[Clinical and molecular characteristics of a child with familial adenomatous polyposis].

OBJECTIVE: To explore the clinical features and molecular mutation of early-onset familial adenomatous polyposis(FAP) in childhood. METHOD: The clinical features, endoscopic findings, pathology and therapeutic effect of sulindac during 11 years follow-up in a child with FAP were retrospectively reviewed . Adenomatous polyposis coli (APC) gene mutation analysis was performed by PCR and first generation sequencing. RESULT: This 6-year-old girl was admitted for intermittent bloody stool during the last one and a half years. Colonoscopy showed hundreds of polyps in the rectum and colon. Pathological examination revealed tubular adenomas with high grade dysplasia. During the follow-up period of 11 years, the child presented intermittent mucous bloody stool. Endoscopy showed the number of polyps in colon and rectum increased to thousands, and found multiple polyps in gastric fundus and body.She was treated with sulindac at the age of 13. Then the number of polyps and the grade of pathology showed a slight improvement and no carcinoma was seen on biopsy. She has not accepted surgery until now. Gene sequencing of this child revealed 5 bp deletion at codon 1,309 of exon 15 (c.3927_3931delAAAGA) of tumor suppressor gene, whereas none of her parents had the same mutation. And no polyps were found on her parents colonoscopy. CONCLUSION: This child with FAP had an early onset of this disease, and clinical conditions were exacerbated with age. Sulindac was partially effective in controlling size and number of polyps. The site of mutation in this case was consistent with classic FAP, and without family history, the mutation may be a sporadic one.

Allergic diseases, immunoglobulin E, and autoimmune pancreatitis: a retrospective study of 22 patients.

BACKGROUND: Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of pancreas. We evaluated the clinical manifestations, imaging, and histological presentations of AIP in Chinese patients, and investigated the roles of immunoglobulin E (IgE) and allergic diseases in the diagnosis and pathogenesis of AIP. METHODS: The clinical records of 22 patients diagnosed with AIP were reviewed and analyzed. All patients with AIP fulfilled the 2006 revised diagnostic criteria proposed by Japan Pancreas Society or the Korean Criteria for AIP. RESULTS: Half (11/22) of AIP patients had allergic diseases. Twenty-one patients had elevated serum IgE levels, and 14 patients had IgE levels more than 3 times that of normal. There were no significant differences between the patients with higher or lower IgE, with or without allergic disease, in clinical features, laboratory tests, diffuse or focal lesions, or the choice of treatment methods; however, more complaints of body weight loss were observed in patients with higher IgE levels. Patients with higher IgE levels and with allergic diseases were more likely to have onset in March, April, May, August, September, or October. IgE levels decreased after therapy, but increased again during recurrence. Increased number of mast cells was found in the pancreatic tissue in AIP. CONCLUSIONS: IgE maybe a useful marker for monitoring therapeutic response and recurrence of AIP. Allergic processes may play an important role in the pathogenesis of AIP.

Relationship of Helicobacter pylori eradication with gastric cancer and gastric mucosal histological changes: a 10-year follow-up study.

