A case of stricture-type ischemic colitis from excessive alcohol consumption, with follow-up to rule out colon cancer

A 69-year-old man was admitted to Hanawa Kousei Hospital with acute hepatitis attributed to alcohol consumption. His condition improved with conservative treatment. Computed tomography (CT) showed localized thickening of the colonic wall at the splenic flexure;carcinoembryonic antigen level was slightly elevated to 9.7 ng/mL. Colonoscopy (CS) showed an ulcerative lesion in the colonic splenic flexure. Ischemic colitis (IC) and type 4 colon cancer were suspected, but biopsy was not confirmatory. Malignancy could not be ruled out by contrast-enhanced CT;repeat CS showed circumferential stenosis of the colonic splenic flexure. Ischemic colitis was suspected based on changes between the first and second CS. Biopsy histopathology led us to diagnose stricture-type IC. Constipation, but not intestinal obstruction, occurred. Conservative treatment improved the stenosis. Excessive alcohol consumption may lead to IC;imaging studies may be useful to distinguish IC from colon cancer. Since most cases of ischemic colitis can be improved with conservative treatment, patients with stricture-type ischemic colitis may also be treated without surgery early on, with follow-up that includes careful, periodic imaging

Pembrolizumab投与中に急性発症1型糖尿病を発症したMSI-High直腸癌の1例

症例は72歳男性。直腸癌に対して腹腔鏡下低位前方切除術が施行された。病理検査結果はpT3（SS）, pN2b, M0, pStageIIIcで，高頻度マイクロサテライト不安定性（microsatellite instabilityhigh: MSI-High）を有する直腸癌であった。その後，多発肺転移を来したためPembrolizumabを開始した。11コース投与後4日目から食欲不振，腹痛，頭痛を自覚し，改善しないため発症3日後に当院を受診した。直腸癌術後で腹部症状を呈していたが，血液検査，画像検査からは腸管の器質的疾患は否定的であった。一方で，随時血糖値は334mg/dLと高値でHbA1c 7.1%と今まで指摘されていなかった耐糖能異常を認めた。精査加療目的に入院としたが，その後も高血糖が持続し，尿中ケトン体の出現，インスリン分泌能の著しい低下が確認されたことにより，Pembrolizumabによる免疫関連副作用（immune-related adverse events : irAE）として急性発症1型糖尿病を発症していると診断した。迅速に十分な輸液とインスリン補充療法を開始したことで重症化することなく経過し，入院16日目に退院とした。退院後もインスリン頻回注射療法を継続しながら，Pembrolizumabによる治療を行っている。irAEは全身のあらゆる臓器で発現する可能性があり，発症頻度は0.7%とまれではあるが1型糖尿病もその一つとして知られ，劇症1型糖尿病に至ることもあり迅速な診断と治療が重要である。今回我々は，Pembrolizumab投与中に急性発症1型糖尿病を発症したMSI-High直腸癌の1例を経験した。免疫チェックポイント阻害薬（immune checkpointinhibitors : ICI）使用中に急激な血糖値の上昇や消化器症状を認めた際には，本疾患を疑い迅速に診断し治療を開始することが重要である。A 72-year-old man underwent laparoscopic low anterior resection for rectal cancer. Pathological examination revealed pT3 (SS), pN2b, M0, pStageIIIc, and rectal cancer with microsatellite instability-high (MSI-High). After that, pembrolizumab was started due to multiple pulmonary metastases. On the 4th day after the 11th course of administration, he noticed anorexia, abdominal pain and headache. Blood tests and computed tomography (CT) showed no intestinal disease. On the other hand, blood glucose level was as high as 334 mg/dL and HbA1c was 7.1%, indicating impaired glucose tolerance, which had not been noted before. He was admitted for detailed examination and treatment, but hyperglycemia persisted thereafter. Based on the presence of urinary ketone bodies and a marked decrease in insulin secretion, we diagnosed him with acute-onset type 1 diabetes mellitus as immune-related adverse events (irAE) caused by pembrolizumab. The patient was discharged on the 16th hospital day after prompt initiation of adequate fluid infusion and insulin therapy without aggravation. After discharge, he has been treated with pembrolizumab while continuing multiple daily injections insulin therapy. IrAEs can occur in any organ of the body. Type 1 diabetes mellitus is known to be one of the rare cases, with an onset frequency of 0.7%, and it may lead to type 1 diabetes mellitus, so prompt diagnosis and treatment are important. We experienced a case of MSI-High rectal cancer who developed acute-onset type 1 diabetes mellitus while receiving pembrolizumab. When a sudden rise in blood glucose level and gastrointestinal symptoms are observed during the use of immune checkpoint inhibitors (ICI), it is important to suspect this disease and to promptly diagnose and start treatment

Modulating toll-like receptor 4 signaling pathway protects mice from experimental colitis

