Pyoderma Gangrenosum with Ulcerative Colitis Successfully Treated by the Combination of Granulocyte and Monocyte Adsorption Apheresis and Corticosteroids.

A 36-year-old woman was admitted to our hospital due to swelling and redness of the left lateral malleolus and dorsum of the left foot with severe pain, with a flare-up of ulcerative colitis (UC). A pathologic examination by skin biopsy led to a diagnosis of pyoderma gangrenosum (PG). She was treated with the intravenous administration of prednisolone (60 mg/day), and granulocyte and monocyte adsorption apheresis (GMA) was performed twice-a-week for 5 weeks. This treatment dramatically improved both the skin and colonic mucosal lesions. These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC.

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres.

BACKGROUND AND AIM: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. METHODS: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 +/- 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. RESULTS: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. CONCLUSIONS: The FSSG score reflects the severity of the endoscopic findings of GERD.

[Immunohistochemical analysis of cell cycle-regulating protein (p21, p27 and Ki67) expression in endoscopic biopsy samples from patients with gastroesophageal reflux disease].

We performed an immunohistochemical analysis of cell cycle-regulating protein (p21, p27 and Ki67) expression in endoscopic biopsy samples from the patients with gastroesophageal reflux disease (GERD) using angled -biopsy forceps. Inflammatory cell accumulation into the lamina propria was detected even in patients with modified Los Angeles (LA) system grades N or M. In grade N or M patients with no changes in the epithelium, the area of p21, p27 and Ki67 positive cells was expanded compared to normal mucosa. The area of p21, p27 and Ki67 positive cells tended to expand upward in the epithelium with GERD severity based on the LA classification grading. These indicate that inflammatory cell infiltration into the lamina propria is initial histological change of GERD.

[Characteristic of elderly patients with ulcerative colitis and therapeutic issue].

AIM: Ulcerative colitis (UC) primarily affects young adults, but the proportion of elderly patients with UC seems to be increasing. It is important that the clinical characteristics of elderly patients be analyzed. METHODS: In the older group consisted of 32 outpatients (23 aged 50-64 years old, 9 aged 65 or over) in our hospital, we evaluated disease duration, severity, therapeutic efficacy and other clinical problems. RESULTS: The age distributions of the disease onset showed a peak at early age and decreased with aging. The degree of severity was mainly mild, and left-sided or pancolitis were more frequent than expected in the older group. Most elderly patients suffered other diseases, and care was required in the administration of steroids. CONCLUSION: The clinical features of elderly patients with UC were similar to those of younger patients. However, It should be considered that elderly patients often have complications requiring care in the use of steroids.

Operative indications for patients with refractory or severe ulcerative colitis.

BACKGROUND/AIMS: The failure of medical treatment for severe ulcerative colitis (UC) can result in an emergency colectomy. Since new treatments using cyclosporin A and leukocytapheresis have been developed, we analyzed historical changes in the operative indications for UC. METHODOLOGY: We retrospectively reviewed the medical record of 40 patients who underwent surgery, and analyzed the medical treatments before surgery using two groups (urgent and elective) and two time periods (1986-1999, 2000-2003). RESULTS: The number of patients who received operations in the severe UC group from 1986 to 1999 was 17 out of 23 patients, but this number decreased from 2000 to 2003. Although 40% of the patients from 2000 to 2003 in the refractory UC group had been treated with steroids only, the mean times of high-dose steroid therapy decreased from 4.3 to 2.5. The total amount of steroids administered in both groups tended to decrease from 2000 onwards. The postoperative questionnaire indicated that about half of them felt that their surgery had been performed too late. CONCLUSIONS: The number of emergency colectomies for severe UC has been decreasing with the introduction of new therapies, but gastroenterologists should carefully monitor the potentially adverse effects of steroids for refractory UC.

Bile acid modulates transepithelial permeability via the generation of reactive oxygen species in the Caco-2 cell line.

