Immune-related colitis and pancreatitis treated with infliximab.

Patients with various cancers benefit from immune checkpoint inhibitors. However, immune checkpoint inhibitor-induced adverse events have also been reported, such as colitis. Prednisolone is the first-line treatment for immune-related adverse events, but second-line therapy for patients refractory to steroids has not been established. Furthermore, the inflammatory cytokine expression pattern in the intestinal mucosa of patients with steroid-refractory immune-related colitis remains unclear. We present the case of a 48-year-old man diagnosed with immune-related colitis and pancreatitis induced by pembrolizumab for advanced lung cancer. First, we administered 50 mg/day of prednisolone, and the patient's abdominal symptoms improved. However, the pancreatic enzyme levels did not return to normal. Furthermore, the patient's diarrhea worsened and hematochezia appeared at a 40 mg/day prednisolone dose. A mucosal cytokine analysis identified a low interleukin-10 messenger RNA level, which has been associated with a poor response to prednisolone. Thus, we administered 5 mg/kg of infliximab; the patient's diarrhea and hematochezia immediately improved, and the pancreatic enzyme levels returned to normal. Infliximab was administered three times every 2 weeks. After, the patient's colitis and pancreatitis did not recur. To our knowledge, this is the first report demonstrating the effectiveness of infliximab for immune-related colitis and pancreatitis.

An older patient with active ulcerative colitis and coronavirus disease 2019 (COVID-19) pneumonia successfully treated with the combination of anti-TNFα therapy and azathioprine.

A 77-year-old patient with ulcerative colitis (UC) was transferred to our department because of worsening bloody diarrhea and abdominal pain, which was consistent with a UC flare. Two days after admission, she complained of cough and high fever. The polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive, and a computed tomography showed pneumonia in the left lobe, consistent with coronavirus disease 2019 (COVID-19) pneumonia. However, frequent bloody diarrhea and abdominal pain due to the UC flare persisted; therefore, an additional immunosuppressive agent needed to be considered. We initiated infliximab biosimilar (IFX-BS), and her abdominal symptoms improved. However, they deteriorated after the second IFX-BS infusion. After confirming that the patient was negative for SARS-CoV-2 by PCR, we administered a combination of azathioprine and IFX-BS. The combination treatment improved her intestinal symptoms without worsening COVID-19 pneumonia. She has remained in remission for over a year since her discharge.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome Precedes the Development of Hepatocellular Carcinoma.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by bilateral synovitis and marked pitting edema of the hands and/or feet. Despite the unknown etiology of RS3PE, several reports have described the putative association of this disease with malignant tumors. We herein report the findings of a 76-year-old man with RS3PE syndrome who developed hepatocellular carcinoma 3 years after achieving clinical remission of RS3PE using corticosteroid treatment; high vascular endothelial growth factor and tumor necrosis factor-alpha levels were considered to have contributed to carcinogenesis in this patient. The sequence of clinical events in this case strongly suggests that careful follow-up, even after clinical remission, is necessary for patients with RS3PE syndrome whose malignancy is not confirmed at diagnosis.

Effectiveness and safety of gemcitabine plus nab-paclitaxel in elderly patients with advanced pancreatic cancer: a single-center retrospective cohort study.

PURPOSE: This study aimed to evaluate the effectiveness and safety of gemcitabine (GEM) plus nab-paclitaxel (GnP) in patients aged ≥ 75 years with advanced pancreatic cancer and compare it with monotherapy (GEM or S-1). METHODS: We retrospectively reviewed the data of consecutive patients with advanced pancreatic cancer aged ≥ 75 years who received either GnP or monotherapy (GEM or S-1) between January 2014 and May 2020. The primary efficacy outcome was overall survival (OS). RESULTS: A total of 96 patients were included in this study; 51 were treated with GnP and 45 with monotherapy (31 with GEM and 14 with S-1). The median OS and progression-free survival were 10.8 and 6.7 months in the GnP group and 10.7 and 4.3 months in the monotherapy group, respectively. The treatment effect on OS was consistently favorable in the GnP group across most subgroups, particularly in patients with locally advanced cancer, modified Glasgow prognostic score of 0 or 1, and neutrophil/lymphocyte ratio < 3.1. The disease control rates were 76% and 48% in the GnP and monotherapy groups, respectively, and grade 3 or 4 neutropenia occurred in 23 (45%) and 11 (24%) patients of the GnP and monotherapy groups, respectively. CONCLUSIONS: This study demonstrated that GnP was not superior to monotherapy with regard to OS. However, multivariate analysis showed that GnP treatment positively affected the OS and could be considered as a treatment option, even for elderly patients.

Pharmacological Treatments Available for Immune-Checkpoint-Inhibitor-Induced Colitis.

Immune checkpoint inhibitor treatment has shown revolutionary therapeutic effects in various carcinomas. However, immune-related adverse events (irAE) following this treatment can sometimes lead to treatment discontinuation. One such frequently encountered adverse event is immune-related colitis (irAE colitis). Corticosteroids (CS) are the first-line treatment for irAE colitis, but we often encounter CS-refractory or -resistant cases. The application of multiple biologics has been proposed as a therapy to be administered after CS treatment; however, the efficacy and safety of biologics for patients with irAE colitis who do not respond to CS have not been established. This review summarizes the treatment regimens available for irAE colitis, focusing on the mechanism of action of corticosteroids, infliximab, vedolizumab, and other drugs.

