Naoshi Nakamura

Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration ☆

BACKGROUND Autoimmune pancreatitis is characterized by high serum IgG4 concentrations and lymphoplasmacytic infiltration. Because of the diversity of extrapancreatic involvement in this disease, the present study sought to identify other associated GI-tract lesions. METHODS EGD findings were compared between a group of 23 patients with autoimmune pancreatitis undergoing ERCP for obstructive jaundice and 230 age- and gender-matched control patients. To clarify the histopathologic differences found between these two groups, the histopathologic findings (Updated Sydney System) and the immunohistochemistry of each IgG subclass were compared between 8 patients with autoimmune pancreatitis and gastric ulcer, and 23 control patients with gastric ulcer from which biopsy specimens had been obtained. RESULTS Gastric ulcer was found significantly more frequently in patients with autoimmune pancreatitis compared with control patients (34.8% vs. 13.5%; p=0.007). There was no significant difference between the groups with respect to the frequency of other GI lesions. Four of 8 gastric ulcers in patients with autoimmune pancreatitis were linear, with the long axis perpendicular to the incisura on the lesser curvature of the stomach. The activity score for the gastric lesions was significantly lower in patients with autoimmune pancreatitis compared with control patients (mean score 0.38 vs. 1.08; p=0.012). There were no significant differences in histopathologic findings with respect to inflammation, atrophy, metaplasia, or Helicobacter pylori scores between the two groups. IgG4-bearing plasma cells were significantly more abundant in gastric lesions in patients with autoimmune pancreatitis compared with those in control patients (mean score 1.75 vs. 0.39; p=0.0008). CONCLUSIONS Autoimmune pancreatitis is closely associated with gastric ulcer with abundant IgG4-bearing plasma cell infiltration.

Histochemical Reactivity of Normal, Metaplastic, and Neoplastic Tissues to α-Linked N-Acetylglucosamine Residue-specific Monoclonal Antibody HIK1083

Monoclonal antibody (MAb) HIK1083, which is obtained by immunizing mice with a preparation of rat gastric mucins, has been shown to bind specifically to α-linked N-acetylglucosamine (α-GlcNAc). We investigated the specificity of MAb HIK1083 by immunostaining normal human organs, mucinous metaplasia of human pancreas, adenocarcinomas of human stomach, pancreas, and colon, and normal rat organs. The specificity was investigated by making comparisons with (a) a stain that labels Class III concanavalin A (ConA)-reactive mucin (Class III mucin), i.e., paradoxical ConA (PCS), and (b) staining with horseradish peroxidase (HRP)-conjugated Griffonia simplicifolia agglutinin II (GSA-II). In normal human and rat organs and in mucinous metaplasia of human pancreas, immunostaining with MAb HIK1083 and PCS showed similar specificities for mucins in glandular mucous cells. In adenocarcinoma of stomach and pancreas, GSA-II showed the most widespread positivity, PCS showed the least, and MAb HIK1083 showed a reactivity between those two extremes. Colon adenocarcinomas were labeled only with GSA-II. These results demonstrate that MAb HIK1083 could be a useful screening tool for Class III mucin in normal, metaplastic, and carcinoma tissues, and that the α-GlcNAc residue is one of the specific sugar residues found in Class III mucin.

Possible Relationship between Helicobacter pylori Infection and Cap Polyposis of the Colon

Background.  Cap polyposis is a rarely encountered disease characterized by multiple distinctive inflammatory colonic polyps located from the rectum to the distal colon. The etiology of this disease is still unknown, and no specific treatment has been established.

Clinicopathologic features and histochemical analyses of proliferative activity and angiogenesis in small cell carcinoma of the esophagus

BackgroundWe investigated clinicopathologic features in patients with esophageal small cell carcinoma (SCEC), and its proliferative activity and angiogenesis.MethodsTen patients with SCEC from 335 esophageal carcinoma patients were analyzed clinicopathologically. For analyses of cell proliferation, apoptosis, and angiogenesis of SCEC, Ki-67 immunostaining, the TUNEL method, and CD31 and CD68 immunostaining were used.ResultsEsophagectomy was performed in nine patients, while one with extensive SCEC was treated by repeated chemotherapy and radiotherapy. Four patients received chemotherapy both before and after surgery, one only before surgery, and four only after surgery. Cisplatin and etoposide were given to five patients, while irinotecan and cisplatin were given to three. Five survived more than 18 months, and two more than 36 months. One of these two had limited SCEC treated by surgery and chemotherapy, whereas the other had extended SCEC treated by repeated chemotherapy and radiotherapy. The microvessel count and the Ki-67 labeling index of SCEC were higher than those of squamous cell carcinoma (P = 0.0033 and P = 0.0005, respectively). Between SCEC with and without preoperative chemotherapy, the Ki-67 labeling index was lower (P = 0.027) and the apoptotic index was higher in the treated SCEC (P = 0.014). Between SCEC patients who survived more or less than 18 months, the microvessel count was lower in those who survived more than 18 months (P = 0.049).ConclusionsEsophagectomy may be indicated for limited SCEC combined with chemotherapy. SCEC has high proliferative activity and rich neovascularization, and its proliferative activity may be suppressed by chemotherapy.

