p53 point mutations in primary human gastric carcinomas

Summary p53 point mutations in primary gastric carcinomas were analyzed by performing cDNA deoxynucleotide sequencing of the gene. Out of 16,9 (56.3%) primary gastric carcinoma cases, including early cancer, showed one or more p53 point mutations in their open-reading frame, and 4 out of 9 cases had a p53 point mutation within highly conserved domains. The characteristics of the p53 mutation spectrum observed in primary tumors were (a) frequent mutation at an A:T pair (50%, 7 out of 14 mutations), (b) high transversion incidence (29%, 4 out of 14 mutations), (c) no transition at CpG, and (d) no G:C to T:A transversion. Our results suggest that p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression with its specific mutation spectrum.Abbreviation PCR-SSCP polymerase chain reaction single-strand conformation polymorphism     

Rare somatic inactivation of the multiple endocrine neoplasia type 1 gene in secondary hyperparathyroidism of uremia

The molecular pathway of autonomous growth of the parathyroid glands in uremic patients is poorly understood. Loss of heterozygosity at the recently identified multiple endocrine neoplasia type 1 (MEN1) gene locus on chromosome 11q13 has been found in a subset of parathyroid glands from patients with refractory hyperparathyroidism. To clarify the role of the MEN1 gene in parathyroid tumorigenesis, we analyzed 81 parathyroid glands from 22 Japanese uremic patients for allelic loss on chromosomal arm 11q13 DNA using 3 flanking markers (PYGM, D11S4946, and D11S449) and for mutations of the MEN1-coding exons by PCR-based single strand conformation polymorphism analysis and sequencing. Allelic loss on 11q13 was observed in 6 glands (7%), and 1 of 6 demonstrated a previously unrecognized somatic frameshift deletion (331delG) of the MEN1 gene. This mutation would probably result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and pathological characteristics of hyperparathyroidism were unrelated to the presence or absence of loss of heterozygosity on 11q13 and MEN1 gene mutations. These observations indicate that somatic inactivation of the MEN1 gene contributes to the pathogenesis of uremia-associated parathyroid tumors, but its role in this disease appears to be very limited.     

Long-term remission by cyclosporine in a patient with eosinophilic fasciitis associated with primary biliary cirrhosis

A 70-year-old man was admitted to the hospital in June 1994 because of cutaneous induration of the extremities. Eosinophilic fasciitis was diagnosed on the basis of the course and distribution of the cutaneous lesions. Cyclosporine (100 mg/day) was given. After 4 weeks of treatment, cutaneous induration and limited joint mobility improved. Liver dysfunction had been diagnosed 5 years before the onset of eosinophilic fasciitis. Primary biliary cirrhosis (PBC) was diagnosed on the basis of the elevated serum biliary-enzyme levels, strongly positive antimitochondrial antibody titer, and histologic features of the liver-biopsy specimens showed stage-3 PBC. These findings suggested that eosinophilic fasciitis developed in association with PBC. PBC is often accompanied by autoimmune diseases, such as Sjögren’s syndrome and Hashimoto’s disease. To our knowledge, eosinophilic fasciitis associated with PBC has not been reported previously. We believe this is the first time a case of eosinophilic fasciitis occurring in a patient with PBC is documented.     

Postoperative complications of repeat hepatectomy for liver metastasis from colorectal carcinoma

BACKGROUND/AIMS: When a repeat hepatectomy is possible, it is the most effective treatment modality for recurrent colorectal liver metastasis. The aim of this study was to evaluate the surgical risks of repeat hepatectomy for liver metastasis from colorectal carcinoma. METHODOLOGY: Between 1986 and 1996, 60 patients with hepatic metastasis from colorectal carcinoma underwent surgery in the Department of Surgery I, Oita Medical University. Ten of them underwent a repeat hepatectomy. The cases of these 10 patients were studied retrospectively; in particular, postoperative complications and intraoperative blood loss were compared between the initial and second operation. RESULTS: During the second surgery, recurrence was detected adjacent to the hepatic stump in 9 of the 10 patients. During the initial surgery, 6 underwent non-anatomic resections, and 4 had anatomic resection, including 1 extended lobectomy, 1 lobectomy, and 2 segmentectomies. For the second surgery, 3 had anatomic resections, including 2 lobectomies, and 1 segmentectomy, and 7 underwent non-anatomic resections. There were no mortalities during the initial or second operation. There was no morbidity following the initial surgeries and 7 postoperative complications (intraabdominal abscess, 4 cases; biloma, 3 cases) following the second surgeries. Mean blood loss during the second operation (1044 mL) was significantly greater than during the initial operation (561 mL). CONCLUSIONS: The present results show that repeat hepatectomy for recurrent liver metastasis from colorectal carcinoma resulted in significantly greater intraoperative blood loss and postoperative complications than those of the initial surgeries. The blood loss and complications in the second operation, the one for the recurrence, were directly associated with the fact that the recurrence was so close to the hepatic stump. Since the resection line in the second surgery was adjacent to the hepatic hilus, resection of the lesion caused much more injury to the main bile duct and main portal vein than that caused by the.