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Early gallbladder carcinoma associated with primary sclerosing cholangitis and ... lesion to be papillary adenocarcinoma localized in the mucosal layer (Fig. 3).
J Gastroenterol 2003; 38:704–706 DOI 10.1007/s00535-002-1126-z

Case report Early gallbladder carcinoma associated with primary sclerosing cholangitis and ulcerative colitis Takatsugu Yamamoto1, Kiyoko Uki2, Kazuo Takeuchi3, Natsuko Nagashima3, Hajime Honjo3, Norio Sakurai3, Chikao Okuda3, Goro Watanabe4, Masaya Mori5, and Yasushi Kuyama1 1

Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan Department of Respiratology, Jichi University School of Medicine, Tochigi, Japan 3 Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan 4 Department of Surgery, Toranomon Hospital, Tokyo, Japan 5 Department of Pathology, Toranomon Hospital, Tokyo, Japan 2

Patients troubled with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at high risk for cholangiocarcinoma, whereas cancer of the gallbladder (GBC) is rarely reported to develop in that population. A Japanese man aged 62 years with a 14-year history of PSC and UC had been found to have a protruding lesion of the gallbladder by screening sonography. The preoperative examination suggested the lesion to be GBC at an early stage. Pathology examination after cholecystectomy proved that the lesion was papillary adenocarcinoma localized in the mucosal layer. Although the prognosis of GBC is poor, the outcome of cholecystectomy against early GBC is relatively good. Early detection of the tumor is required for a better prognosis of patients with GBC. According to the review of the literature, PSC and UC patients are regarded as a high-risk group not only for cholangiocarcinoma but also GBC. It is advocated that clinicians perform repeated radiographic examinations including sonography for patients with PSC and UC even if the diseases are being controlled. Key words: cholangitis, ulcerative colitis, gallbladder carcinoma

Introduction Patients suffering from primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at high risk for cholangiocarcinoma,1 whereas cancer of the gallbladder (GBC) is rarely reported in that population. Our literature survey found only 27 GBCs in PSC patients.2–17

Received: November 29, 2001 / Accepted: August 30, 2002 Reprint requests to: T. Yamamoto

Here we report on a patient with UC and PSC who was found by sonography to have GBC at an early stage. It was resected by cholecystectomy, with cure of the patient.

Case report A 62-year-old Japanese man had been treated with salazosulfapyridine and ursodesoxycholic acid because of UC and PSC since 1984. He had undergone repeated screening sonography, at 3- to 5-month intervals. In October 1998 sonography showed a localized protruding lesion of the gallbladder (Fig. 1). Subsequently, he was admitted to Toranomon Hospital for further examination. Laboratory data showed elevation of hepatic function tests including aspartate aminotransferase (AST) (176 IU/l; normal 11–38 IU/l), alanine aminotransferase (ALT) (88 IU/l; 6–50 IU/l); γglutamyltranspeptidase (γGTP) (1806 IU/l; 9–109 IU/l), and alkaline phosphatase (ALP) (615 IU/l; 117–350 IU/ l). Tumor markers remained normal. Endoscopic retrograde cholangiography indicated the existence of the protruding lesion, as well as stenosis and dilatation of the bile duct (Fig. 2). Endoscopic sonography produced almost the same findings as extracorporeal sonography. Computed tomography and angiography suggested that the lesion was localized in the gallbladder wall without invasion of surrounding tissues or metastases. Based on the above findings, we diagnosed the lesion as probable carcinoma at a relatively early stage. Cholecystectomy with lymph node dissection was performed. The pathology examination proved the lesion to be papillary adenocarcinoma localized in the mucosal layer (Fig. 3). There was no lymph node metastasis, vascular invasion, or hepatic invasion. The patient was discharged after an uneventful postoperative period and has been observed in the outpatient clinic until now without recurrence of carcinoma.

T. Yamamoto et al.: Gallbladder carcinoma and cholangitis

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Fig. 1. Extracorporeal sonography shows a protruding lesion of the gallbladder body. (SSA 260A, 3.75-MHz convex probe, Toshiba, Tokyo, Japan)

Fig. 2. Endoscopic retrograde cholangiography demonstrates stricture and dilatation of the common bile duct. Left The cystic duct is bifurcated from the lower portion of the common bile duct. Right Protruding lesion (arrow) is shown at the body of the gallbladder

Discussion Carcinoma of the gallbladder is a malignancy with a poor prognosis because of the difficulty of detecting it at an early stage as well as its invasive nature. The reported 5-year survival for patients with GBC is less than 5% when the cancer is found at an advanced stage.18,19 However, although only rare cases of early GBC at T stages I and II (TNM classification; tumor localized within mucosa or muscularis propria) are diagnosed, when they are the outcome of cholecystectomy is relatively goods.19 Early detection of the tumor is required for getting a better prognosis for those patients. Of 27

cases reported previously, most were found incidentally by autopsy, during cholecystectomy concomitantly performed with colectomy due to UC, or at a late stage requiring liver transplantation.2–17 Although previous authors have warned that gallbladder lesions also develop with a high incidence in PSC patients, such recognition seems not to be remembered sufficiently.17 This is probably the first report of early GBC in a PSC and UC patient that was found before the operation and curatively resected. The reason for GBC developing in our UC and PSC patient remains unclear. Brandt et al. noted that an association between primary sclerosing cholangitis and GBC may

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Fig. 3. Pathology examination proved that the lesion consists of papillary adenocarcinoma, which is localized in the mucosal layer of the gallbladder. H&E, ⫻ 10

be analogous to the increased frequency of adenocarcinomas of the colon in patients with long-standing UC.17 However, regarding our case, chronic inflammation was not seen in the area surrounding the GBC pathologically, which indicates that the gallbladder had not suffered from PSC. Early detection of GBC in the present case may be attributable to repeated ultrasonographic examinations. Sonography is regarded as the most effective modality for detecting GBC at an early stage, although the detection rate remains unsatisfactory.17,20,21 Previous authors have suggested that PSC patients are at high risk not only for bile duct carcinoma but also GBC, and that cholecystectomy should be performed when laparotomy is required owing to an exacerbation of UC.12 We agree with this opinion because of the high mortality rate associated with GBC. Additionally, it is advocated that clinicians perform repeated radiographic examinations, including sonography, for PSC and UC patients even if these diseases are being controlled.

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