Biliary Intraepithelial Neoplasia With Gallbladder Adenoma and Cirrhosis: A Case Report.

Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of cholangiocarcinoma that has been rarely reported. The present study reports a 56-year-old male with low-grade BilIN of the bile ducts and the cystic duct margin. Stent exchange endoscopy demonstrated an irregular, intraductal mass extending along the common bile duct, common hepatic duct, and hepatic duct bifurcation. The peribiliary mass was found to abut the right portal vein, inferior vena cava, and pancreatic head, and replaced the right hepatic artery. In addition, there was evidence of gallbladder adenoma managed with cholecystectomy and a right-lobed liver lesion and cirrhosis, which prompted the discussion of prophylactic liver transplantation. We emphasize the radiological features of BilIN and associated pathological findings through multiple imaging modalities. Consideration of this diagnosis is indicated in western countries and requires timely management based on available guidelines.

Pyloric adenomatous carcinoma of the gallbladder following laparoscopic cholecystectomy: A case report.

INTRODUCTION: Adenoma and intra-adenoma carcinoma of the gallbladder are relatively rare diseases, and the World Health Organization classification reports a frequency of 0.3% for gallbladder adenomas. Precise preoperative diagnosis of gallbladder cancer, especially in the early stages, is challenging. Herein, we report a case of pyloric adenomatous carcinoma of the gallbladder, diagnosed by laparoscopic cholecystectomy and pathology, along with a literature review. This case was reported in accordance with the SCARE 2020 Guideline (Ref). PRESENTATION OF CASE: A 62-year-old woman was diagnosed with a 4-mm polypoid lesion in the gallbladder during a medical examination. The patient was followed-up by ultrasonography (US) once a year and was referred to our department because of an increase in size. Carcinoembryonic antigen and carbohydrate antigen 19-9 levels were within normal limits. Abdominal ultrasonography revealed a pedunculated polypoid lesion in the body of the gallbladder measuring 8 mm. Computed tomography demonstrated that the whole tumor was enhanced in the early phase without significant lymph node enlargement. Magnetic resonance cholangiopancreatography demonstrated a type Ip polypoid lesion located in the body of the gallbladder without pancreaticobiliary junctional abnormalities. Endoscopic ultrasound detected a superficial nodular-type Ip polypoid lesion in the gallbladder body with a parenchyma-like internal echogenic pattern. DISCUSSION: Based on these findings, the patient was diagnosed with gallbladder adenoma, and laparoscopic cholecystectomy was performed. Histopathological examination revealed the tumor was a papillary growth of atypical high columnar epithelial cells. The final diagnosis was pyloric adenoma with high-grade dysplasia and intra-adenoma carcinoma. The patient is currently undergoing outpatient follow-up without recurrence for 1 year. CONCLUSION: Early gallbladder carcinoma with adenoma should be considered in patients with small gallbladder polypoid lesions. Considering the surgical stress of cholecystectomy and the malignant potential of gallbladder cancer, preceding surgery would be acceptable.

A transcriptome profile in gallbladder cancer based on annotation analysis of microarray studies.

The purpose of the present study was to identify aberrantly expressed genes for gallbladder cancer based on the annotation analysis of microarray studies and to explore their potential functions. Differential gene expression was investigated in cholesterol polyps, gallbladder adenoma and gallbladder cancer using microarrays. Subsequently, microarray results were comprehensively analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the affected biological processes or pathways. Differentially expressed genes (DEGs) of cholesterol polyps, gallbladder adenoma and gallbladder cancer were identified. Following comprehensive analysis, 14 genes were found to be differentially expressed in the gallbladder wall of both gallbladder cancer and gallbladder adenoma. The 20 most significantly upregulated genes were only upregulated in the gallbladder wall of gallbladder cancer, but not in the gallbladder wall of cholesterol polyps and gallbladder adenoma. In addition, 182 DEGs were upregulated in the gallbladder wall of gallbladder adenoma compared with the gallbladder wall of cholesterol polyps. A total of 20 most significant DEGs were found in both the tumor and gallbladder wall of gallbladder cancer. In addition, the most significant DEGs that were identified were only upregulated in the tumor of gallbladder cancer. GO and KEGG analysis indicated that the aforementioned DEGs could participate in numerous biological processes or pathways associated with the development of gallbladder cancer. The present findings will help improve the current understanding of tumorigenesis and the development of gallbladder cancer.

