Endoscopic features with linked-color imaging of non-Helicobacter pylori Helicobacter-associated gastritis: a case study.

Background and Aims: The endoscopic findings of non-Helicobacter pylori Helicobacter (NHPH) are not widely known. Linked-color imaging (LCI) has emerged as a new system for image-enhanced endoscopy (IEE) that enhances color tone and improves visibility. The aim of this case study was to assess how endoscopic findings of NHPH are enhanced with LCI. Methods: We report the case of a 72-year-old woman in whom an NHPH species was found during EGD using LCI. Results: The EGD did not reveal any endoscopic findings of diffuse redness, patchy redness, or atrophy. However, erosions, nonuniform redness, and crack-like mucosa were seen in the antrum, as well as LCI-enhanced endoscopic findings. In addition, nodular gastritis and a white marbled appearance were also observed in the antrum. LCI and blue-laser imaging enhanced the endoscopic findings. Floating bacterial bodies with a fine coil-like shape and diameter longer than that of H pylori were pathologically observed in the mucus, suggesting NHPH. A polymerase chain reaction test led to a diagnosis of Helicobacter suis. Conclusions: Our case demonstrates that IEE is useful in diagnosing NHPH. The detection of NHPH using IEE enabled us to contribute to an improved diagnosis of NHPH.

Germ Cell Neoplasia in Situ Recognized Incidentally with Complaining of Discomfort in the Right Testis: A Case Report.

A 27-year-old man experienced discomfort in his right testis in early September, 2021, and visited the hospital five days later. Physical examination did not detect any abnormalities in the scrotum. However, an ultrasound revealed a tumor in the central part of the right testis, and a Magnetic Resonance Imaging (MRI) showed a tumor 2.7cm in diameter with clear boundaries and a marginally smooth surface. The level of alpha-fetoprotein, human chorionic gonadotropin, human chorionic gonadotropin-ß subunit, and lactate dehydrogenase were within normal limits. A Computed Tomography (CT) scan showed no abnormalities. We can't rule out the possibility of malignancy, right radical orchiectomy was performed with a diagnosis of right testicular tumor in mid-September 2021. The macroscopic lesion was 1.5×1.3 cm in size, and no viable tumorous cells were found pathologically. Atypical cells were observed in the seminiferous tubules from the spermatic cord, which were positively stained with immune-histochemical staining CD117 (c-kit), D2-40, and MIB-1 but negatively with alpha-fetoprotein, human chorionic gonadotropin, and human chorionic gonadotropin-ß subunit. The pathological diagnosis was germ cell neoplasia in situ, and no continuity was observed between these cells and bleeding necrosis. The patient has been followed up for 1 year and 4 months after surgery, with no recurrence or metastasis observed.

Yersinia enterocolitica Enteritis Diagnosed with Erythema Nodosum.

We herein report a rare case of Yersinia enterocolitica enteritis with a fever and abdominal pain followed by erythema nodosum (EN) a few days later. The diagnosis was confirmed based on characteristic colonoscopy and computed tomography findings, pathology, and mucosal culture. Yersinia enteritis is a curable disease provided a proper diagnosis and treatment are performed. Although EN is a rare clinical course, it should still be considered as a differential diagnosis.

Molecular and clinicopathological features of appendiceal mucinous neoplasms.

Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered.

Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis.

