Approximately half of urothelial carcinoma (UC) patients exhibit low or null HER2 expression. Limited data are available on the efficacy of anti-HER2 RC48-ADC (Disitamab Vedotin) in HER2 low and null advanced UC. Patients with locally advanced or metastatic UC (la/mUC) with HER2 low (IHC 1+) and null (IHC 0) expression who received RC48-ADC monotherapy or in combination with programmed cell death protein 1 (PD‐1) inhibitors were enrolled in this multi-center, retrospective study. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). A total of 27 patients were included, with a median age of 64 years, and 17 (63%) were male. Seven (26.0%) patients received RC48-ADC alone, and 20 (74.1%) received RC48-ADC combined with a PD-1 inhibitor. Eight (30.8%) patients achieved partial response (PR), and twelve (46.2%) exhibited stable disease (SD). The ORR was 30.8%, and DCR was 76.9%. The median PFS and OS were 7.4 months and 13.8 months, one-year PFS and OS rates were 29.1% and 57.2%, respectively. Both RC48 monotherapy and combination were well-tolerated. Grade 3 AEs occurred in 4 (14.8%) patients received combination treatment, including 2 cases of anemia, 1 case of increased serum creatinine, and 1 case of autoimmune encephalitis. No grade 3 or higher AEs were observed in RC48-ADC monotherapy. RC48-ADC demonstrated favorable efficacy and manageable safety in la/mUC patients with HER2 low and null expression in real-world settings. Prospective studies with large sample size are warranted to validate this finding.

Background: The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC. Method: Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer. Results: Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer. Conclusion: Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.

Background: Chronic inflammation related to poor genital hygiene is a well-recognized pathogenic trigger for penile cancer (PC). The neutrophil-to-lymphocyte ratio (NLR) is a simple, reproducible systemic inflammatory marker and has been reported to indicate unfavorable outcomes. However, previous studies were limited by small sample sizes, confounding prognostic factors and a lack of high-quality evidence demonstrating the significance of the NLR in PC.Methods: A large multicenter cohort of 582 PC patients who underwent radical inguinal lymphadenectomy with definitive pN stage information was assessed. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of inflammation-related markers. Propensity score matching (PSM) was used to minimize confounding prognostic clinicopathological features. Immunofluorescence was used to assess the immunosuppressive tumor microenvironment (TME).Results: A high preoperative NLR (≥ 3.0) was associated with advanced pT, pN, and pathological grade and lymphovascular invasion in PC patients. After PSM to eliminate interference from clinical factors, pN and the NLR were found to be independent prognostic indicators (both p<0.001). PC patients with high NLRs had shorter progression-free survival (PFS) and poorer cisplatin-based chemotherapy and PD-1 immunotherapy response. We also found that the NLR is associated with proinflammatory cytokine secretion and increased N2 tumor-associated neutrophils (TANs) infiltration and CD8⁺ T-cell exhaustion in TME. N2 TANs induced neutrophil extracellular trap formation might contribute to tumor progression and resistance in high-NLR PC patients.Conclusions: The NLR is an effective, simple and independent prognostic indicator for PC. A high NLR is associated with an immunosuppressive TME and poor outcomes.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Zhi Yong Li1, 2, 3, *, Xin Xiang Fan4, *, Yan Jun Wang1, 2, 3, *, Kai Yao1, 2, 3, Zhuo Wei Liu1, 2, 3, Wen Tao Pan1, 2, 3, Yun Lin Ye1, 2, 3, Ping Yang1, 2, 3, Yi Chuan Huang4, Zhi Ming Wu1, 2, 3, Fang Jian Zhou1, 2, 3 1State Key Laboratory of Oncology in Southern China, Guangzhou, China 2Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 4Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China *These authors contributed equally to this work Correspondence to: Zhi Ming Wu, email: wuzhim@sysucc.org.cn Fang Jian Zhou, email: zhoufj@sysucc.org.cn Keywords: RCC, sorafenib, TKIs, CRVO, unilateral Received: December 07, 2015 Accepted: March 28, 2016 Published: May 11, 2016 ABSTRACT Background: Renal cell carcinoma (RCC) is the most common type of kidney tumor with increasing incidence. Tyrosine Kinase Inhibitors (TKIs) are considered important treatment in the management of metastatic RCC. Some previous studies demonstrated that sorafenib treatment is associated with a significantly increased risk of potentially life-threatening adverse events, like bleeding. But bleeding at the fundus site is the rarest type of hemorrhage. As for TKIs’ risk of bleeding, how we distinguish the degree of bleeding and what optimal strategies should we take to manage bleeding, needs to be studied systematically. Results: With a long-term exposure (17 months) to sorafenib, he experienced blurred vision in his right eye and was hospitalized. The patient’s diagnosis was central retinal vein occlusion (CRVO) of the right eye. Unfortunately sorafenib was terminated. Materials and Methods: The authors describe the first case of unilateral fundus hemorrhage induced by sorafenib. A 42-year-old man was diagnosed metastatic left RCC, with clinical stage and prognostic risk being assessed as T4N1M1 and intermediate. He received a radical left nephrectomy and retroperitoneal lymph node dissection, with taking the oral multi-targeted TKI, sorafenib (800 mg daily) from 7 months to 7 days before the surgery and 7 days after the surgery restarting again until the occurrence of fundus hemorrhage. Conclusions: In this patient, long-term exposure to sorafenib possibly has increased the risk of fundus hemorrhage. This article provides us a previously undescribed morbidity associated with sorafenib, which reminds us of understanding the risk of bleeding and how this complication might be managed systematically.