Background/Aim: Several reports have indicated that environmental factors and defects in innate immunity are central to the pathogenesis of inflammatory bowel disease (IBD). Although bacteria producing lipopolysaccharide (LPS), which is a Toll-like receptor (TLR) 4 agonist, play a crucial role in the development of experimental colitis, LPS tolerance following initial exposure to LPS can result in a state of hyporesponsiveness to subsequent LPS challenge. Therefore, we initiated this study to explore the role of LPS tolerance in the development of colitis. Methods: Dextran sulfate sodium (DSS) colitis was induced in Balb/c mice with or without daily intraperitoneal administration of LPS. Disease activity and cytokine mRNA expression in the colon were evaluated. To confirm LPS tolerance, mouse conventional bone marrow-derived dendritic cells (BMDC) were preincubated with or without LPS, and were restimulated with LPS 24 h after first exposure. Cytokine production was measured by ELISA, and mRNA expression was evaluated by RT-PCR. Furthermore, we investigated the expression of negative regulators of LPS tolerance in BMDC. Results: Administration of LPS significantly suppressed colonic inflammation of DSS-induced colitis. After subsequent stimulation with LPS, TNF-α production was reduced in BMDC. IRAK-M, a negative regulator of TLR4 signaling, mRNA expression was up-regulated in LPS-treated BMDC. Conclusion: LPS tolerance was able to protect mice from DSS-induced colitis, and IRAK-M participated in this tolerance. Taken together, these observations suggest that loss of exposure to LPS is involved in the pathogenesis of IBD

A case of gastrointestinal storomal tumor with pneumomediastinum

A 52-year-old man noticed physical weariness and anorexia in November 2008. Severe anemia was found. Pneumomediastinum was detected using x-ray and CT scanning. Esophagogastroduodenoscopy revealed a submucosal tumor with a deep ulcer in the anterior wall of the upper stomach, causing anemia. Partial gastrectomy was performed because microperforation was suspected. The resected specimen showed spindle-shaped tumor cells that were c-kit positive and CD34 positive on immunohistological staining, suggesting a diagnosis of gastrointestinal stromal tumor (GIST). Although emphysema in the abdominal cavity was not observed, air leakage from gastric GIST with necrosis in the upper stomach was inferred as the cause of pneumomediastinum

Anti-calreticulin antibodies in patients with inflammatory bowel disease

PURPOSE: Although the pathogenesis of inflammatory bowel disease (IBD) is unclear, autoimmune processes seem to play roles in IBD because several types of autoantibodies have been found in it. Calreticulin (CRT) is a soluble Ca2+ binding protein which is present in a wide variety of cells. CRT is localized mainly in the endoplasmic reticulum and is often a target for autoantibodies. The aim of this study was to evaluate the clinical significance of anti-CRT antibodies measured by enzyme-linked immunosorbent assay (ELISA) using the sera of patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We measured the serum anti-CRT antibodies of 31 Japanese patients with UC and 24 with CD by ELISA. The controls were 105 subjects: 30 healthy persons, 44 patients with primary biliary cirrhosis (PBC), 21 with systemic lupus erythematosus (SLE) and 10 with acute colitis (AC). RESULTS: The mean titer of anti-CRT antibodies was significantly higher in patients with UC than in healthy individuals (p <0.05). The prevalence of anti-CRT antibodies in these patients was significantly higher during the initial phase than during the passing phase (p <0.05). In patients with CD, the mean titer of anti-CRT antibodies was not significantly higher than in healthy individuals. The positivity for anti-CRT antibodies, however, was about 30% in those patients, which was as high as in patients with UC, SLE and PBC. In patients with AC, anti-CRT antibodies were all negative. CONCLUSIONS: The positivity of anti-CRT antibodies may have a diagnostic value for IBD, especially in the initial phase of UC

Usefulness of intraoperative esophagogastroduodenoscopy in a patient with lupus enteritis

A 19-year-old Japanese woman had melena 2 months after systemic lupus erythematosus was diagnosed. Colonoscopy showed diffuse ulceration with bleeding in the ileum, suggesting that the melena was due to ischemic enteritis associated with lupus enteritis. Because treatment with high doses of steroid, anticoagulants, and cyclophosphamide pulse was ineffective, surgical intervention was planned. On exploration, it was impossible to determine the extent of resection visually. Intraoperative esophagogastroduodenoscopy clearly revealed the border between the ulcer and normal area, permitting successful resection of the ileum and ileostomy. This is the first report to document the usefulness of esophagogastroduodenoscopy in surgical treatment of ischemic enteritis in a patient with systemic lupus erythematosus

A case of esophageal small cell carcinoma associated with hypercalcemia causing severe acute pancreatitis

A 60-year-old woman was diagnosed with esophageal small cell carcinoma in October 2004 and received chemotherapy. However, the tumor grew gradually and multiple bone metastases occurred. Anorexia, nausea, emesis, numbness in both hands, and disturbed consciousness developed at the end of January 2006, and the patient was admitted to Fukushima Medical University Hospital. Abdominal pain, marked hypercalcemia and hyperamylasemia were noted and the patient was diagnosed with severe acute pancreatitis. Because the level of blood parathyroid hormone-related protein was elevated, we considered that esophageal small cell carcinoma caused human hypercalcemia of malignancy and that metastatic bone tumors caused local osteolytic hypercalcemia, eventually leading to severe acute pancreatitis. This is an extremely rare case of esophageal small cell carcinoma associated with hypercalcemia causing severe acute pancreatitis