Synchronous presentation of acute pancreatitis and splenomegaly with intussusceptions in Peutz‐Jeghers syndrome

Peutz‐Jeghers syndrome (PJS) is a rare, autosomal dominant inherited disorder characterized by gastrointestinal hamartomatous polyps and pigmented mucocutaneous lesions. Intussusceptions and gastrointestinal tract bleeding are frequent complications of PJS caused by larger polyps, but acute pancreatitis and splenomegaly are very rare. Previously, surgical intervention was the only curative modality despite the associated complications. In recent years, double‐balloon enteroscopy (DBE) has become the alternative method as the ideal treatment. We report the case of a 20‐year‐old woman diagnosed with PJS, as she suffered from 4‐day nausea and vomiting with acute abdominal pain, and clinically manifested acute pancreatitis, splenomegaly and duodenojejunal intussusceptions secondary to a huge proximal jejunal polyp (10 cm × 2 cm). We removed the polyp via DBE and found that the acute pancreatitis, splenomegaly and duodenojejunal intussusceptions were simultaneously ameliorated 2 days after treatment. Currently, the patient has been symptom free for 3 months after polypectomy. Acute pancreatitis, splenomegaly and intussusceptions can synchronously occur in PJS patients, and polypectomy via DBE is the effective treatment alternative to surgical intervention for this disease, thereby obviating some complications associated with the latter.     

NODULAR GASTRITIS WITH HELICOBACTER PYLORI INFECTION IS STRONGLY ASSOCIATED WITH DIFFUSE‐TYPE GASTRIC CANCER IN YOUNG PATIENTS

Background: Nodular gastritis (NG), a particular type of gastritis, is now defined as antral nodularity. Recent studies have shown that NG is strongly associated with Helicobacter pylori infection, and we recently showed that it may be associated with diffuse‐type gastric cancer of the corpus. We retrospectively investigated the relation between NG and gastric cancer in patients aged 29 years or less. Patients and Methods: The study group comprised 150 patients (48 males, 102 females; mean age, 27.7 years) who were endoscopically diagnosed with NG and were less than 29 years of age; 3939 sex‐ and age‐matched patients without NG who were H. pylori‐positive served as the control group (1184 males, 2755 females; mean age, 27.5 years). We estimated the risk of gastric cancer development in patients with NG relative to that of patients without NG. Results: The prevalence of gastric cancer was significantly higher in patients with NG than in the control patients (7/150; 4.7% vs 3/3939; 0.08%, P < 0.001). The odds ratio for the risk of gastric cancer in patients with NG was found to be 64.2 (95% confidence interval; 16.4–250.9). The seven cases of gastric cancer with NG showed the same characteristics: all were diagnosed histologically as the diffuse type and were located in the corpus with H. pylori infection. Conclusion: NG with H. pylori infection is strongly associated with diffuse‐type gastric cancer of the corpus in young patients.     

MAGNIFICATION ENDOSCOPIC VIEW OF AN EARLY GASTRIC CANCER USING ACETIC ACID AND NARROW‐BAND IMAGING SYSTEM

A 62‐year‐old woman was referred to Mie University Hospital, Tsu, Japan, for examination of upper gastrointestinal tract. The conventional endoscopy showed a slightly depressed lesion on the greater curvature at the gastric body. The surface of surrounding non‐neoplastic mucosa using magnification endoscopy with acetic acid was gyrus‐villous pattern whereas the surface of the lesion was rough. Furthermore, magnification endoscopy using acetic acid and narrow‐band imaging system visualized clearer fine surface pattern of carcinoma. The lesion had a rough mucosa with irregularly arranged small pits. The lesion was resected completely by endoscopic mucosal resection with insulated‐tip electrosurgical knife. Narrow‐band imaging system with acetic acid may be able to visualize not only the capillary pattern but also the fine surface pattern of gastric carcinoma.     

A CASE OF DIFFUSE‐TYPE EARLY GASTRIC CANCER WITH NODULAR GASTRITIS

A 39‐year‐old woman was referred to Osaka Police Hospital and admitted for surgical treatment of gastric cancer. Barium upper gastrointestinal study and endoscopic examination showed a 3.0 × 3.0 cm depressed lesion in the greater curvature of the middle corpus. An unusual miliary pattern resembling ‘goose flesh’ was observed endoscopically in the antrum. Biopsy specimens from the tumor showed poorly differentiated adenocarcinoma, and specimens from the antrum showed many lymphoid follicles with a germinal center. Rapid urease test and histological tests (Giemsa stain) for Helicobacter pylori were both positive. Early gastric cancer with nodular gastritis (NG) was diagnosed and a partial gastrectomy was performed. Histological examination of the resected specimen showed a stage I tumor consisting mainly of signet‐ring cell carcinoma restricted to the mucosa. Postoperatively H. pylori eradication therapy was performed and proved to be successful. One year after eradication therapy, endoscopy with biopsy showed no recurrence of gastric cancer and the remarkable regression of antral NG.     

