Histologic and Manometric Studies on the Esophagus Following Endoscopic Sclerotherapy

Objective The aim of this work was to study the histologic and manometric changes in the distal esophagus beyond 2 years following endoscopic sclerotherapy (EST) and/or surgical intervention, and to try to understand the etiological factors associated with these changes. Patients and interventions Forty patients, with an average age of 61.5 years, were studied for 2-12 years following sclerotherapy and/or surgical intervention. The causes of liver disease were alcoholic cirrhosis (78.6%), primary biliary cirrhosis (14.3%), and chronic aggressive hepatitis (7.1%). A predominant number of cases (65%) had a mesocaval interposition shunt due to the failure of EST, 32.5% EST alone, and 2.5% esophageal devascularization. All patients had esophageal manometry following mucosal biopsies taken in duplicate endoscopically from three levels of the distal esophagus. Results In the EST and shunt groups, 88.5% had manometric abnormalities, esophagitis, and chronic inflammatory changes. In the EST group, all but two patients had manometric abnormalities and chronic inflammatory changes. Analysis of the patient groups on the basis of the number of EST sessions and the amount of sclerosant injected showed that both histologic changes and dysmotility were more profound in those treated over five times with EST. The differences were significant. Conclusion It appears that EST causes persistent manometric abnormalities and chronic inflammatory changes in the distal esophagus, the severity of which seems to vary directly with the frequency of sclerotherapy and not amount of sclerosant injected

Cytogenetic abnormalities and clonal evolution in an adult hepatoblastoma

Hepatoblastomas usually occur in children < 3 years of age, and only occasional adult cases have been described. To date, 20 cytogenetically abnormal childhood hepatoblastomas have been reported. Karyotypic investigations have shown that most hepatoblastomas are diploid or hyperdiploid, often displaying trisomies for chromosomes 2 and 20. We have cytogenetically investigated an adult hepatoblastoma for which no previous karyotypic data exist. A hypertriploid stemline with multiple numerical and structural chromosomal aberrations, including +2 and +20, was found. In addition, the tumor displayed extensive clonal evolution with 11 subclones. Although the tumor thus displayed some chromosomal abnormalities commonly observed in childhood tumors, providing further support for the importance of these abnormalities in the development of hepatoblastoma, the level of genomic complexity seen in the present case has never been described in childhood hepatoblastomas and may suggest a different etiology or pathogenesis

Frequent rearrangements of chromosomes 1, 7, and 8 in primary liver cancer

Fifteen primary liver carcinomas (PLCs), including 12 hepatocellular carcinomas and three cholangiocellular carcinomas, were investigated cytogenetically after short-term culture. Ten tumors displayed clonal chromosomal abnormalities, whereas only normal karyotypes were detected in four cases, and one sample failed to grow in vitro. Structural rearrangements most often involved chromosomes 1, 7, and 8 and chromosome bands 1p36, 1q25, 3q10, 5q13, 6p10, 7p15, 7q22, 7q32, 8q10, 8q13, 14q10, and 17p11. Frequent genomic imbalances included gains of 1q, 3q, 6p, 7p, and 8q and losses of 1p, 8p, 10q, 14p, 17p, and 19p. A compilation of findings for all 19 cytogenetically abnormal PLCs reported to date, including the present cases, reveals that structural aberrations particularly affect 1p11, 1p22, 1p32, 1p34, 1p36, 1q25, 7p15, 7q22, 8q10, 8q13, 14q10, 16q24, and 17p11, and that the abnormalities frequently result in overrepresentation of 1q, 3q, 6p, 7p10-14, 8q, and 17q and underrepresentation of 1p34-36, 6q27, 7q32-qter, 8p, 13p, 14p, 16q24, and 17p. These genomic regions are likely to harbor genes of importance in hepatocarcinogenesis, and the present cytogenetic mapping may hence be of value for further molecular genetic investigations of PLC

Nonrandom chromosomal aberrations and cytogenetic heterogeneity in gallbladder carcinomas

Chromosome banding analysis of 11 short-term cultured gallbladder carcinomas revealed acquired clonal aberrations in seven tumors (five primary and two metastases). Three of these had one clone, whereas the remaining four were cytogenetically heterogeneous, displaying two to seven aberrant clones. Of a total of 21 abnormal clones, 18 had highly complex karyotypes and three exhibited simple numerical deviations. Double minutes and homogeneously staining regions were observed in one and two carcinomas, respectively. To characterize the karyotypic profile of gallbladder cancer more precisely, we have combined the present findings with our three previously reported cases, thereby providing the largest cytogenetic database on this tumor type to date. A total of 287 chromosomal breakpoints were identified, 251 of which were found in the present study. Chromosome 7 was rearranged most frequently, followed by chromosomes 1, 3, 11, 6, 5, and 8. The bands preferentially involved were 1p32, 1p36, 1q32, 3p21, 6p21, 7p13, 7q11, 7q32, 19p13, 19q13, and 22q13. Nine recurrent abnormalities could, for the first time, be identified in gallbladder carcinoma: del(3)(p13), i(5)(p10), del(6)(q13), del(9)(p13), del(16)(q22), del(17)(p11), i(17)(q10), del(19)(p13), and i(21)(q10). The most common partial or whole-arm gains involved 3q, 5p, 7p, 7q, 8q, 11q, 13q, and 17q, and the most frequent partial or whole-arm losses affected 3p, 4q, 5q, 9p, 10p, 10q, 11p, 14p, 14q, 15p, 17p, 19p, 21p, 21q, and Xp. These chromosomal aberrations and imbalances provide some starting points for molecular analyses of genomic regions that may harbor genes of pathogenetic importance in gallbladder carcinogenesis. Genes Chromosomes Cancer 26:312-321, 1999