Is contrast enhanced ultrasonography an accurate way to diagnose gallbladder adenoma? A systematic review and meta-analysis.

INTRODUCTION: Gallbladder adenoma (GA) is a precancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The aim of present systematic review and meta-analysis was to evaluate the diagnostic accuracy of contrast-enhanced ultrasound in the diagnosis of gallbladder adenoma. METHODS: The searches were conducted by two independent researchers to find the relevant studies published from 1/1/2009 until end of 30/06/2019. The search included published literature in the English language in MEDLINE via PubMed, EMBASE via Ovid, The Cochrane Library, and Trip databases. For literature published in other languages, national databases (Magiran and SID), KoreaMed, and LILACS were searched. The risk of bias of every article was evaluated by using QUADAS-2. On the basis of the results from the 2 × 2 tables, pooled measures for sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curves (AUC) along with their 95% confidence intervals (CIs) were calculated using the DerSimonian Lair methodology. RESULTS: Overall, 868 patients were studied in the 10 studies chosen for inclusion. Of these 10 studies, 5 (50%) were retrospective and 5 (50%) were prospective. The total prevalence of gallbladder adenoma in 10 studies was 16% (95% CI 13%, 18%). The sensitivity and specificity of contrast-enhanced ultrasound were 0.846 (95% CI 0.818-0.871) and 0.870 (95% CI: 0.844-0.894), respectively. The diagnostic odds ratio was 40.807 (95% CI 18.838-88.393). CONCLUSION: CEUS is a reliable, non-invasive, and no-radiation-exposure imaging modality with a high sensitivity and specificity for detection of gallbladder adenoma. Nonetheless, it should be applied cautiously, and large scale, well-designed trials are necessary to assess its clinical value.

Large and unusual presentation of gallbladder adenoma: A case report.

BACKGROUND: Gallbladder adenoma is a relatively rare benign tumor with a potential for malignant transformation if found to be greater than 1 cm in size. CASE SUMMARY: Herein, we report a case of a 51-year-old female with large 3 cm × 3 cm mass of gallbladder adenoma that was misdiagnosed as adenocarcinoma due to its clinical presentation. Computed tomography and magnetic resonance imaging scans showed an irregularly shaped cauliflower-like lump in the gallbladder measuring 38 mm × 32 mm corresponding to a malignant tumor and several gallbladder stones with low diffusion-weighted imaging and equisignal of T1-weighted imaging and T2-weighted imaging; moreover, the CA 19-9 levels were very high (184.1 U/mL). Pathology reports after tumor resection showed adenoma with moderate epithelial atypia and moderate atypia in the focal area with fine pedicle and no clear infiltration. CONCLUSION: Computed tomography and magnetic resonance imaging scans need to be carefully scrutinized in certain rare cases of adenomas with abnormal imaging features.

Ultrasound Radiomics Effective for Preoperative Identification of True and Pseudo Gallbladder Polyps Based on Spatial and Morphological Features.

Purpose: To explore the value of ultrasound radiomics in the preoperative identification of true and pseudo gallbladder polyps and to evaluate the associated diagnostic accuracy. Methods: Totally, 99 pathologically proven gallbladder polyps in 96 patients were enrolled, including 58 cholesterol polyps (55 patients) and 41 gallbladder tubular adenomas (41 patients). Features on preoperative ultrasound images, including spatial and morphological features, were acquired for each lesion. Following this, two-stage feature selection was adopted using Fisher's inter-intraclass variance ratios and Z-scores for the selection of intrinsic features important for differential diagnosis achievement with support vector machine use. Results: Eighty radiomic features were extracted from each polyp. Eight intrinsic features were identified after two-stage selection. The contrast 14 (Cont14) and entropy 6 (Entr6) values in the cholesterol polyp group were significantly higher than those in the gallbladder adenoma group (4.063 ± 1.682 vs. 2.715 ± 1.867, p < 0.001 for Cont14; 4.712 ± 0.427 vs. 4.380 ± 0.720, p = 0.003 for Entr6); however, the homogeneity 13 (Homo13) and energy 8 (Ener8) values in the cholesterol polyp group were significantly lower (0.500 ± 0.069 vs. 0.572 ± 0.057, p < 0.001 for Homo13; 0.050 ± 0.023 vs. 0.068 ± 0.038, p = 0.002 for Ener8). These results indicate that the pixel distribution of cholesterol polyps was more uneven than that of gallbladder tubular adenomas. The dispersion degree was also significantly lower in the cholesterol polyp group than the gallbladder adenoma group (0.579 ± 0.054 vs. 0.608 ± 0.041, p = 0.005), indicating a lower dispersion of high-intensity areas in the cholesterol polyps. The long axis length of the fitting ellipse (Maj.Len), diameter of a circle equal to the lesion area (Eq.Dia) and perimeter (Per) values in the cholesterol polyp group were significantly lower than those in the gallbladder adenoma group (0.971 ± 0.485 vs. 1.738 ± 0.912, p < 0.001 for Maj.Len; 0.818 ± 0.393 vs. 1.438 ± 0.650, p < 0.001 for Eq.Dia; 2.637 ± 1.281 vs. 5.033 ± 2.353, p < 0.001 for Per), demonstrating that the cholesterol polyps were smaller and more regular in terms of morphology. The classification accuracy, sensitivity, specificity, and area under the curve values were 0.875, 0.885, 0.857, and 0.898, respectively. Conclusions: Ultrasound radiomic analysis based on the spatial and morphological features extracted from ultrasound images effectively contributed to the preoperative diagnosis of true and pseudo gallbladder polyps and may be valuable in their clinical management.

