 [95% confidence interval (CI), 0.91-1.00], 0.81 (0.71-0.91), and 0.80 (0.67-0.93), for subjects with pancreatic cancer (n = 41) relative to healthy controls (n = 19), subjects with chronic pancreatitis (n = 35), and pancreatic neuroendocrine tumors (n = 18), respectively. Serum miR-1290 levels were also significantly higher than healthy controls among patients with intraductal papillary mucinous neoplasm (IPMN; n = 20; AUC = 0.76, 0.61-0.91). Serum miR-1290 levels distinguished patients with low-stage pancreatic cancer from controls better than CA19-9 levels, and like CA19-9, higher miR-1290 levels predicted poorer outcome among patients undergoing pancreaticoduodenectomy. Greater numbers of miR-1290 transcripts were detected by FISH in primary pancreatic cancer and IPMN than normal pancreatic duct cells. miR-1290 influenced in vitro pancreatic cancer cell proliferation and invasive ability. Several other circulating miRNAs distinguished sera of patients with pancreatic cancer from those of healthy controls with AUCs >0.7, including miR-24, miR-134, miR-146a, miR-378, miR-484, miR-628-3p, and miR-1825. CONCLUSIONS:The detection of elevated circulating miR-1290 has the potential to improve the early detection of pancreatic cancer.

BACKGROUND:A computed tomography (CT) scan is often the only study needed prior to surgery for resectable solid pancreas masses. However, many patients are evaluated with multiple studies and interventions that may be unnecessary. METHODS:We conducted a retrospective review of patients who presented to the Johns Hopkins Multidisciplinary Pancreas Cancer Clinic with a clearly resectable solid pancreas mass, >1 cm in size over a 2-year period (6/2007-6/2009) and underwent resection. Pancreas specialists reviewed patient records and identified an index CT with a solid pancreas mass deemed to be resectable for curative intent. Data were collected on all studies and interventions between the index CT and the surgery. RESULTS:A total of 101 patients had an index CT. Following the index CT and before surgery, 78 patients had at least one CT, 19 had magnetic resonance imaging, 9 had a positron emission tomography scan, and 66 underwent pancreatic biopsy. Patients underwent a mean of three studies with a mean added cost of $3,371 per patient. Preoperative tests and interventions were associated with a longer time to definitive surgical intervention. CONCLUSION/CONCLUSIONS:Wide variation exists for evaluation of newly discovered resectable solid pancreas masses, which is associated with delays to surgical intervention and added costs.

BACKGROUND AND AIMS/OBJECTIVE:Endoscopic placement of enteral self-expandable metallic stents is an alternative to surgical gastrojejunostomy (GJ) for palliation of malignant gastric outlet obstruction (GOO). Factors associated with clinical outcomes are not known. The aims of this study are to compare the overall complication rate and effectiveness (duration of oral intake) between endoscopic stenting (ES) and GJ in patients with GOO and identify predictors of clinical outcomes. PATIENTS AND METHODS/METHODS:This was a retrospective cohort study at a single tertiary academic center. Patients who underwent ES or GJ for treatment of GOO between 1/2001 and 12/2010 were identified using an institutional claims database. The electronic medical records for each patient were reviewed. Univariate and multivariate logistic regression analyses were performed to study the association of treatment outcomes with patient factors and cancer therapy. RESULTS:120 patients had ES while 227 had GJ. Technical success was higher for GJ (99 vs. 96 %, p = 0.004). Complication rates were higher in the GJ group (22.10 vs. 11.66 %, p = 0.02). Reintervention was more common with ES [adjusted odds ratio (OR) 9.18, p < 0.0001]. Mean length of hospital stay (LOHS) was shorter (adjusted p = 0.005) in the ES compared with the GJ group. However, mean hospital charges, including reinterventions, were greater in the ES group (US $34,250 vs. US $27,599, p = 0.03). ES and GJ had comparable reintervention-free time in patients who had reintervention (88 vs. 106 days, respectively, p = 0.79). Chemotherapy [adjusted hazard ratio (HR) 3 > 0.57, p = 0.04] and radiation therapy (adjusted HR 0.35, p = 0.03) were associated with significantly longer duration of oral intake after ES or GJ. CONCLUSION/CONCLUSIONS:ES is associated with fewer complications, shorter LOHS, but higher reintervention rates and overall charges.