The barrier functions in epithelial and endothelial cells seem to be very important for maintaining normal biological homeostasis. However, it is unclear whether or how bile acids affect the epithelial barrier. We examined the bile acid-induced disruption of the epithelial barrier. We measured the transepithelial electrical resistance (TEER) of Caco-2 cells as a marker of disruption of the epithelial barrier. Reactive oxygen species (ROS) generation was also measured. Cholic acid (CA) decreased the TEER and increased intracellular ROS generation. PLA2 (phospholipase A2), COX (cyclooxygenase), PKC (protein kinase), ERK 1/2 (extracellular signal-regulated kinase 1/2), PI 3 K (phosphatidylinositol 3-kinase), p38 MAPK (p38 mitogen-activated protein kinase), MLCK (myosin light-chain kinase), NADH dehydrogenase, and XO (xanthine oxidase) inhibitors or ROS scavengers prevented the CA-induced TEER decrease. PLA2, COX, PKC, NADH dehydrogenase, and XO inhibitors prevented the CA-induced ROS generation but not ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors. If the cells were treated with ROS generators such as superoxide dismutase, the TEER decreased. ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors prevent these ROS generators from inducing the TEER decrease. These results suggest that ROS play an important role. In addition, PLA2, COX, PKC, NADH dehydrogenase, and XO are located upstream of the ROS generation, but ERK 1/2, PI 3 K, p38 MAPK, and MLCK are downstream during the signaling of CA-induced TEER alterations.

[Histochemical diagnosis of short segment Barrett's esophagus].

Recently, we have many chances of findings of Barrett's esophagus in routine endoscopic examination. It is also reported that we have few frequent findings of typical Barrett's esophagus, long segment Barrett's esophagus (LSBE) which is seen predominantly in Europe and United States, however the frequency of finding of short segment Barrett's esophagus (SSBE) and adenocarcinoma derived from SSBE is gradually increasing in Japan. So it is thought that precise diagnosis of SSBE and the evaluation of potential malignancy of SSBE are needed in the present medical management. The present study has shown the differences of characteristics of mucinous contents and malignant potentials between in SSBE and LSBE by use of biopsy specimen taken by endoscopic procedure. It is well known that Barrett's epithelium is categorized gastric fundic type, junctional type and specialized columnar epithelium, especially Barrett's mucosa is characterized by specialized columnar epithelium, e. g. incomplete epithelial type of intestinal metaplasia. We have set up two characteristic groups, gastric mucin dominant and intestinal mucin dominant by using specific mucin staining for MUC2, MUC5AC, Con A and CD10. In results, we confirmed that 80% of specialized columnar epithelia revealed intestinal mucin dominant in LSBE and 77% revealed gastric mucin dominant as compared with 23%, intestinal mucin dominant. Moreover, we have examined the ability of cell proliferation using Ki67-immunostaining in Barrett's epithelia. It was demonstrated that positive immunoactivity of Ki67 in proliferative zone was shown in 37.5% of gastric mucin dominant and 76.5% of intestinal mucin dominant. The results described above suggested that specialized columnar epithelia with intestinal mucin dominant have a higher potential of malignant transformation. We concluded that the evaluation of characteristics of mucinous contents in specialized columnar epithelia plays an important role in determination of high risk group of carcinogenesis in the case of SSBE.

Budd-Chiari syndrome: a case with a combination of hepatic vein and superior vena cava occlusion.

We here report a recent, rare case of Budd-Chiari syndrome, associated with a combination of hepatic vein and superior vena cava occlusion. A young female, who had been in good health, was admitted to our hospital because of massive ascites. The patient had used no oral contraceptives. Tests for coagulation disorders, hematological disorders, and antiphospholipid syndrome were all negative. Budd-Chiari syndrome was diagnosed by radiographic examination. The patient was suffering from a combination of hepatic vein and superior vena cava occlusion. In particular, the venous flow returned from the liver mainly through a right accessory hepatic vein, and stenosis was recognized at the orifice of this collateral vein into the vena cava. Subsequently, the patient underwent percutaneous balloon dilatation therapy for this stenosis. After this treatment, the massive ascites was gradually reduced, and she was discharged from our hospital. It has now been one year since discharge, and the patient has been doing well. If deteriorating liver function or intractable ascites occur again, a liver transplantation may be anticipated. This is the first case report of Budd-Chiari syndrome associated with a superior vena cava occlusion.