Extensive mucosal sloughing of the small intestine and colon in a patient with severe COVID-19.

Patients with coronavirus disease 2019 (COVID-19) primarily cause respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. The endoscopic characteristics of the GI tract in COVID-19 patients remain unclear. We herein report a 62-year-old male with severe COVID-19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO). Despite the improvement in his respiratory status, GI bleeding developed. Capsule endoscopy and colonoscopy revealed extensive mucosal sloughing in the lower intestinal tract. Additionally, we performed a comprehensive analysis of the mRNA expression levels of various proinflammatory cytokines in the intestinal mucosal tissues. The results suggested a significant elevation of IL-6, which could be involved in the pathophysiology of the GI involvement in COVID-19. Further investigation with more clinical data, including endoscopic findings and molecular analyses, will contribute to a comprehensive understanding of COVID-19-associated GI injury.

Double small bowel cancers leading to the diagnosis of Lynch syndrome with germline MSH6 mutation in an elderly patient.

A female patient in her 80s was referred to our hospital because of an ileal tumor identified by capsule endoscopy. FDG-PET suggested double intestinal tumors not only in the ileum but also in the jejunum. The patient has cancer past history including sigmoid colon, rectum, and endometrium, and also had cancer family history fulfilling the revised Amsterdam criteria. Double balloon enteroscopy disclosed two ulcerated tumors in the jejunum and the ileum. Biopsy was diagnosed as adenocarcinoma pathologically, and microsatellite instability-high (MSI-H) genetically. Surgical resection was performed, and the jejunal and the ileal tumors were tubular (T2N0M0) and mucinous adenocarcinoma (T4N0M0), respectively. Germline mutation analysis revealed a pathogenic splice-site mutation in MSH6.

Clinicopathological comparison between acute gastrointestinal-graft-versus-host disease and infectious colitis in patients after hematopoietic stem cell transplantation.

The aim of this study is to elucidate the differences of the clinicopathological characteristics between acute gastrointestinal (GI)-graft-versus-host disease (GVHD) and infectious colitis (IC) after hematopoietic stem cell transplantation (HSCT). Of the 282 patients who underwent HSCT at our institution between January 1991 and December 2015, we could investigate 182 patients in detail. Of the 182 patients, we selected those who underwent colonoscopy and were diagnosed with acute GI-GVHD or IC after HSCT. Patients' backgrounds, colonoscopic findings, and pathological findings were retrospectively analyzed. There were 30 patients who had colonoscopy performed and diagnosed with acute GI-GVHD or IC after HSCT. Of the 30 patients, 20 had acute GI-GVHD and 10 had IC. All the cases of acute GI-GVHD were diagnosed by endoscopic biopsy and 4 of the IC patients had Clostridium difficile associated colitis. In the IC group, the period from the transplantation up to diagnosis was significantly shorter than acute GI-GVHD group (10.0 days vs. 43.2 days, p = 0.03). In the acute GI-GVHD group, tortoiseshell-like mucosal patterns were significantly more common than the IC group (70% vs. 0%, p < 0.001). Furthermore, there were some cases presenting normal mucosal appearance despite the diagnosis with acute GI-GVHD by pathological findings. Clinically, we should consider IC when abdominal symptoms appeared in the early period after HSCT. Endoscopically, tortoiseshell-like mucosal pattern was a characteristic feature of acute GI-GVHD. In addition, it is essential to perform mucosal biopsy for diagnose of acute GI-GVHD even in patients showing the normal mucosal appearance.

Natural history of gastric cancer from a retrospective review of endoscopic images of older patients with interval gastric cancer.

AIM: Interval gastric cancers (IGC) are defined as those diagnosed after negative results of endoscopy carried out within the past 10 years. We aimed to investigate the characteristics of IGC and the natural history of gastric cancer (GC) from a retrospective view of endoscopic images of older patients with IGC. METHODS: We retrospectively reviewed endoscopic images of 240 patients with GC who were aged >60 years. We compared past endoscopic images with newer ones, in which GC was diagnosed. IGC were classified into two categories: missed cancers and new cancers. RESULTS: Of the 240 patients with GC, 32 had past endoscopic images that qualified for a precise review. A total of 14 cases involved new cancers, whereas 18 involved missed cancers. Most of the IGC were stage I for at least 2 years; however, a small subset was unresectable at >2 years after a negative endoscopy. Furthermore, the rate of endoscopic treatment was significantly higher for IGC compared with that for non-IGC. CONCLUSIONS: In people aged >60 years, most IGC remain in an early stage for at least 2 years; however, at >2 years after a negative endoscopy, some are unresectable. These results suggest that most early-stage GC will not develop into advanced cancers within 2 years; thus, a 2-year interval might be within the permissible range for patients with negative endoscopy results for any lesions. Geriatr Gerontol Int 2018; 18: 997-1002.