BACKGROUND: Helicobacter pylori (Hp) is a common and potentially curable cause of gastric mucosa lesion. This study investigated the relationship of Hp infection with histological changes in gastric mucosa and gastric cancer in Hp-positive patients compared with Hp-eradication patients followed up for ten years. METHODS: From an initial group of 1 006 adults, 552 Hp-positive subjects were randomly assigned to a treatment group (T; n = 276) or a placebo group (P; n = 276). In the randomized, double-blind, placebo-controlled, parallel trial, T group subjects received oral doses of omeprazole, amoxicillin and clarithromycin for 1 week; those in the P group received a placebo. One month after treatment ended, a 13C urea breath test was performed, and Hp was undetectable in 88.89% of the T group. All subjects were followed at 1, 5, 8, and 10 years after treatment, with endoscopy and biopsies for histological examination. RESULTS: Gastric mucosa inflammation was significantly milder in the T group than that in the P group one year after Hp eradication and this persisted for 10 years. Glandular atrophy and intestinal metaplasia (IM) had deteriorated in both groups during ten years. However, the increased score of glandular atrophy at both the gastric antrum and corpus, and IM only at the gastric antrum, in the P group was more obvious than that in the T group. During the 10 years, 9 patients were diagnosed with gastric cancer (2 in the T group; 7 in the P group; P = 0.176). When mucosal atrophy was absent at the gastric antrum and corpus when entering the study, the incidence of gastric cancer in the P group (n = 6) was much higher than that in the T group (n = 0, P = 0.013). CONCLUSIONS: Hp eradication may significantly diminish and help halt progression of gastric mucosal inflammation and delay the development of IM and atrophy gastritis. Hp eradication is helpful for reducing the risk for gastric cancer, especially in the early stage of Hp infection.

Adult colonoscopy or single-balloon enteroscopy-assisted ERCP in long-limb surgical bypass patients.

OBJECTIVE: The aim of this study was to evaluate the usefulness of adult colonoscopy or single-balloon enteroscopy (SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) in long-limb surgical bypass patients. METHODS: Retrospective analysis of 16 patients with long-limb surgical bypasses who underwent therapeutic ERCP because of suspected pancreaticobiliary diseases. Small-bowel intubation was performed by peroral adult colonoscopy or SBE. If colonoscopy success was achieved, ERCP was performed subsequently. But in patients using SBE, a small-caliber colonoscope would be used to replace enteroscope if the SBE success was achieved. ERCP was then performed with the conventional accessories. RESULTS: A total of 21 ERCP procedures were performed. Adult colonoscope was used for ERCP in 8 patients with standard Whipple resection consecutively. Colonoscopy success was achieved in 8 of 8 patients (100%), of whom 7 of 8 (87.5%) achieved ERCP success. SBE-assisted ERCP was attempted in other 8 patients with different types of Roux-en-Y anatomy. SBE success was achieved in 7 of 8 patients (87.5%), of whom 4 of 7 (57.1%) achieved ERCP success. The overall success rate of endoscopy and ERCP was 93.8% (15/16) and 68.8% (11/16), respectively. CONCLUSIONS: Adult colonoscopy has high success rate for performing ERCP after Whipple resection and should be selected for such patient preferentially. By using the facilitated method for endoscopic interventions at pancreaticobiliary disease after Roux-en-Y reconstruction, SBE-assisted ERCP can be attempted when it is difficult to gain access to the papilla of Vater or bilioenteric/pancreaticoenteric anastomosis and long length ERCP accessories cannot be available.

Endoscopic Retrograde Cholangiopancreatography Using a Dual-Lumen Endogastroscope for Patients with Billroth II Gastrectomy.

Objective. To evaluate the safety and efficacy of a dual-lumen forward-viewing endoscope for ERCP in patients with prior Billroth II gastrectomy. Methods. The records of 46 patients treated with ERCP by a dual-lumen forward-viewing endoscope after Billroth II gastrectomy from 2007 to 2012 were reviewed. Results. The success rate of selective cannulation was 82.6% (38/46). Of the 38 cases with successful selective cannulation, endoscopic sphincterotomy was achieved in 23 cases by placing the needle knife through the 2nd lumen, while endoscopic papillary balloon dilatation was conducted in the other 15 cases. Of the 8 failed cases of selective cannulation, 6 had failed afferent loop intubation, and 3 of these 6 patients had Braun's anastomosis. The safety and efficacy of catheter-assisted endoscopic sphincterotomy were increased by placing the needle knife through the 2nd lumen without altering the conventional endoscopic sphincterotomy procedure. Conclusions. A dual-lumen forward-viewing endoscope can be safely and effectively used to perform ERCP in patients with a Billroth II gastrectomy, except for patients with additional Braun's anastomosis.

