Malignant Gallbladder Research Articles

Gallbladder carcinoma: Prognostic factors and therapeutic options

The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ''incidental or occult gallbladder carcinoma'' (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stage-adjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.

Primary signet-ring cell carcinoma of gallbladder resembling linitis plastica: A clinical impostor of chronic cholecystitis

Primary signet-ring cell carcinoma (SRCC) is an extremely rare and aggressive type of malignant gallbladder (GB) neoplasm, which is comprised predominantly (>50%) of signet-ring cells. Owing to its diffusely invading nature, SRCC often confers a linitis plastica like appearance to GB. Such a gross morphology in the background of nonspecific clinical presentation creates confusion with several other benign and more common pathological entities. This dilemma can effectively be settled through clinical, radiological, and pathological correlation. We, here, describe a case of SRCC affecting the GB in a 43-year-old lady. The tumor produced diffuse thickening of GB wall and infiltrated up to subserosa, but not beyond the GB parenchyma.

DNA-PKcs and Ku70 are Predictive Markers for Poor Prognosis of Patients With Gall Bladder Malignancies

Gall bladder cancers (GBCs) are highly resistant to radiotherapy and chemotherapy. Unfortunately, the key molecular mechanisms responsible for therapeutic resistance have not been identified. In this study, the expression of DNA-PKcs and Ku70 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (ACs) were examined by immunohistochemical analysis. Positive DNA-PKcs and Ku70 expression were significantly associated with less lymph node metastasis, invasion, and low TNM stage of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that loss of DNA-PKcs and Ku70 expression significantly correlated with decreased survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that loss of DNA-PKcs and Ku70 expression was an independent poor prognostic predictor in both SC/ASC and AC patients. Our study suggested that DNA-PKcs and Ku70 are tumor suppressors, and loss of DNA-PKcs and Ku70 expression is an important biological marker for metastasis, invasion, and prognosis of GBC. Currently, there is no implication of DNA-PKcs and Ku70 expression in chemoresistance or radioresistance in GBC.

Prognostic significance of nuclear hepatoma-derived growth factor expression in gallbladder cancer.

To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance. We studied 40 patients with gallbladder cancer (GBC) and a control group of 40 patients with cholelithiasis. All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery. None of the patients received chemotherapy or radiotherapy before surgery. All tissue samples were fixed in 4% formalin immediately after removal and embedded in paraffin for immunohistochemical staining. The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining. The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed. Nuclear HDGF expression was significantly higher (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear HDGF levels were associated with histopathological subtype (P < 0.05), clinical stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age, history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival (P < 0.01). Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival. The expression of nuclear HDGF might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

Incidental Gallbladder Cancer at Cholecystectomy

Preoperative predictors of incidental gallbladder cancer (iGBC) have been poorly defined despite the frequency with which cholecystectomy is performed. The objective of this study was to define the incidence of and consider risk factors for iGBC at cholecystectomy. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2009) was used to identify all patients who underwent cholecystectomy (N = 91,260). Patients with an International Classification of Diseases, Ninth Revision, diagnosis of gallbladder malignancy who underwent a laparoscopic cholecystectomy (LC; n = 80,924) or open cholecystectomy (OC; n = 10,336) alone were included. The incidence of iGBC was 0.19% (n = 170) for all cholecystectomy cases, but 0.05% at LC, 0.60% at LC converted to OC (P < 0.001 vs LC), and 1.13% at OC (P < 0.001 vs others). Patients undergoing OC were 17.3 times more likely to have iGBC than LC patients. Age 65 years or older, Asian or African American race, ASA (American Society of Anesthesiologists) class 3 or more, diabetes mellitus, hypertension, weight loss more than 10%, alkaline phosphatase levels 120 units/L or more, and albumin levels 3.6 g/dL or less were associated with iGBC. Multiple logistic regression identified having an OC, age 65 years or older, Asian or African American race, an elevated alkaline phosphatase level, and female sex as independent risk factors. Patients with 1, 2, 3, and 4 of these factors had a 6.3-, 16.7-, 30.0-, and 47.4-fold risk of iGBC, respectively, from a zero-risk factor baseline of 0.03%. Surgeons' suspicion for GBC should be heightened when they are performing or converting from LC to OC and when patients are older, Asian or African American, female, and have an elevated alkaline phosphatase level.

