Surgical management of biliary cystadenoma and cystadenocarcinoma of the liver.

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.

Importance of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vivo.

We have elucidated the importance of a transforming growth factor (TGF) alpha and epidermal growth factor receptor autocrine mechanism on the growth of a human ovarian serous cystadenocarcinoma-derived cell line (SHIN-3) in vitro. In this study, we studied the biological significance of this autocrine mechanism in vivo using female athymic nude (nu/nu) mice. We measured the mouse plasma epidermal growth factor and TGF alpha levels by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Plasma epidermal growth factor concentrations were remarkably decreased by sialoadenectomy (Sx): 410 +/- 65 (SE) pg/ml (n = 10) in intact animals; and undetectable in Sx mice (n = 5). Plasma TGF alpha levels were 90 and 40 pg/ml in intact and in Sx animals, respectively. Ten million SHIN-3 cells inoculated into nu/nu mice formed tumors in 100% of mice, and tumors grew progressively. Implantabilities and tumor growth rates of inoculated cells were not affected by Sx and even by Sx and anti-mouse epidermal growth factor antibody treatment. However, anti-TGF alpha monoclonal antibody (mAb) administered to SHIN-3 cell-inoculated Sx animals drastically reduced the tumor growth. Although 10(7) SHIN-3 cells formed tumors in this group, tumor growth was significantly inhibited by 10 micrograms of anti-TGF alpha mAb given 3 times a week, and growth inhibitions were more by 20 micrograms of anti-TGF alpha mAb. Moreover, as aggressive tumor growth as that in Sx animals was resumed by the cessation of anti-TGF alpha mAb treatments. All these data suggested the biological importance of a TGF alpha/epidermal growth factor receptor autocrine mechanism on the growth of this cell line in vivo.

P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy.

P-glycoprotein (P-gp) expression and DNA topoisomerase (Topo) II are important variables in multidrug resistant tumor cell lines. The aim of this study was to evaluate P-gp expression and Topo I and II activity in benign and malignant epithelial ovarian tumors. P-gp expression was analyzed immunohistochemically in cryostat sections of fresh tumor specimens. In the same specimens Topo I and II activity were measured by, respectively, relaxation of supercoiled plasmid pBR322 DNA and decatenation of kinetoplast DNA. P-gp expression (range, 5-100% positive staining cells) was found in 3 of 6 cystadenomas, 0 of 2 borderline tumors, 15 of 21 untreated ovarian cancers, and 8 of 13 platinum/cyclophosphamide treated ovarian cancers. Median Topo I and II activity were elevated in malignant ovarian tumors compared to benign and borderline tumors. No difference was found between median Topo I activity in untreated ovarian cancer and platinum/cyclophosphamide treated ovarian cancer. High Topo II activity (greater than or equal to 8 x 10(2) units/mg protein) was more frequent in untreated compared to platinum/cyclophosphamide treated samples. Respectively, 8- and 16-fold differences in Topo I and II activity were found in the malignant tumors. Topo II activity in malignant tumors correlated with Topo I activity (r = 0.36, P less than 0.05) and the tumor volume index (r = 0.35, P less than 0.05). However, this last weak correlation cannot explain the 16-fold differences in Topo II activity in malignant tumors. Mitotic index and P-gp expression did not correlate with Topo I or II activity. A large variability in P-gp expression and Topo I and II activity was observed in patients with ovarian cancer.

Impact of menopausal status on the behavior of pancreatic cystic neoplasms in women.

PURPOSE: Pancreatic cystic neoplasms have predilections for occurring in young women, for containing "ovarian-like" stroma, and for expressing estrogen and progesterone receptors; these factors suggest a potentially important influence of the hormonal milieu on the biology of these tumors. Therefore, we examined the impact of menopausal status on the clinical features of pancreatic cystic neoplasms in women. METHODS: Seventy-six women with pancreatic cystic neoplasms treated at our institution from 1992 to 2003 were classified into 2 groups according to menopausal status based on the U.S. average menopausal age of 51 years: group I (premenopausal, ages 22-50; n = 36) and group II (postmenopausal, ages 51-80; n = 40). Chi-square and the 2-tailed t-tests compared categorical and continuous variables, respectively. Kaplan-Meier survival estimates were determined and compared with the log rank test. RESULTS: Abdominal pain at presentation occurred more commonly among group I than among group II patients (78% vs 48%, p < 0.05). Solid pseudopapillary tumors were more prevalent among group I than among group II patients (21% vs 3%, p = 0.02). CONCLUSIONS: The clinicopathologic features of pancreatic cystic neoplasms in premenopausal women are not significantly different from those in postmenopausal women. Menopausal status should not bias diagnostic and treatment algorithms for women with these neoplasms.