BCL10 nuclear expression and t(11;18)(q21;q21) indicate nonresponsiveness to Helicobacter pylori eradication of Chinese primary gastric MALT lymphoma.

The eradication of Helicobacter pylori (H. pylori) with antibiotics induces complete remission in 75% of patients with gastric MALT lymphoma. We investigated the efficacy of H. pylori eradication and assessed the predictive value of BCL10 nuclear expression and t(11;18)(q21;q21) regarding resistance to H. pylori eradication in primary gastric mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) patients from mainland China. Twenty-two gastric MALT cases (Stage I(E)) underwent H. pylori eradication with antibiotics, and sequential endoscopic-bioptic follow-ups were performed and assessed with regular morphologic and immunohistochemical examinations. BCL10 nuclear expression and interphase fluorescence in situ hybridization (FISH) for MALT1 and API2/MALT1 were tested. Thirteen out of the 22 cases (59.1%) achieved complete regression (CR) after the eradication of H. pylori. The longest follow-up period in the 22 patients was 68 months, with 12 patients longer than 24 months. For the 13 CR patients, the longest follow-up period after H. pylori eradication was 53 months, with 6 patients longer than 24 months. BCL10 nuclear expression was detected by immunohistochemical staining in 9 cases, including 7 (77.8%) of 9 cases who showed no response (NR) and 2 (15.4%) of 13 patients who achieved CR following eradication therapy (P < 0.05). t(11;18)(q21;q21) was evaluated by interphase FISH in 18 cases including 11 CR and 7 NR patients after H. pylori eradication. t(11;18)(q21;q21) was found in 4 (57.1%) of 7 patients who showed NR following H. pylori eradication, but one in 11 CR patients (P < 0.05). A total of 59.1% of patients with early gastric MALT lymphoma recruited in this study achieved CR after H. pylori eradication. BCL10 nuclear expression and t(11;18)(q21;q21)-positive gastric MALT lymphomas are likely to be related to a failure to respond to H. pylori eradication in Chinese patients.

Higher rates of t(11;18) in Chinese patients with transformed type of MALT lymphoma suggest novel pathways for progression of the disease.

To detect the t(11;18) chromosome translocation in different stages of mucosa-associated lymphoid tissue (MALT) lymphoma, we established a RT-PCR method by adopting three new primer pairs and using the RNA extracted from the paraffin tissues to amplify the t(11;18) fusion gene API2-MALT1 in shorter lengths. Our results showed five key findings, which are (a) higher detection rates of t(11;18) (21.13%) in Chinese patients with transformed MALT lymphoma, (b) lower detection rates of t(11;18) in stomach MALT lymphoma, (c) different organ localizations of MALT lymphoma in Chinese patients, (d) higher nuclear expression rates of Bcl-10 in low grade MALT (51.72%), and (e) lower response rates (50% CR, and 50% PR) to anti-H.-pylori therapy. These findings suggest novel pathways for low-grade MALT lymphoma to be progressed into transformed MALT lymphoma. This study also suggests that amplification of shorter length of PCR products from the paraffin-fixed tissues increases sensitivity, which is significant in improving the selection of the therapeutic regimen and assessing the prognosis of the disease.

[Expression of t(11;18) and bcl-10 in gastrointestinal MALT lymphoma].

To detect chromosome translocation t(11;18) (q21;q21) and the nuclear expression of bcl-10 in gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma in Chinese, a possible API2-MALT fusion transcript specific to t(11; 18) (q21; q21) in tumors from 42 cases of primary gastrointestinal lymphoma (29 cases of low grade MALT lymphoma, 13 cases of transformed MALT lymphoma) and 40 cases of diffuse large B cell lymphoma was examined by means of RT-PCR and proved by DNA-sequencing. Bcl-10 expression was examined by immunohistochemical method. The results showed that t(11;18) (q21;q21) was 14% positive in cases of low grade MALT lymphomas and 46% positive in transformed MALT lymphomas, but none in cases of DLBCL. Bcl-10 nuclear expression was seen 61% in low grade MALT and 69% in transformed MALT lymphoma. It was suggested that t(11;18) (q21;q21) was related to the prognosis and development of highly advanced MALT lymphoma but not relevant to DLBCL. Bcl-10 nuclear expressions were not significantly different between these two groups, which remains to be explained.

