Clinicopathological features and medium-term outcomes of histologic variants of primary focal segmental glomerulosclerosis in adults:A retrospective study

BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.

Comparative Analysis of Ki-67 Protein as a Proliferative Expression Index in Cutaneous Basal and Squamous Cell Carcinoma in Federal Medical Centre Umuahia, Nigeria

Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.

Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

First-line pazopanib in patients with advanced non-clear cell renal carcinoma:An Italian case series

BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart.New systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC cases.AIM To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup.METHODS The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting.RESULTS Overall,48 patients were included.At the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,respectively.Grade 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were found.CONCLUSION Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.