A case of refractory immune checkpoint inhibitor-induced colitis improved by the treatment with vedolizumab and granulocyte-monocyte apheresis combination therapy.

A 68-year-old man developed immune-related adverse event (irAE) colitis after the initiation of nivolumab and ipilimumab combination therapy for malignant melanoma. We diagnosed the patient with grade 3 irAE colitis and started prednisolone (1 mg/kg/day). Although the symptom improved once, it worsened along with the tapering of prednisolone. Therefore, we started infliximab (IFX). However, symptoms did not improve after two doses of IFX. We discontinued IFX and initiated vedolizumab (VED). Because VED alone did not improve the symptom, we started granulocyte-monocyte apheresis (GMA). Twelve weeks after the onset, the colitis was in remission. Therefore, in addition to vedolizumab, GMA may be considered in cases refractory to treatment.

A Case of Successful Endoscopic Extraction of Common Bile Duct Stones After Closing a Duodenal Perforation Using Over-The-Scope Clip.

A 57-year-old man visited our hospital for acute cholangitis due to common bile duct (CBD) stones in March 2021. Biliary stenting was performed without any complications. The cholangitis improved rapidly. He was re-hospitalized to treat the CBD stones in May 2021. Although endoscopic retrograde cholangiopancreatography was performed, endoscopy caused a perforation of the duodenal bulb. We successfully performed endoscopic closure of the duodenal defect using an over-the-scope clip (OTSC®). Considering that mild CBD dilatation of 10 mm can carry an increased risk of stenosis after surgery, we decided to avoid surgery and perform a follow-up endoscopic treatment. He was re-hospitalized in July 2021. The endoscopy revealed OTSC® in the anterior wall of the duodenal bulb and complete healing of the perforation. We carefully advanced the scope to the second portion of the duodenum while avoiding OTSC®, and the ampulla of Vater was identified. We were then able to remove the stones without any complications. OTSC® was effective in closing a duodenal perforation and enabled us to carry out the retreatment safely and successfully.

Autoimmune Pancreatitis with Gastric Cancer: Some IgG4-related Diseases May Be Paraneoplastic Syndrome.

A 70-year-old man was referred to our department for the treatment of early gastric cancer. Contrast-enhanced computed tomography (CT) incidentally showed diffuse enlargement of the pancreas with a capsule-like rim, and blood tests showed elevated serum IgG4 levels, leading to a diagnosis of autoimmune pancreatitis (AIP). Endoscopic treatment for gastric cancer was performed, and pathological findings showed adenocarcinoma with abundant IgG4-positive plasma cell infiltration. Thereafter, the serum IgG4 levels normalized, and the findings of AIP disappeared on CT without steroid treatment. These findings suggest that the gastric cancer activated an IgG4-related immune response, resulting in the development of AIP.

Endoscopic injection sclerotherapy improves liver function compared with endoscopic variceal ligation.

Liver function is a most important prognostic factor in patients with liver cirrhosis. Also, portal hypertension is a fatal complication of liver cirrhosis and variceal treatment is indispensable. However, changes of liver functions after endoscopic variceal treatments are unknown. The aim of this study was to evaluate prognosis and liver functions after endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL). A total of liver cirrhotic 103 patients who underwent prophylactic EIS and EVL were enrolled. Overall survival rate was higher in EIS group than EVL group (p = 0.03). Multivariate analysis showed that EIS was a negative factor for death (HR: 0.46, 95% confidence interval: 0.24-0.88, p = 0.02). Liver functions were assessed by blood test taken at before and 3 months after treatment. In EIS group, albumin and prothrombin time improved (p < 0.01), leading to improvement of Child-Pugh score, ALBI score and MELD score (p < 0.05). However, these did not improve in EVL group. EIS was a significant factor related to the elevated value of albumin after treatment in linear regression analysis (estimated regression coefficient: 0.17, 95% confidence interval: 0.05-0.29, p = 0.005). These results revealed that EIS could improve liver functions and prognosis.

