Faculty Bibliography

Pancreatic cysts are being identified with increasing frequency due to a combination of increased awareness and more frequent use of cross sectional imaging. Cystic neoplasms of the pancreas range from completely benign to frankly malignant. Identifying pre-malignant cysts offers the opportunity to prevent the development of pancreatic cancer. This article reviews the presentation, workup, and non-operative and operative management of premalignant and malignant pancreatic cysts.

Although patients with surgically resected noninvasive mucinous cystic neoplasms (MCNs) of the pancreas are cured, the behavior of surgically resected minimally invasive adenocarcinomas arising in MCN has not been well established. We report 16 surgically resected MCNs with minimal invasion defined as unifocal or multifocal microscopic invasive adenocarcinoma confined to the ovarian stroma of the MCN without capsular or pancreatic parenchymal invasion. Pathologic findings were correlated with patient demographics, type of surgery, and long-term follow-up. Our study included 15 women and 1 man ranging in age from 25 to 66 years. The patients were followed up for a mean of 48.6 months (range, 12 to 148 mo). The MCNs ranged in size from 3.5 to 25 cm and were all located in the body/tail of the gland. Lymphovascular invasion was not identified in any of the cases, and all lymph nodes were negative for tumor. Ten neoplasms had unifocal invasion, whereas 6 had multifocal invasion. Twelve of the neoplasms were partially submitted for microscopic examination, whereas 4 were submitted entirely. Only 1 of the 16 minimally invasive MCNs recurred, and that tumor had been lighlty sampled pathologically. Our study demonstrates that the majority of patients with minimally invasive adenocarcinoma arising in MCNs are cured by surgery, particularly if the neoplasms are completely examined histologically.

BACKGROUND:Little is known about the risk of subsequently developing a new or progressive intraductal papillary mucinous neoplasm (IPMN) after partial pancreatic resection of a noninvasive IPMN. STUDY DESIGN/METHODS:One hundred thirty patients with more than 1 year of follow-up after resection were included in this analysis. RESULTS:At a median follow-up of 38 months, 22 (17%) developed imaging evidence of a new or progressive IPMN. Eleven (8%) underwent completion resection. Three of the 11 patients had invasive adenocarcinoma. Two other patients developed metastatic pancreatic adenocarcinoma and did not undergo resection. All 5 patients (4%) with cancer had negative margins at initial operation. Sixteen of 100 patients (16%) with negative margins for IPMN at the initial operation developed a new IPMN vs 6 of 30 patients (20%) with margins positive for IPMN (p = ns). Five of 22 patients (23%) with a new IPMN had a family history of pancreatic cancer, while 8 of 108 patients (7%) without a new IPMN had a family history (p < 0.05). Overall, the chances of developing a new IPMN at 1, 5, and 10 years after the initial surgery were 4%, 25%, and 62%, respectively, and of requiring surgery were 1.6%, 14%, and 18%, respectively. The estimated chances of developing invasive pancreatic cancer were 0%, 7%, and 38% at 1, 5, and 10 years, respectively. CONCLUSIONS:Patients who have undergone resection for noninvasive IPMN require indefinite close surveillance because of the risks of developing a new IPMN, of requiring surgery, and of developing cancer. A family history of pancreatic cancer, but not margin status or degree of dysplasia, is associated with a risk of development of a new or progressive IPMN.

BACKGROUND:The goal of this study was to investigate the surgical management and outcomes of patients with primary colorectal cancer (CRC) and synchronous liver metastasis (sCRLM). STUDY DESIGN/METHODS:Using a multi-institutional database, we identified 1,004 patients treated for sCRLM between 1982 and 2011. Clinicopathologic and outcomes data were evaluated with uni- and multivariable analyses. RESULTS:A simultaneous CRC and liver operation was performed in 329 (33%) patients; 675 (67%) underwent a staged approach ("classic" staged approach, n = 647; liver-first strategy, n = 28). Patients managed with the liver-first approach had more hepatic lesions and were more likely to have bilateral disease than those in the other 2 groups (p < 0.05). The use of staged operative strategies increased over the time of the study from 58% to 75% (p < 0.001). Liver-directed therapy included hepatectomy (90%) or combined resection + ablation (10%). A major resection (>3 segments) was more common with a staged approach (39% vs 24%; p < 0.001). Overall, 509 patients (50%) received chemotherapy in either the preoperative (22%) or adjuvant (28%) settings, with 11% of patients having both. There were 197 patients (20%) who had a complication in the postoperative period, with no difference in morbidity between staged and simultaneous groups or major vs minor hepatectomies (p > 0.05). Ninety-day postoperative mortality was 3.0%, with no difference between simultaneous and staged approaches (p = 0.94). The overall median and 5-year survivals were 50.9 months and 44%, respectively; long-term survival was the same regardless of the operative approach (p > 0.05). CONCLUSIONS:Simultaneous and staged resections for sCRLM can be performed with comparable morbidity, mortality, and long-term oncologic outcomes.