Immunohistochemical analysis of short-segment Barrett's esophagus.

BACKGROUND AND AIMS: The majority of dysplasias and adenocarcinomas in Barrett's esophagus are closely associated with the specialized columnar epithelium. In this study, we performed an immunohistochemical analysis of columnar metaplasia presenting in short-segment Barrett's esophagus (SSBE). PATIENTS AND METHODS: The endoscopic biopsy specimens obtained from 91 patients were analyzed. Ten were cases of long-segment Barrett's esophagus (LSBE) and 81 had SSBE. Expression of MUC2, MUC5AC, Con A and CD10 was evaluated using immunohistochemical staining. RESULTS: All samples from LSBE (n = 9) were histologically diagnosed as specialized columnar epithelium. The 81 SSBE samples were divided into gastric fundic-type (n = 26), junctional-type (n = 16) and specialized columnar epithelium (n = 39). In the specialized columnar epithelium of SSBE, there was a predominance of goblet cell-type metaplasia proposed by Watanabe et al. which is characterized by MUC2-positive pyloric epithelium (66.7%). The total percentage of non-goblet cell-type and goblet cell-type was 76.9%. In contrast, 80% of LSBE revealed the large intestinal-type or the large and small intestinal-type. The long oval and villous pit by magnifying endoscope suggests the presence of the specialized columnar epithelium, but the phenotypic classification of Watanabe's criteria was not associated with the endoscopic pit pattern. CONCLUSION: Intestinal metaplasia in Barrett's esophagus changes immunohistochemically with progress of the disease.

[Histopathological examination in gastroesophageal reflux disease (GERD)].

We performed an immunohistochemical analysis of cell cycle-regulating protein (p21, p27 and Ki67) expression in endoscopic biopsy samples from the patients with gastroesophageal reflux disease (GERD) using angled-biopsy forceps. Inflammatory cell accumulation into the lamina propria was detected even in patients with modified Los Angeles (IA) system grades N and/or M. In grade N and M patients with no changes in the epithelium, the area of p21, p27 and Ki67 positive cells was expanded compared to normal mucosa. The area of p21, p27 and Ki67 positive cells tended to expand upward in the epithelium with GERD severity based on the LA classification grading. These indicate that inflammatory cell infiltration into the lamina propria is initial histological change of GERD.

Inflixmab as a possible treatment for the hemorrhagic type of Crohn's disease.

Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease (CD). Although anti-tumor necrosis factor-alpha (TNF-alpha, infliximab) therapy has been established for patients with inflammatory and fistulous CD, there has been little evidence on whether infliximab is effective for the hemorrhagic type of CD. We report a case of a 31-year-old man with CD who had recurrent sudden-onset bloody stool. After a second surgery, he visited our hospital because of bloody stool. Infusion of infliximab stopped the bleeding and promoted the healing of ulcers in the ileum and ileocolon anastomosis. We suggest that infliximab therapy should be tried to stop acute gastrointestinal bleeding in CD before there is a surgical emergency.

N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis.

Dietary fat is an important factor involved in the pathogenesis of inflammatory bowel disease (IBD). It remains unclear how n-3 and n-6 fatty acids modulate intestinal inflammation. In this study, we investigated the effects of n-3 and n-6 fatty acid-rich diets on trinitrobenzene sulfonic acid (TNBS)-induced enteritis. The rats were fed an n-3 or n-6 rich-diet for 12 days, and then starved for the following 2 days. An intraileal injection of TNBS was administered, and TNBS-enteritis subsequently developed. Macroscopic and histological examination was performed after 24 h. Serum cytokine levels were determined by ELISA. The n-6 fatty acid-rich diet markedly enhanced mucosal damage as compared to the n-3 fatty acid-rich diet. The damage score was significantly higher in the n-6 fatty acid-rich diet group (P<0.05). Histological changes in the mucosa were more severe in the n-6 fatty acid-rich diet group than in the n-3 fatty acid-rich group. Serum IL-6 levels were significantly higher in the n-6 fatty acid-rich diet group than in the n-3 fatty acid-rich group (P<0.05). On the other hand, there were no differences in serum TNF-alpha levels. The n-3 fatty acid-rich diet effectively reduced early mucosal inflammation in TNBS enteritis. The effects of the n-3 fatty acids were associated with blockage of mucosal IL-6 secretion. Our data suggest that n-3 fatty acid-rich diet may be applicable for enteral nutrition in the treatment of IBD patients.

