Hiroaki Okazaki

Pachydermoperiostosis associated with juvenile polyps of the stomach and gastric adenocarcinoma

Pachydermoperiostosis (PDP) is a rare syndrome, and the presence of digital clubbing, radiographic periostosis, and coarse facial features are the main diagnostic criteria. Here, we report patient with the primary form of PDP in whom juvenile polyps and gastric cancer developed within 9 years of follow-up. A 27-year-old Japanese man, diagnosed as having the primary form of PDP at 14 years of age, was referred to our department for assessment of chronic anemia. On upper gastrointestinal endoscopic examination, multiple polypoid lesions with a huge polyp were found in the stomach, and biopsy findings indicated juvenile polyps, although no polypoid lesion had been present at the age of 18 years. Bleeding from these polyps was suspected, and endoscopic mucosal resection of the polypoid lesions was performed. Histology of the huge polyp showed hamartoma, adenoma, and adenocarcinoma in part. This is the first case report of the primary form of PDP associated with gastric cancer. In this patient, juvenile polyps and gastric cancer developed within 9 years of follow-up, indicating that the primary form of PDP may be a high risk factor for gastric cancer, and that periodical follow-up with upper gastrointestinal endoscopy is important.

Testing of multiple samples increases the sensitivity of stool decay-accelerating factor test for the detection of colorectal cancer

OBJECTIVES:We previously reported that the measurements of stool decay-accelerating factor (DAF), a membrane-bound, complement regulatory protein, may be valuable for the detection of colorectal cancer. Recently we have refined the immunoassay for stool DAF. In the present study, using the refined assay, we measured stool DAF concentrations in multiple samples from patients with colorectal cancer and in healthy controls to determine whether testing of multiple samples would increase the sensitivity of the stool DAF test.METHODS:DAF was measured in three spontaneously passed stool samples from each of 100 patients with colorectal cancer and 100 control subjects without apparent colorectal disease.RESULTS:The stool DAF concentrations in the patients with colorectal cancer (median 11.1 ng/g stool; interquartile range 2.9–32.7 ng/g) were significantly higher than concentrations in the subjects without colorectal diseases (median 1.6 ng/g stool; interquartile range 0.4–3.4 ng/g) (p < 0.0001). Testing of two samples from each patient significantly increased the sensitivity (72%) of the stool DAF test without significantly decreasing its specificity (92%). The stool DAF test was positive in more than one half of patients with colorectal cancer at a relatively early TNM stage or with negative fecal occult blood test.CONCLUSIONS:These findings suggest that stool DAF is a marker of colorectal cancer independent of fecal occult blood and testing of two samples increases the sensitivity of the stool DAF test. Measurement of stool DAF now seems worthy of further consideration as a noninvasive method for the detection of colorectal cancer.

Release of decay-accelerating factor into stools of patients with colorectal cancer by means of cleavage at the site of glycosylphosphatidylinositol anchor

The expression of decay-accelerating factor (DAF), a cell-membrane-complement regulator, is enhanced in colorectal cancer, and DAF is detected in the stools of patients with colorectal cancer. In this study, to elucidate mechanisms whereby DAF is released into the colonic lumen, we analyzed and compared the properties of DAF in stools and colorectal-cancer tissues. Stool specimens taken before surgery and tissue samples from surgically resected colorectal cancers were obtained from 21 patients. We analyzed DAF in stool and tissue specimens using immunoblotting, ultracentrifugation, and phase separation with Triton X-114. We analyzed the expression profile of DAF mRNA in cancer tissues using reverse transcription-polymerase chain reaction to determine whether DAF transcripts for a secretory form of DAF were present. With the use of immunoblotting, stool DAF was detected as a broad band with a molecular weight of around 70,000 kDa that migrated slightly more slowly than cancer-tissue DAF. About 90% of stool DAF was present as a soluble form that remained in the 100,000 g supernatant after ultracentrifugation. On phase separation with Triton X-114, the soluble stool DAF was partitioned mainly into the aqueous phase, indicating its hydrophilic nature and lack of the fatty-acid glycosylphosphatidylinositol anchor component. In colorectal cancer tissues, reverse transcription-polymerase chain reaction experiments revealed a nonspliced DAF messenger RNA that encodes a secretory form of DAF in just 2 of the 21 specimens examined. These data suggest that DAF is released from colorectal cancer cells by way of cleavage of membrane-bound DAF at the site of the glycosylphosphatidylinositol anchor.

Advances in the development of a reliable assay for the measurement of stool decay-accelerating factor in the detection of colorectal cancer.