BACKGROUND AND AIM: Colonoscopy plays an integral role in the diagnosis, management and surveillance of ulcerative colitis (UC). In the present study we assessed the relationship between endoscopic and histological findings, clinical symptoms, and laboratory data. METHODS: We performed total colonoscopy examinations in 54 consecutive patients with UC. Seven segments (appendiceal region, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were scored for endoscopic and histological activity. The patients were also evaluated using a symptom-activity index and laboratory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) and platelet (plt) counts. RESULTS: There was a significant positive correlation between endoscopic and histological scores (r(s)=0.738), and between symptom activity score, endoscopic score (r(s)=0.444), and histological score (r(s)=0.557). Although the endoscopic and histological scores of distal colonic lesions (rectum-sigmoid, endoscopic: r(s)=0.515, histological: r(s)=0.624) correlated with clinical symptoms, there was no similar correlation for the proximal colon (appendiceal region-descending; endoscopic, r(s)=0.268, histological, r(s)=0.329). CRP, ESR, and WBC count also correlated with the sum of endoscopic and histological scores (CRP, r(s)=0.447, r(s)=0.369; ESR, r(s)=0.483, r(s)=0.589; WBC, r(s)=0.338, r(s)=0.330), whereas platelet count did not (r(s)=0.171, r(s)=0.210). In particular, CRP and ESR were well correlated with the activity of proximal colonic lesions (CRP, r(s) = 0.474, r(s)=0.480; ESR, r(s) = 0.423, r(s)=0.529) rather than with that of distal lesions (CRP, r(s)=0.236, r(s)=0.212; ESR, r(s)=0.368, r(s)=0.497). CONCLUSIONS: In this study, clinical symptoms reflected the activity of distal colonic lesions, whereas CRP and ESR reflected the activity of proximal lesions. Therefore, total colonoscopy may be indicated when CRP or ESR is elevated in UC patients in clinical remission.

[Two cases of gastrointestinal stromal tumor (GIST) of the stomach and a consideration of its malignancy potential and treatment strategy - report of two cases].

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach both of which were assessed as highly malignant, but took different clinical courses. Case 1: A 72-year-old male. Case 2: A 63-year-old female. The tumor size of Case 1 was suggestive of high malignancy, but only a partial gastrectomy was selected because it did not show any invasive findings. This patient has been followed up for 3 years post-operatively and no recurrence or metastasis has been noted. Case 2 had liver and lymph node metastases, which was consistent with high malignancy. We performed a total gastrectomy with distal pancreatosplenectomy and segmental liver resection. But after surgery, liver metastasis recurred therefore, imatinib mesylate was administered as adjuvant chemotherapy and since then, the tumor has been diminishing in size. No definitive evidence for adjuvant therapy has been established so far, but we suggest that post-operative adjuvant therapy is effective for high-risk GIST.

Clinicopathological features of nonpolypoid colorectal tumors as viewed from the patients' background.

BACKGROUND: This study was performed to characterize the clinicopathological features of colorectal tumors with flat-, depressed-, or protruded-type morphology (hereafter referred to simply as flat, depressed, or protruded lesions). METHODS: There are two major types of colorectal tumor: polypoid (protruded) and nonpolypoid (flat and depressed). A total of 130 lesions from 130 patients with colorectal submucosal invasive cancer were classified into three groups according to their macromorphology seen during endoscopy: flat (laterally spreading) and depressed nonpolypoid tumors and protruded polypoid tumors. The following factors in the patients' background were evaluated: indication for colonoscopy, age, and family history of colorectal cancer in first-degree relatives (i.e., parents, siblings, children). We also compared the following characteristics of the tumors: size, location, depth of submucosal invasion, vascular invasion, and frequency of synchronous and metachronous tumor lesions. RESULTS: The incidence of abnormal findings on follow-up studies after polypectomy as an indication for colonoscopy was significantly higher among patients with flat lesions (4/24, 16.7%) and depressed lesions (3/22, 13.6%) than among those with protruded lesions (1/84, 1.2%) (P < 0.01, P < 0.01). Patients with flat lesions (65.8 +/- 7.6 years old) were significantly older than those with protruded lesions (P < 0.05). The patients with flat tumors had a significantly higher rate of a family history of colorectal cancer (6/24, 25.0%) than patients with protruded or depressed lesions (P < 0.01, P < 0.05). The protruded lesions were significantly larger than the depressed lesions (size 13.3 +/- 6.7 mm) (P < 0.05), and the flat lesions (24.1 +/- 10.1 mm) were significantly larger than either the protruded or depressed lesions (P < 0.01, P < 0.01). Seventy-five percent (18/24) of the flat lesions were located in the right colon, and this proportion was significantly higher than that among the protruded or depressed lesions (P < 0.01, P < 0.01). The mean +/- SD depth of submucosal invasion was 1218 +/- 1034 microm in the flat lesions, 2392 +/- 1869 microm in the depressed lesions, and 2761 +/- 1929 microm in the protruded lesions, representing a significant difference (P < 0.05, P < 0.0001). Of the 24 patients with flat lesions, 9 (37.5%) showed vascular invasion; this proportion was significantly lower than that among patients with the depressed or protruded lesions (P < 0.01, P < 0.01). Patients with depressed lesions tended to have higher incidence of synchronous and metachronous malignant polyps than those with protruded or flat lesions. CONCLUSION: It is important to examine the morphology of colorectal tumors when diagnosing them and planning the treatment strategy, including follow-up, after resection of nonpolypoid tumors. It is useful to know the patient's family history so nonpolypoid tumors can be accurately diagnosed.