5'-CpG island methylation of the LKB1/STK11 promoter and allelic loss at chromosome 19p13.3 in sporadic colorectal cancer

BACKGROUND: In patients with Peutz-Jeghers syndrome (PJS), causative germline mutations in the LKB1/STK11 gene on chromosome 19p13.3 have been identified. Because of the loss of heterozygosity (LOH) at 19p13.3 in hamartomas and the cancer susceptibility of patients with PJS, LKB1/STK11 is suggested to act as a tumour suppressor. However, the frequency of genetic and epigenetic inactivation of LKB1/STK11 in sporadic tumours is unclear. AIMS: To investigate the LKB1/STK11 gene for promoter hypermethylation and allelic loss in tumour specimens of patients with sporadic colorectal cancer. METHODS: DNA from 50 consecutive paraffin embedded sporadic colorectal adenocarcinomas and corresponding normal epithelium was extracted. After bisulphite treatment, specimens were analysed for methylation of the LKB1/STK11 promoter 5'-CpG island by methylation specific polymerase chain reaction (MSP). In addition, tumours were analysed for LOH of chromosome 19p13.3. In tumours exhibiting LOH, LKB1/STK11 was sequenced. RESULTS: MSP was successful in 48 of 50 tumour specimens. Of those, four (8%) demonstrated hypermethylation of the LKB1/STK11 promoter 5'-CpG island. Moreover, LOH at either D19S886 or D19S878 was observed in five of 38 (13%) informative tumours. All five tumours showing LOH at 19p13.3 were advanced and four of five were located in the left sided colon. There was no correlation between LOH and LKB1/STK11 promoter hypermethylation or somatic mutation. CONCLUSIONS: In sporadic colorectal cancer, hypermethylation of the LKB1/STK11 promoter and allelic loss at the STK 11 gene locus are rare events. LOH at 19p13.3 was associated with advanced tumour stage and left sided location but not with LKB1/STK11 promoter hypermethylation or somatic mutation.     

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.     

Molecular and Clinical Characteristics in 46 Families Affected with Peutz–Jeghers Syndrome

Germline mutations of the tumor suppressor gene LKB1/STK11 are responsible for the Peutz–Jeghers syndrome (PJS), an autosomal-dominant disorder characterized by mucocutaneous pigmentation, hamartomatous polyps, and an increased risk of associated malignancies. In this study, we assessed the presence of pathogenic mutations in the LKB1/STK11 gene in 46 unrelated PJS families, and also carried genotype–phenotype correlation in regard of the development of cancer in 170 PJS patients belonging to these families. All LKB1/STK11 variants detected with single-strand conformational polymorphism were confirmed by direct sequencing, and those without LKB1/STK11 mutation were further submitted to Southern blot analysis for detection of deletions/rearrangements. Statistical analysis for genotype–phenotype correlation was performed. In 59% (27/46) of unrelated PJS cases, pathogenic mutations in the LKB1/STK11 gene, including 9 novel mutations, were identified. The new mutations were 2 splice site deletion–insertions, 2 missenses, 1 nonsense, and 4 abnormal splice sites. Genotype–phenotype analysis did not yield any significant differences between patients carrying mutations in LKB1/STK11 versus those without mutations, even with respect to primary biliary adenocarcinoma. This study presents the molecular characterization and cancer occurrence of a large cohort of PJS patients, increases the mutational spectrum of LKB1/STK11 allelic variants worldwide, and provides a new insight useful for clinical diagnosis and genetic counseling of PJS families.     

