[A case of immune-related gastroesophagitis with laryngopharyngitis caused by immune checkpoint inhibitors in nonsmall cell lung cancer].

With the advent of immune checkpoint inhibitors (ICI), cancer treatment options have widened in recent years. However, ICI-specific adverse events (irAEs) have been reported. Lower gastrointestinal lesions, such as colitis and enteritis, account for most gastrointestinal irAEs, and reports of upper gastrointestinal lesions are rare. We report a rare case of gastroesophagitis associated with ICI. The patient was a 64-year-old male. He was diagnosed with lung adenocarcinoma stage IIIB (cT2aN3M0), and pembrolizumab (PEM) was started as a first-line treatment. Severe gastroesophagitis with laryngopharyngitis was confirmed 5 months after PEM administration. These improved after withdrawal of PEM and steroid administration. Reports of ICI-associated gastritis remain limited, especially with laryngopharyngitis;therefore, we consider this case as valuable, in which we confirmed the clinical features of ICI-associated gastroesophagitis and its therapeutic effects.

High total Joule heat increases the risk of post-endoscopic submucosal dissection electrocoagulation syndrome after colorectal endoscopic submucosal dissection.

BACKGROUND: We hypothesized that thermal damage accumulation during endoscopic submucosal dissection (ESD) causes the pathogenesis of post-ESD electrocoagulation syndrome (PECS). AIM: To determine the association between Joule heat and the onset of PECS. METHODS: We performed a retrospective cohort study in patients who underwent colorectal ESD from May 2013 to March 2021 in Japan. We developed a novel device that measures swift coagulation time with a sensor adjacent to the electrosurgical coagulation unit foot switch, which enabled us to calculate total Joule heat. PECS was defined as localized abdominal pain (visual analogue scale ≥ 30 mm during hospitalization or increased by ≥ 20 mm from the baseline) and fever (temperature ≥ 37.5 degrees or white blood cell count ≥ 10000 µ/L). Patients exposed to more or less than the median Joule heat value were assigned to the high and low Joule heat groups, respectively. Statistical analyses included Mann-Whitney U and chi-square tests and logistic regression and receiver operating characteristic curve (ROC) analyses. RESULTS: We evaluated 151 patients. The PECS incidence was 10.6% (16/151 cases), and all patients were followed conservatively and discharged without severe complications. In multivariate analysis, high Joule heat was an independent PECS risk factor. The area under the ROC curve showing the correlation between PECS and total Joule heat was high [0.788 (95% confidence interval: 0.666-0.909)]. CONCLUSION: Joule heat accumulation in the gastrointestinal wall is involved in the onset of PECS. ESD-related thermal damage to the peeled mucosal surface is probably a major component of the mechanism underlying PECS.

Early colonoscopy and urgent contrast enhanced computed tomography for colonic diverticular bleeding reduces risk of rebleeding.

BACKGROUND: Colonoscopy within 24 h of hospital admission for colonic diverticular bleeding (CDB) is recommended. However, little is known about rates of rebleeding within 30 d. We posited that a group of patients who underwent contrast-enhanced computed tomography (CT) within 4 h of the last hematochezia and colonoscopy within 24 h would experience fewer incidences of rebleeding. AIM: To evaluate the outcomes of early colonoscopy for CDB among different groups of patients. METHODS: Data from 182 patients with CDB who underwent contrast-enhanced CT and colonoscopy between January 2011 and December 2018 at the study site were retrospectively reviewed. Patients were divided into groups based on the timing of the CT imaging, within or at 4 h were defined as urgent CTs (n = 100) and those performed after 4 h were defined as elective CTs (n = 82). Main outcomes included rebleeding within 30 d and the identification of stigmata of recent hemorrhage (SRH) (i.e., active bleeding, non-bleeding visible vessels, or adherent clots). RESULTS: In total, 182 patients (126 men and 56 women) with median ages of 68.6 (range, 37-92) and 73.7 (range, 48-93) years, respectively, underwent CT imaging and colonoscopy within 24 h of the last hematochezia. Patients for whom CT was performed within 4 h of the last hematochezia were included in the urgent CT group (n = 100) and patients for whom CT was performed after 4 h were included in the elective CT group (n = 82). SRH were identified in 35.0% (35/100) of the urgent CT cases and 7.3% (6/82) of the elective CT cases (P < 0.01). Among all patients with extravasation-positive images on CT, SRH was identified in 31 out of 47 patients (66.0%) in the urgent CT group and 4 out of 20 patients (20.0%) in the elective CT group (P < 0.01). Furthermore, rates of rebleeding within 30 d were significantly improved in the urgent CT and extravasation-positive cases (P < 0.05). Results from the evaluation of early colonoscopy did not show a difference in the ability to detect SRH identification or rebleeding rates. Only cases by urgent CT reduced risk of rebleeding due to the evidence of active bleeding on the image. CONCLUSION: To improve rates of rebleeding, colonoscopy is recommended within 24 h in patients with extravasation-positive CT images within 4 h of the last hema-tochezia. Otherwise, elective colonoscopy can be performed.

