Gallbladder Adenoma Research Articles

Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas

Although most gallbladder carcinomas evolve from dysplasia and carcinoma in situ, the role of gallbladder adenomas in the pathogenesis of gallbladder carcinoma is still controversial. A series of molecular changes including loss of heterozygosity (LOH) at 17p ( TP53 gene), 13q ( RB gene), 18q ( DCC gene), and 9p21 ( CDKN2a gene) chromosomal regions have been identified in dysplasias, carcinomas in situ, and invasive carcinomas of the gallbladder, whereas mutations in K- and N- ras genes are rare. To determine whether the molecular abnormalities of adenomas are similar to those found in carcinomas, we obtained extracted DNA from precisely microdissected tissue from 16 gallbladder adenomas (14 pyloric and 2 intestinal-type). We determined the presence of mutations in TP53, K- and N- ras genes, and LOH at five chromosomal regions (5q22 APC-MCC region, RB, TP53, DCC and 9p21- CDKN2a). For the TP53 mutation study, single strand conformational polymorphism (SSCP) analysis in exons 4 to 8 were performed. K- and N- ras mutations detection was performed by designed restriction fragment length polymorphism (RFLP) method and sequencing. Only a single LOH (at 5q22) was detected in a gallbladder adenoma of intestinal type. No mutations at the TP53 were detected. Four adenomas (25%) showed K- ras mutations (two in codon 12 and two in codon 61). We conclude that gallbladder adenoma lacks the molecular changes frequently detected in dysplasia, carcinoma in situ, and invasive carcinoma of the gallbladder. Likewise the occurrence of K- ras mutations at codon 12 and 61 in 25% of adenomas strongly suggests that these lesions are not precursors of invasive gallbladder carcinoma.

Histological and genetic changes in malignant transformation of gallbladder adenoma

Elucidate the histological and genetic changes in malignant transformation of adenoma of the gallbladder. Forty-three adenomas and 20 intramucosal tumors of carcinoma-in-adenomas were studied for histological and genetic changes (particularly K-ras mutation and p53 protein overexpression by immunohistochemistry) in malignant transformation. The genetic changes were compared with those of 164 carcinomas without anomalous union and 17 carcinomas with anomalous union of pancreatico-biliary duct. Atypical cell foci, i.e. spindle cell foci, were observed only in the adenoma area, with a frequency of 23% in 39 adenomas, and of 45% in 20 tumors of carcinoma-in-adenoma. 129 of 130 spindle cell foci examined were negative for Ki-67 staining and all the spindle cell foci were negative for p53 stain. K-ras mutation and p53 overexpression were not found in all adenomas, pure and with carcinoma i.s., and only one carcinoma (1/16, 6%) with adenoma showed p53 overexpression. K-ras mutation was low (10%, 4/40) in carcinomas without adenoma, but high in carcinomas with anomalous union of pancreatico-biliary duct. While, p53 overexpression was high and similar in carcinomas with and without anomalous union. These results suggest that there are three distinct pathways in gallbladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, de novo carcinoma with anomalous union from K-ras mutation and p53 mutation, and carcinoma-in-adenoma from K-ras-, p53-, and probably APC-gene-related, as yet unknown, alteration.

Differences in c-fos gene product expression in cancers of the gall-bladder and biliary tract.

The c-fos gene encodes a 55 kDa nuclear protein product that complexes to a cellular protein, p39. The pattern of expression of c-fos is particularly complex with increased expression of the protein observed in undifferentiated cultured cells while reduced expression is found during terminal differentiation. The expression of c-fos gene was studied by immunohistochemistry in carcinoma of the gall-bladder (n = 13), biliary tract (n = 5) and ampulla of Vater (n = 9). Non-malignant conditions investigated include chronic cholecystitis (n = 11), gall-bladder dysplasia (n = 3) and adenoma (n = 1), and ampullary carcinoma in situ (n = 3). Strong positive granular cytoplasmic immunostaining for c-fos oncoprotein was present in most gall-bladder adenocarcinomas (n = 11; 85%). The single gall-bladder adenoma and only one of the dysplasia cases were positive. Most of the cases of chronic cholecystitis showed either absent or only focal to patchy and weak to moderate c-fos immunoreactivity in the deeper glands and Rokitansky-Aschoff sinuses but not in the superficial epithelium. None of the biliary tract and ampullary tumors showed immunostaining for c-fos. The difference in c-fos immunoreactivity between gall-bladder carcinoma and chronic cholecystitis was statistically significant (P = 0.0002; chi 2 test with continuity correction). In conclusion, c-fos protein may be important in the development of gall-bladder neoplasia with increased c-fos immunoreactivity in gall-bladder carcinoma but not in chronic cholecystitis, biliary tract and ampullary neoplasms. These findings suggest that gall-bladder carcinoma may arise from a different genetic basis compared to biliary tract and ampullary cancers.