Benign gallbladder diseases: Imaging techniques and tips for differentiating with malignant gallbladder diseases.

Benign gallbladder diseases usually present with intraluminal lesions and localized or diffuse wall thickening. Intraluminal lesions of the gallbladder include gallstones, cholesterol polyps, adenomas, or sludge and polypoid type of gallbladder cancer must subsequently be excluded. Polyp size, stalk width, and enhancement intensity on contrast-enhanced ultrasound and degree of diffusion restriction may help differentiate cholesterol polyps and adenomas from gallbladder cancer. Localized gallbladder wall thickening is largely due to segmental or focal gallbladder adenomyomatosis, although infiltrative cancer may present similarly. Identification of Rokitansky-Aschoff sinuses is pivotal in diagnosing adenomyomatosis. The layered pattern, degree of enhancement, and integrity of the wall are imaging clues that help discriminate innocuous thickening from gallbladder cancer. High-resolution ultrasound is especially useful for analyzing the layering of gallbladder wall. A diffusely thickened wall is frequently seen in inflammatory processes of the gallbladder. Nevertheless, it is important to check for coexistent cancer in instances of acute cholecystitis. Ultrasound used alone is limited in evaluating complicated cholecystitis and often requires complementary computed tomography. In chronic cholecystitis, preservation of a two-layered wall and weak wall enhancement are diagnostic clues for excluding malignancy. Magnetic resonance imaging in conjunction with diffusion-weighted imaging helps to differentiate xathogranulomatous cholecystitis from gallbladder cancer by identifying the presence of fat and degree of diffusion restriction. Such distinctions require a familiarity with typical imaging features of various gallbladder diseases and an understanding of the roles that assorted imaging modalities play in gallbladder evaluations.

The correlation of contrast-enhanced ultrasound vascular mode with gallbladder polyp nature and size / 中华医学超声杂志（电子版）

Objective To evaluate the correlation between enhancement vascular mode and gallbladder polyp nature and size with contrast-enhance ultrasound (CEUS).Methods From December 2014 to May 2016,patients with gallbladder polyp lesions (GPL) larger than 1.0 cm were enrolled in this study.Before cholecystectomy,every patient underwent ultrasound (US) and CEUS examination.All features of US and CEUS were analyzed by two doctors who were blind to the patient clinical data.According to the pathological findings,GPL were divided into cholesterol polyp group and gallbladder adenoma group.The US features and enhancement vascular mode were analyzed statistically by t test and x2 test.The independent risk factors were analyzed by Logistic regression.The relationship between enhancement vascular mod and size of GPL were determined by bivariate correlation analysis.Results There were 103 patients with GPL larger than 1.0 cm.Eighty-two cases were cholesterol polyp and 21 cases were gallbladder adenoma.There were differences in size and color Doppler blood flow between two groups (t=-5.97 and 7.94,P ＜ 0.05).Dotted,branched vascular mod and irregular vascular mode were statistical different between two groups (x2=10.09 and 8.43,P ＜ 0.05).Regression analysis data proved that the size and branch vascular mod were the independent risk factors related with adenoma (P ＜ 0.05).In both cholesterol polyp group and adenoma group,there were weak positive correlation between enhancement vascular mode and size of GPL (r=0.188,0.397,P ＜ 0.05).Conclusions Branch vascular mod and size of GPL were help to distinguish gallbladder adenoma from cholesterol polyp.Comprehensive analysis of GPL's size and vascular mode could offer important guidance for differentiation diagnosis.