Cystadenoma of the proximal common hepatic duct: the use of abdominal ultrasonography and transhepatic cholangiography in diagnosis.

Cystadenoma of the extrahepatic bile ducts is a rare cause of obstructive jaundice. In a case seen recently at our institution, the combined findings are abdominal ultrasonography and transhepatic cholangiography were diagnostic; such studies should provide evidence for preoperative recognition.

Are pancreatic tumors hormone dependent?: A case report of unusual, rapidly growing pancreatic tumor during pregnancy, its possible relationship to female sex hormones, and review of the literature.

The occurrence of a pancreatic tumor in a young patient is rare. However, when one identifies a pancreatic mass during pregnancy and particularly when the lesion is located in the tail of the pancreas, "unusual tumors" of the pancreas should be considered. The management of these tumors during pregnancy presents unusual challenges because of rapid tumor growth probably related to elevated levels of sex hormones. An immunohistochemical study was done to evaluate for hormone receptors of the tissue removed from the tumor. We present a case of a 37-year-old female patient in her 4th week of pregnancy who was found to have a pancreatic mass; she was followed with ultrasonography. At the 23rd week of gestation, the tumor increased in size to more than 12 cm and required resection. Immunohistochemical studies were done to evaluate receptors for progesterone, estrogen, PS2-estrogen-related protein, pancreatic polypeptide antigen, flow cytometry, DNA ploidy, and proliferative activity in tumor cells. Pathology showed a low-grade multiloculated mucinous cystic neoplasm of the pancreas. There was a positivity for progesterone receptor and PS2-estrogen-related protein but not for estrogen receptor in the tumor. We conclude that a pancreatic mass detected during pregnancy requires a different consideration for its management. Early tissue diagnosis with CT or ultrasound-guided biopsy is essential. Even those lesions diagnosed as benign would require early intervention because of their rapid growth, probably influenced by female sex hormones.

Ovarian cystomas and ovulation, a histogenetic concept.

The current histologic classification of tumors of the ovary and testis is reviewed, and their relative frequency is illustrated by notifications to the Swedish Cancer Registry from 1959 to 1965. By far the most common neoplasms were epithelial tumors of the ovary (i.e., cystomas). These do not occur in the testis. Cystomas are believed to originate from the surface epithelium (coelomic epithelium, mesothelium) of the ovary, but there is no generally accepted explanation of how the epithelial cells enter the ovary. Based on the absence of cystomas in the testis, the suggestion is advanced that epithelial inclusions may arise during the reparative period following ovulation. The implications of this concept for the histogenesis of cystomas are discussed.

[Hepatobiliary cystadenoma with mesenchymal stroma: a hormone dependent tumor. Report of five cases with immunohistochemical study of hormone receptors]. / Cystadénome hépatobiliaire à stroma mésenchymateux: une tumeur hormonodépendante?

Hepatobiliary cystadenomas with mesenchymal stroma are rare neoplasms, which occur only in females; they have a strong tendency to recur and a potential for malignant transformation. Microscopic features are characteristic but clinical findings are highly variable and laboratory data non specific. We report 5 cases with immunohistochemical study, showing the characteristics of mesenchymal stromal cells: myofibroblastic phenotype and expression of progesterone receptors in all cases and estrogen receptors in 3 out of 5 cases. These results point out the possible hormonal dependance of this tumor.

[Clinical course of benign epithelial ovarian tumors]. / Klinicheskoe techenie dobrokachestvennykh épitelial'nykh opukholei iaichnikov.

The author reports epidemiological and clinical data on 739 patients with benign epithelial ovarian tumors of various histotypes. Serous cystadenomas were found in 46%, mucinous--in 25.3%, endometroid--in 20%, mixed epithelial--in 6.7%, the Brenner tumor--in 2.02%. Benign ovarian tumors are more frequently observed at the age from 31 to 60. The patients show the tendency to the late menstrual cycle and reduced reproductive function. The clinical picture of the lesion is described.

