Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection.

Reactivation of a former hepatitis B virus (HBV) infection can be triggered by immunosuppressive therapy, diseases associated with an immunocompromised state, organ transplantation or the withdrawal of antiviral drugs. Despite the absence of such risk factors, a spontaneous reactivation of HBV replication occurred in two elderly patients with resolved or occult HBV infection. A 73-year-old male underwent coronary artery bypass grafting in October 2008, and was negative for HBsAg but positive for anti-HBs. In July 2009, his serum became positive for HBsAg, HBeAg and HBV DNA (6.4 log copies/ml; genotype C), but negative for anti-HBc IgM, with abrupt elevation of the liver enzymes. The entire genomic sequence of HBV recovered from this patient revealed no mutations in the core promoter and precore regions that interfere with HBeAg production. A 76-year-old male with a history of endoscopic mucosal resection for esophageal cancer in 2002 and an initial diagnosis of diabetes mellitus in 2009, at which time he was negative for HBsAg. He was found to be positive for HBsAg in September 2012 during a laboratory examination performed prior to the resection of recurrent esophageal cancer, despite a low HBV load (2.1 log copies/ml). Three months later, without the administration of any anticancer drugs, the HBV DNA (genotype B) level increased to 5.1 log copies/ml. A precore G1896A variant with high quasispecies diversity was recovered from the patient. Aging, surgical stress and complication of disease(s) associated with compromised immunity, such as cancer, arteriosclerosis and diabetes mellitus may trigger spontaneous HBV reactivation.

Gallbladder carcinoma with ultrasonographically intact outer hyperechoic layer: A sign of a favorable outcome.

Thirty-one of 40 patients with gallbladder carcinoma whom we treated from December 1983 through June 1999 underwent resection of cancers extending from the mucosa (m) (pTis-pT1a) to the subserosa (ss) (pT2). The patients were classified into five groups according to the layered-structure of the gallbladder wall and the internal echo of tumors visualized in ultrasound images. Group A included pedunculated polyps with round margins, homogeneous hypoechoic internal echoes, and intact outer hyperechoic layers; group B, broad-based lesions with homogeneous hypoechoic internal echoes and intact outer hyperechoic layers; group C, broad-based lesions with intact outer hyperechoic layers and more heterogeneous hypoechoic internal echoes in their centers than those in the marginal lesions; group D, broad-based lesions with irregularity and/or thinning of outer hyperechoic layers; and group E, tumors that could not be evaluated. The ultrasonograms and histopathologic findings of groups A through D were compared, and the surgical techniques used in each group were examined. Outcomes achieved by groups A through C, with their intact outer hyperechoic layers, were compared with those achieved by groups D and E.The six tumors in group A were all well-differentiated adenocarcinomas confined to the mucosa (pTis), and simple cholecystectomy was considered appropriate. The eight tumors in group B comprised three cases of m (pTis-pT1a) cancer, two cases of cancer invading the muscularis propria (mp) (pT1b), and three cases of cancer minutely scattered in the infiltrating subserosal fibrous layer (ss fibrous layer) (pT2). Accordingly, because of the difficulty of determining depth of invasion, resection of the liver bed was considered appropriate in group B. Histopathologic examination of group C showed that the tumors had invaded the ss fibrous layer (pT2) in all six patients. Although the ss fat layer had not been invaded, metastasis to the lymph nodes of the cystic duct (30%) had occurred, suggesting that a favorable outcome could be expected if the patient underwent resection of the liver bed and lymphadenectomy of the cystic duct, pericholedochal, hilar, peripancreatic, periportal, common hepatic, and proper hepatic lymph nodes. Group D comprised two patients with cancers that had invaded the ss fat layer (pT2). All nine tumors in group E were ss (pT2) cancers. The 5-year survival rate was 100 percent in groups A, B, and C; 50 percent in group D, and 45 percent in group E. Five-year survival rates were significantly lower in groups D and E than in groups A, B, and C, in which the outer hyperechoic layer remained intact (p<0.01).Gallbladder carcinomas with intact outer hyperechoic layers were classified into three groups (groups A, B, and C), in which depth of invasion ranged from m (pTis-pT1a) to the ss fibrous layer (pT2). These three groups were associated with favorable outcomes, although different surgical techniques were required for each group. An intact outer hyperechoic layer in the ultrasonogram is a predictor of a favorable outcome in patients with gallbladder carcinoma.