Impact of the Concomitant Use of Immunomodulator and a Lower Week 8 Partial Mayo Score on the Persistence of Adalimumab in Refractory Ulcerative Colitis.

Objective Real-world data of adalimumab (ADA) in the treatment of ulcerative colitis (UC) are scarce. We aimed to study the ADA response rates and predictors of response in UC treatment. Methods This observational, prospective and multi-center study assessed the clinical outcome of refractory UC patients treated with ADA who previously had an inadequate response to either conventional therapies or other anti-TNF antibodies or tacrolimus. The primary endpoint was the proportion of UC patients achieving a clinical response and remission at 8 and 52 weeks. We also evaluated the parameters which were associated with a clinical response at 8 and 52 weeks. Results A total of 35 patients were enrolled from 11 centers. The clinical responses at 8 and 52 weeks were 60.0% and 51.4%, respectively. The clinical remission rates at 8 and 52 weeks were 45.7% and 48.6%, respectively. Positive predictors for week 52 response were combination of ADA with immunomodulator (IM) (OR: 27.229; 95% CI; 1.897-390.76; p=0.015) and a week 8 lower partial Mayo score (OR: 0.406; 95% CI; 0.204-0.809; p=0.010). A receiver operation characteristic curve analysis revealed the optimal week 8 partial Mayo score to be 2.5, therefore a partial Mayo score of ≤2 was a positive predictor for the continuation of ADA. No malignancy or death occurred during this study. Conclusion ADA was effective for inducing and maintaining both a clinical response and remission in patients with refractory UC. It remains possible that the concomitant use of IM and a week 8 partial Mayo score of ≤2 may predict the long-term response of ADA.

Meckel's Diverticulum Bleeding Missed by the First but Detected by the Second Capsule Endoscopy.

A 13-year-old boy was admitted to our hospital because of bloody stools. Although a Meckel's diverticulum (MD) was suspected, capsule endoscopy (CE) revealed no remarkable findings. Seven months later, he was admitted again because of rebleeding. CE was performed again and revealed an elevated lesion and fresh blood in the ileum. A single balloon endoscopic examination revealed a diverticulum with an elevated lesion in it. Histologic findings showed ectopic gastric mucosa, thus we diagnosed this patient as having MD. Although CE is useful for the examination of obscure gastrointestinal bleeding, a single CE is not enough to diagnose MD bleeding. The timing in performing CE and the evaluation of other modalities would be valuable for patients suspected of having MD.

Influence of gastroesophageal flap valve on esophageal variceal bleeding in patients with liver cirrhosis.

OBJECTIVES: Esophageal variceal bleeding can be fatal in patients with liver cirrhosis. The aim of this study was to investigate the relationship between gastroesophageal flap valve (GEFV) and esophageal variceal bleeding. METHODS: Subjects were cirrhotic patients with endoscopically diagnosed esophageal varices treated at our hospital between 2005 and 2019, excluding those with F3 form and red color (RC) signs at first endoscopy. Sixty-five patients with normal GEFV (Hill grade I or II) and 42 with abnormal GEFV (Hill grade III or IV) were enrolled. Propensity score matching eliminated the baseline differences, resulting in a sample size of 30 patients per cohort. The primary endpoint was esophageal variceal bleeding, and the secondary endpoint was variceal bleeding or appearance of RC sign. We analyzed the cumulative incidences and predictors of each endpoint. RESULTS: The 3-, 5-, and 10-year cumulative incidences of the primary endpoints were all 3.4% in the normal GEFV group, and 19.0%, 24.6% and 34.0% in the abnormal GEFV group, respectively (log-rank P = 0.011). Cumulative incidence of the secondary endpoint was 13.8%, 33.1% and 39.2% in the normal GEFV group, and 42.2%, 54.6% and 84.9% in the abnormal GEFV group, respectively (log-rank P = 0.001). In multivariate Cox regression analyses, hazard ratios of abnormal GEFV of the primary and secondary endpoints were 12.79 (95% confidence interval 1.331-122.8) and 3.600 (1.653-7.840), respectively. CONCLUSIONS: Abnormal GEFV was an independent risk factor for esophageal variceal bleeding and appearance of RC sign.