Local Gastric and Serum Concentrations of Rebamipide Following Oral Ingestion in Healthy Volunteers

The purpose of this study was to investigate whether sufficient concentrations of rebamipide (COR) are actually present in the stomach after its oral ingestion at an ordinary clinical dose. Twenty healthy volunteers (total 42 man-days) participated in the study. After ingestion of 100, 200, or 300 mg of rebamipide, endoscopy was performed at 1, 2, 4, and 6 hr, and gastric mucosa or gastric mucus was taken from the antrum. Venous blood samples were taken simultaneously. Samples were analyzed by high-performance liquid chromatography. The COR in the gastric mucosa and gastric mucus did not depend on the original amount ingested. After ingestion of rebamipide, each COR was higher than 10−4 M(37 μg/g tissue) at 1 or 2 hr. On the other hand, the COR in serum did depend on the amount ingested and was lower than 10−6 M(0.37 μg/ml) at every time tested. These results suggest that the COR in the stomach exceeds the levels that are needed for various antiulcer actions and that the rebamipide levels present in the gastric mucosa and gastric mucus result from local penetration.

A case of primary follicular lymphoma of the duodenum with BCL-2 gene rearrangement

B-cell rearrangements of the BCL-2 gene. However, karyotypic analyses of the chromosomes of the cultured cells showed no abnormalities. Trisomy-3 was not detected in the specimens, using fluorescence in situ hybridization. Two of the five sampled lymph nodes showed lymphoid involvement. On the basis of these findings, the tumor was finally diagnosed according to the WHO classification as a stage II1 FL, large-cell type, of the duodenum. Because of the lymphoid involvement, adjuvant chemotherapy was administered. The patient has had no recurrence for the 48 months following surgery. Although the present case was detected at an early stage and the lymphoma cells were limited to the duodenal mucosa and submucosa, lymphoid involvement was observed. Yoshino et al.1 have reported two cases of primary FL of the duodenum with lymphoid involvement, despite the early stage. FL generally progresses slowly, but it may have a tendency toward lymphoid involvement. In our patient, we performed surgical resection as the initial treatment modality because FL generally tends to be resistant to chemotherapy. Shia et al.2 have reported 26 cases of primary FL of the GI tract, and, of the four patients who received chemotherapy alone, only one achieved a complete initial response and the other three achieved only a partial response. Another patient who received chemotherapy and abdominal radiation achieved a complete initial response, but the disease recurred 44 months after the initial treatment. Recently, the effectiveness of conservative treatment modalities for malignant lymphoma of the GI tract has been reported; however, there is ongoing controversy on the necessity of surgical resection. Though primary follicular center lymphoma (FL) of the gastrointestinal (GI) tract is relatively rare, the incidence of FL is unexpectedly high in the duodenum compared with that in other portions of the GI tract.1 We report a case of FL of the transverse part of the duodenum that was diagnosed based not only on microscopic findings but also on molecular genetic assessment of a BCL-2 gene rearrangement. A 48-year-old woman was referred to our hospital on October 17, 1997, for further examination and for the treatment of a duodenal tumor. She had first undergone an upper GI endoscopy as part of a health screening. Physical examination and laboratory data showed no significant abnormalities, but endoscopic observation revealed a whitish granular elevation in the duodenum (Fig. 1). Hypotonic duodenography showed a granular flat elevated lesion, of about 30mm, in the transverse part of the duodenum (Fig. 2). The biopsy specimens showed infiltrates of atypical lymphoid cells, which had destroyed and diminished glands with a giant lymphoid follicle structure. The atypical cells were positive for L-26, CD10, and BCL-2, but negative for UCHL-1, cyclin D1, and CD5. Other examinations, including computed tomography, gallium scintigram, colonoscopy, and bone marrow aspiration, showed no abnormal findings. The patient was diagnosed as having stage I primary FL of the duodenum. On February 13, 1998, the patient underwent partial duodenal resection and sampling of peripheral lymph nodes. Histological examination revealed that the lesion in the duodenum was composed of atypical lymphoid cells, which formed giant lymphoid follicles in the duodenal mucosa and submucosa (Fig. 3). Immunohistochemical studies showed staining of the tumor cells with antibodies to L-26 and overexpression to BCL-2. Further, a Southern blot hybridization study detected

Endoscopic pancreatic sphincter balloon dilation for effective retrieval of pancreatic duct stone

To facilitate pancreatic stone retrieval, four patients with chronic pancreatitis and pancreatic stones underwent endoscopic pancreatic sphincter balloon dilation (EPSBD) rather than pancreatic sphincterotomy. Extracorporeal shock wave lithotripsy combined with endoscopic removal was carried out in three patients. Stone removal following EPSBD was completely successful in all four patients. Patients showed no severe complications during the dilation procedure. In one patient, to prevent pancreatitis, an endoscopic nasopancreatic drain was placed for 1 week after EPSBD. Compared with pancreatic sphincterotomy, EPSBD can be performed safely in patients with chronic pancreatitis to assist in the extraction of pancreatic duct stones. Use of the EPSBD procedure in cases of chronic pancreatitis provides a useful approach to improve endoscopic clearance of pancreatic duct stones.

Application of short tandem repeat of genomic DNA and mitochondrial DNA for identification of mixed-up tissue specimens

Deoxyribonucleic acid (DNA) typing methods, short tandem repeat of genomic DNA and mitochondrial DNA with the use of polymerase chain reaction amplification, were applied to formalin‐fixed, paraffin‐embedded tissues submitted for diagnosis, to identify and sort out mixed‐up tissue specimens. These techniques were found to be reliable, reproducible and specific for personal identification, and thus to eliminate the need for further examinations and to prevent unnecessary surgery.