[Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report].

A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.

Usefulness of Serum Leucine-Rich Alpha-2 Glycoprotein as a Surrogate Marker of Small Bowel Mucosal Injury in Crohn's Disease.

Introduction: Although the importance of mucosal healing has been suggested in Crohn's disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a surrogate marker of endoscopy. However, few studies have investigated a correlation between LRG and mucosal injury of the entire small bowel. Methods: We retrospectively analyzed the clinical data of 30 patients with Crohn's disease from June 2020 to August 2022 at Yamaguchi Red Cross Hospital. All the patients were surveyed through the gastrointestinal tract by esophagogastroduodenoscopy, total colonoscopy, and capsule endoscopy (CE). Subjects with mucosal injury only in the small bowel were selected. Then, we assessed the relationship between serum biomarkers (LRG, C-reactive protein [CRP], hemoglobin, albumin) and small bowel mucosal injury scores (Lewis score [LS], Capsule Endoscopy Crohn's Disease Activity Index [CECDAI], and Crohn's Disease Activity in Capsule Endoscopy [CDACE]) calculated by CE. Results: LRG and CRP were significantly correlated with small bowel mucosal injury scores (LS, CECDAI, CDACE) (p < 0.05, Spearman's rank correlation coefficient). The degree of correlation was greater for LRG than for CRP. Conclusions: LRG is a useful surrogate marker that closely reflects small bowel mucosal injury in the entire small bowel.

[A case of chronic enteropathy associated with SLCO2A1 gene diagnosed by capsule endoscopy and successfully treated by ferric carboxymaltose].

Chronic non-specific multiple ulcers of the small intestine is a disease condition postulated in Japan. It is an uncommon gastrointestinal disease that causes chronic anemia and hypoalbuminemia by causing numerous ulcers without any histopathologically identifiable features. In recent years, it has been revealed that the mutations of SLCO2A1, which codes the prostaglandin transporter protein, are the cause of this disease;it is called the new name "chronic enteropathy associated with SLCO2A1 gene." The ileum, except the terminal ileum, is the most common place making it difficult to identify major lesions. Other than conservative treatments, such as nutrition therapy and iron supplements, no effective treatment has been identified so far. We present a case of chronic non-specific multiple ulcers of the small intestine diagnosed by capsule endoscopy and effectively treated by ferric carboxymaltose. A 48-year-old female had chronic iron deficiency anemia since around the age of 15. Because of severe anemia, the patient had upper and lower endoscopy at the age of 47 to find the source of the bleeding, but it was not detected. Except for the terminal ileum, the capsule endoscopy revealed ring-like ulcers, tape-like ulcers, and oblique ulcer scars in the ileum. Genetic analysis showed a homozygous mutation in intron 7, c.940+1G>A, indicating a definitive diagnosis of non-specific multiple ulcers of the small intestine. Anemia and anemia-related symptoms such as general malaise persisted despite continuous oral administration of iron drugs. Three intravenous injections of ferric carboxymaltose increased hemoglobin and enhanced the symptoms.

Acceleration of ammonium nitrite denitrification by freezing: determination of activation energy from the temperature of maximum reaction rate.

A reaction of ammonium nitrite in ice was investigated. Upon freezing, some nitrite is oxidized by dissolved oxygen and some nitrite reacts with ammonium to produce nitrogen and water in a denitrification reaction. The former reaction was accelerated only during freezing, and the latter one was accelerated even after the whole sample was frozen. The denitrification reaction proceeded at very low concentration in ice, which were conditions under which the reaction would not proceed in solution. The nitrogen production increased linearly with increasing initial concentration of ammonium nitrite. The concentration factor in the unfrozen solution in ice was estimated to be 50.6 when the initial concentration was 0.5 mmol dm(-3), as obtained from comparison of reaction rates in solution and in ice. A new method for determination of the activation energy is proposed that gives a value of 53 to 61 kJ mol(-1) for denitrification. The reaction order of the denitrification process is also determined using our method, and it is concluded to follow third-order kinetics.

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: a clinicopathologic and molecular study with reference to antibiotic treatment.