Contrast-enhanced ultrasound may distinguish gallbladder adenoma from cholesterol polyps: a prospective case-control study.

PURPOSE: The aim of this study was to find the independent risk factors related with gallbladder (GB) adenoma compared to cholesterol polyp by contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Between January 2010 and September 2014, a total of 122 consecutive patients undergoing cholecystectomy for GB polypoid lesions were enrolled. Before cholecystectomy, each patient underwent conventional US and CEUS examination and all image features were documented. The patients were divided into adenoma group and cholesterol polyp group according to the pathological findings. All the image features between two groups were statistically compared. RESULTS: There were differences in patient age, lesion size, echogenicity, and vascularity of lesion between two groups (P < 0.05). There were differences in stalk width and enhancement intensity between the two groups (P < 0.05). Multiple logistic regression analysis proved that enhancement intensity, stalk of lesion, and vascularity were the independent risk factors related with GB adenoma (P < 0.05). CONCLUSIONS: CEUS could offer useful information to distinguish adenoma from cholesterol polyp. The treatment algorithm for gallbladder polyp lesions would likely benefit from CEUS as a routine imaging investigation, especially in cases where the polyp is larger than 1 cm.

Expression of heat-shock protein gp96 in gallbladder cancer and its prognostic clinical significance.

PURPOSE: To detect the expression and prognostic clinical significance of heat-shock protein gp96 (HSP gp96) in gallbladder cancer. METHODS: Immunohistochemistry was used to detect and compare the rate of HSP gp96 expression in 107 samples of gallbladder cancer, 70 of gallbladder adenoma and 67 of chronic cholecystitis. The association of clinicopathological factors and patients' survival were calculated by univariate and multivariate (Cox proportional hazard regression method) analysis. RESULTS: The expression positive rate of HSP gp96 was 90.7% (97/107) in gallbladder cancer, 71.4% (50/70) in gallbladder adenoma and 47.76% (32/67) in chronic cholecystitis respectively. The positive rate of HSP gp96 in gallbladder cancer tissues was significantly higher than that in gallbladder adenoma and chronic cholecystitis tissues (P < 0.01). Multivariate and Cox regression analysis showed that positive of HSP gp96 (P = 0.026) expression was an independent poor prognostic predictor in gallbladder cancer. CONCLUSIONS: HSP gp96-positive expression is closely correlated with poor survival in gallbladder cancer.

Value of contrast-enhanced ultrasound in the differential diagnosis between gallbladder adenoma and gallbladder adenoma canceration.

OBJECTIVES: To investigate the value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between gallbladder adenomas and gallbladder adenomas canceration. METHODS: CEUS data from 34 patients (25 patients with gallbladder adenomas and 9 patients with gallbladder adenomas canceration) were retrospectively analyzed, including the characteristics of contrast arrival time, time to peak enhancement, enhancement extend, enhancement morphology and the intactness of gallbladder wall below the lesions. RESULTS: On CEIS, the contrast arrival time and the time to peak enhancement were significantly shorter in patients with gallbladder adenomas than in patients with gallbladder adenomas canceration (12.63 ± 3.37 s vs. 18.11 ± 3.26 s, P < 0.001; 17.42 ± 3.69 s vs. 24.56 ± 4.36 s, P < 0.001). The time to iso-enhancement showed no significant difference between the two groups; while the time to hypo-enhancement was significantly shorter in patients with gallbladder adenomas canceration than in patients with gallbladder adenomas (55.56 ± 15.48 s vs. 84.71 ± 36.07 s, P = 0.027), and the enhancement time of the liver was significantly slower in patients with gallbladder adenomas canceration than in patients with gallbladder adenomas (22.78 ± 5.28 s vs. 16.63 ± 4.66 s, P = 0.004). Using receiver operating characteristic (ROC) analysis, the time to peak enhancement greater than 20 s had 89% sensitivity and 84% specificity for detecting patients with gallbladder adenomas canceration. The enhancement level showed no difference between the two groups. Inhomogeneous enhancement was found in 33% (3/9) gallbladder adenoma canceration and none (0/25) of gallbladder adenoma (P < 0.01). Destruction of gallbladder wall intactness was found in 66.7% (6/9) gallbladder adenoma canceration and none (0/25) of gallbladder adenoma (P < 0.01). CONCLUSION: CEUS is useful in differentiation between gallbladder adenoma and gallbladder adenoma canceration. The time to peak enhancement, the enhancement morphology and the intactness of gallbladder wall below the lesions are the diagnostic clues in differentiating diagnosis between gallbladder adenoma and gallbladder adenoma canceration.