P-0152 - Gallbladder and Biliary Tract Malignancies – Experience of a Center

P-0152 - Gallbladder and Biliary Tract Malignancies – Experience of a Center

Biliary tract malignancies in HIV infected persons: a case series

Case series We report 3 cases of biliary tract malignancy associated with HIV infection from Prayas Amrita clinic, an NGO based HIV clinic in Pune, India. Two of the cases were diagnosed with gall bladder malignancies (GBM) and the third one had cholangio carcinoma (CC). All presented with advanced stage of malignancy with metastases and had poor prognosis. All were males with median age at presentation being 47 years (range 46-48 years) They were diagnosed to have HIV for a median duration of 102 months (range: 69-118 months) . Median nadir CD4 count was 77cells/cmm (range: 71–163 cell/cmm). They were on first line ART for median 63 months (range: 41– 72 months). A patient with GBM was Hepatitis B co infected. Prior AIDS related events of anemia, immune thrombocytopenic purpura and tuberculosis were present in the patient with CC and progressive multifocal leukoencephalopathy was in one of the patients with GBM. Being managed in resource limited setting; the absence of other risk factors is corroborative and lacks evidence.

Contrast-Enhanced Harmonic Endoscopic Ultrasonography in the Differential Diagnosis of Gallbladder Wall Thickening

Differentiation of gallbladder (GB) carcinoma from benign GB wall thickening is challenging. The recent introduction of second-generation ultrasonic contrast agents has made contrast harmonic imaging with EUS possible. The aim of our study was to evaluate the utility of contrast-enhanced harmonic EUS (CH-EUS) for the differential diagnosis of GB wall thickening. Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then underwent surgery were enrolled in this study. After the lesions were observed with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C: experienced gastroenterologist with expertise in transabdominal ultrasound but no EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS. The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was compared. Final diagnoses based on surgical histology were GB carcinoma in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3. Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98% (p < 0.001) and 73.1 versus 94.4% (p < 0.001). The inter-observer agreement for H-EUS was moderate (κ = 0.51), whereas that for CH-EUS was substantial (κ = 0.77). The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of malignant GB wall thickening. CH-EUS has the potential to improve the preoperative diagnostic accuracy and inter-observer agreement in the differential diagnosis of GB wall thickening.

Carcinosarcoma, an atypical subset of gallbladder malignancies

Carcinosarcoma represents an atypical subset of gallbladder malignancies, and sonographic imaging features have not yet been precisely defined. Previously reported cases have shown a heterogeneously echogenic solid mass protruding into and filling the gallbladder lumen. We present herein a case of carcinosarcoma and propose another finding suggestive of this tumor. The patient was a woman in her 70s. Abdominal sonography revealed that the gallbladder lumen was half-filled by a large mass (maximum diameter, 68mm) showing heterogeneous echogenicity slightly higher than that of bile. However, despite the large size of the mass, gallbladder shape was well-preserved. Considering the findings on computed tomography, cholecystectomy was performed under a diagnosis of gallbladder malignancy. Pathological examination revealed two types of malignant histology: a sarcomatous element of malignant spindle cells and a carcinomatous element of adenocarcinoma tissue. Foci of malignant cartilage and bone areas were also found sporadically. Accompanied by immunohistochemical examination, the mass was diagnosed as carcinosarcoma. The present case showed somewhat different imaging findings from those of ordinary gallbladder carcinoma. Carcinosarcoma should be considered when a well-preserved shape of the gallbladder is recognized along with protrusion of a large heterogeneously echogenic mass into and filling the gallbladder lumen.

