Helicobacter pylori (H pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-hydroxyprostaglandin dehydrogenase (15–PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H pylori. 15-PGDH expression in gastric biopsies from H pylori-infected (n=25) and non-infected (n=15) subjects was analyzed by quantitative real-time PCR, western blot analysis, and immunohistochemisty. 15-PGDH DNA methylation was evaluated by methylation specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, ERK1/2, TLR4 and MyD88 in response to H pylori infection was assessed by immunoblot analysis. Compared to negative specimens, H pylori positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H pylori infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of epidermal growth factor receptor (EGFR)-Snail. Inhibition of Snail and MyD88 reversed suppression of 15-PGDH expression and small interfering Myd88 reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 and EGFR inhibitor also restored 15-PGDH expression. Heliocobacter pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 or EGFR - Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H pylori-induced gastric carcinogenesis.
Gastric cancer; Helicobacter pylori; 15-prostaglandin dehydrogenase
15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is downregulated during the early stages of colorectal carcinogenesis. The aim of the present study was to investigate the potential role of 15-PGDH in normal-appearing colorectal mucosa as a biomarker for predicting colorectal neoplasms. We obtained paired tumor and normal tissues from the surgical specimens of 32 sporadic colorectal cancer patients. mRNA expression of 15-PGDH was measured using a quantitative real-time PCR assay. We evaluated the association between 15-PGDH mRNA expression in normal-appearing mucosa, the presence of synchronous adenoma, and the cumulative incidence of metachronous adenoma. The relative 15-PGDH expression of normal-appearing mucosa in patients with synchronous adenoma was significantly lower than in patients without synchronous adenoma (0.71 vs 1.00, P = 0.044). The patients in the lowest tertile of 15-PGDH expression in normal-appearing mucosa were most likely to have synchronous adenoma (OR: 10.5, P = 0.024). Patients with low 15-PGDH expression in normal-appearing mucosa also demonstrated more advanced stage colorectal cancer (P = 0.045). However, there was no significant difference in the cumulative incidence of metachronous adenoma according to 15-PGDH mRNA expression in normal-appearing mucosa (P = 0.333). Hence, 15-PGDH in normal-appearing colorectal mucosa can be a useful biomarker of field effect for the prediction of sporadic synchronous neoplasms.
15-Hydroxyprostaglandin Dehydrogenase; Biological Markers; Colorectal Neoplasms
A 66-year-old female presented with a 1-month history of dyspepsia. An initial upper gastrointestinal endoscopy with biopsy revealed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. A rapid urease test was positive for Helicobacter pylori. Endoscopic ultrasound (EUS) and computed tomography (CT) revealed a 30×15-mm lymph node (LN) in the subcarinal area. Histopathologic and phenotypic analyses of the biopsy specimens obtained by EUS-guided fine-needle aspiration revealed a MALT lymphoma, and the patient was diagnosed with a stage 4E gastric MALT lymphoma. One year after H. pylori eradication, the lesion had disappeared, as demonstrated by endoscopy with biopsy, CT, fusion whole-body positron emission tomography, and EUS. Here, we describe a patient with gastric MALT lymphoma that metastasized to the mediastinal LN and regressed following H. pylori eradication.
Marginal zone B-cell lymphoma; Stomach
ALADIN gene has been known to cause achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome. A considerable proportion of achalasia patients has been known to show alacrima (decreased secretion of tear). However, the genetic mechanism between achalasia and alacrima has not been defined yet. We postulated that ALADIN gene may be involved in the occurrence of early-onset achalasia; thus, we investigated the correlation of ALADIN gene in early-onset achalasia patients.
From 1989 to 2007, patients who were diagnosed as primary achalasia before age 35 were enrolled. All of the enrolled patients were asked for (1) blood sampling for DNA, (2) Shirmer test and (3) dysphagia questionnaires.
