Comparison of the perioperative outcomes of using the Firefly system with indocyanine green during robotic-assisted cystectomy with urinary diversion.

INTRODUCTION: Use of indocyanine green (ICG) with near-infrared fluorescence (NIRF) has been demonstrated to be an effective tool for intraoperative assessment of bowel and ureteric vascularity. This study aimed to evaluate the impact of ICG on postsurgical outcomes such as anastomotic bowel leak and uretero-enteric stricture formation during robot-assisted cystectomy (RAC) and intracorporeal urinary diversion (ICUD). METHODS: We identified 238 patients who underwent RAC at the University of Louisville between September 2012 and August 2021. Patients were divided into two groups based on the utilization of ICG. Demographic, perioperative outcomes, and rate of anastomotic bowel leak were compared. RESULTS: In total, 138 patients were in the ICG group and 100 patients were in the non-ICG group. More intracorporeal urinary diversions and more simple cystectomies were observed in the ICG group (p < 0.001 and p = 0.015, respectively). The ICG group patients initiated an oral diet sooner than the control group (4.9 vs. 7.1 days, p < 0.001). The mean length of stay of the ICG group was shorter than the non-ICG group (8.3 vs. 12.8 days, p < 0.001). The rate of postoperative ileus was not significantly different between cohorts. No patients in the ICG group experienced a bowel leak compared with five patients in the non-ICG group (p = 0.008). CONCLUSIONS: In our study, the use of ICG for intraoperative assessment of bowel and ureteric vascularity was associated with earlier bowel recovery and a shorter length of stay. It was also significantly correlated with a lower rate of anastomotic bowel leak.

Identify risk factors for perioperative outcomes in Intracorporeal Urinary Diversion and Extracorporeal Urinary Diversion with Robotic Cystectomy.

INTRODUCTION: The increasing adoption of robotic-assisted cystectomy with intracorporeal urinary diversion (ICUD), despite its complexity, prompts a detailed comparison with extracorporeal urinary diversion (ECUD). Our study at a single institution investigates perioperative outcomes and identifies risk factors impacting the success of these surgical approaches. METHODS: In this retrospective analysis, 174 patients who underwent robotic-assisted cystectomy at the University of Louisville from June 2016 to August 2021 were reviewed. The cohort was divided into two groups based on the urinary diversion method: 30 patients underwent ECUD and 144 underwent ICUD. Data on demographics, complication rates, length of hospital stay, and readmission rates were meticulously collected and analyzed. RESULTS: Operative times were comparable between the ICUD and ECUD groups. However, the ICUD group had a significantly lower intraoperative transfusion rate (0.5 vs. 1.0, p=0.02) and shorter hospital stay (7.8 vs. 12.3 days, p<0.001). Factors such as male sex, smoking history, diabetes mellitus, intravesical therapy, higher ASA, and ACCI scores were associated with increased Clavien-Dindo Grade 3 or higher complications. Age over 70 was the sole factor linked to a higher 90-day readmission rate, with no specific characteristics influencing the 30-day rate. CONCLUSION: Robotic cystectomy with ICUD results in shorter hospitalizations and lower intraoperative transfusion rates compared to ECUD, without differences in operative time, high-grade postoperative complications, or readmission rates. These findings can inform clinical decision-making, highlighting ICUD as a potentially more favorable option in appropriate settings.

Genitourinary Blastomycosis in a Young Male Patient: A Case Report and Review of Diagnostic Challenges.

Disseminated blastomycosis is an endemic fungal infection that rarely manifests with genitourinary involvement. We present a unique case of a 28-year-old professional male gamer with a remote history of hemoptysis and cervical lymphadenopathy who presented with hematospermia, lower urinary tract symptoms (LUTS), and persistent groin abscesses after left orchiectomy at an outside hospital. He underwent drainage of groin abscess and prostate biopsy for an abnormal digital rectal exam which revealed disseminated blastomycosis requiring systemic, long-term antifungal treatment. We have also included a review of literature to note clinical patterns in presentations and highlight the diagnostic challenges that this infection presents.