Gallbladder carcinoma: a New Zealand centre's 10‐year experience with presentation, ethnic diversity and survival rate

Gallbladder cancer is a high-mortality cancer with a wide range of incidence worldwide. Some indigenous populations are known to have a higher incidence of gallbladder cancer. Commonly, it is incidentally discovered during routine gallbladder surgery. The primary aim was to determine the incidence and characteristics of gallbladder cancer in a New Zealand population. The secondary aim was to determine if inequalities in gallbladder cancer rates between Māori and non-Māori have decreased. A retrospective cohort study utilizing an online database was conducted to identify all patients with gallbladder malignancy treated in the Waitemata District Health Board from 2003 to 2013. The outcomes measured were staging of cancer, histology, ethnicity, incidental finding and survival rates. The age-standardized incidence (ASI) rate of gallbladder carcinoma is 0.60/100 000. The gender-specific ASI rates were 0.21/100 000 (men) and 0.76/100 000 (women). The incidence for Māori was 0.96/100 000 (men) and 1.37/100 000 (women). Gallbladder carcinoma was found incidentally in 0.44% of cholecystectomies, which made up 46.2% of all cases. Right upper quadrant pain was the most common presenting symptom (74.4%). Surgery was the most common treatment modality (66.7%). Mean survival across all patients was 12.24 months. Our study found that the ASI of gallbladder carcinoma when compared with the Koea et al. study has decreased for men from New Zealand, but appears to have increased slightly for women from New Zealand. The raw incidence for Māori men and women appears to have decreased, but inequality in gallbladder cancer incidence between Māori and non-Māori remains.

CT differentiation of 1–2-cm gallbladder polyps: benign vs malignant

To evaluate MDCT findings of 1-2-cm sized gallbladder (GB) polyps for differentiation between benign and malignant polyps. Institutional review board approval was obtained, and informed consent was waived. Portal venous phase CT scans of 1-2-cm sized GB polyps caused by various pathologic conditions were retrospectively reviewed by two blinded observers. Among the 36 patients identified, 21 had benign polyps with the remaining 15 having malignant polyps. Size, margin, and shape of GB polyps were evaluated. Attenuation values of the polyps, including mean attenuation, maximum attenuation, and standard deviation, were recorded. As determined by visual inspection, the degree of polyp enhancement was evaluated. Using these CT findings, each of the two radiologists assessed and recorded individual diagnostic confidence for differentiating benign versus malignant polyps on a 5-point scale. The diagnostic performance of CT was evaluated using a receiver operating characteristic curve analysis. There was no significant difference in size between benign and malignant GB polyps. Ill-defined margin and sessile morphology were significantly associated with malignant polyp. There was a significant difference in mean and maximum attenuation values between benign and malignant GB polyps. Mean standard deviation value of malignant polyps was significantly higher than that of benign polyps. All malignant polyps showed either hyperenhancement or marked hyperenhancement. A z value for the diagnosis of malignant GB polyps was 0.905. Margin, shape, and enhancement degree are helpful in differentiating between benign and malignant polyps of 1-2-cm sizes.

Evaluation of Microsatellite Instability and Apoptosis in Gall Bladder Malignancy from Patients of a Cohort Exposed to Methylisocyanate

The molecular alterations are considered to play an important role in the both carcinogenesis and biological behavior of a variety of human malignancies. However, cancer of gallbladder is an obscured phenomenon and highly malignant with a poor survival due to underprivileged diagnosis. Tissues of 92 cases of gallbladder cancer patients (31 men and 61 women, age range 16-85 yrs, mean age 45.83 ± 1.50 yrs) were examined for microsatellite instability (MSI) of six microsatellite markers (D16S539, D13S317, D7S820, F13A01, FES/FPS, vWA) and apoptosis of malignant epithelial cells through M30CytoDEATH assay. Analysis of microsatellite markers revealed 08.7% (08/92) in gallbladder cancer, in which 10.0% (07/70) instability found in adenocarcinoma. The sensitivity of this test in adenocarcinoma, adenosquamous carcinaoma and adenoma with dysplasia was found to be 10.0%, 00.0% and 08.3% respectively suggesting its role in the multistage disease invasiveness. The immunohistochemical examination confirmed the presence of CK18 in moderately, well and poorly differentiated adenocarcinoma with the frequency of viz., 18.8%, 15.4% and 11.1% respectively showing positive sign of apoptosis. The mixed chimerism of STR loci and positive staining of caspase cleaved CK18 in epithelial cells of the gallbladder cancer tissues showed their independent and noteworthy character in the gallbladder carcinogenesis. Further investigations are in progress to undertake similar studies on archived tumor tissues of varied origins and forms. These might also provide modalities to translate forceful and reproducible strategies for defined clinical utility.

