Extramammary Paget’s disease: Updates in the workup and management

Objective:Extramammary Paget’s disease(EMPD)is a rare cutaneous malignant disease.Due to its rarity,there is a paucity of data regarding best treatment strategy.EMPD primarily affects apocrine gland-bearing skin areas such as the vulva,scrotum,and penis.Our objective was to provide a present-day rationale for diagnosis,pathogenesis,and treatment of EMPD with a focus on recent progress in workup and management of the disease.Methods:Literature on EMPD until February 2022 was assessed through PubMed,MEDLINE databases,and Google scholar.A narrative review of the most relevant articles was provided.Results:EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ.The foundation of EMPD treatment centers around prompt and accurate diagnosis,wide local or Mohs micrographic surgical excision with proper management towards the margin status,and careful consideration for lymphadenectomy in patients with regionally positive disease.Conventional chemotherapies are alternative treatments modality for patients with distant metastases;however,they sometimes have suboptimal efficacy.At present,there is no agreement regarding adjuvant or systemic therapies,although recent studies have shown several insights into the molecular pathogenesis,tumor biology,and genomics of the development and advancement of EMPD,which may lead to novel and targeted treatment approaches for metastatic EMPD in the future.Conclusion:Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling.These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression.Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors,and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

A novel preoperative inflammatory marker prognostic score in patients with localized and metastatic renal cell carcinoma

Objective:Several inflammatory markers have been studied as potential biomarkers in renal cell carcinoma(RCC),however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies.We hypothesize that a combination of specific inflammatory markers into an RCC Inflammatory Score(RISK)could serve as a rigorous prognostic indicator of overall survival(OS)in patients with clear cell and non-clear cell RCC.Methods:Combination of preoperative C-reactive protein(CRP),albumin,erythrocyte sedimentation rate(ESR),corrected calcium,and aspartate transaminase to alanine transaminase(AST/ALT)ratio was used to develop RISK.RISK was developed using grid-search methodology,receiver-operating-characteristic(ROC)analysis,and sensitivity-specificity trade-off analysis.Prognostic value of RISK was analyzed using the KaplaneMeier method and Cox proportional regression models.Predictive accuracy was compared with RISK to Size,Size,Grade,and Necrosis(SSIGN)score,University of California-LOS Angeles(UCLA)Integrated Staging System(UISS),and Leibovich Prognosis Score(LPS).

Survival benefit with extended lymphadenectomy for advanced renal malignancy: A population-based analysis

Objective:We used population-based data to examine the possible benefit of extended lymphadenectomy for patients with renal malignancy in the setting of more advanced disease.Methods:The Surveillance,Epidemiology,and End Results(SEER)database was utilized to identify non-metastatic,T3-T4 renal cancer patients from 2004-2015 treated with removal of≥1 lymph node at the time of nephrectomy.Non-parametric bivariate statistics were used to assess associations between covariates of interest and extended lymphadenectomy(≥10 lymph nodes removed).Cancer-specific survival(CSS)and overall survival(OS)benefit was evaluated using Kaplane-Meier analysis.Results:Of the 4397 patients identified,816(18.6%)underwent extended lymphadenectomy.For patients with T3a disease,5-year CSS and OS benefit with extended lymphadenectomy did not reach statistical significance(CSS:hazard ratio[HR]0.98,95%confidence interval[CI]0.77-1.24;OS:HR 0.96,95%CI 0.77-1.20).Conversely,for those with T3b-T3c disease,extended lymphadenectomy led to statistically significant improvements in both 5-year CSS and OS compared to non-extended lymphadenectomy(CSS:HR 0.78,95%CI 0.61-0.99;OS:HR 0.72,95%CI 0.58-0.90).Finally,for those with T4 disease,use of extended lymphadenectomy had OS benefit after 5 years(OS:HR 0.51,HR 0.29-0.90,p = 0.02).Conclusion:Based on population-level data,extended lymphadenectomy was associated with improved survival in select patients with advanced renal malignancy treated with surgical nephrectomy.Understanding the basis of these real-world findings in the face of conflicting randomized trial results will be key,moving forward.

Elevated preoperative neutrophil-tolymphocyte ratio may be associated with decreased overall survival in patients with metastatic clear cell renal cell carcinoma undergoing cytoreductive nephrectomy

Objective:Inflammatory serum markers have proven to be a powerful predictive tool of patient prognosis in cancer treatment for a wide variety of solid organ malignancies,predominantly in the context of localized disease.In this study we evaluated the preoperative neutrophil-to-lymphocyte ratio(NLR)as a predictive tool in patients with metastatic clear cell renal cell carcinoma(RCC).Methods:Sixty-four patients with metastatic clear cell RCC undergoing nephrectomy were selected.Only patients with preoperative NLR were included for survival analysis.Patients were categorized into high and low NLR score determined by plotting the NLR ROC curve.Multivariable analysis was performed.Results:Median age was 60.8 years(38.2-81.2).Median follow-up time was 8.1 months(0.1-106.3).Fuhrman grade distribution was:2(3.1%)grade 1,6(9.4%)grade 2,24(37.5%)grade 3 and 32(50.0%)grade 4.Median NLR score was 3.5(1.4-31.0).NLR
4 was associated with decreased overall survival compared toNLR<4(p=0.017).Multivariable survival analysis showed NLR
4 as an independent predictor of survival(Hazard ratio(HR)2.41,95%CI 1.05-5.50,p=0.03).Conclusion:Elevated preoperative NLR is associatedwith poor prognosis in patients withmetastatic kidney cancer.Preoperative NLR is a useful tool,which can predict prognosis,stratify patients for postoperative surveillance,and help guide decisions for therapy.

Major histocompatibility complex I upregulation in clear cell renal cell carcinoma is associated with increased survival

Objective:To examine the prognostic value of tumor major histocompatibility complex I(MHCI)expression on survival and recurrence in patients with clear cell renal cell carcinoma(RCC).Methods:Fifty-three patients that underwent nephrectomy at our institution for clear cell RCC(T1eT3)with
4 years of follow-up were queried from our nephrectomy database.Immunohistochemical staining for MHCI was performed on tumor specimens and MHCI expression was quantified with an automated image analysis technique.Patients were divided into high and low MHCI expression groups in order to study the relationship between MHCI expression and prognosis using the KaplaneMeier method and log-rank test.Results:Overall survival and recurrence free survival were increased in the high MHCI expression group compared to the low MHCI expression group(log-rank,p=0.036 and p=0.028,respectively).Patients alive at the end of the study had higher MHCI expression(mean positivity score 0.82)than those that died of disease(mean positivity score 0.76,t test,p=0.030).Patients that did not develop recurrence during the study period had higher MHCI expression(mean positivity score 0.83)than those that did develop recurrence(mean positivity score 0.78),but this difference was not significant(t test,p =0.079).