Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma

The prognosis of locally advanced or recurrent squamous cell carcinoma(SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months(range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer

Accurate methods for identifying pelvic lymph node metastasis(LNM)of prostate cancer(PCa)prior to surgery are still lacking.We aimed to investigate the predictive value of peripheral monocyte count(PMC)for LNM of PCa in this study.Two hundred and ninety-eight patients from three centers were divided into a training set(n=125)and a validation set(n=173).In the training set,the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses,and the optimal cutoff value was calculated by the receiver operating characteristic(ROC)curve.The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort.Finally,a nomogram based on the PMC was constructed for predicting LNM.Multivariate analyses of the training cohort demonstrated that clinical T stage,preoperative Gleason score,and PMC were independent risk factors for LNM.The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405×10^(9)l^(−1)with a sensitivity of 60.0%and a specificity of 67.8%.In the validation set,the optimal cutoff value showed significantly higher sensitivity than that of conventional magnetic resonance imaging(MRI)(0.619 vs 0.238,P<0.001).The nomogram involving PMC,free prostate-specific antigen(fPSA),clinical T stage,preoperative Gleason score,and monocyte-to-lymphocyte ratio(MLR)was generated,which showed a robust predictive capacity for predicting LNM before the operation.Our results indicated that PMC as a single agent,or combined with other clinical parameters,showed a robust predictive capacity for LNM in PCa.It can be employed as a complementary factor for the decision of whether to conduct pelvic lymph node dissection.

Up-regulation of indoleamine 2,3-dioxygenase 1(IDO1)expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (Trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penilesquamous cell carcinoma (PSCC) and explored their clinical significance.Methods: IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn)were examined in 114 PSCC patients by immunohistonchemistry and solid-phaseextraction-liquid chromatography-tandem mass spectrometry. The survival was analyzed using Kaplan-Meier method and the log-rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were definedby principal component analysis. The correlativity was assessed by Pearson’s correlation analysis.Results: The expression level of IDO1 in PSCC cells was positively correlatedwith serum Kyn concentration and Kyn/Trp radio (KTR;both P < 0.001) but negatively correlated with serum Trp concentration (P = 0.001). Additionally, IDO1 upregulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P < 0.001) and high pathologic grade (P = 0.008and 0.032, respectively). High expression level of IDO1 in cancer cells and serumKTR were associated with short disease-specific survival (both P < 0.001). However, besides N stage (hazard radio [HR], 6.926;95% confidence interval [CI],2.458-19.068;P < 0.001) and pathologic grade (HR, 2.194;95% CI, 1.021-4.529;P = 0.038), only serum KTR (HR, 2.780;95% CI, 1.066-7.215;P = 0.036) was anindependent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon-𝛾 (IFN𝛾, P < 0.001) and immunosuppressivemarkers (programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 and 2;all P < 0.05), and the infiltration ofimmune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumorassociated macrophages, and myeloid-derived suppressor cells;all P < 0.001) inPSCC tissues. Furthermore, the expression of IDO1 was induced by IFN𝛾 in a dosedependent manner in PSCC cells.Conclusions: IFN𝛾-induced IDO1 plays a crucial role in immunoediting andimmunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1catabolic activity, can be utilized as an independent prognostic factor for PSCC.