Leptomeningeal dissemination in gall bladder carcinoma: sequelae of long-term survival?

Patients with gall bladder malignancies usually present at an advanced stage with less than 20% cases being resectable at presentation and over a half harbouring distant metastases to liver or paraaortic nodes. Long-term cure is uncommon and so is the presence of central nervous system metastases. We present the case of a middle-aged woman with adenocarcinoma gall bladder, treated with postoperative locoregional irradiation following simple cholecystectomy, who developed headache, backache, vision loss, and multiple joint pains six years following adjuvant therapy. A diagnosis of leptomeningeal carcinomatous meningitis was established with cerebrospinal fluid cytology positivity for carcinoma. She deteriorated on palliative cranial irradiation and was managed with best supportive care.

Features Suggestive of Gallbladder Malignancy

Gallbladder cancer carries an extremely high mortality rate, with a 5-year survival rate as low as 12%. Survival is dependent on the diagnosis of these tumors in their earliest stages. This study sought to describe the clinical and imaging features of stages T1, T2, and T3 gallbladder tumors and to illustrate features that may allow radiologists to make an early diagnosis. After approval from the institutional review board, a search of the pathology department database yielded 18 patients with surgically proven T1, T2, and T3 gallbladder cancers with available preoperative computed tomography (CT) or magnetic resonance imaging. The imaging was reviewed for lesional morphology (focal polyploid mass, focal wall thickening, circumferential wall thickening), enhancement characteristics, liver invasion, locoregional lymphadenopathy, and distant metastatic disease. The electronic medical record was also searched for demographic information and clinical presentation. There were 10 women and 8 men with a mean age of 69 years. Virtually all patients were symptomatic, with most patients demonstrating symptoms suggestive of underlying malignancy (including jaundice, weight loss, and chronic abdominal pain). Tumors on CT and MRI included 6 polyploid masses, 9 tumors with focal wall thickening, and 3 with circumferential wall thickening. The mean attenuation of those tumors imaged with CT was 59.4 Hounsfield units (HUs) on the arterial phase and 86.5 HUs on the venous phase, with a mean increase in Hounsfield attenuation between the arterial and venous phases of 28.2 HUs. Twelve of the 18 patients were correctly diagnosed prospectively on CT. The imaging findings of gallbladder cancer can be subtle, regardless of whether the tumor presents as a discrete mass, focal wall thickening, or circumferential diffuse wall thickening, and radiologists should be aware of the wide range of different possible appearances. Moreover, the vast majority of these patients had clinical symptoms suggestive of an underlying malignancy, and this should precipitate a careful evaluation of the gallbladder in all such cases.

Prognostic significance of metastasis associated in colon cancer 1 (MACC1) expression in patients with gallbladder cancer.

The clinical significance of metastasis associated in colon cancer 1 (MACC1), in human gallbladder cancer, is not yet established. This study was performed to assess the expression of MACC1 in benign and malignant gallbladder lesions, and to assess its clinicopathological significance. Tissue samples from resected gallbladder cancer (n=70) and cholelithiasis (n=70) were evaluated for MACC1 expression by immunohistochemical staining. Their expression was correlated with different clinicopathological parameters. Cytoplasmic MACC1 expression was significantly higher (58.6%) in gallbladder cancer than in chronic cholecystitis (27.1%, P<0.001). High MACC1 levels were associated with lymph node metastasis (P<0.05), tumor node metastasis (TNM) stage (P<0.01), and perineural invasion (P<0.01), but not with sex, age, history of gallstones or histological grade (P>0.05). The univariate Kaplan-Meier analysis showed that a positive MACC1 expression was associated with decreased overall survival (P<0.001). The multivariate Cox regression analysis showed that MACC1 expression and the histopathological subtypes were independent risk factors for disease-free survival. The expression of MACC1 might be closely related to carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