An autopsy case of a patient with systemic sclerosis who developed marked pulmonary hypertension because of pulmonary tumor thrombotic microangiopathy caused by gastric carcinoma.

We performed an autopsy on a patient with systemic sclerosis who developed uncontrollable pulmonary hypertension due to pulmonary tumour thrombotic microangiopathy (PTTM) caused by gastric carcinoma. The case was of a 62-year-old woman with systemic sclerosis who was admitted to the intensive care unit (ICU) with severe pulmonary hypertension accompanied by respiratory insufficiency. Pulmonary hypertension could not be controlled despite aggressive medical treatment including vasodilators. Approximately 10 days after admission, a unilateral pleural effusion developed. Thoracentesis was performed, and cytology examination of the pleural fluid revealed carcinomatous pleurisy. Because of the presence of a known gastric carcinoma, PTTM was clinically diagnosed. Although chemotherapy was administered, she died 33 days after ICU admission. An autopsy revealed diffuse fibrocellular intimal thickening of the peripheral pulmonary arterioles, which indicated PTTM. In patients with connective tissue disease complicated with pulmonary hypertension, it is necessary to differentiate not only pulmonary arterial hypertension but also other pathological conditions such as PTTM.

Usefulness of magnifying endoscopy and endoscopic ultrasonography for the gastric involvement of follicular lymphoma.

A 61-year-old man received an esophagogastroduodenoscopy for further investigation of mesenteric lymphadenopathy. Esophagogastroduodenoscopy revealed swollen gastric folds and cobble stone mucosa in the gastric body. Magnifying endoscopy with narrow-band imaging showed branched abnormal vessels and the absence or destruction of gastric pits. Endoscopic ultrasonography (EUS) depicted homogeneously hypoechoic thickening of the submucosal layer where the mucosal changes were observed. The patient was diagnosed with follicular lymphoma by biopsy of these lesions. We should recognize that these endoscopic features are consistent with follicular lymphoma involving the stomach and that concurrent EUS is useful for diagnosis and identification of adequate biopsy sites.

Effect of direct-acting antivirals on platelet-associated immunoglobulin G and thrombocytopenia in hepatitis C virus-related chronic liver disease.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection has been known to cause various extrahepatic autoimmune disorders. The prevalence of platelet-associated immunoglobulin G (PA-IgG) has been high in patients with HCV infection. Because thrombocytopenia in HCV-related liver diseases is a notable problem, we performed prospective study on the effect of direct-acting antivirals (DAAs) treatment on PA-IgG and platelet count. METHODS: A total of 215 patients with HCV-related liver disease were enrolled in this study. The patients who discontinued DAAs or did not undergo adequate laboratory examinations and who did not achieve sustained virologic response were excluded and finally a total of 187 patients were investigated. RESULTS: A total of 171 patients (91.4%) were PA-IgG positive (>46 ng/107 cells) before starting DAAs (baseline). The PA-IgG level elevation was significantly correlated with higher liver inflammation and fibrosis markers (P < 0.05) and lower platelet count (P = 0.000019). The platelet count of the patients with low PA-IgG titer tended to be higher at baseline, end of treatment (EOT), and at 12 and 24 weeks after EOT. The platelet count increased at EOT (P < 0.05) and 24 weeks after EOT (P < 0.01). The PA-IgG levels were significantly decreased at EOT, 12 and 24 weeks after EOT (P < 0.01). Multiple regression analysis found that only platelet count at baseline was closely associated with negative conversion of PA-IgG at 24 weeks after EOT (P = 0.004). CONCLUSIONS: Eradication of HCV by DAAs treatment successfully decreased PA-IgG level and increased platelet count.

Impact of examining additional deeper sections on the pathological diagnosis of endoscopically resected early gastric cancer.