Exposure of environmental trace elements in prostate cancer patients: A multiple metal analysis.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men. To elucidate the connection between trace elements (arsenic: As, cadmium: Cd, lead: Pb, chromium: Cr, and nickel: Ni) and the risk of PCa, we analyzed trace element levels in the serum, urine, and tissues of PCa patients, while also examining their smoking status. We correlated these levels with their smoking habits. Notably, levels of Cd (P ≤ 0.05) and As (P ≤ 0.01) were significantly higher in the tumor tissue than in adjacent tissues. No significant differences were observed in the levels of Pb, Cr and Ni. Additionally, urinary Cd levels in 70% and arsenic levels in 2.3% of the PCa cohort were markedly higher than the CDC-reported cutoff (Cd ≤ 0.185 µg/L & As ≤100 µg/L). None displayed elevated levels of urinary Pb, Cr, and Ni. Conversely, in serum samples, the concentration of arsenic exceeded the CDC-determined limit (As ≤1.0 µg/L) in 31.69% of PCa patients. However, only 7.04% of patients had higher serum Cd levels than the CDC standard values (Cd ≤ 0.315 µg/L), while all PCa patients exceeded the Cr CDC limit (Cr ≤ 0.16 µg/L) and the Ni CDC limit (Ni ≤ 0.2 µg/L). On the contrary, no significant differences were observed in serum Pb (Pb ≤ 35.0 µg/L). Our findings establish a positive link between Cd and arsenic tissue concentrations and the risk of PCa. Subsequent studies are essential to determine whether elevated trace element levels pose a risk for the development of prostate carcinogenesis. Interestingly, among the PCa cohort comprising smokers, notably higher Cd levels were observed only in tumor tissues (P ≤ 0.01) and urine (P ≤ 0.05) compared to other elements or in other specimens.

Colo-renal Fistula in a Patient With Refractory Anemia and Recurrent Urinary Tract Infections: A Case Report and Review of the Literature.

Although rare, colo-renal fistulas pose diagnostic challenges due to their varied presentations and etiologies. Here, we present a unique case of a woman with recurrent pyelonephritis, severe anemia, and unintended weight loss, who was eventually diagnosed with a colo-renal fistula. Delayed imaging following intraoperative fluoroscopy revealed the abnormal connection between the colon and upper urinary tract. The patient underwent nephrectomy and colon resection. This case report emphasizes the need for suspicion in diagnosing such fistulas and highlights their varied management. This case adds to the literature by illustrating an unusual presentation and underscores the complexity of diagnosis and treatment.

Identification of risk factors and prediction models for secondary malignant neoplasms (SMNs)-free survival and SMNs-specific survival in testicular cancer survivors.

OBJECTIVE: This research endeavored to determine the key demographic and pathological factors tied to secondary malignant neoplasms (SMNs) in survivors of testicular cancer and to develop a predictive model. METHOD: A total of 53,309 testicular cancer patients from the SEER national database (1975-2016) were included in our analysis. The primary outcome measured was SMNs-free survival, defined as the duration from testicular cancer diagnosis to the detection of a non-testicular malignancy. The secondary outcome was SMN-specific survival, defined as the period from testicular cancer diagnosis until the patient's death due to SMNs. FINDINGS: Of the patients in the SEER cohort, 2978 (5.6%) developed non-testicular cancer SMNs. Higher age, receipt of chemotherapy, and radiation treatment were all significantly associated with the development of SMNs in survivors of testicular cancer (all p < 0.001). Kaplan-Meier analysis revealed a worse SMNs-free survival and poor SMN-specific survival in patients who underwent radiation therapy (both p < 0.001). Multivariable Cox regression analysis found non-Hispanic Black ethnicity, higher age, chemotherapy, and radiation therapy to be significantly associated with worse SMNs-free survival (p = 0.002, p < 0.001, p < 0.001, and p < 0.001, respectively), while lymphoma histology was associated with better SMNs-free survival (p < 0.001). The most common SMN types in patients receiving radiation therapy were prostate, lung, and bladder cancers. Predictive nomograms for SMNs-free survival and SMNs-specific survival were developed, with a C-index of 0.776 and 0.824, respectively. CONCLUSION: The age of diagnosis, non-Hispanic Black ethnicity, lymphoma histology, and treatment history with chemotherapy and radiation therapy were identified as prognostic factors for SMNs-free survival.