The ALADIN gene in exon 1, 2, 10, 11 and 12 from 19 patients was investigated (M:F = 12:7). The mean age of patients at diagnosis was 27 ± 5 (15-35) years old. Eight out of 19 (42%) showed alacrima by the positive Shirmer test. In spite of thorough exam in the genetic study, there was no definite abnormal genetic finding in this study.
A considerable number of achalasia patients showed alacrima. Due to the limitation of this study, it is difficult to conclude that early-onset achalasia may have significant correlations with the ALADIN gene.
AAAS protein; Esophageal achalasia; Human; Shirmer test
The levels of pepsinogen (PG) I and the PGI/II ratio are useful serologic markers for chronic atrophic gastritis. This study evaluated the performance and clinical implications of these markers in patients undergoing endoscopic mucosectomy.
We enrolled 142 consecutive patients with early gastric tumors and Helicobacter pylori infection who were eligible for mucosectomy. Chronic gastritis and atrophy were assessed using four defined biopsy procedures. Serum PGs were measured by an enzyme immunoassay. Optimal diagnostic cut-offs and performance were determined using receiver operating characteristic curves.
The PGI level and the PGI/II ratio decreased with corpus-dominant gastritis and as atrophy advanced toward the corpus greater curvature (GC). For the presence of corpus GC atrophy, the areas under the PGI and PGI/II-ratio curves were 0.82 and 0.77, respectively. The optimal cut-off levels were 59.3µg/L for PGI (sensitivity, 83.3%; specificity, 78.4%) and 3.6µg/L for PGI/II ratio (sensitivity, 70.0%; specificity, 78.4%). Using these serologic cut-off levels, we found that the frequency of corpus tumor location differed significantly (32.9% vs 11.1% for PGI <59.3 and ≥59.3µg/L, respectively; and 31.1% vs 14.8% for PGI/II ratio <3.5 and ≥3.5, respectively; p<0.05).
A low PGI level and PGI/II ratio are valuable serologic markers for predicting corpus GC atrophy, and have clinical implications with respect to the corpus location of tumors in mucosectomy patients.
Pepsinogens; Atrophic gastritis; Stomach neoplasia; Helicobacter pylori; Endoscopy
Benign bronchoesophageal fistula (BEF) is a rare condition that is usually treated surgically; however, less invasive endoscopy procedures have been attempted to overcome the disadvantages of surgery. The aim of this study was thus to determine the results of endoscopic management as a primary treatment in patients with BEF.
We retrospectively analyzed data from 368 patients with BEF who were treated at a tertiary care, academic medical center between January 2000 and August 2009.
Benign causes were found for only 18 of the 368 patients. Of these, seven were treated endoscopically and the others by surgery or other methods. The first endoscopy procedures failed in all seven patients, with second trials of endoscopy performed in four patients at a median of 8 days (range, 3 to 11 days) after the first procedure. The second endoscopic procedure was successful in two out of four patients; one patient showed no recurrence of the fistula, whereas the second patient experienced a recurrence after 24 months. All patients underwent successful surgical procedures after the failure of endoscopic treatment, with no further recurrences.
Although we observed a low rate of success for primary endoscopic treatment of benign BEF, the invasive nature of surgery suggests the need for a prospective study with a large number of patients to evaluate the efficacy of less invasive procedures such as endoscopic treatment.
Esophageal fistula; Endoscopy; Fibrin glue
Helicobacter pylori eradication may facilitate the healing of iatrogenic ulcer after endoscopic resection of gastric neoplasm. This study involved designing a randomized, double-blinded, placebo-controlled, multicenter trial, performed by the Korean College of Helicobacter and Upper Gastrointestinal Research and the Medical Research Collaboration Center, Seoul National University Hospital.
We intend to enroll up to 232 patients H.-pylori-positive patients who have gastric adenoma or early gastric cancer after endoscopic resection. The enrolled patients are being randomly allocated to the H.-pylori-eradication-plus-proton-pump-inhibitor group or the placebo-plus-proton-pump-inhibitor group based on their histology results and the size of the resected specimen. After random allocation, the iatrogenic ulcer size and stage are evaluated at 4- and 8-week follow-ups (with a window of ±7 days). The primary end point is the healing rate of the ulcer by stage, and the secondary end point is the rate of ulcer size reduction, relief rate from ulcer-related symptoms, and adverse-event rates.
