Intraductal Papillary Mucinous Neoplasm of the Pancreas in Young Patients: Tumor Biology,Clinical Features,and Survival Outcomes

Aim

The aim of this paper is to describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in young patients.

Methods

We evaluated 1693 patients from the Pancreatic Surgery Consortium who underwent resection for IPMN and classified them as younger or older than 50 years of age at the time of surgery. We assessed the relationship of age with clinical, radiological, pathological, and prognostic features.

Results

We identified 90 (5%) young patients. Age was not associated with differences in main pancreatic duct size (P = 0.323), presence of solid components (P = 0.805), or cyst size (P = 0.135). IPMNs from young patients were less likely to be of gastric type (37 vs. 57%, P = 0.005), and more likely to be of oncocytic (15 vs. 4%, P = 0.003) and intestinal types (44 vs. 26%, P = 0.004). Invasive carcinomas arising from IPMN were less common in young patients (17 vs. 27%, P = 0.044), and when present they were commonly of colloid type (47 vs. 31% in older patients, P = 0.261) and had better overall survival than older patients (5-year, 71 vs. 37%, log-rank P = 0.031).

Conclusion

Resection for IPMN is infrequent in young patients, but when they are resected, IPMNs from young patients demonstrate different epithelial subtypes from those in older patients and more favorable prognosis.

     

Surgical Outcomes in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis

Background

Different approaches to surgical treatment of portal vein tumor thrombosis (PVTT) have been advocated. This study investigated the outcomes of different surgical approaches in hepatocellular carcinoma (HCC) patients with PVTT.

Methods

We reviewed prospectively collected data for all patients who underwent hepatectomy for HCC at our hospital between December 1989 and December 2010. Patients were excluded from analysis if they had extrahepatic disease, PVTT reaching the level of the superior mesenteric vein, or hepatectomy with a positive resection margin. The remaining patients were divided into three groups for comparison: group 1, with ipsilateral PVTT resected in a hepatectomy; group 2, with PVTT extending to or beyond the portal vein bifurcation, treated by en bloc resection followed by portal vein reconstruction; group 3, with PVTT extending to or beyond the portal vein bifurcation, treated by thrombectomy.

Results

A total of 88 patients, with a median age of 54 years, were included in the analysis. Group 2 patients were younger, with a median age of 43.5 years versus 57 in group 1 and 49 in group 3 (p = 0.017). Group 1 patients had higher preoperative serum alpha-fetoprotein levels, with a median of 8,493 ng/mL versus 63.25 in group 2 and 355 in group 3 (p = 0.004), and shorter operation time, with a median of 467.5 min versus 663.5 in group 2 and 753 in group 3 (p = 0.018). No patient had thrombus in the main portal vein. Two (2.8 %) hospital deaths occurred in group 1 and one (10 %) in group 2, but none in group 3 (p = 0.440). The rates of complication in groups 1, 2, and 3 were 31.9, 50.0, and 71.4 %, respectively (p = 0.079). The median overall survival durations were 10.91, 9.4, and 8.58 months, respectively (p = 0.962), and the median disease-free survival durations were 4.21, 3.78, and 1.51 months, respectively (p = 0.363). The groups also had similar patterns of disease recurrence (intrahepatic: 33.8 vs. 28.6 vs. 40.0 %; extrahepatic: 16.9 vs. 14.3 vs. 0 %; both: 28.2 vs. 42.9 vs. 40.0 %; no recurrence: 21.1 vs. 14.3 vs. 20.0 %; p = 0.836).

Conclusions

The three approaches have similar outcomes in terms of survival, complication, and recurrence. Effective adjuvant treatments need to be developed to counteract the high incidence of recurrence.     