Prognostic significance of AgNOR Proliferative Index in gallbladder carcinoma - A potential alternative to frozen section analysis

Introduction: Number of Argyrophillic Nucleolar Organizer Regions (AgNORs) is a good indicator of cellular proliferation activity and is useful diagnostic tool to estimate the malignant potential of tumors. Methods: Tissue sections from 40 cases of gall bladder disease, including 27 cases of gallbladder carcinoma and 13 cases of chronic cholecystitis, were studied for AgNORs count. The correlation of the AgNOR was carried out with various clinco-pathological parameters. Results: Mean AgNOR counts in gallbladder cancer (11.354 ± 1.7866) were significantly higher than chronic cholecystitis (2.0815 ± 0.3731). Amongst patients with gallbladder carcinoma, well-differentiated (9.5867 ± 1.8928), moderately-differentiated (11.1971 ± 1.3181) and poorly-differentiated adenocarcinoma (13.1829 ± 0.9779) showed statistically significant difference in AgNOR counts. On inter stage comparison, study revealed progressive and statistically significant increase in AgNOR count from Tis to T4 stage. Mean AgNOR count for GBCs without metastasis was lower (10.5186 ± 1.6911) than metastatic GBC (12.2538 ± 1.4581), difference being statistically significant (p=0.009). Discussion and conclusions: Our results demonstrate that AgNOR parameters are useful indicators to evaluate malignant behavior of gallbladder carcinoma and its combination with conventional cytology may increase the diagnostic accuracy. AgNOR index can be used as a rapid, inexpensive and easily performed diagnostic tool to aid in early confirmation of a suspicious case of malignant gallbladder disease.

Diffusion-weighted MRI for differentiation of benign from malignant lesions in the gallbladder

To investigate the value of diffusion-weighted imaging (DWI) for differentiating benign from malignant gallbladder lesions. One hundred and twenty-six patients who had undergone magnetic resonance imaging (MRI) with DWI, in whom the histopathological diagnosis of their gallbladder lesions was confirmed by biopsy or surgery were retrospectively analysed. Thirty-six malignant and 90 benign lesions were included. Two radiologists categorized gallbladder lesions into seven types on two imaging sets [T2-weighted imaging (WI) alone and combined T2WI and DWI (b = 800 s/mm(2))] according to the presence of wall thickening, layered patterns, morphology of the mass, and diffusion restriction. Disagreements were resolved in consensus. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging set for diagnosing gallbladder carcinoma were calculated. The diagnostic performance of each imaging set was calculated using receiver operating characteristic (ROC) curve analysis. Additionally, ADC values of malignant and benign gallbladder lesions were compared separately for 1.5 and 3 T MRI. The sensitivity, specificity, PPV, and NPV of diagnosis at T2WI were 97.2%, 86.7%, 74.5%, and 98.7%, respectively. The sensitivity, specificity, PPV, and NPV using combined T2WI and DWI were 97.2%, 92.2%, 83.3%, and 98.8%, respectively. Diagnostic accuracy for gallbladder carcinoma slightly improved after adding DWI, from 0.92 to 0.95 (p < 0.05). ADC values for gallbladder carcinoma were significantly lower than those for benign lesions. Mean ADC values of malignant and benign lesions were 0.97 ± 0.25 × 10(-3) and 1.72 ± 0.56 × 10(-3) mm(2)/s, respectively, at 1.5 T (p < 0.001), and 1.04 ± 0.38 × 10(-3) and 2.2 ± 0.72 × 10(-3) mm(2)/s, respectively, at 3 T (p < 0.001). DWI can improve diagnostic accuracy for differentiating benign from malignant gallbladder lesions.