Background: Radical cystectomy and urinary diversion remains the standard surgical treatment for patients with muscle‐invasive or high‐risk or recurrent non‐muscle‐invasive bladder cancer. Although this approach prolongs patient survival remarkably, there are postoperative complications associated with urinary diversion. This study aimed to assess the efficacy of modified ileal conduit surgery for reducing early and late stoma‐ and ureteroileal anastomosis‐related complications, as compared with conventional ileal conduit urinary diversion. Methods: We retrospectively evaluated the clinical data of bladder cancer patients treated with radical cystectomy and ileal conduit urinary diversion at Sun Yat‐sen University Cancer Center between January 1, 2000 and June 30, 2016. Ileal conduit was created by the conventional or a modified technique. The clinicopathologic features of the conventional and the modified ileal conduit groups were compared using the t test and the Chi square test. Multivariable logistic regression analysis and multivariable Cox regression analysis were performed to determine the odds of developing stoma‐ and ureteroileal anastomosis‐related complications in the two groups. Results: 145 and 100 patients underwent the modified and conventional ileal conduit surgery, respectively. The two groups were comparable with regard to clinicopathologic features. The rate of stoma‐related complications was significantly lower in the modified ileal conduit group than in the conventional ileal conduit group (0.7% vs. 17.0%, P < 0.001). No late stoma‐related complications were seen in the modified ileal conduit group, but were seen in 13 (13.0%) patients in the conventional ileal conduit group. The rate of ureteroileal anastomosis‐related complications was significantly lower in the modified ileal conduit group than in the conventional ileal conduit group (4.8% vs. 15.0%, P = 0.001). In multivariable analyses, the modified ileal conduit group was significantly less likely to develop stoma‐ (odds ratio [OR] = 0.024, 95% confidence interval [CI] 0.003–0.235; P = 0.001) or ureteroileal anastomosis‐related complications (OR = 0.141, 95% CI 0.042–0.476; P = 0.002) than the conventional ileal conduit group. Conclusions: Our modified surgical technique for ileal conduit urinary diversion may be effective for reducing early and late complications related to the stoma and the ureteroileal anastomosis. Prospective randomized clinical trials are needed to confirm our results.