Background Polycystic kidney diseases (PKD) are an important cause of chronic kidney disease (CKD). ADPKD due to PKD1 or PKD2 mutations is the most common form, but other genes can be responsible for ADPKD or its phenocopies. Among them, a form of atypical ADPKD caused by DNAJB11 mutations (DNAJB11-PKD) has been recently described. Methods We retrospectively recruited a cohort of 27 patients from 6 different families sharing common ancestries and harboring the same DNAJB11 mutation (c.100C > T, p.Arg34*), and we compared it with a cohort of 42 typical ADPKD patients. Results DNAJB11-PKD patients show small/normal sized kidneys, with significantly smaller cysts and a slower progression to end-stage kidney disease (ESKD) than ADPKD patients. In the DNAJB11-PKD cohort the cystic phenotype could not be detected by ultrasound in about half of the patients, but all cases with available CT/MR displayed cysts. Clinically, DNAJB11-PKD patients displayed proteinuria (mostly albuminuria). Compared to ADPKD, DNAJB11-PKD patients were older and had higher prevalence of type 2 diabetes mellitus (19 vs 0%; P = 0.007) and nephrolithiasis (62 vs 29%; P = 0.01), while the prevalence of cardiac valvular defects was lower (4 vs 51%; P < 0.001). Conclusions Overall, clinical features of DNAJB11-PKD were more subtle compared to those of ADPKD. DNAJB11-PKD shows a unique renal and extra-renal phenotype, clinical presentation, and natural history. Therefore, our data support that this genetic disease is classified separately from ADPKD.

Sensitivity to endocrine therapy of patients with estrogen receptor (ER)-positive metastatic breast cancer and germline BRCA1/2 mutations is not yet fully elucidated. Furthermore, the registration trials of CDK 4/6 inhibitors in combination with endocrine therapy lacked of a pre-specified subgroup analysis in BRCA1/2 mutation carriers. We report clinical history of two patients with BRCA-mutated, ER-positive metastatic breast cancer treated with letrozole plus the CDK 4/6 inhibitor palbociclib. Biological and clinical implications of the treatment outcome observed in the two cases are discussed with the knowledge of scientific evidence to date available. Overall, biological rationale, preclinical, and clinical data support the prominent role of CDK 4/6 inhibitors plus endocrine therapy, even in combination with PARP inhibitors, in the treatment of BRCA-mutated, ER-positive breast cancers. However, the interaction between Cyclin/CDK pathway, ER and BRCA is complex and evidences reported so far, albeit reliable, await confirmation in the context of future randomized clinical trials.

Background Medullary sponge kidney (MSK) is a rare disease characterized by cystic dilatation of papillary collecting ducts. Intravenous urography is still considered the gold standard for diagnosis. We identified a cohort of patients from our outpatient clinic with established diagnosis of MSK to outline some ultrasonographic characteristics that may help establish a diagnosis. Methods We conducted a retrospective study of patients seen between January 1st 2009 and January 1st 2019 in our clinic. Out of 4321 patients, 18 had a diagnosis of MSK. We reviewed their clinical and family history, laboratory data and imaging studies. Specifically, we focused on ultrasound imaging. Results Patients were referred to our outpatient clinic because of renal impairment (44%), family history of nephropathy (17%), nephrolithiasis or an established diagnosis of MSK (39%). Seventy-two percent of patients presented with chronic kidney disease, 22% required hemodialysis. Urinary tract infections (44%), nephrolithiasis (33%), microscopic hematuria (50%) and proteinuria (44%) were reported. Seven patients underwent computed tomography; all of them received ultrasound. Ultrasound examination showed bilateral renal cysts, usually small and located in the renal medulla, and microcalcifications located in the medulla or within the cysts. Conclusion We identified a peculiar tetrad associated with MSK: 1) hypoechoic medullary areas, 2) hyperechoic spots, 3) microcystic dilatation of papillary zone, 4) multiple calcifications (linear, small stones or calcified intracystic sediment) in each papilla. The presence of this diagnostic tetrad, added to laboratory data and clinical history, could be helpful in the differential diagnosis to identify patients with MSK.

Purpose To test radiomics for prognostication of intrahepatic mass-forming cholangiocarcinoma (IMCC) and to develop a comprehensive risk model. Methods Histologically proven IMCC (representing the full range of stages) were retrospectively analyzed by volume segmentation on baseline hepatic venous phase computed tomography (CT), by two readers with different experience (R1 and R2). Morphological CT features included: tumor size, hepatic satellite lesions, lymph node and distant metastases. Radiomic features (RF) were compared across CT protocols and readers. Univariate analysis against overall survival (OS) warranted ranking and selection of RF into radiomic signature (RSign), which was dichotomized into high and low-risk strata (RSign*). Models without and with RSign* (Model 1 and 2, respectively) were compared. Results Among 78 patients (median follow-up 262 days, IQR 73–957), 62/78 (79%) died during the study period, 46/78 (59%) died within 1 year. Up to 10% RF showed variability across CT protocols; 37/108 (34%) RF showed variability due to manual segmentation. RSign stratified OS (univariate: HR 1.37 for R1, HR 1.28 for R2), RSign* was different between readers (R1 0.39; R2 0.57). Model 1 showed AUC 0.71, which increased in Model 2: AUC 0.81 (p < 0.001) and AIC 89 for R1, AUC 0.81 (p = 0.001) and AIC 90.2 for R2. Conclusion The use of RF into a unified RSign score stratified OS in patients with IMCC. Dichotomized RSign* classified survival strata, its inclusion in risk models showed adjunct yield. The cut-off value of RSign* was different between readers, suggesting that the use of reference values is hampered by interobserver variability.

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