BACKGROUND: The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphoma develops in Helicobacter pylori-associated chronic gastritis. Little is still known regarding the clinicopathologic features of gastric MALT lymphoma not associated with H. pylori infection. METHODS: One hundred thirty-seven patients with gastric MALT lymphoma, in whom H. pylori status was evaluated using at least both serology and histology, were enrolled. Clinical, histopathologic, and molecular findings were compared between H. pylori-negative group (n = 12; 9%) and H. pylori-positive group (n = 125; 91%). t(11;18)(q21;q21) was investigated by reverse-transcription polymerase chain reaction and interphase fluorescence in situ hybridization. RESULTS: In cases without diffuse large B-cell lymphoma (DLBCL) component, H. pylori-negative lymphomas located more frequently in the proximal stomach (70%), less frequently appeared as superficial type (40%), and frequently invaded the submucosa or beyond (70%). Histologically, lymphoepithelial lesions (57%), lymphoid follicles (43%), and background mucosal atrophy (50%) in the H. pylori-negative group were less frequent than in the H. pylori-positive group (91%, 93%, and 100%, respectively). The frequencies of t(11;18)(q21;q21) (100%) and BCL10 nuclear expression (100%) in the H. pylori-negative group were significantly higher than in the H. pylori-positive group (2% and 27%, respectively). Response to antibiotic treatment was observed not only in the H. pylori-positive group (75%), but also in the H. pylori-negative group (2 of 7 patients, 29%). In cases with a DLBCL component, such differences were not observed between the 2 groups. CONCLUSIONS: H. pylori-negative gastric MALT lymphoma is characterized by frequent t(11;18)(q21;q21). Antibiotic treatment should be considered also for this disease, although cases with t(11;18)(q21;q21) may need additional strategies.

Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphoma.

BACKGROUND: Although caspase recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) and CARD9 play important roles in lymphocyte activation, the significance of CARMA1 and CARD9 in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma remains to be elucidated. METHODS: By using reverse transcription-polymerase chain reaction analysis, the expression levels of mRNA of CARMA1, CARD9, Bcl10, and the apoptosis inhibitor 2 (API2)-MALT1 chimeric transcript were determined in tissue specimens from 65 patients with primary gastric B-cell lymphoma (43 patients with low-grade MALT lymphoma, 16 patients with MALT lymphoma plus diffuse large B-cell lymphoma [DLBL], and 6 patients with DLBL without MALT lymphoma) and in tissue specimens from 18 patients with chronic gastritis. The expression levels of CARMA1 and BCL10 were examined immunohistochemically in 30 patients with lymphoma. RESULTS: CARMA1 mRNA was detected in 55% of lymphoma patients but in only 17% of chronic gastritis patients. The positive rates for CARD9, Bcl10, and API2-MALT1 chimeric transcript in the lymphoma patients were 48%, 98%, and 8%, respectively, whereas the 3 molecules were not detected in any specimens from patients with chronic gastritis. The expression of CARMA1 and CARD9 was frequent in the Helicobacter pylori-negative patients (100% and 86%, respectively), in the API2-MALT1 chimeric transcript-positive patients (100% and 100%, respectively), and in the specimens from patients who did not respond to H. pylori eradication (76% and 71%, respectively). In addition, CARMA1 expression was positive more frequently in patients of DLBL without MALT lymphoma (100%) than in patients of MALT lymphoma (51%). CARMA1 protein expression was correlated significantly with the expression of CARMA1 mRNA and also with the expression of nuclear BCL10. CONCLUSIONS: The overexpression of CARMA1 and CARD9 presumably is associated with the development or progression of gastric B-cell lymphoma, especially among patients who have disease in which the pathogenesis is not related to H. pylori.

Long-term clinical outcome of Helicobacter pylori eradication for gastric mucosa-associated lymphoid tissue lymphoma with a reference to second-line treatment.

BACKGROUND: The goals of the current study were to elucidate the long-term outcome of Helicobacter pylori eradication therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to clarify the therapeutic efficacy of stomach-conserving treatments for patients not responding to eradication therapy. METHODS: Ninety-six patients with gastric MALT lymphoma, including 17 patients with areas of diffuse large B-cell lymphoma, were treated by H. pylori eradication. Patients not responding to eradication therapy underwent either a gastrectomy, multiagent chemotherapy, oral monochemotherapy (OMC), or radiotherapy (RT). Predictive factors for the response to eradication therapy, overall survival (OS), and event-free survival (EFS) were determined by the Kaplan-Meier analysis with the log-rank test. The efficacy of second-line treatment was compared between OMC and RT. RESULTS: After eradication therapy, 62 (65%) patients achieved complete disease remission (CR). Transient histologic disease recurrence was confirmed in 4 (6.5%) of 62 patients with CR during the follow-up (median, 37.5 months). The OS and EFS probabilities after 5 years were 0.96 and 0.80, respectively. Second-line treatment was performed in 31 patients; gastrectomy in 4 patients, multiagent chemotherapy in 5 patients, OMC in 12 patients, and RT in 10 patients. There were no differences in the CR rate, OS, EFS, or toxicity between the OMC and RT groups. CONCLUSIONS: H. pylori eradication therapy was an effective first-line treatment for patients with gastric MALT lymphoma, which led to a favorable long-term outcome. OMC and RT had an equivalent efficacy as a second-line treatment in nonresponding patients to eradication therapy.