Prognostic significance of the p53 mutation in esophageal cancer.

In the esophagus, alterations in the p53 tumor suppressor gene are associated with the development of preinvasive neoplastic lesions to invasive carcinoma. The role of p53 gene mutation in the progression of esophageal cancer still remains unclear. In this study, 82 DNA samples extracted from formalin-fixed, paraffin-embedded esophageal cancer tissues were analyzed for p53 mutation by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. All the patients had been treated surgically and were Japanese. Exons 5 through 8 of the p53 gene were amplified in DNAs and the mutations detected in 28 cases (34%) did not correlate with tumor location, histopathologic classification, histologic depth of tumor invasion, lymph node involvement or clinical stage. Among 39 patients with stage 3 and 4 disease who had undergone radical esophageal resection, those with p53 mutation had a poorer prognosis, the two-year survival being 25.4% compared with 61.2% for those without p53 mutation (P<0.01). These results suggest that p53 gene mutations play an important role not only in the genesis but also the progression of human esophageal cancer.

Laparoscopic repair of a colonic perforation sustained during colonoscopy.

A patient who sustained a colonic perforation during therapeutic colonoscopy was treated successfully by laparoscopic repair. Laparoscopy was performed 5 h after polypectomy. Fecal matter was not identified in the peritoneal cavity. Local peritonitis was mild. The laceration was oversewn with five sutures using the extracorporeal endoscopic knot technique. The appendix epiploica was then anchored over the lesion. The postoperative recovery was rapid and uneventful. Laparoscopic surgery may become a useful tool for the safe, effective, and minimally invasive management of iatrogenic colonic perforation.

Intratumoral heterogeneity of hst-1 gene amplification in esophageal carcinoma with reference to DNA stem line heterogeneity.

Amplification of the hst-1 gene was examined in 112 neoplastic lesions from 27 patients with esophageal carcinoma. Ninety specimens were separately obtained from two or more sections of each individual primary tumor with DNA stem line heterogeneity and 22 specimens were obtained from metastatic lymph node lesions. The assessment was that hst-1 gene amplification within each individual primary tumor was identical in all 27 cases (100%) and that the intensity of amplification in the primary tumor matched that in the metastatic lesion in 18 of 22 cases (82%). When we examined 33 endoscopic biopsy specimens from esophageal carcinoma in the same manner, the intensity of hst-1 gene amplification in the specimens was similar to that obtained in surgical specimens from 26 of the 33 patients (79%). These results suggest that hst-1 gene amplification might occur in a homogeneous manner as a relatively early genetic event prior to lymph node metastasis, and that therefore, prior to surgical treatment, it can be evaluated from a single biopsy specimen.

High amplification of the hst-1 gene correlates with haematogenous recurrence after curative resection of oesophageal carcinoma.

Amplification of the hst-1 gene was examined in 82 patients with oesophageal carcinoma by dot blot hybridization to assess the potential of haematogenous recurrence after curative resection. Intensity of amplification was considered negative (one- to twofold increase) in 45 patients, low (three-sixfold increase) in 19 and high (greater than sevenfold) in 18. Haematogenous recurrence after curative resection was found in seven of eight patients with high amplification and was significantly higher in such patients than in those without amplification (P < 0.05). The finding that sevenfold or greater amplification of the hst-1 gene seems to be associated with haematogenous recurrence of oesophageal cancer after resection may serve to assess the clinical outcome.

A case of chronic necrotizing pulmonary aspergillosis due to Aspergillus nidulans.

A 55-year old man without immunosuppression clinically showed a coin lesion in the right lower lung on the chest radiographs. Aspergillus nidulans was isolated and identified in both trans-bronchial lung biopsy specimen and resected tissue. The specimens revealed characteristics of chronic necrotizing pulmonary aspergillosis pathologically. Very few reports on cases of pulmonary aspergillosis due to A. nidulans exist, and we were not able to find any reports of similar cases. This case may be the first reported case of chronic necrotizing pulmonary aspergillosis due to A. nidulans.

Extended survival time for esophageal cancer patients treated with aggressive surgery and concurrent chemoradiation.

In attempts to improve overall long-term survival of patients with esophageal cancer, including medically inoperable patients and operable ones with disseminated disease, we treated operable patients with aggressive surgery and postoperative chemoradiation, and inoperable patients with chemoradiation alone. Chemoradiation consisted of 5,000-6,000 cGy of radiation and two courses of chemotherapy (cisplatin, vindesine, and pepleomycin). Of 90 patients seen between 1986 and 1991, 63 operable patients underwent surgery and 35 received postoperative chemoradiation, while 19 of 27 inoperable patients received chemoradiation. Results were compared with those of 48 unselected historical control patients treated since 1981. Survival at 5 years was significantly improved for the multimodality group (17.7 +/- 5.0%), as compared with the historical control group (10.4 +/- 4.4%). Thus, the overall therapy for patients with esophageal cancer has been improved.

Cloning and nucleotide sequence of a cDNA of the human erythrocyte NADPH-flavin reductase.

