Comparative effectiveness of first-line immune checkpoint inhibitors plus tyrosine kinase inhibitors according to IMDC risk groups in metastatic renal cell carcinoma: a meta-analysis.

Aim: Immune checkpoint inhibitor (ICI)-based combinations have become the new standard of primary systemic treatment for metastatic renal cell carcinoma patients. We performed a meta-analysis aimed at evaluating ICIs plus tyrosine kinase inhibitors (TKIs) combinations across International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups. Materials & methods: All the relevant randomized clinical trials were retrieved through Cochrane library, PubMed/Med and EMBASE; three Phase III randomized clinical trials were included. Results: ICI-TKI combinations significantly decreased the risk of death in IMDC poor- and intermediate-risk patients. Conversely, a nonstatistically significant benefit was observed in favorable-risk patients. Conclusion: Our results suggest that IMDC poor-risk patients benefit most from ICI-TKI combinations, while a proportion of metastatic renal cell carcinoma patients could respond to targeted agent monotherapy.

Severe uropathy and normal amniotic fluid volume in a male fetus: sonographic surveillance leading to the diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome.

The widespread use of sonography as a screening tool for fetal anomalies has facilitated prenatal detection of several fetal conditions characterized by urinary tract dilatation. These conditions are more common in male fetuses and are generally a result of an anatomic defect causing obstruction along the urinary tract system. Although the prognosis of these conditions largely depends on the specific anomaly, several poor prognostic factors have been described. These factors include detection at an early gestational age, bilateral marked dilatation, a persistently obstructed bladder, oligohydramnios causing pulmonary hypoplasia, and the presence of associated fetal or chromosomal anomalies. We report a case in which a male fetus at 14 weeks' gestation had a diagnosis of rapidly progressing bilateral hydronephrosis, massive bladder dilatation, hydroureter, and a surprisingly normal amniotic fluid volume. Serial sonographic surveillance assisted us in obtaining the correct diagnosis, which was important for adequately consulting the patient regarding the fetal prognosis in the affected index pregnancy as well as the likelihood of recurrence in future gestations.

Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the intestinal tract that typically occur in adults over the age of 40 years. GISTs in younger patients are rare and not well characterized. The objective was to define the characteristics of GISTs in children and young adults (<30 years old). Clinicopathologic and molecular features, including KIT/PDGFRA genotype, in GISTs from 5 children and 10 young adults were analyzed. Gene expression analysis was performed on 5 gastric tumor samples from 2 children, 2 gastric tumors from young adults, and 10 gastric GISTs from older adults using an U133A Affymetrix platform (22,000 genes). All five pediatric GISTs occurred in girls, involved the stomach as multiple nodules, showed predominantly an epithelioid morphology, often involved lymph nodes, and lacked KIT or PDGFRA mutations. Although all five patients developed recurrence (four in the liver, three in the peritoneum, and two in both sites), four are still alive with disease. Of the 10 GISTs in young adults, half occurred in the small bowel and had spindle cell morphology, and one case had lymph node metastasis. KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. Seven patients developed recurrence, and at last follow-up two patients had died of disease. Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors. The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies.