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Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are rare biliary duct neoplasms. This study investigated reasonable management strategies of cystic neoplasms in the liver. Charts of 39 BCA/BCAC patients (9 males, 30 female; median age 53.74 ± 14.50 years) who underwent surgery from January 1999 to December 2009 were reviewed retrospectively. Cyst fluid samples of 32 BCA/BCAC patients and 40 simple hepatic cyst patients were examined for the tumor markers carbohydrate associated antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). The most frequent symptoms were abdominal pain (N = 10), abdominal mass (N = 7), abdominal distension (N = 4), jaundice (N = 2), and fever (N = 3); the remaining patients showed no clinical symptoms. Liver resection (N = 17) or enucleation (N = 22) was performed in the 39 patients. Ultimately, 35 patients were diagnosed with intrahepatic BCA and four patients were diagnosed with BCAC. The median CA19-9 level was significantly higher in BCA/BCAC patients than in simple hepatic cyst patients. The median CEA levels in BCA/BCAC patients and controls were 6.83 ± 2.43 and 4.21 ± 2.91 mg/L, respectively. All symptoms were resolved after surgery, and only one BCAC patient showed recurrence. The incidence of intrahepatic cystic lesions was 1.7%. Increased CA19-9 levels in the cyst fluid is a helpful marker for distinguishing BCA/BCAC from common simple cysts. The presence of coarse calcifications is suggestive of BCAC. Complete surgical removal of these lesions yielded satisfying long-term outcomes with a very low recurrence rate.

Background: Better pancreatic cyst fluid biomarkers are needed., Objective: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers., Design: Retrospective study., Setting: Tertiary-care referral center., Patients: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts., Intervention: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed., Main Outcome Measurements: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve)., Results: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts., Limitations: Small sample sizes., Conclusion: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Objective: Although human chemokinelike factor (CKLF)-like MAL and related proteins for vesicle trafficking transmembrane, domain-containing member 5 (CMTM5) has been proved to play an important role in carcinogenesis and apoptosis in several types of human tumors, the expression of CMTM5 in ovarian cancer remains unclear. We aimed to investigate the association between CMTM5 expression and the survival of patients with epithelial ovarian cancer., Methods: Normal surface ovarian epithelium tissues, ovarian cystadenoma tissues, ovarian cancer tissues, and 5 ovarian cancer cell lines were collected. The CMTM5 expressions were determined by reverse transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. The survival information was analyzed by the Kaplan-Meier method., Results: The CMTM5 expression was down-regulated in ovarian cancers. The expression of CMTM5 was absent in 30% (24 of 80) of ovarian cancers compared with 4.55% (1 of 22) of normal surface ovarian epithelium tissues and ovarian cystadenomas by immunohistochemistry. The results from the reverse transcription polymerase chain reaction were consistent with those from Western blotting. Furthermore, we found that although CMTM5 expression has no significant correlation with the age of the patients (P = 0.342), clinical stages (P = 0.155), pathologic types (P = 0.0605), or status of metastasis (P = 0.554), it was associated with the 3 groups of different differentiation levels (P = 0.0026) and an increase of CMTM5 loss of expression ratio in patients with preoperative CA125 level more than 500 mIU/mL compared to those with less than 500 mIU/mL (48.57% vs 16.67%, P = 0.0130). Statistical analysis by the Kaplan-Meier method showed that CMTM5 expression had no significant impact on the prognosis of patients with ovarian cancer (P = 0.24)., Conclusions: The reduced expression of CMTM5 correlates significantly with poorly differentiated ovarian cancer and high preoperative CA125 level. CMTM5 may contribute to the pathogenesis of human epithelial ovarian cancer.

Aim: To study the gene expression changes in pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer., Methods: Using the pBC-SV40Tag transgenic mice model of pancreatic cystic neoplasm, we studied the gene expression changes by applying high-density microarrays. Validation of part gene expression profiling data was performed using real-time PCR., Results: By using high-density oligonucleotide microarray, of 14113 genes, 453 were increased and 760 decreased in pancreatic cystic neoplasm, including oncogenes, cell-cycle-related genes, signal transduction-related genes, skeleton-related genes and metabolism-related genes. Among these, we confirmed the changes in Igf, Shh and Wnt signal pathways with real-time PCR. The results of real-time PCR showed similar expression changes in gene chip., Conclusion: all the altered expression genes are associated with cell cycle, DNA damage and repair, signal pathway, and metabolism. SV40Tag may cooperate with several proteins in promoting tumorigenesis.