Expression of HER2 and bradykinin B1 receptors in precursor lesions of gallbladder carcinoma.

AIM: To determine the expression of HER2 and bradykinin B(1) receptors (B(1)R) in the two pathogenic models of gallbladder cancer: the metaplasia-dysplasia-carcinoma and the adenoma-carcinoma pathways. METHODS: Receptor proteins were visualized by immunohistochemistry on 5-µm sections of paraffin-embedded tissue. Expression of both receptors was studied in biopsy samples from 92 patients (6 males and 86 females; age ranging from 28 to 86 years, mean 56 years). High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridization. Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker. RESULTS: HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium. On the contrary, there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia (22/24; 91.7%) and carcinoma in situ (9/10; 90%), the lesions that displayed a significantly high proliferation index. Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene amplification. A similar result was observed in invasive carcinomas (0/12). The B(1)R distribution pattern mirrored that of HER2 except that B(1)R was additionally observed in the adenomas. The B(1)R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia (24/24; 100%) and carcinoma in situ (10/10; 100%) and in the epithelial cells of adenomas. In contrast, both HER2 (4/12; 33%) and B(1)R (1/12; 8.3%) showed a low expression in invasive gallbladder carcinomas. CONCLUSION: The up-regulation of HER2 and B(1)R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis.

Histopathologic Analysis of Adenoma and Adenoma-related Lesions of the Gallbladder / 대한소화기학회지

BACKGROUND/AIMS: In order to determine the malignant potential of gallbladder adenoma for progression to carcinoma, we evaluated the histopathologic features of adenoma and adenoma-related lesions on cholecystectomized specimens. METHODS: Among 1,847 cholecystectomized specimens, 63 specimens from 26 benign adenomas, 9 carcinomas in situ (CIS), and 28 invasive carcinomas were selected. A pathologist reviewed all specimens and selected benign adenomas, CIS in the adenoma, and adenoma residue in invasive carcinomas. Adenomas and adenoma-related lesions were classified according to morphology (tubular, tubulopapillary, and papillary) and the consisting epithelium (biliary, pyloric metaplasia, and intestinal metaplasia). The age and the size of the benign adenomas and carcinomas in the adenoma were also compared. RESULTS: Adenoma and adenoma-related lesions were found in 34 out (1.8%) of all resected gallbladder. Among 9 CIS and 28 invasive carcinomas, adenoma-related lesions were detected in 7 and 1 case, respectively. All eight carcinomas arising in the adenoma were well-differentiated solitary tumors. The diameters of the carcinomas in the adenoma were, on average, larger than that of the benign adenomas (1.8 cm vs. 0.9 cm, p=0.01). The patients with carcinomas in the adenoma were, on average, older than those with benign adenomas, although the difference was insignificant (57 years vs. 47 years, p=0.09). The morphology and consisting epithelium did not differ between the benign adenomas and carcinomas in the adenoma. The malignant transformation occurred in 23.5% of adenomas. CONCLUSIONS: Gallbladder adenoma is a rare disease, although malignant transformation occurs frequently. Adenoma is a precancerous lesion and the adenoma-carcinoma sequence is one of the gallbladder cancer carcinogenesis.

Nuclear morphometry and PCNA analysis of adenoma and carcinoma in gallbladder / 中华肝胆外科杂志

Objective To make clear the relationship between adenoma,malignant transformation of ade- noma and carcinoma in gallbladder.Methodes The nuclear morphometry was performed with a TJTY-300 Auto- matic Image Analyser and PCNA was measured with immunohistochemisty in 25 cases of carcinoma,20 cases of adenoma and 3 cases of normal gallbladder.Results (1) Cell DNA content,atypia and PCNA index were in- creased gradually from the normal cell to dysplasia to malignant transformation of adenoma to carcinoma in gallblad- der;(2) Aneuploidy in gallbladder adenoma and PCNA index had significant relationship to the size of adenoma and gallstones (P