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The development of tyrosine-kinase inhibitors has improved survival rates for patients with gastrointestinal stromal tumors (GISTs). Despite the progress, not all the patients can universally receive the benefit from treatment due to the individual underlying conditions in a real-world setting. The present study focused on the well-known but understudied condition of GIST with hypoglycemia. Hypoglycemia in GIST is characterized by hypoglycemic symptoms such as dizziness, sweating and confusion. It is caused by several factors such as multiple liver metastases, drug adverse effects, postoperative complications and paraneoplastic syndrome [non-islet cell tumor hypoglycemia (NICTH)]. Comprehensive analysis of this condition has been hindered due to its rarity, and has been mostly limited to case reports. In the present study, a single-institution retrospective analysis of GIST with hypoglycemia was conducted to investigate its prevalence and prognosis, and the cause of this condition. The present study identified that the prevalence of hypoglycemic episodes of GIST was 4.1% in all patients with GIST, and recurrent hypoglycemic cases had a poor prognosis. The present study identified 1 case with recurrent hypoglycemia due to NICTH. Since NICTH is a rare hypoglycemic cause and requires further evaluation, an autopsy and genetic sequencing were performed using the available clinical materials. Through this histological and genetic investigation, the histological diversity of NICTH-GIST was revealed and insulin-like growth factor II (IGF-II) amplification was identified. Furthermore, a chronological analysis was performed using multiple resected archived samples from the same case, and revealed that diffuse IGF-II expression may have occurred in the early phase of tumor development. The present study catalogued the characteristics of GIST with hypoglycemia with a focus on NICTH-GIST. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the risk factors for immune-related adverse events (irAEs) induced by immune checkpoint inhibitors. The authors conducted a retrospective study in which patients with malignant melanoma, non-small-cell lung cancer, gastric cancer or renal cell carcinoma who received anti-PD-1/PD-L1 antibodies were included. Of 247 patients, 118 developed a total of 182 irAEs. In the multivariate Fine-Gray regression analysis, serum albumin level ≥3.6 g/dl (hazard ratio: 1.62; 95% CI: 1.10-2.39; p = 0.015) and history of Type I hypersensitivity reactions (hazard ratio: 1.48; 95% CI: 1.02-2.14; p = 0.037) were significantly associated with the development of irAEs. High serum albumin levels and history of Type I hypersensitivity reactions are risk factors for irAEs. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in real-world practice. Patients and Methods: We conducted a retrospective study on patients with recurrent or metastatic non-small-cell lung cancer, malignant melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model and the shared frailty model. Results: Of 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. The median OS was significantly longer in the irAEs than in the no-irAE group (28.1 months vs 12.7 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.33– 0.73; P = 0.0004). Moreover, the OS of patients with multiple irAEs was significantly longer than that of patients with a single irAE (42.3 months vs 18.8 months; HR, 0.473; 95% CI, 0.346– 0.647; P < 0.0001). Conclusion: Our single-center retrospective study revealed a significant tendency associating the development of multiple irAEs with favorable prognoses. [ABSTRACT FROM AUTHOR]

Scirrhous gastric cancer tends to disseminate to the peritoneum and retroperitoneum, where it induces fibrosis. Retroperitoneal fibrosis (RPF) frequently causes acute renal failure due to ureteral obstruction and it tends to make many of physicians hesitate to initiate systemic chemotherapy. The present study reported the case of a 68-year-old man who was diagnosed with scirrhous gastric cancer with peritoneal and retroperitoneal dissemination, causing acute renal failure due to RPF. Before initiating systemic chemotherapy, the patient became anuric and introduced hemodialysis (HD). Although the patient's performance status was poor, there were no contraindications, such as active infection or severe complications, for systemic chemotherapy. Weekly 5-FU/l LV (5-FU 600 mg/m2, l-LV 250 mg/m2 on days 1, 8, 15, 22, 29 and 36; 8 weeks/cycle) was selected as the feasible treatment for the patient. After chemotherapy the patient opted to withdraw from HD and suffered from no severe toxicity. This indicates, retrospectively, that earlier systemic chemotherapy administration prior to HD introduction may result in improvement of renal function and avoidance of HD. [ABSTRACT FROM AUTHOR]

The activity of periplasmic arylsulfatase (Ars), which catalyzes the cleavage of sulfate from aromatic sulfur compounds, was detected in cells acclimated to the sulfate-deficient conditions in a unicellular green alga Chlamydomonas reinhardtii Dangeard, but not in Chlorella. Scenedesmus. Dunaliella and Porphyridiom. Upon the transfer of cells to sulfate-deficient autotrophic media under high-CO[sub2] conditions, the induction of Ars was observed only in the light, but not in the light with dichlorophenyldimethylurea (DCMU) nor in the dark. However, Ars was induced in the light with DCMU or in the dark when acetate was present as an organic carbon source, but not citrate. Under similar high-CO[sub2] conditions, high-CO[sub2] requiring mutants of cia-3 and cia-5, whose photosyn-thetic activities are greatly limited under low CO[sub2], showed much lower level of Ars activittes than wild type cells. Under low-CO[sub2] conditions the induction of Art was greatly suppressed even in wild type and no induction was observed in both mutants. These results suggest that the stimulation of photosynthetic or respiratory carbon metabolism are necessary for the induction of Ars. In contrast, the induction of periplasmic carbonic anhydrase (CA) which was synthesized de novo specifically under 002-limited conditions was strongly suppressed by the addition of organic carbon sources, such as acetate and citrate. When cells are subjected to CO.,-limitation and sulfate-deficiency simultaneously, the induction of CA was initiated immediately, while that at Ars was initiated following the completion of CA induction with an about 4-h lag. When the concentration of CO[sub7] was suddenly lowered during the induction of Ars, the induction of Ars ceased quickly, and the induction of CA was initiated instead. From these results the induction of CA was suggested to have priority over that of Ars under the dual stress of CO, and sulfate deprivation. [ABSTRACT FROM AUTHOR]