Effect of cell migration-inducing hyaluronidase 1 on biological function of gallbladder cancer GBC-SD cells and its mechanism / 中华肝胆外科杂志

Objective:To investigate the effect of cell migration-inducing hyaluronidase 1 (CEMIP) on biological function of gallbladder cancer GBC-SD cells and its possible mechanism.Methods:The expression of CEMIP in biliary epithelial cell line HIBEC and gallbladder cancer cell line NOZ and GBC-SD was detected by Western blot. GBC-SD cells in logarithmic growth phase were divided into blank control group, negative control group (transfection with nonsense siRNA), siCEMIP-1 group (transfection with siCEMIP-1) and siCEMIP-2 group (transfection with siCEMIP-2). The expression of CEMIP and binding immunoglobulin protein (Bip) and calreticulin (CRT) in GBC-SD cells was detected by Western blot after culturing for 48h in blank control group, negative control group, siCEMIP-1 and siCEMIP-2 group. The relative survival rate was determined by CCK-8 assay. The wound healing rate and apoptotic rate was detected by wound healing assay and flow cytometry. The migration and invasion abilities were evaluated by Transwell chamber assay. Twelve 5-week-old BALB/c-nude mice were selected and divided into control group and experimental group (6 mice in each group). GBC-SD cells and GBC-SD cells with silenced CEMIP were subcutaneously injected into the right armpit (forelimb) of the two groups of mice, respectively. The volume and weight of transplanted tumor were compared 33 days later.Results:Compared with HIBEC cells, the relative protein level of CEMIP in gallbladder cancer GBC-SD cells [(0.750±0.034) vs. (0.120±0.002)] and NOZ cells [(0.690±0.013) vs. (0.120±0.002)] was significantly higher ( P<0.05). Compared with blank control group and negative control group, the relative protein level of CEMIP, Bip and CRT in siCEMIP-1 group and siCEMIP-2 group was significantly lower ( P<0.05). Compared with blank control group and negative control group, the relative survival rate and wound healing rate and number of migration cells and invading cells in siCEMIP-1 group and siCEMIP-2 group were also significantly lower ( P<0.05). While the apoptotic rate in siCEMIP-1 group and siCEMIP-2 group were higher than that in blank control group and negative control group ( P<0.05). Compared with control group, the average tumor volume [(543.6±114.7) vs. (801.5±256.3) mm 3] and tumor weight [(0.453±0.093) vs. (0.728±0.278) g ] of the experimental group was significantly decreased ( P<0.05). Conclusions:CEMIP was up-regulated in gallbladder cancer cell line GBC-SD and NOZ. Silencing CEMIP inhibited cell proliferation, wound healing rate, migration and invasion, and promoted apoptosis in gallbladder cancer GBC-SD cells, which may be related to the inhibition of endoplasmic reticulum chaperone Bip and CRT expression.

Utility of triple tumor markers CA19-9, CA125 and CEA in predicting advanced stage of carcinoma gallbladder: a retrospective study

Background: A combination of serum tumor markers are used in the evaluation and prognosis of carcinoma gallbladder (GBC). Aim of the study was to find the significance of combined use of CA19-9, CA125 and CEA in advanced stage of GBC and to find the cut-off value of each of these tumor markers in metastatic GBC.   Methods: This was a retrospective observational cohort study over 1 year, which was carried out in 42 cases of advanced GBC. The patients were grouped in to locally advanced and metastatic stage on the basis of CECT scan findings. CA19-9, CA125 and CEA were assayed in all patients. These tumor markers were analysed with these two groups of GBCs. Statistical analysis was performed using R statistical software v3.6.2.Results: Out of 42 cases CA19-9 was elevated in 18 (78%), CA125 in 16 (70%) and CEA in 9 (39%) patients with metastatic disease. The cut-off value of CA19-9, CA125 and CEA was determined by ROC curve were >109 U/ml, 55.4 U/ml and 2.56 μg/l respectively. CA19-9 had the highest sensitivity 78.3% followed by CA125 69.6% and CEA has the highest specificity 68.4% for the diagnosis of metastatic stage of the disease. Specificity of these tumor markers were highest when used in combination.Conclusions: Combined use of triple tumor markers increases its specificity in the diagnosis of advanced stage of GBC but their cut-off level is statistically not significant in predicting metastatic GBC.