Sonographic-Pathologic Correlation of Gallbladder Adenoma: Adenoma versus Adenoma with Dysplasia

Sonographic-Pathologic Correlation of Gallbladder Adenoma: Adenoma versus Adenoma with Dysplasia

Percutaneous Endoscopic Polypectomy of Gallbladder Polyps

We report here our preliminary experience with percutaneous endoscopic polypectomy of gallbladder polyps. Five patients with a total of 17 cholesterol polyps (size: 4-6 mm) and one patient with two gallbladder adenomas (size: 5 mm), four of whom were symptomatic and all of whom refused cholecystectomy, underwent a single-stage procedure under epidural anesthesia. All patients had functioning gallbladders, as assessed by oral cholecystography after stimulation. Following a small incision, the gallbladder was pulled out of the abdominal wall, incised, and a cholecystoscope introduced. The polyps were coagulated at their stalk using microwave irradiation (70-80 mA, 9 sec) and removed for histopathological evaluation thereafter. A catheter was left in situ for ten days. Follow-up for a mean of 11.6 months (8-16 months) showed all patients to be symptom-free and without recurrence of polyps on ultrasonography. Gallbladder function was assessed in five cases by meal-stimulated oral cholecystography, and in one by hepato-iminodiacetate acid (HIDA) scan and was found to be well preserved. The preliminary results warrant further evaluation of this method of removing indeterminate gallbladder polyps.

A cace of gallbladder adenoma based on cholesterol polyp

A cace of gallbladder adenoma based on cholesterol polyp

大腸腺腫症術後に発見された十二指腸乳頭部癌と胆嚢腺腫の１例

大腸腺腫症で大腸全摘除術後3年目に発見された十二指腸乳頭部癌と胆嚢腺腫の1例を経験したので,若干の文献的考察を加え報告する,症例は61歳,女性.昭和60年1月,当科で直腸癌と上行結腸癌を伴う大腸腺腫症の診断にて,大腸全摘除および回腸瘻造設術を施行.その後外来で経過観察中,背部鈍痛が出現,増強してきたため入院となった.内視鏡的逆行性膵胆管造影(ERCP)では乳頭部に易出血性の腫瘤と胆嚢内に陰影欠損を認めた,乳頭部腫瘍の生検で腺癌と診断され昭和63年12,月7日,膵頭十二指腸刧除術施行.切除標本では乳頭部に約2×2×lcmの隆起病変を認め,病理組織学的に高分化型管状腺癌であり,また十二指腸と胆嚢にみられたポリープは腺管腺腫であった.平成元年3月31日退院となり,現在再発もなく外来通院中である.

Morphometrical analysis of gall-bladder adenoma and adenocarcinoma with reference to histogenesis and adenoma-carcinoma sequence

In order to examine whether our subdivision of gall-bladder adenoma and adenocarcinoma into non-metaplastic and metaplastic types is reasonable from the viewpoint of their cytological features, a morphometrical analysis was conducted on 17 adenomas and 59 adenocarcinomas. The morphometrical parameters used were nucleo-cytoplasmic ratio (N/C ratio) and nuclear areas (NA). N/C ratio in the metaplastic type of both adenoma and adenocarcinoma was significantly larger than that in the non-metaplastic. This result shows that the different tumour types are associated with a different N/C ratio. Continuous measurement of N/C ratio and NA in progressing from non-cancerous mucosa to the lesion was made and the data obtained were analysed by the Lowess method. In some adenomas the total area of polypoid lesions was serially measured and these data were also analysed by the Lowess method. The results showed different processes in non-metaplastic and metaplastic types of adenoma and adenocarcinoma from the standpoint of nuclear changes of N/C ratio and NA. These results indicate that our histogenetic classification of adenocarcinoma is reasonable in morphometrical nuclear analysis. We also investigated the adenoma-carcinoma sequence as a possible histogenesis for gall-bladder carcinoma. Eight (72.7%) of 11 metaplastic adenomas and two (33.3%) of six non-metaplastic adenomas had foci of atypical gland proliferation and were considered to be carcinomas. Moreover, these carcinomatous areas were surrounded by severe dysplasia. These findings indicate that adenoma-carcinoma sequence accounts for one of the histogenesis of gall-bladder carcinoma.

TWO RESECTED CASES OF GALLBLADDER POLYP DIFFICULT TO DIFFERENTIATE FROM CARCINOMA

This paper describes our recent experiences of gallbladder bed resection with lymph node dissection for gallbladder adenoma (Case 1) and gallbladder carcinoma in adenoma (Case 2), the diagnoses of which were polypoid gallbladder carcinomas before surgery because the lesions were large. We also present our view that the operative method of gallbladder bed resection may be benefical for gallbladder lesions in which it is difficult to decide whether they are benign or malignant before and during surgery and it is hard to clear tumor invasion in the resected wedge of the gallbladder bed when simple cholecystectomy is performed. In these cases, a microwave tissue coagulator was very useful for the gallbladder bed resection. Case 1 was a 67-year-old woman. Polypoid lesions about 3cm and 1cm in diameter were found at the peritoneal side and hepatic side of the body of the gallbladder by transabdominal ultrasonography. Gallbladder bed resection and lymph node dissection were performed because of the suspicion of gallbadder carcinoma, though aspiration cytology of the tumor performed preopeartively had revealed Papanicolaou Class III. Case 2 was a 49-year-old woman. A polypoid lesion about 4cm in diameter was found at the peritoneal side of the body of the gallbladder by transabdominal ultorasonography and aspiration cytology before surgery revealed Papanicolaou Class II. Gallbladder bed resection with lymph node dissection was performed bacuse it was difficult to decide whether the lesion was benign or malignant on histological examination with the frozen specimen taken intraoperatively.

Fragile papilloma (papillary adenoma) of the gallbladder

Abstract This case study of a young man with a papillary adenoma of the gallbladder documents the potential for benign tumors of the gallbladder to present with symptoms of biliary colic. The case illustrates the mechanism by which free-floating, detached, tumor particles cause intermittent obstruction of the cystic duct, and it presents the attendant symptoms.

胃癌に重複した胆嚢腺腫内癌の１例

胃癌に重複した胆嚢腺腫内癌の１例