[Morphological characteristics of cystic pancreatic tumors]. / Morfologicheskaia kharakteristika kistoznykh opukholei podzheludochnoi zhelezy.

The results of 86 clinical observations of cystic pancreatic tumor are adduced. The expediency of the postoperative pathomorphological investigation conduction was substantiated because of high degree of the cystic pancreatic tumors polymorphism presence and low informativity of preoperative and intraoperative investigations.

The expression of FOXL2 in pancreatic, hepatobiliary, and renal tumors with ovarian-type stroma.

FOXL2, a gene encoding a member of the fork-head-winged-helix family of transcription factors, is one of the earliest expressed genes during female gonadal development. It is expressed in normal ovarian stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST. Clinical information was available for 37 patients. Seventy-eight percent of the patients had a history of obesity, heavy alcohol use, or hormone-related therapy. The 2 male patients had histories significant for morbid obesity and chronic alcoholism. FOXL2 is expressed from the early stages of ovarian development and has been shown to be mandatory for normal ovarian function. We have shown that it is also expressed in the aberrant ovarian-type stroma characteristic of PMC, HBC, and MEST. Most of such patients, including the rare male patients, have risk factors for hormonal abnormalities such as obesity and hormonal replacement therapy.

Papillary adenoma of the gallbladder associated with regurgitation of pancreatic juice through abnormally shaped union. Case report.

In a 52-year-old woman papillary adenoma of the gallbladder was associated with regurgitation of pancreatic juice into the biliary tract via an abnormally shaped union, not a long common channel. The condition was demonstrated by endoscopic retrograde cholangiography and histologically confirmed. Extended cholecystectomy and lymph-node dissection were performed.

[Clinico-enzymologic parallels in patients of reproductive age with benign epithelial ovarian tumors]. / Kliniko-énzimologicheskie paralleli u bol'nykh dobro-kachestvennymi épitelial'nymi opukholiami iaichnikov v reproduktivnom vozraste.

Proteolytic enzymes and their inhibitors have been assayed in sera of 120 patients with benign epithelial ovarian tumors during preoperative menstrual cycles and in 3 years following surgery. The patients showed imbalances in protease inhibitors which failed to be improved by the operative treatment in a proportion of patients. Follow-up of this patient population is recommendable. A serum elastase test was proposed to predict benign epithelial ovarian tumors.

[High-dose CDDP therapy using a balloon-occluded arterial infusion (BOAI) in recurrent ovarian cancer].

An intraarterial high-dose CDDP, using a balloon catheter, has been infused into five patients with a recurrent ovarian cancer. The dose of CDDP was 150 mg-200 mg/body. Two patients experienced a partial tumor regression, whereas three showed no change. With regard to the toxicity, the NAG index (NAG activity/urinary creatinine) rose markedly in all patients, but toxicity was almost similar to that seen from a systemic administration. No significant catheter complication occurred.

Promotion of cholangiocarcinogenesis in the hamster liver by bile duct ligation after dimethylnitrosamine initiation.

Administration of hepatocarcinogenic nitrosamines before or after infection with the liver fluke, Opisthorchis viverrini (OV), results in marked development of cholangiocellular and hepatocellular precancerous and cancerous lesions in the hamster liver. The promoting effects of OV are believed to be exerted either mechanically, chemically or immunologically. To test the influence of possible mechanical effects, Syrian hamsters were initiated with a single i.p. injection of dimethylnitrosamine (DMN) 20 mg/kg and subjected 2 weeks later either to a sham operation or to complete ligation of the extrahepatic bile duct to the left lateral lobe. At the end of week 40, the animals receiving DMN-initiation and ligation had a 60.9% incidence of cholangiofibrosis, 21.7% of mucous cystadenomas and 39.1% of cholangiocarcinomas, whereas the group given DMN alone only developed cholangiofibrosis, limited to 5% of the animals. In the latter case neither cystadenomas nor cholangiocarcinomas were observed. The incidence of hepatocellular nodules did not differ between the two groups and no tumorous lesions developed in either the ligated or the untreated groups without DMN pretreatment. Complete ligation of the bile duct itself led to a series of events; obstruction of bile flow being followed by dilatation, cyst formation, and necrosis of the bile duct epithelium and surrounding affected areas leading to regenerative proliferation. The results are in line with the conclusion that parasite-associated proliferation in target cell populations is, at least in part, responsible for the influence of OV on liver tumor development.