Application of Internet-based multidisciplinary management in patients with genitourinary cancers in China: A brief introduction to a new model of healthcare service for cancer survivors during COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has triggered multiple global healthcare system crises. Apart from the pandemic itself, the travel restriction and social distance policy for the purpose of epidemic control has cast a shadow on the management of cancer survivors. Cancer survivors suffered a double blow from both the epidemic and cancer. To deal with the challenge, we explored a new Internet-based patient management model. This model has overcome the limitation of time and space and thus can help oncologists to provide remote multidisciplinary healthcare services for cancer survivors. These patients can get high-quality cancer management from multidisciplinary experts without too much transportation. This model has been applied in patients with genitourinary cancers and proved to be effective and efficient. Our study demonstrated that more patients benefited from this model during the pandemic of COVID-19, especially in those affected heavily by COVID-19. These results suggested that it can also give insight into the management of other cancer survivors in China. Given the long-term impact of the COVID-19 pandemic, we would like to introduce our new model of healthcare service and the application of Internet-based multidisciplinary management to our global peers and medical industries to help their cancer survivors who are delayed in treatment due to the COVID-19 pandemic.

Identification of High Serum Apolipoprotein A1 as a Favorable Prognostic Indicator in Patients with Multiple Myeloma.

This study is to explore the prognostic significance of serum lipid profiles in patients with multiple myeloma (MM). The study retrospectively enrolled 307 MM patients in Zhongshan Hospital, Shanghai, China, from 2007 to 2016. We evaluated the prognostic significance of the pre-diagnostic serum lipid profile [cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), Apolipoprotein A1 (Apo A1) and Apolipoprotein B (Apo B)]. Prognostic factors identified through univariate and multivariate analysis were used to construct a new model based on Lasso Cox regression. Results indicated that lipid levels showed significant difference between ISS stages: Apo A1, Apo B, Cholesterol and LDL levels were lower in late ISS stage. However, only Apo A1 showed statistically significance in overall survival (OS), progression free survival (PFS) and cause specific survival (CSS) (P=0.038, P=0.028, P=0.011) in univariate Cox regression. Patients with higher Apo A1 displayed longer OS (median OS, 67 months vs. 30 months; P<0.001). Also, Apo A1 was revealed to be an independent prognostic indicator through multivariate analysis. Combining the Apo A1 level, Zhongshan Score model was constructed with Lasso regression for prognosis prediction. This model exhibited higher accuracy than International Staging System (ISS) and Durie and Salmon (DS) system. In conclusion, among all the serum lipid profiles, serum Apo A1 is a powerful prognostic indicator for patients with MM.

Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion.

BACKGROUND: Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities. OBJECTIVE: To seek a potential therapeutic target in glutamine-addicted ccRCC. DESIGN, SETTING, AND PARTICIPANTS: Tumors from ccRCC patients from a Shanghai cohort and ccRCC tumor data from The Cancer Genome Atlas (TCGA) cohort were analyzed. In vivo and in vitro studies were conducted with fresh human ccRCC tumors and murine tumor cells. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Immune cell numbers and functions were analyzed by flow cytometry. Glutamine and cytokine concentrations were determined. Survival was compared between different subpopulations of patients using Kaplan-Meier and Cox regression analyses. RESULTS AND LIMITATIONS: We found that in ccRCC, high interleukin (IL)-23 expression was significantly associated with poor survival in both TCGA (overall survival [OS] hazard ratio [HR]=2.04, cancer-specific survival [CSS] HR=2.95; all p<0.001) and Shanghai (OS HR=2.07, CSS HR=3.92; all p<0.001) cohorts. IL-23 blockade prolongs the survival of tumor-bearing mice, promotes T-cell cytotoxicity in in vitro cultures of human ccRCC tumors, and augments the therapeutic benefits of anti-PD-1 antibodies. Mechanistically, glutamine consumption by ccRCC tumor cells results in the local deprivation of extracellular glutamine, which induces IL-23 secretion by tumor-infiltrating macrophages via the activation of hypoxia-inducible factor 1α (HIF1α). IL-23 activates regulatory T-cell proliferation and promotes IL-10 and transforming growth factor ß expression, thereby suppressing tumor cell killing by cytotoxic lymphocytes. The positive correlations between glutamine metabolism, IL-23 levels, and Treg responses are confirmed in both TCGA cohort and tumors from Shanghai ccRCC patients. Study limitations include the unclear impacts of glutamine deprivation and IL-23 on other immune cells. CONCLUSIONS: Macrophage-secreted IL-23 enhanced Treg functions in glutamine-addicted tumors; thus, IL-23 is a promising target for immunotherapy in ccRCC. PATIENT SUMMARY: In this study, we analyzed the immune components in glutamine-addicted clear cell renal cell carcinoma (ccRCC) tumors from two patient cohorts and conducted both in vitro and in vivo studies. We found that ccRCC tumor cell-intrinsic glutamine metabolism orchestrates immune evasion via interleukin (IL)-23, and IL-23-high patients had significantly poorer survival than IL-23-low patients. IL-23 should thus be considered a therapeutic target in ccRCC, either alone or in combination with immune checkpoint inhibitors.

