RESUMO
Carcinoma of the gallbladder is a rare disease. Gallbladder carcinoma is detected in less than 1% of all gallstone operations. With the introduction of laparoscopic surgery and the higher acceptance of this technique, gallbladders are now removed much earlier than they used to be. With the increase of cholecystectomies, the diagnosis of unexpected gallbladder carcinoma became more frequent. We report on how to proceed in patients with a diagnosis of gallbladder carcinoma and discuss the additional problems that have arisen since laparoscopic cholecystectomy became established. From June 1990 to December 1999, we performed 6230 cholecystectomies in the surgical department of Moabit Hospital in Berlin. Of these, 42 (0.6%) were identified as carcinoma. There were 37 women and five men, and the mean age was 69 years. In 16 patients (39%), there was a preoperative suspicion of malignancy. In 26 patients (61%), malignancy was suspected intraoperatively or diagnosed postoperatively after pathologic examination of the resected gallbladder. In these patients, an open repeat operation was necessary in seven cases to achieve an adequate curative resection and staging. This involved additional liver bed resection and lymph node dissection of the hepatoduodenal ligament. Abdominal wall (port site) recurrence in the absence of distant metastasis was present only in two patients. We recommend removal using a bag in all gallbladders with wall thickening, irregularities, or scleroatrophic calcified gallbladder area. In stage Tis or T1, laparoscopic cholecystectomy is sufficient. In stage T2 and T3, we perform a repeat operation with liver bed resection and lymphadenectomy.
Assuntos
Colecistectomia Laparoscópica/estatística & dados numéricos , Neoplasias da Vesícula Biliar/cirurgia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/patologia , Alemanha/epidemiologia , Hepatectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Reoperação , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The AF-4 gene on human chromosome 4q21 is involved in reciprocal translocations to the ALL-1 gene on chromosome 11q23, which are associated with acute lymphoblastic leukaemias. A set of recombinant phage carrying genomic fragments for the coding region and flanking sequences of the AF-4 gene were isolated. Phage inserts were assembled into four contigs with 21 exons, and an intron phase map was produced enabling the interpretation of translocation-generated fusion proteins. The gene contains two alternative first exons, 1a and 1b, both including a translation initiation codon. The translocation breakpoint cluster region is flanked by exons 3 and 6 and two different polyadenylation signals were identified. Polyclonal antisera directed against three different portions of the AF-4 protein were produced and used to detect a 116 kD protein in cellular extracts of human B-lymphoblastoid and proB cell lines. In mitogen-stimulated human peripheral blood mononuclear cells the AF-4 antigen was predominantly located in the nucleus. The AF-4 gene is a member of the AF-4, LAF-4 and FMR-2 gene family. The members of this family encode serine-proline-rich proteins with properties of nuclear transcription factors. Comparison of AF-4 protein coding sequences with the LAF-4 and FMR-2 sequences revealed five highly conserved domains of potential functional relevance.
Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 4/genética , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas/genética , Transativadores , Translocação Genética , Sequência de Aminoácidos , Sequência de Bases , Western Blotting , Proteínas de Ligação a DNA/química , Éxons/genética , Humanos , Íntrons/genética , Dados de Sequência Molecular , Proteínas Nucleares/química , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Análise de Sequência , Fatores de Elongação da TranscriçãoRESUMO
The ALL-1 gene is an important regulator of embryonal and hematopoietic development, and structural variants of the human gene generated by chromosomal translocations and other genomic alterations presumably act as oncogenes in the pathogenesis of acute leukemias and other hematological malignancies. Antisera against two different epitopes of the human ALL-1 protein (anti-ALL1-N and anti-ALL1-C) were produced. Both sera revealed indistinguishable patterns of antigen localization in human peripheral blood mononuclear cells (PBMCs). In resting PBMCs, the antigen was distributed in a speckled pattern across the nuclei, with an increased density at the nuclear envelope and the nuclear indentation. In mitotically stimulated PBMCs, the antigen surrounded the condensing chromosomes but did not colocalize with chromatin or the nuclear scaffold. The antigen is considered a marker for a novel nuclear subcompartment, a perichromosomal area termed the "chromosomal envelope." In Western blot experiments, the anti-ALL1-N serum reacted with a polypeptide corresponding to the expected full-length 430-kDa ALL-1 protein. Recombinant proteins representing the AT-hook and zinc binding subdomains of the ALL-1 protein interacted in vitro with a degenerate mixture of double-stranded oligodeoxynucleotides. Thus, the ALL-1 protein probably is a DNA-binding protein with both a sequence-unspecific (AT-hook) and a sequence-specific (zinc binding subdomains) double-stranded DNA binding mode.
Assuntos
Proteínas de Ligação a DNA/sangue , Leucócitos Mononucleares/metabolismo , Proto-Oncogenes , Fatores de Transcrição , Animais , Divisão Celular/fisiologia , Núcleo Celular/metabolismo , Células Cultivadas , DNA Complementar/genética , Proteínas de Ligação a DNA/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Histona-Lisina N-Metiltransferase , Humanos , Imuno-Histoquímica , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Mitógenos/farmacologia , Proteína de Leucina Linfoide-Mieloide , Coelhos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Dedos de ZincoRESUMO
The human ALL-1/MLL/HRX gene on chromosome 11q23 is the site of many locally clustered chromosomal alterations associated with several types of acute leukemias, including deletions. partial duplications and reciprocal translocations. Structurally variant proteins derived from an altered ALL-1 gene presumably make essential contributions to the malignant transformation of hematopoietic progenitor cells. The ALL-1 gene is spread over approximately 92 kb and consists of at least 37 exons. An exon/intron map including the position of the 3'-end of the gene and a detailed restriction map were produced and an updated map is presented. Data from other laboratories were incorporated where compatible. Exon/intron boundaries were sequenced and an intron-phase analysis was performed. The results are expected to contribute to a better understanding of those structural alterations of the gene that conserve the open reading frame and produce presumably oncogenic variants of the ALL-1 protein. They will also facilitate the rapid molecular diagnosis of structural alterations of this gene and the choice of therapeutic options. Mechanisms that may potentially account for the striking clustering of the translocation breakpoints in the breakpoint cluster region of the gene are discussed.