More than 90% of the target subjects have already been enrolled into the study and are receiving ongoing periodic monitoring by the Medical Research Collaboration Center.
Completion of the study should reveal whether H. pylori eradication can facilitate the healing of ulcer after endoscopic resection in Korea.
Helicobacter pylori; Iatrogenic ulcer; Endoscopic resection; Eradication; Medical Research Collaboration Center
The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole- and rabeprazole-based triple therapies.
A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C13-urea breath test.
Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795).
The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms.
Helicobacter pylori; CYP2C19; Proton pump inhibitor; Lansoprazole; Rabeprazole
The incidence of Barrett's cancer is increasing in Western countries, but there have been only a few case reports of this condition in Korea. The aim of this study was to elucidate the endoscopic and pathologic characteristics of Barrett's cancer in a single center in Korea.
We retrospectively reviewed the demographic, endoscopic, and pathologic characteristics of six patients with Barrett's cancer, defined as a tumor centered above the esophagogastric junction and surrounded by Barrett's esophagus.
All six patients were male, and three (50%) were symptomatic. Barrett's cancer had developed from short-segment Barrett's esophagus in all patients. All tumors were located on the right side of the lower esophagus and showed hyperemic mucosal changes. Three patients were treated surgically and three by endoscopic resection. All cases had pathologic evidence of Barrett's cancer.
Early detection of Barrett's cancer requires meticulous endoscopic observations of subtle mucosal color and morphological changes around the esophagogastric junction.
Barrett esophagus; Esophageal neoplasms
We report a case of malignant fibrous histiocytoma (MFH) of the right buttock with multiple metastases to the lung, bone, and small intestine. He received resection and end-to-end anastomosis of the jejunum for the jejunal metastatic tumor, and mass excision of the metastatic tumor of the left femur followed by closed reduction and internal fixation and palliative radiotherapy. In addition, he received palliative radiotherapy to the metastatic pulmonary tumor with suspicious invasion into the thoracic aorta. However, one month after the completion of the aggressive local treatments, metastatic tumors recurred in the abdominal cavity, an extremely unusual site, resulting in peritoneal dissemination. He died of progressive disease 5 months after the initial diagnosis.
Malignant fibrous histiocytoma; Buttock; Peritoneal cavity; Neoplasm seeding
Small bowel perforation due to hematogenous metastatic tumor emboli is a rare event, especially in a patient with rectal cancer. We report a 75-year-old man with relapsed rectal cancer who developed an acute abdomen, which was found to be due to a perforated terminal ileum. Emergency surgery involved segmental resection and ileostomy. The pathology of the resected small bowel showed multifocal and extensive metastatic tumor emboli in the entire wall, leading to transmural infarction followed by perforation, without a discrete tumor mass. The pathology with immunohistochemistry showed a rectal tumor that was positive for CK-20 but negative for CK-7 and TTF-1. This extremely rare complication of rectal cancer resulted from ischemia and infarct caused by disseminated metastatic tumor emboli without direct invasion or mass formation.
Small intestine; Infarction; Intestinal perforation; Rectal cancer; Tumor embolism
We report on an exceptional vascular cause of gastrointestinal hemorrhage. A 30-yr-old man was admitted because of recurrent hematochezia. Colonoscopy showed circumferential, erythematous, and nodular vascular distensions with hematocystic spots in the terminal ileum resembling varicosis and subsequent computed tomography with 3-dimensional angiographic reconstruction revealed a vascular architecture around the terminal ileum. No other potential source of bleeding was identified. The patient was treated by ileocecectomy and the final diagnosis was of an arteriovenous malformation confined to the terminal ileum. He has been followed-up without a further hemorrhagic episode.
Congenital; Arteriovenous Malformation; Ileum; Varix; Bleeding