Tumor stroma-infiltrating mast cells predict prognosis and adjuvant chemotherapeutic benefits in patients with muscle invasive bladder cancer.

Which subgroups patients with muscle-invasive bladder cancer (MIBC) could benefit most from adjuvant chemotherapy (ACT) is blurred. Here we tried to stratify MIBC patients with tumor infiltrating mast cells (TIMs), explore the prognostic and predictive value of TIMs, and provide possible cellular explanations. We selected 259 MIBC patients who underwent radical cystectomy from two independent clinical centers between 2002 and 2014. TIMs were evaluated and prognostic and predictive value was assessed. The CIBERSORT method, Gene Set Enrichment Analysis (GSEA) and differential gene expression analyses were performed to explore the possible cellular mechanisms. TIMs infiltration was distinct between stromal and epithelial area of MIBC specimens. Patients with higher stromal TIMs had a significant worse overall survival and recurrence free survival (HR = 2.228, 95%CI: 1.467-3.550; P = 0.001 and HR = 1.984, 95%CI: 1.105-3.374; P = 0.016). More importantly, pT2 patients with low stromal TIMs tended to have a lower risk of death and recurrence after ACT (HR = 0.233, 95%CI: 0.020-0.814; P = 0.033 and HR = 0.180, 95%CI: 0.022-0.722; P = 0.031). A negative correlativity between TIMs and CD8 + T cells was identified on TCGA-BLCA cohort. Immunohistochemistry results validated that high stromal TIMs were negatively correlated with CD8 + T cells (Spearman's rho = -0.215, P < 0.001). Differential gene expression suggested that low TIMs might represent a state of immune activation in MIBC. To conclude, high stromal TIMs infiltration was an independent unfavorable prognosticator for MIBC patients. Patients with low stromal TIMs might benefit the most from ACT, especially in pT2 stage.

B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients.

BACKGROUND: The expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC). METHODS: There were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results. RESULTS: B4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression. CONCLUSIONS: Our evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.

Identification and Validation of Stromal Immunotype Predict Survival and Benefit from Adjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer.

Purpose: This study aims to construct the stromal immunotype, which could improve the prediction of postsurgical survival and adjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC).Experimental Design: A total of 118 patients with MIBC from Shanghai Cancer Center, 140 patients with MIBC from Zhongshan Hospital, and 287 patients with MIBC from TCGA cohort were included in the study. Immune cell infiltration was evaluated by IHC staining or CIBERSORT method. Five immune features were selected out of 22 immune features to construct immunotypes based on the LASSO Cox regression model.Results: Using the LASSO model, we classified patients with MIBC into stromal immunotype A subgroup (CTLhighNKhighTreglowMacrophagelowMClow) and stromal immunotype B subgroup (CTLlowNKlowTreghighMacrophagehighMChigh). Significant differences were found between immunotype A and immunotype B in the combined cohort with 5-year overall survival (OS, 76.0% vs. 44.0%; P < 0.001) and 5-year disease-free survival (DFS, 62.8% vs. 48.3%; P < 0.001). Stromal immunotype was revealed to be an independent prognostic indicator in multivariate analysis in all cohorts separately. Either OS or DFS was not improved by adjuvant chemotherapy (ACT) in pT2 stage patients or pT3+pT4 patients, but further analysis revealed that OS and disease-free was significantly improved by ACT in pT3+pT4 patients (P = 0.016 and P = 0.006, respectively). Finally, stromal immunotype A showed higher immune checkpoint molecules (PD-L1, PD-1, and CTLA-4) expression.Conclusions: The stromal immunotypes could effectively predict survival and recurrence of MIBC. Furthermore, the immunotypes might be a practical predictive tool to identify pT3+pT4 patients who would benefit from ACT. Clin Cancer Res; 24(13); 3069-78. ©2018 AACR.

