Yoshito Ikematsu

Chronic Gastric Anisakiasis Presenting as Pneumoperitoneum

Typically, the diagnosis of gastric anisakiasis is made at endoscopy with the identification of anisakis larvae. We report a case of gastric anisakiasis presenting as pneumoperitoneum. A 70-year-old Japanese woman was admitted to our hospital with abdominal fullness and pain. Plain chest X-ray in the upright position showed the presence of free gas below the diaphragm. A tentative diagnosis of perforation peritonitis was made and an emergency laparotomy was performed. At laparotomy, a 4 cm, circumscribed red mass was noted on the anterior wall of the upper body of the stomach near the lesser curvature and a partial gastrectomy was carried out. The histological diagnosis showed a foreign body, assumed to be a part of anisakis larvae, seen in the centre of the granuloma. On the serosal aspect, there was histological evidence of peritonitis with fibrin and neutrophils. In addition, an antianisakis larvae immunoglobulin G antibody test was positive. Chronic gastric anisakiasis was suspected because of the presence of eosinophilic granuloma in the resected area and denatured anisakis larvae. Thus, we interpret this case as gastric perforation acutely based on chronic gastric anisakiasis.

IN VITRO PANCREATIC DUCTAL CELL CARCINOGENESIS

Our experiments were designed to identify initial biochemical and biological changes that occur during pancreatic carcinogenesis. TAKA‐1, an immortal hamster pancreatic ductal cell line, was treated in vitro for up to 11 weeks with the pancreatic carcinogen N‐nitorosobis(2‐oxopropyl)amine (BOP). These treated cells were designated TAKA‐1 + BOP. The growth of TAKA‐1 and TAKA‐1 + BOP cell lines was investigated in soft agar and in hamsters intradermally. The resulting tumor from TAKA‐1 + BOP was re‐cultured in vitro and designated TAKA‐1 + BOP‐T. Mutation of c‐K‐ras and p53 oncogenes, chromosomal changes, expression of transforming growth factor alpha (TGF‐α) and epidermal growth factor (EGF) receptor and several biochemical markers were examined in all cell lines. TAKA‐1 + BOP but not TAKA‐1 cells grew in soft agar and produced an invasive tumor in vivo. However, there were no differences in cell growth rate, DNA flow cytometry, or immunohistochemical findings between the non‐transformed and transformed cells. TAKA‐1, TAKA‐1 + BOP and TAKA‐1 + BOP‐T cells all expressed mRNA of TGF‐α and EGF receptor in a comparable pattern. DNA sequence analysis following polymerase chain reaction showed that neither TAKA‐1 nor TAKA‐1 + BOP cells has a mutation of c‐K‐ras or p53. Karyotype analysis demonstrated that TAKA‐1 + BOP cells had more chromosomal abnormalities compared with TAKA‐1 cells. Mutation of c‐K‐ras and p53 was not essential for carcinogenesis in hamster pancreatic ductal cells in vitro. In conclusion, immortality of the TAKA‐1 cells caused expression of TGF‐α to the same extent as in malignant cells. Chromosomal and ultrastructural patterns were the only differences detected between the non‐transformed and BOP‐transformed cells. Int. J. Cancer 72:1095–1103, 1997.

Species differences in the expression of transforming growth factor-alpha (TGF-α) in the submandibular gland and pancreas

SummaryConclusionSignificant differences exist in the expression of transforming growth factor-alpha (TGF-α) in the submandibular glands (SMG) and the pancreas of different species and among cell components in the same species.BackgroundOur previous studies have shown marked differences in the expression of TGF-α in the pancreas of humans and Syrian hamsters. To examine whether these differences also exist in other species, we examined the expression of TGF-α in the pancreas of mouse, rat, Syrian hamster, guinea pig, rabbit, pig, dog, and monkey. We included the SMG of these species for comparison.Materials and MethodsThe formalin-fixed tissues of these species (n=3) were investigated by immunohistochemistry using a monoclonal antibody to TGF-α. The SMG of rat, mouse, hamster, rabbit, pig, dog, and monkey were examined by RT-PCR to assure the specificity of the antibody.ResultsRemarkable species differences were found in the expression of this peptide in both the SMG and the pancreas. In the SMG, the expression varied in different cell components, even in the same tissue of the species. Although excretory and secretory ducts of the SMG of most species reacted with the antibody, intercalated ducts were immunoreactive only in mouse and guinea pig. Acinar cells were either weakly positive or nonimmunoreactive. In the pancreas of most species, the cells of the large and medium-size ducts expressed TGF-α, whereas centroacinar cells of only rat and dog reacted with the antibody. Marked differences were found in the expression of TGF-α in islet cells and in its spatial distribution. Differences were also found in the immunoreactivity of mesenchymal and neural cells among the species.

Photofrin-PDT for Gastric Cancer in the Era of Endoscopic Submucosal Dissection

Background: Endoscopic mucosal resection (EMR) was originated to treat early gastric cancer (EGC). EMR was suitable for small, mucosal and well-differentiated adenocarcinoma without ulceration. It was difficult to resect larger tumors en bloc by this method. In recent years, a more useful method, endoscopic submuscosal dissection (ESD) has been developed, which enables en bloc resection of large mucosal lesions. On the contrary, photodynamic therapy (PDT) is applicable to submucosal, poorly differentiated, or carcinoma with ulceration. In the era of ESD, we evaluated the value of Photofrin-PDT. Patients & Methods: We applied PDT to 36 patients including three advanced cancers, who had been excluded from EMR (ESD) and were at high risks for surgery or refused surgery. Four EGC patients who had not been cured by EMR (ESD) were included. Our PDT procedure consisted of polyhematoporphyrin ether/ester administration (Photofrin, 2 mg/Kg) and pulsed excimer dye laser irradiation at 630 nm 48 hours (and 96 hours) after sensitization. Results: Complete response (CR) at three months was obtained in 84% (21/25) of mucosal cancer and in 50% (4/8) of submucosal cancer. Although three patients with an advanced cancer improved but were not cured, quality of their life was maintained. There were no serious side effects except skin photosensitivity. Conclusion: Photofrin-PDT should be applied not only EGC patients who are excluded from ESD and have not been cured by ESD with poor risk for surgery, and have high possibilitiy to be cured by PDT, but also advanced cancer patients for local improvement of lesions.

Biliary Inflammation and Biliary Carcinogenesis

Biliary carcinoma has been reported as a late complication of bilioenterostomy. The present study was designed to find out if bilioenterostomy promotes biliary carcinogenesis, and to clarify the relationship between biliary inflammation and biliary carcinogenesis in hamsters. Syrian hamsters were subjected to simple laparotomy (SL), choledochoduodenostomy (CD), or choledochojejunostomy (CJ). All hamsters received subcutaneous injections of the chemical carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP), and were killed 20 weeks after surgery. Neoplastic lesions in the biliary tree were examined histologically, and the presence and degree of cholangitis was evaluated with special reference to the biliary carcinogenesis. The incidence of bile duct carcinoma did not differ significantly among the three groups. However, numerous bile duct carcinomas were recognized in the bilioenterostomized animals, especially in the CJ group. Moreover, there was a significant correlation between biliary carcinogenesis and the presence of cholangitis in the CD and CJ groups, but not in the SL control group. Severe cholangitis was evident in the CJ group, and the number of biliary carcinomas was well correlated with the degree of cholangitis. These findings suggest that the risk of carcinoma in the biliary tract is increased when cholangitis persists after biliary reconstruction.