ASO Visual Abstract: Diagnostic Immunostaining and Tumor Markers Predict Prognosis of Patients with Esophageal Neuroendocrine Carcinoma

Annals of Surgical Oncology -     

Incidental Detection of Pancreatic Neuroendocrine Tumors: An Analysis of Incidence and Outcomes

Background

Pancreatic neuroendocrine tumors (NETs) are increasingly discovered incidentally during radiologic or endoscopic examinations. The frequency of incidental detection is unknown. It is also unclear whether patients with incidentally discovered, early-stage, asymptomatic tumors should be treated similarly to patients who present with tumor-related symptoms.

Methods

Patients with nonmetastatic pancreatic NETs treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were assigned a stage (I?CIII) on the basis of the new American Joint Committee on Cancer classification. The frequency of incidentally diagnosed tumors was evaluated and stratified by stage. Progression-free survival was measured by log rank testing to compare patients with incidentally detected versus symptomatic tumors. Multivariate analysis was performed controlling for other prognostic factors including tumor stage, grade, and location, and patient age.

Results

Among 143 patients with nonmetastatic pancreatic NETs, 56 patients (40%) had tumors that were discovered incidentally. Most stage I tumors (55%) were incidental. The 5-year progression-free survival rate was 86% for incidentally diagnosed tumors, versus 59% for symptomatic tumors (P?=?0.007). On multivariate analysis, incidental detection of tumors was the strongest prognostic factor for progression.

Conclusions

A sizable fraction of patients with early-stage pancreatic NETs are diagnosed incidentally during evaluations for other conditions or unrelated symptoms. This study highlights the necessity of developing guidelines for management of patients with incidentally discovered early-stage tumors.     

Acute Pancreatitis in Patients After Bariatric Surgery: Incidence,Outcomes, and Risk Factors

Background

The incidence of acute pancreatitis (AP) in bariatric surgery patients is not known. Ouraim was to determine the incidence, outcomes, and risk factors of AP in post-bariatric surgery patients.

Methods

An historical cohort study was conducted of all patients who underwent Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding, and revisional procedures at our institution from January 2004 to September 2011. Patients who developed AP were identified by review of the electronic medical record. A nested case-control study using Cox regression analysis was done to identify risk factors.

Results

A total of 2695 patients underwent bariatric surgery. Twenty-eight patients (1.04 %) developed AP during a median follow-up of 3.5 years (interquartile range [IQR] 1.9–5.8). One patient had severe AP, and there was one AP-related death. In the case-control study, the only baseline variable that predicted post-operative AP was a prior history of AP. Three other variables identified after surgery were associated with AP: (1) rapid weight loss as measured by percent of excess weight loss (EWL) at the first post-operative visit, (2) abnormal findings on post-operative ultrasound (stones, sludge or ductal dilation), and (3) post-operative complications of bowel leak or anastomotic stricture.

Conclusions

The incidence of AP in this cohort is 1.04 %, which is higher than that reported for the general population (~17/100,000, 0.017 %). Most cases were clinically mild and managed conservatively with good outcomes. Rapid post-operative weight loss and the presence of gallstones or sludge on post-operative ultrasound were significant risk factors for AP.     

A Composite Adenoendocrine Carcinoma of the Stomach Arising from a Neuroendocrine Tumor

Gastric neuroendocrine tumors (carcinoids) are relatively uncommon neoplasms. Some 70 to 80% of these lesions occur in patients with autoimmune body gastritis. This disorder, however, is also a risk factor for the development of conventional gastric adenocarcinomas. We report a case of a patient with autoimmune body gastritis and a well-differentiated neuroendocrine tumor of the stomach, which was removed with endoscopic full-thickness resection in sano upon signs of invasive growth several years after its first diagnosis. Histological examination surprisingly showed a composite glandular-endocrine gastric carcinoma. We discuss the histopathological genesis of the tumor and provide evidence that endoscopic full-thickness resection might be an oncologically appropriate minimally invasive treatment for such gastric lesions.     