Efficacy and safety of short-term therapy with indigo naturalis for ulcerative colitis: An investigator-initiated multicenter double-blind clinical trial.

INTRODUCTION: Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. OBJECTIVE: We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. METHODS: A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5-10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. RESULTS: The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. CONCLUSIONS: Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

Multikinase inhibitor-associated hand-foot skin reaction as a predictor of outcomes in patients with hepatocellular carcinoma treated with sorafenib.

AIM: To investigate the relationship between the onsets of multikinase inhibitor (MKI)-associated hand-foot skin reaction (HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib. METHODS: We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival (OS) after the initiation of treatment. RESULTS: The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this group. CONCLUSION: Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.

[Esophagogastric variceal bleeding in a case of liver cirrhosis associated with thalassemia].

A 58-year-old man was admitted to our hospital because of hematemesis. Laboratory tests indicated microcytic hypochromic anemia and iron overload. We performed urgent endoscopic examination, and diagnosed bleeding from esophagogastric varices. Abdominal CT showed liver cirrhosis and marked splenomegaly, but no evidence of gastrorenal shunt. The varices were treated by Hassab's operation and splenectomy. Pathologic examination revealed hepatocytes in the cirrhotic nodules filled with iron pigment. The cause of the liver cirrhosis was considered to be due to iron overload resulting from thalassemia. We diagnosed the cause of the microcytic anemia as thalassemia by gene analysis, which revealed heterozygosity of a deletion (deltabeta thalassemia Jpn-type II) and one point mutation (-31A-->G).

[A case of portal vein thrombosis associated with congenital protein S deficiency].

A 25-year-old man was admitted to our hospital because of abdominal pain, nausea and low-grade fever. An abdominal CT showed remarkable thickening of the wall of the small intestine and extensive thrombosis of the mesenteric, portal and splenic veins. Because neither intestinal infarction nor peritonitis was seen, anticoagulation therapy was chosen. Heparin was administered intravenously and was used alternatively with warfarin later. The patient's symptoms and clinical data improved gradually. Concerning the etiological factors of the thrombosis, only protein S activity definitely decreased. Genetic analysis indicated a variant of protein S, protein S Tokushima.

[A case of gastrointestinal stromal tumor with liver and bone metastases effectively treated with radiofrequency ablation and imatinib mesylate].

A 58-year-old man was admitted because of perforation of the small intestine by a gastrointestinal stromal tumor (GIST). First, the small intestine including a GIST was resected; and then 2 month later, a part of the liver (S5) conforming to metastatic lesion was surgically removed. Twelve months later, another liver metastases was found, and surgical treatment was recommended; but the patient requested non-surgical therapy, so a radiofrequency ablation (RFA) was successfully performed. After that, recurrence of liver metastasis was not observed, but another metastasis was observed on the fifth lumbar vertebra; so administration of imatinib mesylate was started. 28 months after the initial administration the metastatic liver lesion was still invisible, and the bone metastatic lesion had not grown. The patient is alive with good performance status. This report shows that multi-modality therapy by surgery, RFA and imatinib mesylate was effective for liver and bone metastases of GIST.