Pancreatic cancer (pancreatic adenocarcinoma) remains one of the deadliest malignancies in the western hemisphere despite improved surgical technique, chemotherapy, and radiation therapy. The appropriate management of this malignancy should incorporate multiple treatment modalities for optimal opportunity for cure. Recent trials with a variety of treatment techniques confer improved survival of patients with pancreatic cancer, even in the metastatic setting. In this review, the importance of multidisciplinary management of pancreatic cancer based on disease stage is discussed.

PURPOSE/OBJECTIVE:TNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy. PATIENTS AND METHODS/METHODS:In all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m(2) per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 10(11) particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m(2) intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity. RESULTS:The analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P < .001) but both arms had similar rates of grade 3 to 4 toxicities (all P > .05). CONCLUSION/CONCLUSIONS:SOC + TNFerade is safe but not effective for prolonging survival in patients with LAPC.

OBJECTIVE:The criteria for resection of solitary pancreatic side-branch intraductal papillary mucinous neoplasm (IPMN) have been well described by the Sendai consensus statement. However, the management of multiple pancreatic cystic lesions is less certain, with no clear guidelines in the literature to date. The purpose of this study was to evaluate the histopathologic findings in pancreatic IPMNs in patients with multiple (≥ 4) pancreatic cysts. MATERIALS AND METHODS/METHODS:The CT scans of all patients with a pathologically proven IPMN at our institution were reviewed, and a total of 52 patients with four or more pancreatic cysts were found. Each case was reviewed for the number of cysts and the presence of signs of invasive malignancy including a coexistent solid pancreatic mass, pancreatic ductal dilatation, and mural nodularity. RESULTS:A total of 52 patients (19 men, 33 women; mean age, 71.8 years) were found to have multifocal IPMNs, defined as four or more cysts, on CT. Of these 52 patients, nine also had evidence of a solid pancreatic mass on CT. Retrospective review of the pathologic results for the remaining 43 patients (17 men, 26 women; mean age, 71.76 years) showed 18 cases of an IPMN with either high-grade dysplasia or a coexistent invasive carcinoma. Most important, 37% (7/19 patients) had no CT findings of an invasive malignancy according to the Sendai criteria (i.e., cysts ≥ 3 cm in the axial plane, main pancreatic ductal dilatation ≥ 6 mm, or mural nodularity within a cyst) but were found to have an IPMN with either high-grade dysplasia or invasive carcinoma. When the pancreas contained 10 or more cysts, high-grade dysplasia or invasive carcinoma tended to be more likely than low- or intermediate-grade dysplasia (odds ratio, 3.83; 95% CI, 0.87-16.8; p = 0.075). CONCLUSION/CONCLUSIONS:The presence of multiple pancreatic cysts should be looked on with suspicion, particularly when there are a large number of cysts, even when none of the cysts individually meet the imaging criteria for resection according to the Sendai consensus recommendations. At the very least, these patients need to be followed very closely.

OBJECTIVE:The objective of our study was to determine the prevalence and CT appearance of cystlike changes of pancreatic neuroendocrine tumor (NET), particularly of small (≤ 3 cm) tumors. MATERIALS AND METHODS/METHODS:The clinical records, images, and pathologic reports of 74 consecutive patients (average age, 55.5 years) with surgically resected pancreatic NETs who underwent preoperative CT were retrospectively reviewed. The size and location of the pancreatic NETs were recorded. The tumors were classified on the basis of CT appearance as small (≤ 3 cm) or large (> 3 cm) and as solid, partially (≤ 50% or > 50%) cystic, or purely (≈ 100%) cystic. Peripheral contrast enhancement on CT was characterized, and lymph node and liver metastases found by pathologic examination were recorded. RESULTS:A total of 78 pancreatic NETs were reviewed. Five were not visualized on CT, leaving 73 pancreatic NETs in 69 patients (multiple tumors were visualized on CT of three patients) for analysis. The mean size of the 73 tumors was 3.0 ± 2.6 (SD) cm (range, 0.7-13.1 cm); 52 tumors were 3 cm or smaller and 21 tumors were larger than 3 cm. Gross pathologic results confirmed that 13 of the 73 (17.8%) tumors were predominantly (> 50% or ≈ 100%) cystic: 10 of the 52 (19.2%) tumors 3 cm or smaller and three of the 21 (14.3%) tumors larger than 3 cm. Peripheral contrast enhancement was seen in 11 of the 13 (85%) predominantly cystic pancreatic NETs. Compared with solid pancreatic NETs, predominantly cystic pancreatic NETs were less commonly associated with lymph node and liver metastases. CONCLUSION/CONCLUSIONS:Cystic pancreatic NETs are not rare and should be included in the differential diagnosis of a cystic pancreatic mass, particularly if the cystic mass is associated with peripheral contrast enhancement. A minority of cystic pancreatic NETs can present with no peripheral enhancement.