Frequent hypermethylation of RASSF1A in early flat-type colorectal tumors.

Flat colorectal tumors, characterized by high-grade dysplasia from early small flat mucosal lesions, exhibit a relatively aggressive clinical behavior and are known for their infrequent K-ras mutations. In this study, we investigated the methylation status of the RASSF1A promoter in association with 3p LOH and K-ras mutations in 48 flat colorectal tumors (39 early carcinomas and nine intramucosal high-grade dysplasias). RASSF1A hypermethylation was detected in 39 of 48 (81.3%) tumors and RASSF1A methylation was also detected in 19 of 39 (49%) normal colonic mucosal tissues. 3p21.3 LOH was detected in 20 of 42 (47.6%) cases, but RASSF1 methylation was detected in cases with LOH (14 cases) and retention of 3p21.3 (20 cases). K-ras mutations were detected in seven of 48 (14.6%) tumors and the concordant occurrence of K-ras mutation and RASSF1A methylation was detected in three of 48 cases (6.3%). Overall, there was a statistically significant mutually exclusive relationship between K-ras mutations and RASSF1A methylation. In conclusion, promoter hypermethylation of RASSF1A is a frequent event and may start early in the background normal mucosa in this tumor type. An alternative cascade of abnormalities in RAS transduction pathways may be responsible for the flat morphology and aggressive nature of flat colorectal neoplasms.

Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis.

BACKGROUND: The esophageal tight junction is responsible for the paracellular sealing of the epithelium. Alteration of the expression of tight-junction proteins plays crucial roles in the pathogenesis of some human diseases. The aim of this study was to investigate the distribution and expression pattern of tight-junction proteins in the esophageal mucosa of control rats and rats with reflux esophagitis. METHODS: Chronic acid reflux esophagitis was experimentally induced by operation in rats. The animals were killed on days 7 and 14 after the operation. The thickness of the mucosa and the 5-bromo-2-deoxyuridine (BrdU) labeling index were assessed. The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats. RESULTS: In the esophagitis model, the thickness and BrdU labeling index increased with time. In control rats, claudin-1, -3, and -4 were localized on the cellular membranes of esophageal epithelial cells, mainly in the spinous and granular layers, while claudin-2 was not detected in any layer. Occludin was seen on the cellular membranes in all esophageal mucosal layers. In the esophagitis rats, the expression of claudin-1 was increased both in the plasma membrane and in the cytoplasm around the erosion in the spinous and granular layers. The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers. In contrast, the expression of claudin-3 was decreased in the spinous and granular layers. CONCLUSIONS: The localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.

Imaging and Antitumoral Effect of a Cyclo-oxygenase 2-specific Replicative Adenovirus for Small Metastatic Gastric Cancer Lesions.

BACKGROUND: Long-term outcomes of patients with peritoneal dissemination of gastric cancer remain unsatisfactory despite advances in treatment modalities. Internal luminescence conditionally replicative adenovirus (CRAd) presents a novel approach for cancer treatment and imaging. MATERIALS AND METHODS: 3CL is a modified cyclooxygenase-2 (COX2) promoter-driven CRAd which contains the luciferase expression gene for bioluminescence imaging. The visualizing and therapeutic effect of 3CL was evaluated in a mouse model of peritoneal dissemination. RESULTS: Intraperitoneal injection of 3CL achieved the shrinkage and reduction of lesions of peritoneal dissemination. Six model mice treated with 3CL had a significantly longer mean survival time than 6 mock-treated mice (85.7 versus 34.3 days, p=0.0005). By whole-body bioluminescent imaging, the sensitivity and specificity of peritoneal dissemination detection through macroscopic inspection were 58.1% and 83.2%, respectively, whereas 3CL viral imaging modality yielded corresponding values of 78.8% and 99.3%. Peritoneal lesions detected by imaging histologically contained cancer cells and necrotic tissue, which originated from viral oncolytic effects. CONCLUSION: Cox2 CRAds with 5/3 chimeric-fiber modification, therefore, appear to be a promising imaging and therapeutic tools for peritoneal dissemination of gastric cancer.