T(11;18)(q21;q21) in gastric MALT lymphoma and diffuse large B-cell lymphoma of Chinese patients.

T(11;18)(q21;q21) occurs at variable frequencies in mucosa-associated lymphoid tissue (MALT) lymphomas of different sites. In gastric MALT lymphoma, it occurs in 30% cases and the translocation positive tumours are frequently at advanced stages and do not respond to Helicobacter pylori eradication. Intriguingly, t(11;18)(q21;q21) has been observed only rarely in mucosal diffuse large B-cell lymphomas (DLBCL), despite that at least a proportion of these tumours are believed to be the result of transformation of an MALT lymphoma. We previously examined t(11;18)(q21;q21) in gastric MALT lymphoma of Chinese in Taiwan and found the translocation in one of the three transformed MALT lymphomas studied. To extend this observation, we have examined t(11;18)(q21;q21) in a large cohort of gastric lymphomas of Chinese in China including 39 MALT lymphomas (12 with high-grade components) and 53 DLBCL by reverse transcription and PCR. Of these cases, RNA samples extracted from 36 MALT lymphomas including 10 cases with high-grade component and 46 DLBCL were adequate for detection of the translocation as judged by control RT-PCR of a house-keeping gene. T(11;18)(q21;q21) was found in 8/36 (22%) MALT lymphomas and 1/46 (2%) DLBCL. None of the MALT lymphoma with high-grade component showed t(11;18)(q21;q21). Our results suggest that t(11;18)(q21;q21) occurs only occasionally in transformed MALT lymphoma.

[Changes of gastric mucosa histopathology after Helicobacter pylori eradication].

OBJECTIVE: To investigate the relationship between Helicobacter pylori (Hp) infection and gastric cancer through the changes of gastric mucosa histopathology within 5 years after Hp eradication in Hp-positive subjects in the high incidence region of gastric cancer. METHODS: One thousand and six adults were selected from general population in Yantai, Shandong Province, the high incidence region of gastric cancer. Gastroscopy and CLO test were performed in all subjects. Biopsy samples from the gastric antrum and body were obtained for histology and assessment of Hp infection. All the Hp-positive subjects were then randomly divided into two groups: treatment group receiving OAC triple therapy and placebo as controls. These subjects were endoscopically followed up in the second and fifth year. In this article, we compared the endoscopic appearance and histology of the biopsy specimens from the same site obtained at the first and final visit. Statistical analysis was done by chi(2) test. RESULTS: All the 552 Hp-positive subjects were randomly divided into treatment group or control group, 276 in each. During the five-year follow-up, the number of patients who continued to be negative or positive for Hp was 161 and 198, respectively. Statistical analysis revealed that: (1) At the initial visit, there were no significant differences in the severity and activity of inflammation between the biopsy specimens from the antrum (P = 0.105) and body (P = 0.084) in both groups. But the proportion of atrophy and intestinal metaplasia in the antrum was much higher than that in the body (P = 0.000). (2) The severity and activity of inflammation in both the antrum and body were markedly reduced after Hp eradication (P = 0.000). (3) Within the five years after Hp eradication, intestinal metaplasia in the antrum regressed or had no progression, while the proportion of intestinal metaplasia in the Hp-positive group increased significantly (P = 0.032). (4) After Hp eradication, the atrophy in both the antrum and body had no significant regression. P value was 0.223 and 0.402, respectively. CONCLUSIONS: Hp eradication results in remarkable reduction in the severity and activity of chronic gastritis, marked resolution of intestinal metaplasia in the antrum. On the other hand, continued Hp infection leads to progressive aggrevation of atrophy and intestinal metaplasia.