Deterioration of Hepatic Functional Reserve in Patients with Hepatocellular Carcinoma after Resection: Incidence,Risk Factors,and Association with Intrahepatic Tumor Recurrence

Hepatocellular carcinoma (HCC) is frequently associated with liver cirrhosis. Patients with HCCs undergoing surgical resection may have declining hepatic functional reserve over time. However, the incidence and risk factors of hepatic decompensation, and its relation to postoperative tumor recurrence are unknown. This study investigated 241 HCC patients (208 male; age 61 ± 13 years) undergoing resection with a long-term follow-up. The Child-Pugh scoring system was used to evaluate the postoperative deterioration of liver reserve, defined as a sustained increment in the Child-Pugh score by 2 or more. The 1-, 3-, and 5-year cumulative probabilities of postoperative decompensation were 14%, 32%, and 56%, respectively, during a follow-up period of 27 ± 18 months (range 3-75 months). The average increment in Child-Pugh score was 1.4 ± 1.1 in 2.3 ± 1.5 years, or 0.6 point per year. Altogether, 74 (31%) patients developed postoperative hepatic decompensation during the follow-up period, 43 (58%) of whom had decompensation within 2 years of resection. Large (> 3 cm) tumor size was the only independent predictor associated with hepatic decompensation (relative risk 1.7, 95% confidence interval 1.1–2.8, p = 0.041) and was a significant risk factor for intrahepatic tumor recurrence (p = 0.018). Patients with tumor recurrence more frequently (40% of 109 patients vs. 23% of 132 patients, p = 0.005) and more rapidly (0.8 vs. 0.4 point per year) developed hepatic decompensation than those without recurrence. In conclusion, large HCCs are closely associated with hepatic decompensation in patients after resection. Tumor recurrence may predispose to the development of hepatic decompensation in these patients.     

Cystic Neoplasia of the Pancreas: Pathology and Biology

In contrast with solid tumors, most of which are invasive ductal adenocarcinoma with dismal prognosis, cystic lesions of the pancreas are often either benign or low-grade indolent neoplasia. Those that are mucinous, namely, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), constitute the most important category, not only because they are the most common, but more importantly because they have well-established malignant potential, representing an adenomacarcinoma sequence. While many are innocuous adenomas — in particular, those that are small and less complex, and in the case of IPMN, those that are branch-duct type are more commonly benign, some harbor or progress into in situ or invasive carcinomas. For this reason, pancreatic cysts with mucinous differentiation ought to be evaluated carefully, preferably by experts familiar with subtle evidences of malignancy in these tumors. In the past few years, the definition of IPMNs and MCNs has become more refined. The presence of ovarian-type stroma has now almost become a requirement for the diagnosis of MCN, and when defined as such, MCN is seen almost exclusively in women of perimenopausal age group as thick-walled multilocular cystic mass in the tail of the pancreas in contrast with IPMN which afflicts an elder population, both genders in almost equal numbers, and occur predominantly in the head of the organ. While mucinous lesions have well-established pre-malignant properties, most of the entities that fall into the nonmucinous true cyst category such as serous tumors, lymphoepithelial cysts, congenital cysts, and squamoid cyst of ducts have virtually no malignant potential. In contrast, the rare cystic tumors that occur as a result of degenerative/necrotic changes in otherwise solid neoplasia such as the rare cystic ductal adenocarcinomas, cystic endocrine neoplasia, and most importantly, solid-pseudopapillary tumor (SPT) in which cystic change is so common that it used to be incorporated into its name (“solid-cystic,” “papillary-cystic”) are malignant neoplasia, albeit variable degrees of aggressiveness. SPT holds a distinctive place among pancreatic neoplasia because of its highly peculiar characteristics, undetermined cell lineage, occurrence almost exclusively in young females, association with β-catenin pathway, and also by being a very low-grade curable malignancy. In conclusion, cystic lesions in the pancreas constitute a biologically and pathologically diverse category most (but not all) of which are either benign or treatable diseases; however, a substantial subset, especially mucinous ones, has malignant potential that requires careful analysis. This paper was originally presented as part of the SSAT/AGA/ASGE State-of-the-Art Conference on Management of Cystic Lesions of the Pancreas at the SSAT 48th Annual Meeting, May 2007 in Washington, DC. The other articles presented in the conference were Scheiman JM, Management of Cystic Lesions of the Pancreas: Diagnosis: Radiographic Imaging, EUS and Fluid Analysis; Tseng JF, Management of Serous Cystadenoma of the Pancreas; Fernández-del Castillo C, Mucinous Cystic Neoplasms; and Farnell MB, Surgical Management of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas.     