Loss of heterozygosity in clonal evolution with genetic progression and divergence in spindle cell carcinoma of the gallbladder.

Spindle cell carcinoma (SpCC) of the gallbladder is a rare neoplasm that shows carcinoma with a variable component of sarcomatoid spindle cells. The clinical and pathological features of this neoplasm have been well documented, but the histogenesis has long been a matter of speculation. In an attempt to clarify the clonality and genetic relationships involved in the evolution of this neoplasm, we microdissected a total of 18 carcinomatous and sarcomatous foci from 2 gallbladder SpCCs and analyzed the allelic status with 42 microsatellite markers on chromosomal arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11p, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. The 2 cases examined had a polypoid tumor in the gallbladder, in which both adenocarcinomatous and sarcomatoid spindle cell components were identified histologically. In both SpCCs, homogenous allelic losses were identified in both the carcinomatous and sarcomatous components; 17p, 18q, and 5q in case 1 and 17p and 11q in case 2. These indicated that both SpCCs had a single clonal origin. In case 1, additional loss of heterozygosity (LOH; 6q) consisting of genetic progression occurred in both the carcinomatous and sarcomatoid components. In case 2, there was additional LOH (9p) in the carcinomatous components and additional microsatellite instability at D5S644 in both the carcinomatous and sarcomatoid components, indicating a monoclonal neoplasm with genetic progression and divergence. In the 2 cases, the genetic changes indicated that an original clone of a pure adenocarcinoma apparently acquired sarcomatoid spindle cell phenotype by successive genetic changes. On the other hand, we saw no evidence of tumors in which a sarcomatoid spindle cell appeared to give rise to a carcinomatous subclone in the examined cases. In conclusion, the current study includes the first LOH analyses of SpCC of the gallbladder. Our data support the concept that gallbladder SpCC is derived from a single clone originating from a carcinoma. Furthermore, we showed genetic heterogeneity accompanying the phenotypic divergence, with patterns of genetic alterations that are consistent with both the progression and divergence within the individual tumors.

Numerical chromosomal abnormality in gastric MALT lymphoma and diffuse large B-cell lymphoma.

BACKGROUND: We investigated numerical chromosomal abnormalities, using the fluorescence in situ hybridization (FISH) method, in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBL). We also compared the histopathological findings, including the presence or absence of Helicobacter pylori infection, with the analytical results. METHODS: Sixteen patients who underwent operation for malignant gastric lymphoma in our department were divided into three groups: patients with low-grade gastric MALT lymphoma (l-MALT; n = 5), those with high-grade gastric MALT lymphoma (h-MALT; n = 8), and those with DLBL (n = 3). Numerical abnormalities of chromosomes 8, 9, 12, and 17 were investigated by the FISH method, and the presence or absence of H. pylori infection was microscopically examined. RESULTS: Numerical abnormality was observed in chromosome 12 in 11 patients (68.8%), in chromosome 8 in 10 (62.5%), and in chromosome 17 in 5 (31.3%), showing a high frequency. H. pylori infection was detected in 80% and 50% of patients with l-MALT and h-MALT, respectively, but no H. pylori infection was observed in patients with DLBL. CONCLUSIONS: A new biological characteristic of gastric MALT lymphoma was obtained, i.e., a high frequency of numerical abnormalities of chromosomes 12, 8, and 17. There was no correlation between the numerical chromosomal abnormalities and the clinicopathological findings.

Pleomorphic adenoma in nasal cavity: immunohistochemical study of three cases.

