Effect of cystathionine beta-synthase variant 844ins68bp and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5-FU efficacy and doubling time

The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling time of tumors with a variant C allele (AC or CC) in MTHFR-A1298C was significantly longer than that of tumors with a normal allele (AA) (P=0.0008). Twenty-nine cellular proliferation-related genes were associated with MTHFR-A1298C genotyping and with the doubling time.     

Primary amyloidosis of the urinary bladder.

Amyloidosis is a systemic disease that usually occurs in the gastrointestinal tract or in muscular or adipose tissue. Primary amyloidosis of the urinary bladder is a rare disease that can mimic bladder cancer on cystoscopic examination as well as in its clinical presentation of painless gross hematuria. This report describes a 49-year-old male with repeated painless gross hematuria, who underwent transurethral resection of a suspected bladder tumor. Pathologic examination revealed papillary urothelial hyperplasia with vascular ectasia and no signs of malignancy. Massive gross hematuria occurred 2.5 years later. Cystoscopy showed multiple papillary lesions with yellowish-brown submucosal plaques on the posterior bladder wall. A second transurethral tumor resection was performed and histologic examination revealed plasma cell infiltration and eosinophilic amorphous deposits in the subepithelial stroma and vascular wall. The deposits were positive for Congo red and apple-green birefringence under polarized light examination but negative for Masson's trichrome stain, indicating that they were not fibrotic in nature. Hence, the diagnosis of amyloidosis of the urinary bladder was confirmed. Screening for amyloidosis was negative in other organ systems and the patient has remained disease-free up to the last follow-up 4 years after the second transurethral resection. Amyloidosis should be considered in the differential diagnosis of patients with recurrent hematuria who have symptoms characteristic of bladder cancer but negative pathologic study for malignancy. Correct diagnosis relies on clinical alertness and the use of a special staining technique during pathologic examination.     

A CASE OF EARLY GASTRIC CANCER ACCOMPANIED BY DIEULAFOY ULCER IN A YOUNG WOMAN

A case of early gastric carcinoma accompanied by Dieulafoy ulcer is presented. The patient, a 26‐year‐old female, visited our emergency room with chief complaints of massive hematemesis and tarry stool. The initial endoscopic examination revealed a superficial depressed lesion with a faded color accompanied by a tiny ulcer with converging folds at the anterior wall of the middle gastric body. Although no active bleeding vessel was found at that time, the patient was admitted to our hospital for further check‐ups and treatment. On the 6th hospital day, she developed massive hematemesis resulting in shock. Urgent endoscopy, this time, disclosed an exposed bleeding vessel at the small ulcer floor previously mentioned, and endoscopic hemostasis was achieved. Since, however, a biopsy at initial examination from the surrounding depressed area proved carcinoma, a partial distal gastrectomy was subsequently carried out. Histological examination of the resected specimen confirmed the diagnosis of carcinoma limited to the mucosa and submucosa along with findings consistent with Dieulafoy ulcer. This is a rare case of combination of early cancer and Dieulafoy ulcer particularly in such a young patient. A review of the literature is also presented.     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.     

Reduction mammaplasty by central pedicle flap with short submammary scar

Reduction mammaplasty was performed in 30 patients by combining the central pedicle flap method with the short submammary scar (3-S) technique to avoid the common drawbacks of currently popular dermoglandular procedures. Reduction was accomplished by using perforating vascular branches from the pectoralis major muscle and its fascia supplying the nipple and breast parenchyme instead of the subdermal plexus. The central vascular pedicle supplying the nipple-areola complex was preserved. Only the periphery of the breast parenchyme was resected circumferentially, with the exception of the inferolateral portion, so as not to injure the sensory nerve. The remaining breast parenchyme was preserved in an inverted cone shape. The nipple-areola complex was safely transposed with great freedom, and the amount of resection was accurately adjusted for symmetry. No cases of nipple-areola complex sensory change occurred postoperatively, and lactation is possible because of preservation of the lactiferous ducts. The length of postoperative scars was reduced by using the short submammary scar technique. We believe this combined method is ideal in patients requiring resections ranging from 200 to 600 g per breast with good skin elasticity and moderate degree of ptosis.Presented at the Sixth Asian Pacific Congress of the International Confederation for Plastic and Reconstructive Surgery, in Seoul, Korea, October 1993.