OBJECTIVES: The pathological diagnosis of endoscopically resected early gastric cancer (EGC) is performed by evaluating a few representative sections from the specimen. We aimed to determine whether evaluating twice as many sections as usual by essentially cutting the original sections in half could improve the pathological diagnosis of EGC. METHODS: We retrospectively investigated 85 EGC in 82 patients who had undergone endoscopic resection at our hospital from August 2008 to October 2012. EGC without indications of curative resection were excluded. We re-examined the original paraffin blocks after shaving away approximately half their original thickness, and evaluated whether the pathological diagnoses were affected. This technique essentially doubled the number of sections examined. RESULTS: Ten pathological diagnoses of 68 EGC (14.7%) were changed from curative resection to non-curative resection when we evaluated twice as many sections as in the standard method. The median tumor size was 25 mm in the changed diagnosis group versus 14.5 mm in the no change group (P = 0.03). The univariate analysis also showed that tumor size was a significant predictor of changed diagnosis (P = 0.015). Both the changed diagnosis group and no change group had no recurrence during follow up. CONCLUSIONS: Histological evaluation of twice as many sections as usual changed the initial pathological diagnosis of EGC, although the clinical implication of an additional deeper section was controversial because there was no recurrence. Our analysis also emphasized the importance of detailed histological evaluation to confirm a radical cure in endoscopic resection, especially in the case of larger EGC.

A Young Adult Patient with Nonalcoholic Steatohepatitis Developed Severe Gastroesophageal Varices Associated with Severe Obesity and Diabetes Mellitus.

Obesity is a major contributor to insulin resistance and nonalcoholic fatty liver disease, which is the most common cause of chronic liver diseases. Nonalcoholic steatohepatitis (NASH) can progress to liver cirrhosis and end-stage liver diseases. Some cases already show severe liver fibrosis at the time of diagnosis. We present the case of a 44-year-old male with overt obesity who was admitted with hematemesis due to the rupture of gastric varices. We diagnosed him with NASH with severe liver fibrosis. This case shows that we should be concerned about the progression of liver fibrosis due to NASH associated with severe obesity even in young patients.

Recombinant Thrombomodulin Used to Successfully Treat Cronkhite-Canada Syndrome with Disseminated Intravascular Coagulation due to Sepsis in a Compromised Patient.

Cronkhite-Canada syndrome (CCS) is a rare non-inherited disease characterized by gastrointestinal polyposis, chronic diarrhea, ectodermal dysplasia, skin hyperpigmentation, hair loss and nail atrophy. Although the efficacy of corticosteroid and immunomodulatory agents has been demonstrated, no standard therapy regimen has been established, and the prognosis of CCS is still poor due to various complications. We here in report a CCS patient complicated with severe sepsis and disseminated intravascular coagulation who was successfully treated by combined modality therapies, including recombinant human soluble thrombomodulin.

Carcinosarcoma of the Extrahepatic Bile Duct Presenting with Stone-like Radiological Findings.

A 73-year-old woman was referred to our hospital due to epigastralgia and jaundice. The radiological findings showed a stone-like tumor in the extrahepatic bile duct. The patient was initially thought to have adenocarcinoma of the bile duct based on the findings of a pathological examination of the bile duct biopsy specimen and underwent pancreaticoduodenectomy; the final diagnosis of the lesion was so-called carcinosarcoma of the extrahepatic bile duct. She died of liver metastasis six months after the surgery. This case suggests that surgical resection is not adequate for achieving a radical cure, and the optimal treatment for extrahepatic bile duct carcinosarcoma should be established immediately.

[A case of primary gastric malignant lymphoma with chylous ascites].

An 87-year-old man presented with appetite loss and abdominal distension. Routine blood tests revealed hypoproteinemia. Abdominal computed tomography revealed ascites, which was subsequently drained. Biochemical analysis of the ascitic fluid detected chyle. Esophagogastroduodenoscopy revealed nodular swelling of the mucosa, swelling folds, and widespread erosions in the stomach. Stage I diffuse large B-cell gastric malignant lymphoma was diagnosed on the basis of the Lugano International Conference classification system. Six courses of R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine (Oncovin(®)), and prednisolone] therapy were administered, following which complete remission was achieved and the chylous ascites mostly disappeared.