Intranasal pleomorphic adenoma is a rare neoplasm, and thus only one case report addressed immunohistochemical findings of this neoplasm. To define immunohistochemical features of intranasal pleomorphic adenoma, we studied three cases of the pleomorphic adenoma developed from the nasal septum. Subsequently, immunohistochemical reactivities of the tumor cells for various cytokeratins, glial fibrillary acidic protein (GFAP), S100 protein, alpha-smooth muscle actin (SMA), and vimentin were similar to those of pleomorphic adenoma of the parotid gland. The tumors examined in this study had different histological components, such as predominance of myxoid area, solid area, or tubuloductal structure, but immunoreactivity of both epithelial and myoepithelial tumor cells were the same in the tumors. Therefore, immunoreactivity of the tumor cells were the same among the intranasal pleomorphic adenoma having various histological components.

Pneumothorax developing for the first time in a 73-year-old woman diagnosed with Birt-Hogg-Dubé syndrome.

Spontaneous pneumothorax in the elderly commonly occurs due to underlying pulmonary diseases, such as chronic obstructive pulmonary disease, interstitial lung disease, lung cancer, etc. A 73-year-old woman developed pneumothorax for the first time that was a clinical clue to a diagnosis of Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant condition characterized by fibrofolliculomas of the skin, renal tumors and multiple lung cysts predisposing to pneumothorax. Although BHDS patients frequently develop pneumothorax during their twenties to forties, the present case indicates that BHDS should be considered as an underlying cause of pneumothorax in the elderly with undisclosed BHDS.

Sigmoid colon carcinoma that developed from a sessile-type cancer in a short period of time.

We report a case of sigmoid colon carcinoma that developed from a sessile-type cancer in a short period of time. An 83-year-old man was found to have a round sessile polyp, about 2 cm in diameter, in the sigmoid colon. Because he had taken anticoagulants, immediate endoscopic mucosal resection and biopsy were not performed. Forty-three days later, the apical surface of the sessile polyp had become depressed and ulcerated, and we judged that an endoscopic resection was not indicated for this lesion. The histologic diagnosis of the biopsy specimens was a well-differentiated adenocarcinoma. We recommended surgical treatment; however, the patient was not in favor of surgical treatment and would not consent to surgery. Two more examinations were performed and the tumor was found to have developed into an invasive cancer with ulcerated, nodular margins involving 3/4 of the colonic lumen. At 271 days after the initial examination, the patient finally consented to surgery and a partial resection of the sigmoid colon was performed. The tumor was classified as stage I (T2N0M0). The several examinations performed from presentation within a short time span provide evidence of the morphologic changes that occur when a sessile-type cancer develops into an ulcerating invasive cancer. We hypothesize that remarkable configuration changes and development take place when a tumor becomes invasive in the muscularis propria from massive submucosal invasion. Our findings suggest that among the tumors discovered as typical ulcerating invasive type colon cancers are those that developed from protuberant tumors in a short period of time.

Does ampullary carcinoma arise from distended glands in the papilla of Vater?

BACKGROUND/PURPOSE: Glands near the surface of the papilla of Vater may become distended with mucus and become hyperplastic; that is, become distended. In this study, we tried to clarify carcinogenesis in these distended glands. METHODS: Twenty-nine pancreatoduodenectomized nontumorous duodenal papilla specimens from carcinoma of the pancreas and bile duct and 34 resected ampullary carcinoma specimens were studied histopathologically and immunohistochemically, using cytokeratins and mucin immunohistochemical features/phenotypes. RESULTS: Distended glands were found in 11 of the 29 pancreatoduodenectomized specimens. These glands were immunopositive for cytokeratin (CK) 7 and MUC-5AC Glycoprotein (MUC5AC), but not for CK20, while the intrapapillary portion was CK7-positive and CK20-negative, but mostly negative for MUC5AC. Immunopositivity for CK7, CK20, and MUC5AC was found in 25, 21, and 18 of the 34 specimens of ampullary carcinoma, respectively. In 23 of the 34 specimens, immunoreactivity for MUC5AC and that for CK7 was coincident, that is, when the former was immunopositive, so was the latter, and vice versa, while in 25 of the 34 specimens, immunoreactivity for MUC5AC was opposite to that for CK20. Among the 23 cases in which immunoreactivity for MUC5AC and CK7 was coincident, 10 were MUC5AC+, CK7+, CK20- and 7 were MUC5AC-, CK7-, CK20+, suggestive of disease arising from the pancreaticobiliary mucosa or the distended glands in the former and disease arising from the duodenal mucosa in the latter. In MUC5AC+ cases, other than the 10 cases of MUC5AC+, CK7+, CK20-, 6 were double-positive and 1 was double-negative for CK7 and CK20, and 1 was CK20-positive, and at least 1 case showing double-negativity for CK7 and CK20 was suggestive of disease arising from the distended glands. CONCLUSIONS: Although most ampullary carcinomas arise from the duodenal mucosa or intra-ampullary mucosa, both CK7-positive and MUC5AC-positive or only MUC5ACpositive ampullary carcinomas may arise from the distended glands.