OBJECTIVE:Evaluation of the imaging features of pathology-proven acinar cell carcinomas (ACCs) of the pancreas using computed tomography (CT). METHODS:We reviewed the CT features, clinical presentations, and clinical outcomes of 15 patients (9 men, 6 women, mean age 62.3) with pathology-proven pancreatic ACCs. An abdominal radiologist retrospectively evaluated each patient's initial imaging study with respect to the lesion's size, location, attenuation (Hounsfield units) on arterial and venous phase images, peripancreatic lymphadenopathy, and distant metastases. Additional parameters studied included biliary and pancreatic ductal dilatation, intratumoral hemorrhage, calcification, the presence of cystic/necrotic components, and whether the tumor was intraparenchymal or exophytic. RESULTS:The ACCs in this series were evenly distributed between the head/uncinate and the tail, were predominantly exophytic (73%), tended to be large (average size 5.1 cm), and were mostly hypodense to the surrounding pancreas on both the arterial and venous phase images. A sizeable proportion demonstrated a cystic or necrotic component (53%) and/or an enhancing capsule (53%). Of those lesions in the head or uncinate process, very few resulted in pancreatic (28%) or biliary (14%) ductal dilatation. None of the lesions in this series showed internal calcification or intratumoral hemorrhage. CONCLUSION/CONCLUSIONS:While a prospective diagnosis is difficult, ACCs have several features which can differentiate them from ductal adenocarcinoma, including their large size, lack of biliary or pancreatic ductal dilatation, exophytic nature, and the presence of an enhancing capsule.

BACKGROUND:The median age of pancreatic ductal adenocarcinoma (PDAC) patients is 71 years. PDAC rarely affects individuals under the age of 45. We investigated features of PDAC occurring in young patients (≤45 years) who underwent surgical resection in order to determine if any difference exists in comparison to elderly patients (≥70 years). METHODS:A retrospective analysis of patients with PDAC who were ≤ 45 years on the date of surgery between 1975 and 2009 was performed. This cohort was compared with PDAC patients whose ages were over 70 years on the date of surgery over the same time interval. Information reviewed included demographics, Charlson Age-Comorbidity Index (CACI), pathological staging, surgical management, and death or last follow-up. RESULTS:Seventy five patients with PDAC of age ≤ 45 years at surgery were identified. The reference group consisted of 870 patients with a median age of 75. The most common symptoms of young patients were jaundice (45 %), abdominal pain (32 %), or weight loss (33 %). This did not differ significantly from older patients. Among the younger patients, 7 (9 %) underwent total pancreatectomy, 60 (80 %) underwent pancreaticoduodenectomy, and 8 (11 %) had distal pancreatectomy. The distribution of type of surgery was similar between two groups. Fifty-two of the young patients (69 %) had an R0 resection and this did not differ from the older age group (n = 616; 71 %). The rate of lymph node positivity was 68 % for younger patients and 74 % for older patients (p = 0.27). Of the younger patients, 11, 13, 49, and 2 were classified as stage I, IIA, IIB, and III, respectively, and did not differ from the older age group. The median overall survival for the young patients cohort was 19 months (95 % CI 15-22 months) which is longer than 16 months (95 % CI 14-17 months) of the older group (p = 0.007). The actual 5- and 10- year survival in young age group (24 and 17 %) was longer than that in old age group (11 and 3 %) (p < 0.05). The median CACI of the younger patients was 0.5 and was lower than 4.1 of the older patients (p < 0.0001). CONCLUSIONS:The demographic, pathologic, and treatment characteristics of PDAC patients younger than 45 years were similar to those older than 70 years. Younger patients had fewer complications after curative resections. The better survival among younger patients is likely related to fewer comorbidities in this group. These findings will be useful in counseling young patients with resectable pancreatic cancer.