A durable response after the discontinuation of immune checkpoint-inhibitor therapy has previously been reported in several cancers. We herein describe a patient with gastric cancer who maintained a durable response after the discontinuation of nivolumab. A 65-year-old man was treated with nivolumab as a sixth-line therapy for recurrent gastric cancer. After four cycles of nivolumab therapy, he showed a partial response. But the treatment was discontinued when two immune-related adverse events occurred after six cycles. Disease regression was sustained for approximately 2 years, without the re-administration of nivolumab. The characteristics leading to such responses are unclear, and further studies are warranted in this regard.

Background/Aim: Bevacizumab-based chemotherapy is the standard treatment for metastatic colorectal cancer (mCRC) but has several specific adverse events. The cumulative bevacizumab dose (CBD) increases with longterm treatment as it is often used beyond the first disease progression, based on existing evidence. However, the association between CBD and the frequency and severity of adverse events in mCRC patients who received bevacizumab for long-term treatment remains unclear. Patients and Methods: Among the mCRC patients who received bevacizumab-based chemotherapy between March 2007 and December 2017 at the University of Tsukuba Hospital, those who continued treatment for more than 2 years were eligible for the study. The onset and worsening of proteinuria, hypertension, bleeding, and thromboembolic events were assessed to determine their relationship with CBD. Results: Of the 109 patients who received bevacizumab-based chemotherapy, 24 were included in the study. Grade 3 proteinuria was observed in 21 (88%) and 9 (38%) patients. The severity of proteinuria markedly increased after administering >100 mg/kg of CBD and progressed to grade 3 at concentrations exceeding 200 mg/kg. Thromboembolic events were observed in three (13%) patients, and two of them developed acute myocardial infarction after receiving a CBD of >300 mg/kg. Grade 2 or higher hypertension and grade 1 bleeding were observed in 9 (38%) patients and in 6 (25%) patients, respectively, regardless of the CBD. Conclusion: Proteinuria and thromboembolic events occurred and worsened in mCRC patients when the bevacizumab dose exceeded the threshold dose.Colorectal cancer is the third leading cause of cancer-related deaths worldwide and the second leading cause of cancerrelated deaths in Japan (1). For metastatic colorectal cancer (mCRC), bevacizumab, an angiogenesis inhibitor, is used as the standard treatment in fluoropyrimidine combination with oxaliplatin or irinotecan-based doublet chemotherapy, which is generally administered at 2.5 mg/kg/week (2). The median progression-free survival time with first-line chemotherapy, including bevacizumab, is 8-15 months (2-4). In addition, the significance of continuing bevacizumab treatment even after disease progression has been proven in a previous randomized phase III trial; bevacizumab is frequently used as a second-line treatment after failure of bevacizumab-based first-line therapies (5-7). Although the long-term administration of bevacizumab has shown a survival benefit, the increased incidence and severity of bevacizumab-related adverse events (AEs) remain a concern.Bevacizumab-related AEs included proteinuria, hypertension, arterial or venous thrombosis, bleeding, gastrointestinal perforation, and delayed wound healing (2). Several studies have investigated the association between bevacizumab treatment duration and bevacizumab-related AEs. The severity of proteinuria and cardiovascular events increases with longterm use of bevacizumab (8). A similar relationship has been shown between the risk of protein...

Ectopic varices due to extrahepatic portal vein obstruction (EHO) after hepaticojejunostomy have been previously reported. However, few case reports have described angiodysplasia‐like lesions due to EHO around the hepaticojejunal anastomosis because they comprise small vessels in the mucosal surface and cannot be detected by contrast‐enhanced computed tomography. Physicians need to insert the endoscope into the long afferent limb to diagnose angiodysplasia‐like lesions around the hepaticojejunal anastomosis. Some reports have described that endoscopy stops bleeding from angiodysplasia‐like lesions around the hepaticojejunal anastomosis; however, a standard methodology remains to be established. We present three cases of bleeding from an angiodysplasia‐like lesion around the hepaticojejunal anastomosis that were successfully treated using argon plasma coagulation (APC) with balloon‐assisted enteroscopy. Although one patient died owing to cancer progression 3 months after APC hemostasis, the hemostatic effect persisted for >2 years in the remaining two patients. These results suggest that APC is a good treatment option to stop bleeding from angiodysplasia‐like lesions at hepaticojejunal anastomosis.

Dihydropyrimidine dehydrogenase (DPD) deficiency induces severe adverse events in patients receiving fluoropyrimidines. We encountered a 64-year-old DPD-deficient man with a severe capecitabine-related gastrointestinal disorder. He received capecitabine-containing chemotherapy after rectal cancer resection. During the first course of chemotherapy, he developed severe diarrhea, a fever, and hematochezia. Endoscopy revealed mucosal shedding with bleeding throughout the gastrointestinal tract. DPD deficiency was suspected because he developed many severe adverse events of capecitabine early and was finally confirmed based on the finding of a low DPD activity level in peripheral blood mononuclear cells. After one month of intensive care, hemostasis and mucosal healing were noted, although his gastrointestinal function did not improve, and he had persistent nutritional management issues.

Nanoparticle albumin-bound (nab)-paclitaxel has shown promising activity in advanced gastric cancer treatment. We herein report a case of advanced gastric cancer involving long-term management with a single administration of nab-paclitaxel. A 71-year-old man diagnosed with advanced gastric cancer with malignant ascites was treated with nab-paclitaxel as a second-line chemotherapy. He refused treatment continuation because of various severe toxicities in the first treatment cycle; he was therefore followed-up without any further treatments. Despite this, no disease progression was observed over 9 months. After progression, he received dose-dense paclitaxel, but he did not respond to this treatment and eventually died.