Laparoscopy-assisted transanal pull-through at the time of suction rectal biopsy: a new approach to treating selected cases of Hirschsprung disease.

AIM: We present a new approach to treating selected cases of Hirschsprung disease (HD) where suction rectal biopsy (SRBx) is performed in an operating room, and rapid acetylcholinesterase staining (RAST) is used to identify histopathology within 20 minutes, allowing primary laparoscopy-assisted transanal pull-through (PLTPT) to be commenced "immediately" (n = 7). MATERIALS AND METHODS: All subjects had an obvious caliber change in the rectum/sigmoid colon on barium enema and were strongly suspected of having HD. RESULTS: Rapid acetylcholinesterase staining clearly demonstrated acetylcholinesterase-positive hypertrophic nerve trunks and absence of ganglion cells in all SRBx specimens, indicating that all 7 patients had HD. All 7 proceeded to uneventful PLTPT. By taking this approach, SRBx results were available extremely quickly, and hospital stay was reduced by 2 to 4 days. DISCUSSION: Our approach enhanced the treatment of selected cases of HD by proceeding immediately to PLTPT after SRBx specimens were examined using RAST.

Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

OBJECTIVE: It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. MATERIAL AND METHODS: Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. RESULTS: The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial. CONCLUSIONS: The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Improvement of gastric atrophy after Helicobacter pylori eradication therapy.

BACKGROUND: It remains controversial whether gastric atrophy is reversible after Helicobacter pylori eradication therapy. AIM: To clarify whether gastric atrophy improves after H. pylori eradication therapy using a histologic approach. METHODS: Subjects were 87 H. pylori infection-cured patients (treatment group) and 29 continuously H. pylori-infected patients (control group). The subjects in the treatment and control groups were followed for 10-49 months (mean, 22 months) and 11-50 months (mean, 22 months), respectively. Biopsy specimens were obtained from the greater curvature of the antrum and corpus at the beginning and end of the observation period; histologic analyses of these specimens were performed for detection of activity, inflammation, atrophy, and intestinal metaplasia. Results were scored without any clinical information according to the Sydney system. RESULTS: In the treatment group, the histologic score for atrophy was improved in the corpus but not in the antrum. Intestinal metaplasia was not improved in either the antrum or the corpus. There were no significant differences during the follow-up in gastric atrophy and intestinal metaplasia in the control group. CONCLUSION: Gastric atrophy was improved in the corpus approximately 2 years after H. pylori eradication therapy.

Advanced colorectal carcinomas measuring 20 mm or less exhibit markedly higher invasiveness despite their size.

To analyze the biology of small (20 mm or less) advanced colorectal carcinomas (SAC), 24 cases, 22 small early colorectal carcinomas (SEC) of similar size, and 52 advanced colorectal carcinomas (AC) were studied. The proliferative (Ki-67) labeling index for SAC was 65.9+/-17.1%, significantly higher than those for SEC (30.9+/-13.7%) or AC (43.0+/-17.1%) (P < 0.01). Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-2 expressions for SAC were 62.5 and 79.2%, respectively, significantly higher than those for SEC (4.5, 13.6%) or AC (21, 33%) (P < 0.01). Small advanced carcinomas have higher invasiveness than SEC or AC and may represent a different type of cancer.