CHARACTERISTICS AND ROLE OF ENDOSCOPIC MUCOSAL RESECTION USING CAP‐FITTED PANENDOSCOPE FOR EARLY GASTRIC CANCER

Background: It is accepted in Japan and in the gastric cancer treatment guidelines that small gastric mucosal cancers without lymph node metastasis can be curatively treated by endoscopic mucosal resection (EMR). Various techniques of EMR for early gastric cancer have been reported, and in the present study, the results of EMR using cap‐fitted panendoscope (EMRC) for early gastric neoplastic lesions are examined, and the characteristics and the role of EMRC procedure are discussed. Methods: From August 1992 to March 2003, 181 gastric neoplastic lesions in 155 patients were treated by EMRC at the Department of Surgery, Esophagogastric Division, Tokyo Medical and Dental University. The frequency of residue and the cause of residue following EMRC for 181 gastric neoplastic lesions were examined. Five‐year survival rates were calculated and compared according to the 49 patients who underwent en bloc resection and the 49 patients who underwent planned fractionated resection by EMRC for early gastric cancer. Results: There was residue in nine (5%) of 181 lesions treated by EMRC. Residues from four elevated lesions resulted from muscular resection and insufficient additional resection; residues from five depressed lesions resulted from incorrect diagnosis of the spread of the lesions prior to resection and insufficient additional resection. In the EMRC patients, the survival rates for 49 patients treated by en bloc resection (93%) and 49 patients by planned fractionated resection (91%) were not significantly different. Conclusion: The EMRC technique, that is en bloc and planned fractionated resection by EMRC procedure, has an important role as an easy and curative EMR method for almost all of the indicated early gastric cancers by the gastric cancer treatment guidelines with no limitations from the lesion sites.     

NARROW‐BAND IMAGING COMBINED WITH MAGNIFIED ENDOSCOPY FOR CANCER AT THE HEAD AND NECK REGION

While detection of lesions at an earlier stage in head and neck mucosal sites would obviously be of great merit to patients, there has been no modality to discover such lesions. Herein, we investigate a possibility of clinical application of narrow‐band imaging (NBI) endoscopy, which is a brand new optical technique that allows non‐invasive visualization of the microvessels at the organ surface. We found that NBI technology could be a promising and powerful tool for identifying carcinomas at an earlier stage in head and neck mucosal sites. This may open a new door in the field of head and neck oncology.     

THERAPEUTIC OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION OF UNDIFFERENTIATED‐TYPE INTRAMUCOSAL GASTRIC CANCER WITHOUT ULCERATION AND PREOPERATIVELY DIAGNOSED AS 20 MILLIMETRES OR LESS IN DIAMETER

Aim: The aim of the present study was to examine therapeutic outcomes of endoscopic submucosal dissection (ESD) of undifferentiated‐type intramucosal gastric cancer and the problems of diagnosis. Methods: We reviewed 58 patients with preoperatively diagnosed undifferentiated‐type intramucosal early gastric cancer (EGC) without ulceration with a diameter of 20 mm or smaller (expanded‐indication lesion) who underwent ESD at the Cancer Institute Hospital between September 2003 and August 2008. Results: The overall rates of one‐piece resection and complete resection were 98% and 90% respectively, and the median operation time was 70 min. Bleeding was seen in 8.6% and perforation in 3.4%. The curative resection rate was low at 79%. Factors responsible for non‐curative resection were most commonly submucosal invasions. If limited to pathologically diagnosed expanded‐indication lesions, the curative resection rate was 98%. The difference in tumor size between a macroscopic diameter and a histological diameter was within ±5 mm in 96% of expanded‐indication lesions, with none of these cases having a histological diameter that exceeded the macroscopic diameter by more than 5 mm. Conclusion: ESD was technically feasible for expanded‐indication lesions of undifferentiated‐type EGC. We achieved a high rate of curative resection by the markings at sites 5 mm beyond the preoperatively determined lesion area. Factors responsible for non‐curative resection were most commonly submucosal invasions. We should diagnose the depth of such lesions more carefully.     

Differences between men and women in the regulation of adipose 11β‐HSD1 and in its association with adiposity and insulin resistance

This study explored sex differences in 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) activity and gene expression in isolated adipocytes and adipose tissue (AT), obtained via subcutaneous biopsies from non‐diabetic subjects [58 M, 64 F; age 48.3 ± 15.3 years, body mass index (BMI) 27.2 ± 3.9 kg/m²]. Relationships with adiposity and insulin resistance (IR) were addressed. Males exhibited higher 11β‐HSD1 activity in adipocytes than females, but there was no such difference for AT. In both men and women, adipocyte 11β‐HSD1 activity correlated positively with BMI, waist circumference, % body fat, adipocyte size and with serum glucose, triglycerides and low‐density lipoprotein:high‐density lipoprotein (LDL:HDL) ratio. Positive correlations with insulin, HOMA‐IR and haemoglobin A1c (HbA1c) and a negative correlation with HDL‐cholesterol were significant only in males. Conversely, 11β‐HSD1 activity in AT correlated with several markers of IR and adiposity in females but not in males, but the opposite pattern was found with respect to 11β‐HSD1 mRNA expression. This study suggests that there are sex differences in 11β‐HSD1 regulation and in its associations with markers of obesity and IR.