Biliary cystic tumors, which are also called biliary cystadenoma and cystadenocarcinoma, are thought to be a heterogeneous disease entity, and some of them are known to show a luminal communication to the bile duct. In this study, we examined the clinicopathological features of nine cases of biliary cystic tumors with bile duct communication. They were composed of five males and four females with an average age of 67 years (52-84 years). They were multilocular (eight cases) or unilocular (one case), and all cases contained mucinous fluid. A direct luminal communication with the bile ducts was identified in five cases on preoperative or intraoperative cholangiographies. Biliary cystic tumors examined in this study were histologically adenoma (one case), adenocarcinoma in situ (six cases), and adenocarcinoma associated with microinvasive mucinous carcinoma (two cases). One case of adenocarcinoma in situ also had the adenoma component (adenocarcinoma in adenoma). Dysplastic mucinous epithelium proliferated in flat, micropapillary and papillary fashions within the intracystic spaces. Intraepithelial neoplasm was observed within non-dilated adjacent bile ducts, suggesting a direct luminal communication between the cystic tumors and the bile duct. Ovarian-like stroma was not observed in their walls in any cases. Immunohistochemically, seven cases expressed MUC1 or MUC2 in the neoplastic biliary epithelium. All cases except one were alive without any evidences of tumor recurrence after total excision (3-156 months after surgery). These clinicopathological features resembled those of intraductal papillary neoplasm of the bile duct, which had been reported as a biliary counterpart of pancreatic intraductal papillary mucinous neoplasm. In conclusion, biliary cystic tumors with bile duct communication could be regarded as intraductal papillary neoplasm with a prominent cystic dilatation of the bile duct and mucin retention, rather than true biliary cystic neoplasms., (Published online 2 June 2006.)

Aim: To compare the clinico-pathological features of intraductal papillary mucinous cystic tumours (IPMT) and mucinous cystic tumours (MCT) of the pancreas., Methods: Eighteen patients with IPMT and 18 with MCT who underwent surgical resection between 1990 and 2004 were retrospectively reviewed. Their clinico-pathological features were compared using univariate analysis. Statistical analyses of potential predictive factors of malignancy for each of these two groups were also conducted., Results: Patients with IPMT were found to be older (64+/-10 vs 43+/-18 years, p<0.001) and were predominantly male (male:female ratio, 5:4 vs 1:17, p=0.003) as compared to patients with MCT. MCTs were found in the body-tail region (100%) whereas IPMTs were more evenly distributed (50% in the head) (p=0.001). Pathologically, IPMT was distinct from MCT in terms of size (3.8+/-3.2 vs 9.1+/-4.4 cm, p=0.001), association with secondary pancreatitis (50 vs 0%, p=0.011), communication with the pancreatic duct (94 vs 0%, p<0.001), presence of a dilated main pancreatic duct (61 vs 0%, p<0.001) and the presence of ovarian-type stroma (0 vs 44%, p=0.003)., Conclusion: IPMT and MCT are distinct clinico-pathological entities. This distinction is important as management and outcome of these entities may differ.

Hepatobiliary cystadenoma and cystadenocarcinoma of the gall bladder have rarely been reported. An 88-year-old Japanese man was admitted to our clinic because of hypochondralgia and jaundice. Imaging techniques revealed hemobilia and a multilocular cystic tumor in the fundus of the gall bladder, and cholecystectomy was performed. Grossly, the tumor (3.5 x 3 x 3 cm) was multicystic, containing seromucous fluid. The tumor was located in the fibromuscular layer and subserosa of the gall bladder fundus, and protruded into the serosal surface, not into gall bladder lumen. The mucosa appeared free of tumor involvement, and no gall stones were recognized. Microscopically, the tumor was located in the fibromuscular layer, subserosa and tiny focus of the mucosal surface. The tumor consisted of mucin-rich benign columnar cells, dysplastic mucous cells, malignant papillotubular cells and invasive carcinoma cells. Malignant and atypical tumor cells were located in the center of the tumor and in the tiny area of the mucosal surface, while benign tumor cells were located in the peripheral portions of the tumor and in the serosal side. Neither ovarian stroma-like mesenchymal stroma nor an oncocytic change in tumor cells was recognized. Non-tumorous gall bladder showed chronic cholecystitis. Immunohistochemically, benign and carcinoma cells were positive for cytokeratins, epithelial membrane antigen, CA19-9, MUC1, MUC5AC and MUC6, and carcinoma cells were also positive for carcinoembryonic antigen and p53 protein. The present case indicates that hepatobiliary cystadenocarcinoma without mesenchymal stroma may occur in the gall bladder of old men, and suggests that hepatobiliary cystadenoma without mesenchymal stroma may transform into hepatobiliary cystadenocarcinoma in the gall bladder.

