Yukinari Yoshida

Interplay of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-I Receptor, COX-2, and Matrix Metalloproteinase-7, Play Key Roles in the Early Stage of Colorectal Carcinogenesis

Purpose: The aim of this study was to characterize the relationship of insulin-like growth factor (IGF)-II expression with IGF-I, IGF-I receptor (IGF-IR), cyclooxygenase-2 (COX-2), and matrix metalloproteinase (MMP)-7 in early colorectal carcinogenesis. Experimental Design: With the semiquantitative reverse transcriptase-PCR, 90 human colorectal tumor tissues (63 adenomas and 27 submucosal pT1 cancers) were analyzed for IGF-II, IGF-IR, IGF-I, COX-2, and MMP-7 expression. Ninety-nine adenoma tissues and 60 pT1 cancer tissues were also analyzed immunohistochemically for IGF-II expression. Loss of imprinting of the IGF-II gene was analyzed. Paired carcinoma and adenoma tissues obtained from a carcinoma in adenoma lesion was analyzed by a cDNA array. Results: IGF-II mRNA expression was detected in 37.8% of the 90 colorectal tumor tissues. The frequency of IGF-II mRNA expression was significantly higher in pT1 cancer (70.4%) than in adenoma (23.8%). Immunohistochemical IGF-II expression was also more frequently detected in pT1 cancer (58.3%) than in adenoma (25.3%). Loss of imprinting of the IGF-II gene was observed in 15 (44.1%) of the 34 colorectal tumors in which IGF-II was overexpressed. IGF-II expression was positively correlated with the expression of IGF-IR and IGF-I. COX-2 and MMP-7 mRNA expression was detected in 42.2% and 77.8% of the tumor tissues, respectively, and both were positively correlated with IGF-I, IGF-II, and IGF-IR expression. IGF-II was the most differentially expressed gene between carcinoma and adenoma lesions. Conclusions: IGF-II, in conjunction with IGF-IR, IGF-I, COX-2, and MMP-7, seems to play a key role in the early stage of colorectal carcinogenesis.

Decreased DCC mRNA expression in human gastric cancers is clinicopathologically significant.

Loss of heterozygosity (LOH) or decreased expression of the deleted in colorectal cancer (DCC) gene, a candidate tumor suppressor gene, has been suggested to correlate with progression in several types of tumors. In human gastric cancers, although DCC LOH has been reported to be frequent in expanding‐type tumors, the relation of decreased DCC mRNA expression with clinicopathological features, including metastatic events, remains to be investigated in detail. Therefore, expression levels of DCC mRNA were examined in 52 advanced gastric cancers by the reverse transcription‐polymerase chain reaction method combined with Southern blot analysis. Overall, decreased DCC mRNA expression was observed in 27 of the tumors (52%). According to Mings [Cancer 39, 2475–2485 (1977)] classification, the expanding type showed a significantly higher incidence (71%) than the infiltrative type (17%) (p = 0.0002). Immunohistochemical analysis demonstrated the presence of DCC expression in cancer but not non‐cancerous cells in infiltrative‐type lesions. An additional follow‐up study of tumor recurrence in 42 patients undergoing curative resection implicated decreased DCC expression in metachronous liver metastasis. The results indicate that decreased DCC mRNA expression is closely associated not only with the expanding‐type phenotype but also with liver metastasis of gastric cancers. Assessment of this parameter in primary lesions may thus find predictive application. Int. J. Cancer (Pred. Oncol.) 79:634–639, 1998.

Diaphragm disease of small intestine diagnosed by double-balloon enteroscopy.