ABSTRACT We have previously shown that stool concentrations of decay-accelerating factor (DAF; CD55), a membrane-bound complement-regulatory protein, are significantly elevated in patients with colorectal cancer and that the measurement of stool DAF may be a valuable test for the detection of colorectal cancer. Accordingly, we are working to develop a clinically useful immunoassay for fecal DAF. A requirement for such assay is a plentiful and reliable supply of anti-DAF antibodies. We developed a sandwich enzyme-linked immunosorbent assay (ELISA) for DAF in stool specimens, using two monoclonal anti-DAF antibodies recognizing different epitopes on the DAF molecule. When we first used a biotin-labeled antibody and enzyme-linked streptavidin method, we often observed stool interference, probably due to the presence of a substance(s) with biotin activity which non-specifically bound to the Fc portion of IgG of the first anti-DAF antibody on the ELISA wells. By the use of inorganic salts in the sample-dilution buffer and HRP-labeled anti-DAF as second antibody, we circumvented the stool interference and established that the new ELISA system could reliably measure DAF at low concentrations in stool specimens. Because the new assay system uses only monoclonal antibodies, we can now consistently supply ample amounts of antibodies for routine measurement of stool DAF.

Complement regulatory proteins in normal human esophagus and esophageal squamous cell carcinoma.

Background:  Altered expression of three complement regulatory proteins, decay‐accelerating factor (CD55), membrane cofactor protein (CD46) and homologous restriction factor 20 (CD59) has been identified in human gastrointestinal malignancies, but their expression in esophageal cancer has not been described. Therefore the purpose of the present paper was to study the distribution of these proteins in human normal and malignant esophageal mucosa.

CONCURRENT GASTRIC AND COLONIC LOW-GRADE MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMATA IN A PATIENT WITHOUT HELICOBACTER PYLORI INFECTION

Mucosa‐associated lymphoid tissue (MALT) lymphomata observed simultaneously in the stomach and colon are rare. We report concurrent gastric and colonic low‐grade MALT lymphomata that originated from the same clone in a 58‐year‐old Japanese man without Helicobacter pylori infection. Endoscopy showed multiple erosive lesions in the gastric body and antrum, and a single flat elevation with an irregular margin in the sigmoid colon. Histopathological findings of both lesions suggested low‐grade MALT lymphoma. Lymphoepithelial lesions were evident in the gastric lesions, but not in the colonic lesion. Southern blot analysis of lymphoma cells revealed the same immunoglobulin heavy‐chain rearrangement pattern. The chromosomal translocation t(11;18)(q21;q21) was also observed. After six courses of cyclophosphamide, doxorubicin, vincristine and predonisolone, the gastric lesions disappeared endoscopically, while the colonic lesion persisted. A sigmoidectomy was consequently performed. The chromosomal translocation may be related to the pathogenesis of the present MALT lymphoma case without H. pylori infection. It is interesting that the gastric and colonic lesions differed in response to treatment and in their endoscopic and histologic features, despite having the same origin.

Centrifugal leukocytapheresis therapy for ulcerative colitis without concurrent corticosteroid administration.

Abstract:  Corticosteroid administration is an important therapy for active ulcerative colitis. However, long‐term corticosteroid use is associated with serious complications such as osteoporosis, diabetes, and growth retardation. The effect of combination therapy corticosteroid plus leukocytapheresis has been previously reported, but that of leukocytapheresis with no corticosteroid is unknown. We carried out a preliminary study of six patients (two men and four women) with active ulcerative colitis (severe in two, moderately severe in four) who did not respond to 5‐aminosalicylate derivatives, but refused corticosteroid use. Centrifugal leukocytapheresis was carried out once per week totaling four sessions per course. Treatment was considered effective when patients experienced clinical remission, which was defined as a frequency of diarrhea of four times or less and absence of visible blood in the stool, after one course. Leukocytapheresis was effective in five of six patients(83%). With cases stratified by severity, both severe cases and three of four moderately severe cases showed effectiveness. Clinical activity scores according to Lichtiger et al. in cases where leukocytapheresis was effective decreased from 9.8 to 6.6 at 1 week (P < 0.0001), declining further 2.4 at the end of the course. No obvious complications of leukocytapheresis were noted except for a decrease in hemoglobin by 1 g/dL. Centrifugal leukocytapheresis without corticosteroid treatment can induce remission in patients with active ulcerative colitis, and might be particularly beneficial for patients in whom adverse effects preclude the use of corticosteroids.

Reversal of Protein-Losing Enteropathy with Heparin Therapy in an Adult Patient with Congenital Heart Disease

tion, is a serious problem because PLE reportedly occurs in up to 13.4% of patients, within 10 years of receiving a Fontan operation [2] . Surgical and medical treatments have been reported to be effective in only 60% of PLE cases, and the total morDear Sir, Protein-losing enteropathy (PLE) is defined as the excessive loss of plasma proteins through the intestine [1] . PLE can result from a number of diseases, including congenital heart malformations. PLE after heart surgery, especially a Fontan operaPublished online: March 6, 2007