We performed flow cytometry and AgNOR counts on 117 serous and mucinous ovarian tumours, comprising 56 cystadenomas, 21 borderline tumours, and 40 cystadenocarcinomas. DNA aneuploidy was present in one cystadenoma and in 11% of mucinous and 46% of serous cystadenocarcinomas. All borderline tumours were DNA diploid. Major and minor FIGO stages and flow cytometrically determined DNA ploidy and DNA index were prognostically significant. Age, histological type (serous versus mucinous), flow cytometric proliferative index, and AgNOR counts were not predictive of survival. Cystadenomas and borderline tumours had lower rates of proliferation than cystadenocarcinomas. AgNORs correlated with DNA ploidy and proliferative index. Borderline tumours showed elevated AgNOR numbers despite low proliferative indices and universal DNA diploidy, suggesting that AgNOR numbers may be related to nuclear events other than proliferation and DNA ploidy.

Cystadenoma with mesenchymal stroma is a rare neoplasm of the liver that occurs exclusively in young women and has a potential for malignant transformation. A light microscopic and immunohistochemical study of a case of biliary cystadenoma and another of biliary cystadenocarcinoma revealed a range of differentiation of the lining epithelial cells. The lining cells in the cystadenoma resembled the cells of the normal intrahepatic bile ducts. In contrast, the epithelial lining in the case of cystadenocarcinoma had features of intestinal mucosa, including goblet, Paneth, and endocrine cells similar to those found in other mucinous cystic neoplasms of the foregut area. The compact "ovarianlike" mesenchymal stromal cells had immunohistochemical characteristics of myofibroblasts. These are reactive contractile cells that may proliferate in response to the expanding cysts and female hormones, and they differ immunohistochemically from ovarian stromal cells.

Patient records, imaging films, macroscopic and microscopic features, and clinical follow-up data of seven Japanese patients with a mucin-hypersecreting tumor of the pancreas were reviewed. The mucin-hypersecreting tumor was defined as an enlarged major or minor papilla with a dilated orifice and visible mucin oozing on endoscopy. The series consisted of six men and one woman ranging from 47 to 79 yr old. The excretion of mucin through a patulous orifice of the enlarged ampulla of Vater was seen in six patients and of the enlarged minor papilla in the other patient with pancreas divisum. The main pancreatic duct was dilated in all patients. Amorphous mucin was seen in the dilated duct of five patients, and papillary nodules were present in two patients. Computed tomography and/or ultrasonography showed dilatation of the main pancreatic duct with multilocular cysts in six patients and with a solid tumor in the other patient. The tumor was located diffusely in the main pancreatic duct in one patient, whereas it was confined to branches in the head (four patients), body (one patient), or tail (one patient) of the pancreas in the six other patients. Histopathologic diagnosis was a cyst lined by hyperplastic mucus-secreting epithelium in one patient, mucinous cystadenoma in two, and mucinous cystadenocarcinoma in two. Five patients underwent resection and have survived for 1-46 months after the operation. The authors would like to emphasize this endoscopic syndrome because about half of mucin-hypersecreting tumors are malignant with a favorable prognosis.

In this paper, we presented an interesting case with a cystic ovarian tumor, which consisted of the mucinous cystadenoma and the mucinous cystadenocarcinoma separated by a partition. The determination of ferritin concentrations in the both displayed ferritin levels of 87.5 ng/ml in the former and 14,812.0 ng/ml in latter respectively. This fact suggested the production of ferritin by the malignant tumor cells. To clarify this possibility, measurement of ferritin levels in the content of cystic ovarian tumors in fifteen cases and in the ascites of various origin in sixty-five cases was done. This study also supported a possibility that malignant tumor cells produce and/or secrete much more ferritin into the body fluid than benign tumor cells.

Peripheral and ovarian venous concentrations of testosterone, androstenedione, estradiol-17 beta, and estrone were measured in 30 postmenopausal women. Ovarian venous concentrations of testosterone and estradiol-17 beta were 5.6 and 4.3 times the peripheral concentrations of women with normal ovaries. This suggests that the ovaries of postmenopausal women continue to secrete these two steroids. Mean peripheral testosterone concentrations in 14 postmenopausal women with a nonfunctional or functional ovarian tumor were increased significantly. Ovarian venous concentrations of these four steroids from the side draining the tumor-bearing ovary were increased in 40 to 80% of the women. The venous concentrations from the normal ovary were also increased in 22% or more of the women with an ovarian tumor. Any ovarian neoplasm in postmenopausal women may be associated with increased ovarian sex-steroid secretion.