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Phenotypic alteration of interstitial cells of Cajal in idiopathic sigmoid megacolon

BackgroundInterstitial cells of Cajal (ICCs) are detected as a pacemaker of gastrointestinal movement and express c-kit and CD34. Recently, ICCs have implicated pathogenesis in several human diseases presenting gastrointestinal motor dysfunction. This study was performed to clarify the role of ICCs in idiopathic sigmoid megacolon using histological and immunohistochemical examinations.MethodsFour adult patients with idiopathic sigmoid megacolon and 11 controls were studied. Histology and immunocytochemistry using NSE, S100, c-kit, and CD34 were performed in conjunction with quantitative analysis using the public domain NIH image program.ResultsLittle histological change in neuromuscular structures in megacolon was observed. Immunohistochemistry demonstrated remarkable decrease of c-kit expressing ICCs without reduction of CD34 expression in the similar interstitial cell population. This observation was further supported by quantitative assessment using public domain NIH image program.ConclusionsA specific downregulation of c-kit in ICCs may be a cause of idiopathic sigmoid megacolon in adults.

Gastric antral vascular ectasia in 2‐yr‐old girl undergoing unrelated cord blood stem cell transplantation

Abstract:  Gastrointestinal bleeding is a common complication after hematopoietic stem cell transplantation (HSCT) and is often related to acute graft‐vs.‐host disease (aGVHD). Gastric antral vascular ectasia (GAVE), recently recognized as a complication after HSCT, is a rare cause of severe gastrointestinal bleeding, which has only been reported in adult patients so far. We report a 2‐yr‐old girl who developed GAVE after unrelated cord blood stem cell transplantation (CBSCT) as treatment of intractable Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis (EBV‐HLH). Her conditioning regimen for CBSCT consisted of etoposide, busulfan, and cyclophosphamide. She was doing well after CBSCT without recurrence and developed only grade I aGVHD. She suddenly developed coffee ground emesis, tarry stools and severe anemia 76 days after CBSCT. As antacids were ineffective, esophagogastroduodenoscopy was performed and revealed GAVE on day 97. Endoscopic coagulation therapy was performed twice; subsequently, she needed no further transfusions and there was no clinical recurrence of GAVE.

A case of pneumatosis cystoides intestinalis with dermatomyositis in which EUS was useful for the diagnosis

Dear Editor: Pneumatosis cystoides intestinalis (PCI), first described in 1730, is a rare benign condition in which multiple air-filled cysts develop in the bowel walls. The disease has been reported in patients with a variety of collagen diseases, including progressive systemic sclerosis (PSS), polymyositis (PM), dermatomyositis (DM), rheumatoid arthritis (RA), overlap syndrome, systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). There has been only one report in the English literature of DM with PCI in an adult [1]. To the best of our knowledge, this is the first report of a case of PCI with DM in which endoscopic ultrasonography (EUS) was useful for diagnosis. A 69-year-old Japanese woman with a 10-year history of dermatomyositis (DM) had been treated with low-dose corticosteroid (predonisolone at 15 mg daily). Although this therapy relieved her symptoms and remission had been maintained, she experienced diarrhea and fever and abdominal distention in December 2002. Despite her symptoms, her serum creatine kinase and aldolase levels were within normal ranges and she had no muscle weakness. Erythrocyte sedimentation rate was 21mm/h and C-reactive protein was elevated (2.74 mg/dl). All cultures for Mycobacterium tuberculosis and other infectious agents were negative. Abdominal distention was present with normal peristalsis. Signs of peritoneal irritation were absent. Plain abdominal radiographs revealed megacolon and intestinal gas with niveau, but there was no accumulation of intraluminal gas. Antibiotic therapy was started, but it had little effect. She was admitted to our hospital in January 2003 for detailed examinations. Abdominal CT revealed mega intestinal gas and intraluminal gas accumulation suggestive of PCI in the right hypochondrium. Therefore, small-bowel barium examination was done. A markedly dilated jejunum and tightly located jejunal folds were clearly demonstrated. These findings are similar to the so-called “coiled-spring appearance” seen in intussusception. On the other hand, polypoid lesions (10 cm in the major axis) were seen in the ileum. Colonoscopy was performed to examine the colon and ileum. Although the colon and rectum were intact, polypoid lesions like submucosal tumors (SMTs) with redness of the mucosa were seen in the ileum (about 30 cm beyond the ileum end). The polyps were elastic and movable, and biopsy specimens showed nonspecific inflammation with no airfilled cysts. Based on the findings of the small-bowel barium examination and colonoscopy, we suspected PCI with DM. EUS (15 MHz) was performed to examine the inner parts of the polyps. The polyps were hyperechoic lesions with acoustic shadows and existed in the submucosal layer. K. Nosho (*) . K. Hatakeyama . Y. Hamamoto . A. Goto . H. Yamamoto . Y. Yoshida . Y. Arimura . T. Endo . K. Imai First Department of Internal Medicine, Sapporo Medical University, S.-1, W.-16, Chuo-ku, Sapporo, 060-8543, Japan e-mail: nosho@sapmed.ac.jp Tel.: +81-11-6112111 Fax: +81-11-6112282