Ultrasound Guided Fine Needle Aspiration Cytology of Gallbladder Lesions Suspected to be Carcinoma Gallbladder: Experience of a Tertiary Care Hospital

Gallbladder carcinoma is the most common biliary tract malignancy in the world. Radiologicalinvestigations are helpful in diagnosing the gallbladder diseases especially carcinoma in most of thecases, but confirmation of diagnosis requires cytopathological correlation. We have undertaken astudy on 29 patients, who underwent ultrasound guided FNAC for evaluation of gallbladder lesionssuspected to be carcinoma gallbladder. 82.75% of patients had malignancy or suspicion of malignancyand 10.34% patients had abscesses, while in 6.9 % patients FNAC was inconclusive. Adenocarcinoma(NOS) was the most common diagnosis and was found in 62.6 % of patients. Poorly differentiatedcarcinoma, cytology suspicious of malignancy and abscesses were present in 7 % of patients each.Papillary carcinoma and squamous cell carcinoma were only seen in 3.44 % patients each. None ofthe patients in our study developed any minor or major complications during the procedure. A precisecytological examination is required not only to diagnose or rule out gallbladder malignancy, but alsofor prognostication of these carcinomas.

Evaluation of Gallbladder Diseases

Gallbladder diseases are very common entities with diverse features of presentation at clinical, radiological and pathological settings with variable morbidities and mortalities. It implies an altered hepatobiliary function. A majority of gallbladder diseases involve gallstones, which form about 95% of all gallbladder diseases. The noncalculus disease forms only about 4–5% of the cases. Inflammations of gallbladder, either acute or chronic, are commonly seen in association with calculus gallbladder. Benign neoplasms are very rare compared to malignant neoplasms that are more common but uncommon compared to inflammatory conditions. Gallbladder diseases are very common and it is appropriate to emphasise that knowledge of these diseases is imperative. In the present study of 50 patients an attempt was made to correlate the clinical, radiological and pathological features of gallbladder diseases and to ascertain the sensitivity of ultrasound in the evaluation of gallbladder diseases. The radiological diagnosis in gallbladder diseases had favourable results against the clinical diagnosis and has also been shown to be impressive against the pathological diagnosis. In our study the radiological diagnosis of gallbladder diseases is shown with reference to most of the disease conditions.

Biological behavior and disease pattern of carcinoma gallbladder shown on 64-slice CT scanner: A hospital-based retrospective observational study and our experience.

Purpose: The aim of this diagnostic observational study was to assess the spread and biological behavior of gallbladder cancer using 64-slice computerized tomography (CT) scanner in this particular geographic belt (eastern Uttar Pradesh, western Bihar, and northern Madhya Pradesh provinces of North India). Indians are ethnically and culturally different from their Western counterparts among whom the incidence of this disease is comparatively low. Subjects and Methods: After systemic examination, all patients (87) were subjected to ultrasonographic examination. All cases were histopathologically proven. Confirmed cases were subjected to volumetric CT examination of abdomen and pelvis, plain, post contrast and delayed phase. Results: Majority of the cases were adenocarcinoma. There was female preponderance with majority belonging to fifth and sixth decades. Commonest presentation was diffuse, irregular, enhancing wall thickening in 49.4%. Majority had invasion of liver parenchyma (74.7%). Cholelithiasis was seen in 48.3% cases. Invasion of biliary radicals was high (13.8-18.4%). Eleven cases had invasion of portal vein and tumor thrombus, with hepatic artery invasion in one case. In two cases, both hepatic artery and portal vein invasion was seen. Portal and peripancreatic nodal metastasis was seen in 58.5%. Distant metastasis was reported. Conclusion: Few studies involving the Indian population have attempted to use multi-row detector CT to define the biological behavior of carcinoma gallbladder. The opinion whether the pathology is operable or non-operable can reasonably be given. This large-scale, single-center study gives insight about the epidemiology and biological behavior of carcinoma gallbladder.

Gallbladder Mucosal Changes Associated with Chronic Cholecystitis and Their Relationship with Carcinoma Gallbladder.

384 cholecystectomy specimens were examined during a period of one year from Oct 2005 to Oct 2006, in the department of Pathology, ASCOMS, Sidhra. Jammu, for studying the histological patterns of chronic cholecystitis, the frequency of associated mucosal changes, the age related incidence and the relationship of carcinoma with various mucosal changes. Majority of patients presented in the fourth decade of life. The youngest patient was 16 years and the oldest 78 years of age. Acute and chronic inflammatory lesions were associated with ulceration in 13.02%, mucosal hyperplasia in 25.26% and antral metaplasia in 53.40%. Intestinal metaplasia constituted 9.11%, cholesterolosis was seen in 12.25%, dysplasia in 3.64% and neoplasia in 0.78% of cases. All the cases of carcinoma were associated with gallstones. Histological continuity between epithelial changes was seen in 35 cases. 8 cases had continuity of antral metaplasia, intestinal metaplasia and dysplasia. 2 cases showed continuity of intestinal metaplasia with dysplasia and carcinoma and 1 case showed continuity of dysplasia with carcinoma.It is inferred that antral metaplasia, intestinal metaplasia, dysplasia and carcinoma have an inter-relationship. There is a significant higher incidence of carcinoma gallbladder in patients who harbor gallstones for longer period. Histopathological examination is thus important in every case of cholecystectomy for identifying metaplasia, dysplasia and carcinoma.