A cDNA of human erythrocyte NADPH-flavin reductase was cloned from a lambda gt 11 human reticulocyte cDNA library by polymerase chain reaction using degenerate primers and followed by a plaque hybridization. The nucleotide sequence of the cDNA contains an open reading frame of 621 base pairs which encodes 206 amino acid residues including an initial methionine. The amino acid sequence deduced from the base sequence coincided well with peptide sequence determined for the purified human erythrocyte NADPH-flavin reductase. A homologous sequence to the FMN-binding site of flavodoxins was found at the amino-terminal region.

DNA stem line heterogeneity in esophageal cancer accurately identified by flow cytometric analysis.

BACKGROUND: This study was designed to evaluate the importance of DNA stem line heterogeneity in determining the malignant potential of esophageal cancer. METHODS: Flow cytometric analysis of intratumor heterogeneity of DNA contents was performed on step-sectioned slices of 57 resected esophageal carcinomas. RESULTS: DNA stem line heterogeneity, as assessed by DNA content measurements, was present in 25 (44%) tumors; 6 (11%) were a combination of diploid and aneuploid DNA pattern, and 19 (33%) had two or more aneuploid peaks with different DNA contents (multiploid). Of the remaining 32 homogeneous tumors, 4 showed only a diploid DNA pattern in all samples examined, whereas 28 tumors had only the aneuploid pattern. Tumors with the heterogeneous DNA pattern had a significantly higher frequency of lymph node metastasis than did those with the homogeneous DNA pattern (P < 0.05). CONCLUSIONS: For evaluation of the highly malignant potential of esophageal carcinoma by nuclear DNA contents, it is important to identify accurately intratumoral heterogeneity. Because different DNA stem lines were evident in different areas of the lesion, evaluation of multiple specimens from a wide area of each lesion is needed to determine with accuracy the degree of intratumor DNA stem line heterogeneity.

Cisplatin, vindesine, pepleomycin and concurrent radiation therapy following esophagectomy with lymph adenectomy for patients with an esophageal carcinoma.

Between 1986 and 1991, 35 patients with esophageal cancer (TNM stages II-IV) underwent transthoracic esophagectomy with lymph adenectomy and were subsequently treated with 5,000 cGy of radiation (days 1-40) and concurrently with two courses of chemotherapy (cisplatin, vindesine and pepleomycin, days 21-26 and 49-54). Results were compared with those of 26 historical control patients, treated with radiation since 1981. Tolerance in all patients was good. The survival rate at 5 years was significantly improved for the multimodality-treated patients (30.9 +/- 9.4%), as compared with findings in historical controls (5.1 +/- 4.8%). The concurrent chemoradiation therapy using these three drugs following extensive surgery is worthy of consideration for patients with a localized esophageal cancer.

[Preoperative evaluation of malignant potential in esophageal carcinoma by nuclear DNA contents].

Employing surgically resected specimens from patients without preoperative radiation therapy, we measured the nuclear DNA contents in order to evaluate the malignant potential of esophageal carcinoma. The association of the DNA index (DI) > or = 1.7 and the intratumoral DNA heterogeneity of biopsy specimens from patients with or without preoperative radiotherapy was also analyzed in relation to problems related to preoperative evaluation of nuclear DNA contents using biopsy specimens and the influence of irradiation on nuclear DNA contents. Esophageal carcinomas in 128 cases were studied. Nuclear DNA content was measured for biopsy specimens as well as surgically resected tumors by flow cytometry according to the method of Hedley and colleagues. HET was found in 42% of surgically resected specimens, but in only 18% of biopsy specimens. In 90% of cases, dominant DI of the resected tumor was also found in the biopsy specimens. Cases of DI > or = 1.7 showed a poorer prognosis than those with DI < 1.7 in cases with preoperative radiotherapy (p < 0.05) as well as in those without it. These results indicated that DI can be an indicator for highly malignant potential of esophageal carcinoma when measuring nuclear DNA contents using not only biopsy specimens but also specimens from irradiated cases.

[The intensity of hst-1 gene amplification and malignant potential of esophageal carcinoma in relation to intratumoral heterogeneity].

Amplification of hst-1 gene is associated with poor prognosis in patients with esophageal carcinoma. Since there is a high frequency of DNA stem-line heterogeneity, we studied intratumoral heterogeneity of hst-1 amplification, and evaluated whether or not the intensity of hst-1 amplification is associated with the malignant potential of esophageal carcinoma. A total of 73 patients with esophageal carcinoma who had undergone esophagectomy were studied. Intratumoral heterogeneity of hst-1 amplification was examined in two to four sections of tumour specimens which showed mainly DNA heterogeneity in 27 of these patients. The judgement of hst-1 amplification in the same tumor was identical in all of the 27 patients, although its intensity was not identical in some cases. And in 73 patients, postoperative recurrence in organs showed a high incidence (78%) in the hst-1 amplification group with a high intensity (over 7-fold). Therefore, hst-1 amplification exceeding 7-fold can serve as an indicator to predict the high grade of malignant potential of esophageal carcinoma.