Ability of FDG‐PET/CT in the detection of gallbladder cancer

To assess the value of FDG-PET/CT in the evaluation of gallbladder carcinomas (GBC). A prospective cohort of patients with suspicion of or confirmed GBC was studied with FDG-PET/CT. Diagnostic accuracy parameters were calculated in comparison with pathology and/or the clinical course of patients. Clinical impact of PET/CT imaging was estimated. Forty-nine patients were enrolled (34 malignant tumors, 15 benign lesions; 37 staging, 12 restaging). Overall diagnostic accuracy was 95.9% for the diagnosis of the primary lesion, 85.7% for lymph node involvement and 95.9% for metastatic disease. Mean SUVmax in malignant gallbladder lesions was 7.92 ± 6.25 Analysis of ROC curves showed a SUVmax cut-off value of 3.62 for malignancy (S: 78.1%; Sp: 88.2%). Diagnostic accuracy in the restaging group reached 100%. FDG-PET/CT changed the management of 22.4% of the population. Diagnosis of malignancy or benignity of suspicious gallbladder lesions is accurately made with FDG PET/CT, allowing a precise staging of GBC due to its ability to identify unsuspected metastatic disease. SUVmax has a complementary role in addition to visual analysis.

AUGIS trainee prize winner: Antimicrobial prophylaxis prior to pancreatico-duodenectomy

AUGIS trainee prize winner: Antimicrobial prophylaxis prior to pancreatico-duodenectomy

Gallbladder FISH: An Unusual Case of Early Detection and Cure of Gallbladder Cancer

Introduction: This is a case report of early diagnosis of gallbladder malignancy using fluorescence in situ hybridization (FISH) that led to surgical resection and cure from a malignancy, which otherwise has a very poor prognosis. Case Description: A 66-year-old Caucasian man with a 12-year history of ulcerative colitis (UC) was evaluated because of abnormal liver function tests and suspected primary sclerosing cholangitis (PSC). He had an abdominal CT scan that showed mildly dilated intrahepatic ducts with no other biliary ductal or gallbladder abnormalities. His Ca 19.9 was elevated at 80 units/mL. He underwent an endoscopic retrograde cholangiography (ERC) that showed irregularity in the distal common bile duct (CBD) and stricturing in the right hepatic duct (RHD) consistent with PSC. Brushing for cytology and FISH were obtained from the CBD and the RHD. Cytology showed reactive cellular atypia and acute inflammation and FISH showed 5 cells with gains of two or more chromosomes, 3(D3Z1), 7(D7Z1), and 17(D17Z1), and greater than 10 cells with gains of a single chromosome, 7(D7Z1). These results were consistent with malignancy. An endoscopic ultrasound was performed showing asymmetric gallbladder wall thickening and no evidence of a mass. The distal CBD was also mildly thickened. He was planned to undergo colectomy for colonic dysplasia in the setting of longstanding UC so he underwent a concomitant cholecystectomy based on our recommendations. Pathology showed a well-differentiated 2.2 cm gallbladder carcinoma with perimuscular invasion but no extension beyond the serosa or into the liver and no malignant adenopathy (stage T2 N0 M0). The patient has been followed-up closely for 2 years with multiple MRIs and ERCs with cytology and FISH being performed. These have been consistently negative for malignancy. He has no other clinical findings suggestive of cholangiocarcinoma. Discussion: While the molecular pathogenesis of adenocarcinoma of the biliary tree remains poorly understood, evidence suggests that there is a field carcinogenic effect in patients with PSC putting them at an increased risk of both cholangiocarcinoma and gallbladder cancer. A positive FISH in our patient with no clear evidence of cholangiocarcinoma prompted a careful examination of the gallbladder with findings suspicious enough to lead to cholecystectomy. This thorough evaluation led to early detection and long-term cure from gallbladder cancer, which otherwise has a very poor prognosis unless detected incidentally on cholecystectomy done for a different etiology.