Resection of Isolated Renal Cell Carcinoma Metastases of the Pancreas: Outcomes from the Johns Hopkins Hospital

Purpose

This study aims to assess outcomes and characteristics associated with resection of metastatic renal cell carcinoma (mRCC) to the pancreas.

Materials and Methods

From April 1989 to July 2012, a total of 42 patients underwent resection of pancreatic mRCC at our institution. We retrospectively reviewed records from a prospectively managed database and analyzed patient demographics, comorbidities, perioperative outcomes, and overall survival. Cox proportional hazards models were used to evaluate the association between patient-specific factors and overall survival.

Results

The mean time from resection of the primary tumor to reoperation for pancreatic mRCC was 11.2 years (range, 0–28.0 years). In total, 17 patients underwent pancreaticoduodenectomy, 16 underwent distal pancreatectomy, and 9 underwent total pancreatectomy. Perioperative complications occurred in 18 (42.9 %) patients; there were two (4.8 %) perioperative mortalities. After pancreatic resection, the median follow-up was 7.0 years (0.1–23.2 years), and median survival was 5.5 years (range, 0.4–21.9). The overall 5-year survival was 51.8 %. On univariate analysis, vascular invasion (hazard ratio, 5.15; p?=?0.005) was significantly associated with increased risk of death.

Conclusions

Pancreatic resection of mRCC can be safely achieved in the majority of cases and is associated with long-term survival. Specific pathological factors may predict which patients will benefit most from resection.     

Incidence of Additional Primary Malignancies in Patients with Pancreatic and Gastrointestinal Neuroendocrine Tumors

Background

The incidence of secondary malignancies is increased in patients with malignant and premalignant conditions. Although neuroendocrine tumors (NET) are uncommon, their incidence is increasing. We evaluated the rate of additional malignancies in patients with NET.

Methods

Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified a cohort of patients with pancreatic NET (PNET) or gastrointestinal NET (GINET). We determined the incidence of additional cancers diagnosed either before or after the diagnosis of PNET or GINET, by comparing these rates with the general population. Using multivariable regression, we evaluated factors that increased the risk of an additional malignancy.

Results

A cohort of 9,727 NET patients was identified. A total of 3,086 additional cancers occurred in 2,508 patients (25.8 %). The most common sites of additional malignancies included colorectal (21.1 %), prostate (14.5 %), breast (13.3 %), and lung (11.6 %). Among patients with PNET, the incidence of breast, lung, uterine, lymph, and pancreatic cancers was less than expected in the general population, whereas in patients with GINET, the observed incidence of nearly all malignancies exceeded that expected. Increasing age, marital status, and localized NET were associated with increased risk.

Conclusion

Our study shows that the incidence of additional malignancies in patients with PNET and GINET is 25.8 %. Patients with GINET are at increased risk of additional malignancies, whereas patients with PNET have a decreased risk compared with the general population. More vigilant surveillance for secondary malignancies should be performed in patients with GINET. Studies investigating potential etiologic oncogenic pathways are warranted.     

Plasma Neuroendocrine Markers in Patients with Benign Prostatic Hyperplasia and Prostatic Carcinoma

Purpose

Approximately 50 percent of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2 percent of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determined the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease.

Materials and Methods

The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study.

Results

Significantly elevated levels of chromogranin A were detected in 15 percent of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55 percent and 30 percent of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma.

Conclusions

Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs known to be active against neuroendocrine tumors.