A five-year follow-up study on the pathological changes of gastric mucosa after H. pylori eradication.

OBJECTIVES: To investigate the relationship between H. pylori infection, gastric cancer and other gastric diseases through the changes in gastric mucosa and the status of different gastric diseases within 5 years after H. pylori eradication in H. pylori-positive subjects in a high incidence region of gastric cancer. METHODS: One thousand and six adults were selected from the general population in Yantai, Shandong province, a high incidence region for gastric cancer in China. Gastroscopy and Campylobacter-like organism (CLO) testing were performed on all subjects. Biopsy samples from the gastric antrum and body were obtained for histology and assessment of H. pylori infection. All H. pylori-positive subjects were then randomly divided into two groups: treatment group receiving Omeprazole Amoxicillin Clarythromycin (OAC) triple therapy and placebo as controls. These subjects were endoscopically followed up in the second and fifth year. We compared the endoscopic appearance and histology of the biopsy specimens from the same site obtained at the first and last visits. RESULTS: All 552 H. pylori-positive subjects were randomly and evenly divided into treatment group or control group. During the five-year follow-up, the numbers of patients who continued to be negative or positive for H. pylori were 161 and 198, respectively. Statistical analysis revealed that: (1) At the initial visit, there were no significant differences in the severity and activity of inflammation, atrophy and intestinal metaplasia between the biopsy specimens from the antrum and body respectively in both groups. (2) The severity and activity of inflammation in both the antrum and body were markedly reduced after H. pylori eradication (P = 0.000). (3) Within five years after H. pylori eradication, intestinal metaplasia in the antrum either regressed or had no progression, while the proportion of intestinal metaplasia in the H. pylori-positive group increased significantly (P = 0.032). (4) After H. pylori eradication, the atrophy in both the antrum and body had no significant regression. The P value was 0.223 and 0.402, respectively. CONCLUSIONS: H. pylori eradication results in remarkable reduction in the severity and activity of chronic gastritis, marked resolution of intestinal metaplasia in the antrum. On the other hand, continuous H. pylori infection leads to progressive aggravation of atrophy and intestinal metaplasia.

Archival fixed histologic and cytologic specimens including stained and unstained materials are amenable to RT-PCR.

Formalin-fixed and paraffin-embedded tissues are increasingly used for analysis of gene expression. However, a large proportion of archival fixed histologic specimens including spare paraffin sections and stained slides, as well as archival cytologic materials, have not been investigated for their suitability for RNA-based analysis. The current study addressed this issue by reverse transcription and polymerase chain reaction (RT-PCR) of the glucose-6-phosphate dehydrogenase (G6PD) transcript in a series of archival histologic and cytologic specimens. The histologic specimens included freshly prepared paraffin sections, spare paraffin sections, hematoxylin and eosin-stained slides, immunostained slides, and decalcified bone marrow trephines. The cytologic specimens comprised cervical smears and various stained and unstained needle aspirates and cell sediments. The G6PD was amplified for five different fragment sizes ranging from 67 bp to 453 bp. It was found that the majority of archival materials were amenable to RT-PCR of small fragments with the overall success rates of 95% and 79% for 67 bp and 151 bp of the G6PD mRNA, respectively. Neither staining nor prolonged storage up to 15 years had major negative effects on RT-PCR, although fine-needle aspirates showed a higher rate of RT-PCR of 242-bp fragment than other types of cytologic specimens and so did Papanicolaou-stained samples than May Grounwald and Giemsa-stained samples. RT-PCR of minute cell populations microdissected from immunostained sections of tonsils and t(11;18)-positive mucosa-associated lymphoid tissue lymphomas showed that as few as 100 cells were adequate for RT-PCR of G6PD and translocation-associated fusion transcript as long as the target fragment was limited to less than 150 bp. Our results demonstrate that archival fixed histologic and cytologic specimens are valuable resources for RT-PCR-based molecular investigations.