Construction of a high-throughput rat genetic mapping system with 466 arbitrarily primed-representational difference analysis markers

Abstract. Linkage mapping of quantitative trait loci (QTLs) requires genetic markers that can be efficiently genotyped for a large number of individuals. To isolate genetic markers suitable for this purpose, we previously established the arbitrarily primed RDA (AP-RDA) method. Dot-blotting AP-PCR products (AP-amplicons) onto filters at a high density and hybridization of the filters with the AP-RDA markers made it possible to genotype a large number of individuals simultaneously for multiple loci. In this study, by using 25 primers or primer combinations, we isolated a total of 419 AP-RDA markers by subtracting the AP-amplicon of BUF rats from that of ACI rats, and vice versa. By combining 47 previously isolated markers, a rat genetic map was drawn with 466 AP-RDA markers. Between two given strains of rats other than ACI and BUF, the average informativeness of the markers was 38%. As for the intercross of ACI and BUF rats, 12 selected primers served to genotype 259 loci. In addition, the amounts and quality of genomic DNA to be used for AP-PCR were examined to guarantee reliable genotyping. Now, initial genome scanning of the rat for linkage analysis can be performed efficiently using this mapping system with AP-RDA markers.

Jejunal carcinoid tumor mimicking leiomyosarcoma: preoperative diagnosis by endoscopic biopsy

Abstract: Primary carcinoid tumor of the jejunum is rare, and is an unusual cause of massive gastrointestinal bleeding. A case of primary jejunal carcinoid tumor in a 39-year-old woman who presented with massive hematochezia is described. Both upper and lower gastrointestinal endoscopies showed no abnormalities. An abdominal computed tomographic scan, small-bowel barium contrast studies, and small-bowel endoscopy showed a subserosal mass, of 5 × 4 cm, with a cavity suggesting central necrosis, and a deep mucosal ulceration, located in the proximal jejunum. Although these clinical presentations were strongly suggestive of a leiomyosarcoma, histologic examination of biopsy samples obtained by enteroscopy confirmed the diagnosis of jejunal carcinoid tumor. The patient underwent radical jejunal resection and recovered uneventfully. In spite of the large size of the tumor, there was one solitary lymph node metastasis, but no evidence of liver metastases. This kind of jejunal carcinoid tumor, presenting with massive gastrointestinal bleeding and a subserosal bulky growth mimicking a leiomyosarcoma, has not been reported previously. Moreover, this is a rare case of a jejunal carcinoid which was diagnosed preoperatively by small bowel-endoscopic biopsy.

Oncocytic Type Intraductal Papillary Mucinous Neoplasm of the Pancreas with Unusually Low Mucin Production Mimicking Intraductal Tubulopapillary Neoplasm: A Report of a Case Diagnosed by a Preoperative Endoscopic Biopsy

We herein report the case of a 78-year-old woman with an intraductal tumor with scant mucin production in a moderately dilated main pancreatic duct that resembled an intraductal tubulopapillary neoplasm (ITPN) on imaging. An endoscopic transpapillary forceps biopsy enabled an accurate preoperative diagnosis of the tumor as an oncocytic type intraductal papillary mucinous neoplasm (IPMN) of the pancreas microscopically showing papillary growth consisting of oncocytic cells with a typical mucin expression profile, although with few intraepithelial lumina containing mucin. This is the first case of an oncocytic type IPMN mimicking an ITPN that was able to be diagnosed preoperatively.