Prognostic and Predictive Value of O6-methylguanine Methyltransferase for Chemotherapy in Patients with Muscle-Invasive Bladder Cancer.

PURPOSE: DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O6-methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown. MATERIALS AND METHODS: Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]. MGMT messenger RNA (mRNA) analysis was conducted using patients' clinical and fragments per kilobase of exon model per million mapped fragments mRNA data from The Cancer Genome Atlas (TCGA) database (n = 245). RESULTS: In our cohorts, high MGMT expression was significantly correlated with shorter overall survival (OS) in patients with platinum-based adjuvant chemotherapy [hazard ratio (HR) 2.386, p = 0.048; HR 2.920, p = 0.007; HR 2.324, p = 0.004, respectively, in FUSCC, ZS, and combination sets], but not in patients without chemotherapy. These findings were corroborated by the TCGA set (HR 1.952 and 0.697 for patients with and without chemotherapy, respectively). The chemotherapy-MGMT interaction for OS was significant in both the surgery set (p = 0.045) and TCGA set (p = 0.034). CONCLUSIONS: We demonstrated that high MGMT expression is an independent poor prognostic factor in MIBC patients with platinum-based adjuvant chemotherapy, but not in patients without chemotherapy. MGMT expression may be a potential predictor for administration of adjuvant chemotherapy.

High CXC chemokine receptor 1 level represents an independent negative prognosticator in non-metastatic clear-cell renal cell carcinoma patients.

CXC chemokine receptor 1 (CXCR1) signaling has been shown as an essential molecular nexus regarding cancer cell proliferation, tumor inflammation, and angiogenesis in clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the prognostic significance of CXCR1 in patients with non-metastatic ccRCC. Data from 446 consecutive non-metastatic ccRCC patients, operated between 2003 and 2008 at a single institution, were evaluated retrospectively. The cohort was split into a training set (n = 223) and a validation set (n = 223). CXCR1 expression was assessed by immunohistochemistry staining and its association with clinicopathologic features and prognosis were evaluated. High CXCR1 epithelial expression presented prognostic value, and indicated poor overall survival (OS) (P = 0.010 and P = 0.015, respectively) and recurrence-free survival (P = 0.011 and P = 0.019, respectively) in the training and validation sets. The incorporation of CXCR1 into the T stage and SSIGN score would help to refine individual risk stratification. Multivariate analysis identified increased epithelial CXCR1 was statistically significantly associated with a poor outcome for OS (HR [95% CI] 1.808 [1.184-2.761]; P = 0.006) and RFS (HR [95% CI] 1.570 [1.076-2.290]; P = 0.019) in all non-metastatic ccRCC patients. Predictive nomograms were generated with identified independent prognosticators to assess patient overall survival and recurrence-free survival at 3, 5 and 10 y. Furthermore, high CXCR1 expression were correlated with elevated infiltrated neutrophils and enriched MMP family gene expression. To conclude, high CXCR1 level within epithelial area represented a potential independent negative prognostic factor regarding OS and RFS in non-metastatic ccRCC patients after nephrectomy.

Prognostic value of granulocyte colony-stimulating factor in patients with non-metastatic clear cell renal cell carcinoma.