Gastric inflammatory fibroid polyp treated with Helicobacter pylori eradication therapy.

Gastric inflammatory fibroid polyps (IFPs) are rare benign lesions that occur in the distal stomach. We describe a 70-year-old woman with Helicobacter pylon-positive gastric IFP treated with eradication. Gastroduodenal endoscopy revealed a pyramidal-shaped, broad-based tumor with an ulcerated apex at the antrum. Helicobacter pylori was positive by both histology and tissue culture, and eradication (a proton pump inhibitor, amoxicillin, and clarithromycin) was performed. After 3 months, the tumor morphologically changed and the apex ulcer was markedly enlarged. This case suggests that H. pylori may play a role in the pathophysiology of IFPs.

Collagenous gastritis in a young Japanese woman.

Collagenous gastritis, a counterpart of collagenous colitis, is a rare disorder with less than 20 cases reported in the literature. A case of collagenous gastritis in a Japanese woman in her early 20s who had been receiving treatment for atopic dermatitis and bronchial asthma is reported. The patient complained of repeated epigastric pain, and endoscopy revealed multifocal atrophic areas and scars in the gastric body. Biopsy specimens showed a thickened eosinophilic band-like structure with entrapped capillaries approximately 30-70 micro m thick beneath the surface epithelium. It was regarded as a collagen band because it was positive on Azan staining but negative on amyloid staining. This finding was accompanied by marked infiltration of mononuclear cells and eosinophils in the lamina propria; however, no evidence of lymphocytic gastritis was found. Helicobacter pylori infection was not detected and inflammatory cell infiltration was minimal in the mucosa without the collagen band. Immunohistochemical analysis revealed that the band was positive for type III and type VI collagen. The size of the collagen band did not change for 2 years. These findings suggest that subepithelial collagen deposition was due to an abnormal local immune response based on generalized allergic disorder.

Immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in gastroesophageal reflux disease.

BACKGROUND: The aim of this study was to carry out an immunohistochemical analysis of cell cycle-regulating-protein (p21, p27, and Ki-67) expression in endoscopic biopsy samples obtained using angled biopsy forceps. METHODS: The study was based on the examination of endoscopic esophageal biopsy specimens obtained from 46 patients with evidence of reflux and from 10 normal control subjects without clinical reflux. RESULTS: The percentage of samples containing the lamina propria was 5.7% using standard forceps ( n = 53) and 83.3% using the angled forceps ( n= 67). The use of angled forceps allowed the detection of inflammatory cell accumulation in the lamina propria even in patients with modified Los Angeles (LA) system grades N and M. In normal esophageal mucosa, Ki-67-positive cells were detected within the lower parts of the basal zone, and p21- and p27-positive cells were not detected. In samples from grade N and M patients, no histological changes were detectable by standard H&E staining. However, the area of Ki-67-positive cells was slightly expanded compared with normal mucosa, and p21- and p27-positive cells were clearly detectable from the lower to middle part of the epithelium. The area of Ki-67-, p21-, and p27-positive cells tended to expand upward in the epithelium with gastroesophageal reflux disease (GERD) severity based on the LA classification grading. CONCLUSIONS: The use of angled biopsy forceps allows the evaluation of inflammatory responses at the level of the lamina propria and makes it possible to assess the expression of cell cycle-regulating proteins in the entire epithelium. The evaluation of these responses may be helpful in the diagnosis of endoscopically negative GERD.