Granulocyte colony-stimulating factor is a well-known cytokine to stimulate inflammatory cells. We sought to investigate the prognostic value of its expression in patients with non-metastatic clear cell renal cell carcinoma. Enrolled in this study were 228 eligible patients treated with curative nephrectomy for clear cell renal cell carcinoma during 2008. Granulocyte colony-stimulating factor expression was detected by immunohistochemistry in patient specimens, and was divided into three groups according to the distribution of its immunohistochemistry score. Subgroup analyses were performed to evaluate its risk stratification ability. Cox regression models were applied to analyze the impact of prognostic factors. We found that high granulocyte colony-stimulating factor expression was associated with diminished recurrence-free survival (P<0.001). Its expression had stronger stratification ability in late disease patients, and was further identified as an independent prognosticator for recurrence-free survival. Moreover, nomogram based on granulocyte colony-stimulating factor expression presented a better prognostic ability compared with current prognostic systems (the concordance index = 0.874). To conclude, intratumoal granulocyte colony-stimulating factor expression could be a potential prognosticator for recurrence-free survival in non-metastatic clear cell renal cell carcinoma patients. Incorporating its expression into other pathologic factors provided a finer individual model for non-metastatic clear cell renal cell patients.

Galectin-9 as a prognostic and predictive biomarker in bladder urothelial carcinoma.

PURPOSE: Galectin-9, a member of the "tandem repeat" type galectins performing as animal lectins with an affinity for ß-galactosides, has been well documented to exert crucial functions in immunomodulation, survival, and growth of various tumors. This study aims to reveal the clinical significance of galectin-9 in urothelial carcinoma of the bladder (UCB) postoperatively. MATERIALS AND METHODS: We retrospectively included 202 patients with UCB who underwent radical cystectomy at a single institute from 2002 to 2014. Galectin-9 expression was assessed by immunohistochemistry on tissue microarrays. The Kaplan-Meier method was conducted to plot survival curves. Prognostic nomograms were constructed via integrating all the independent indicators from multivariate Cox analysis for recurrence-free survival (RFS) and cancer-specific survival (CSS). In addition, we evaluate whether patients with increased or decreased galectin-9 expression might benefit from adjuvant chemotherapy. RESULTS: Low galectin-9 expression was significantly correlated with lymphovascular invasion (P = 0.002), early recurrence (P = 0.010), and short CSS (P = 0.002). Furthermore, multivariate analysis identified galectin-9 expression as a potential independent indicator for RFS (hazard ratio = 0.62; 95% CI: 0.40-0.95; P = 0.030) and CSS (hazard ratio = 0.46; 95% CI: 0.26-0.81; P = 0.008). Moreover, the benefit associated with adjuvant chemotherapy was superior among galectin-9 low patients than among galectin-9 high patients (P = 0.014). CONCLUSIONS: Expression of galectin-9 is an independent prognostic factor for RFS and CSS in patients with UCB. Evaluation of galectin-9 expression may predict the benefit from adjuvant chemotherapy.

Tumor Infiltrating Mast Cells (TIMs) Confers a Marked Survival Advantage in Nonmetastatic Clear-Cell Renal Cell Carcinoma.

PURPOSE: The role played by the innate immune system in determining the clinical outcome of clear-cell renal cell carcinoma (ccRCC) was still blurred. This study was designed to investigate the prognostic significance of tumor infiltrating mast cells (TIMs) in ccRCC. METHODS: The study retrospectively enrolled a training set (474 patients) and a validation set (188 patients) with nonmetastasis (pT1-4N0M0) ccRCC from two institutional medical centers of China. TIMs was evaluated by immunohistochemical staining of tryptase and its association with clinicopathologic features and prognosis were evaluated. RESULTS: In ccRCC tissues, TIMs ranged from 0 to 103 cells/mm2 and 0 to 113 cells/mm2 in the training set and validation set, respectively. TIMs was negatively correlated with tumor size (P < 0.001 and P < 0.001, respectively), pathological T stage (P = 0.005 and P = 0.007, respectively) and Fuhrman grade (P < 0.001 and P < 0.001, respectively). Patients with abundant TIMs infiltration showed significantly longer cancer-specific survival in the training cohort and the validation cohort (P < 0.001 and P < 0.001). Patients with abundant mast cell infiltration showed significantly longer overall survival in the TCGA cohort (P < 0.001). Moreover, multivariate analysis identified TIMs as an independent prognostic factor for cancer-specific survival (CSS) and relapse-free survival (RFS). Also, TIMs was significantly correlated with CSS and RFS of the mediate and high-risk patients in the training cohort and the validation cohort. CONCLUSIONS: TIMs density is a powerful independent prognostic factor for CSS and RFS in patients with nonmetastasis (pT1-4N0M0) ccRCC.