Shi Lin Zhang

Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy.

miR‐21 has been recognized as an “onco‐microRNA” with the activity of negatively modulating the expression of tumor‐suppressor genes. However, its role in prostate cancer (CaP) has not been well‐documented. We designed this study to assess the potential function of serum miR‐21 in the progression of CaP.

Predicting Pelvic Lymph Node Metastases in Penile Cancer Patients: A Comparison of Computed Tomography, Cloquet’s Node, and Disease Burden of Inguinal Lymph Nodes

Background: The aim of this study was to evaluate the role of computed tomography (CT), Cloquet’s node, and disease burden of inguinal lymph nodes (LNs) in predicting pelvic lymph node metastases (LNM) of penile cancer. Patients and Methods: Bilateral inguinal lymph node dissection was performed in 73 penile cancer patients and revealed that 33 groin basins exhibited inguinal LNM. Results: Of the 33 groin basins, 16 (48.5%) had pelvic LNM. The sensitivity of pelvic CT in detecting metastatic LNs was 37.5%, and the specificity was 100%. Cloquet’s node had a sensitivity of 30.0% and a specificity of 94.1% in pelvic CT-negative groin basins. Pathological characteristics of the inguinal LNs - number of positive LNs, lymph node ratio (number of positive LNs/total number removed), extranodal extension and the expression of p53 - were significantly associated with pelvic LNM. Furthermore, enlarged inguinal LNs = 3 in preoperative CT imaging and lymph node size = 3.5 cm in long diameter were prognostic factors for pelvic LNM (p = 0.001 and 0.003, respectively). Conclusion: Pelvic CT imaging and tumor status of Cloquet’s node is of limited use in predicting microscopic pelvic LNM. Pathological characteristics of the inguinal LNs remain the essential indicators of pelvic LNM.

External validation of a nomogram using RENAL nephrometry score to predict high grade renal cell carcinoma.

PURPOSE A novel nomogram using the RENAL ([R]adius maximal diameter in cm, [E]xophytic/endophytic properties, [N]earness of the tumor to the collecting system or sinus in mm, [A]nterior/Posterior, [L]ocation relative to the polar lines and [H]ilar) nephrometry score was developed to predict high grade renal cell carcinoma. It showed good performance in internal evaluation. We externally validated the prediction model. MATERIALS AND METHODS We identified a cohort of 391 Chinese patients in whom renal cell carcinoma was surgically resected at our institution from 2008 to 2011. Fuhrman grade was reviewed by an experienced genitourinary pathologist and radiological images were independently assessed by 2 senior urologists. Using a 2-tiered system high grade disease was defined as Fuhrman grade III/IV. The statistical performance of the prediction model was evaluated by discrimination, calibration and clinical usefulness. RESULTS Of the 391 patients 45.5% were considered to have high grade tumors. External validation of the nomogram revealed an AUC of 0.73. The calibration plot showed that the predicted probability of high grade disease had concordance comparable to the observed frequency. On decision curve analysis the prediction model provided a superior net benefit and reduction at a greater than 20% probability threshold. CONCLUSIONS We confirm the predictive value of the nomogram using the RENAL nephrometry score to identify high grade renal cell carcinoma in an independent cohort. Further research is required to evaluate its performance using a head-to-head comparison with renal biopsy results.

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

The skeleton is the most common metastatic organ in patients with prostate cancer (PCa). Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia (BPH), 20 with localized PCa and 30 with bone-metastatic PCa (10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa). A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis (P<0.001). There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendalls bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels (P=0.012 and P<0.001, respectively). The serum miR-141 level was found to be positively correlated with alkaline phosphatase (ALP) level in patients with skeletal metastasis, using Pearsons bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen (PSA) level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.

Visceral Obesity and Risk of High Grade Disease in Clinical T1a Renal Cell Carcinoma

PURPOSE Accurate assessment of disease characteristics is a prerequisite for treatment decision making regarding small renal masses. In this study we evaluate the association between visceral obesity and Fuhrman grade in patients with cT1a renal cell carcinoma. MATERIALS AND METHODS We retrospectively collected data on 186 patients with surgically treated cT1a renal cell carcinoma. Single slice computerized tomography was used to measure the area of visceral and subcutaneous adipose tissue. Visceral obesity was calculated as the proportion of visceral adipose tissue to overall adipose tissue. Other analyzed factors included clinical characteristics (age, gender, body mass index and tumor size) and anatomical features of the tumor defined by the R.E.N.A.L. nephrometry score. The association between predictors and high grade disease (Fuhrman grade III or IV) were assessed using logistic regression analyses. RESULTS A total of 47 (25.3%) tumors were classified as high grade. The percentage of visceral adipose tissue was higher in male participants but did not correlate with body mass index, age or tumor size. In univariate analyses the percentage of visceral adipose tissue and tumor size were significantly associated with higher Fuhrman grade. Multivariate analysis showed that the percentage of visceral adipose tissue (OR 1.06, p = 0.0018) and tumor size (OR 1.91, p = 0.047) were independent predictors of high grade cancer. Addition of the percentage of visceral adipose tissue to a model including clinical characteristics and anatomical features of the tumor remarkably improved its discriminatory ability (p = 0.0010). CONCLUSIONS Increased visceral obesity was found to be strongly associated with higher Fuhrman grade in patients with cT1a renal cell carcinoma. Further studies are needed to confirm these findings and discover the underlying biological mechanism.

Tumor cytoreduction results in better response to androgen ablation-a preliminary report of palliative transurethral resection of the prostate in metastatic hormone sensitive prostate cancer

OBJECTIVES To investigate the oncologic influence of transurethral resection of the prostate (TURP) as a cytoreductive surgery in metastatic hormone sensitive prostate cancer (mHSPC), in the setting of continuous complete androgen blockade (CAB). MATERIALS AND METHODS Medical histories of 146 consecutive Chinese males with newly diagnosed mHSPC, registered in our institution in 2006 and 2007, were reviewed. All of these patients received CAB as initial systematic therapy. Demographics and cancer control outcomes from 39 mHSPC patients who underwent TURP for a relief of bladder outlet obstruction were compared with those of the other 107 who received CAB only when they were still hormone-sensitive. Median follow-up was 15 months (3 to 27 months). RESULTS Age at diagnosis, baseline PSA, and biopsy Gleason score were comparable between the 2 groups. Patients who underwent a TURP had lower PSA nadir (median 0.15 ng/ml vs. 0.82 ng/ml, P = 0.015) and longer time to PSA nadir (11.2 months vs. 6.4 months, P < 0.001). More patients in the non-TURP group developed hormone refractory prostate cancer (P = 0.007). The TURP group had a tendency towards longer disease-specific survival and overall survival (24.4 months vs. 24.1 months and 24.4 months vs. 22.9 months, respectively), though this did not reach statistical significance. CONCLUSIONS TURP resulted in a better and more prolonged response to hormone therapy in mHSPC, with a trend towards positive influence in disease specific survival and overall survival. To date, our preliminary report is the first study regarding long-term survival of cytoreductive surgery in mHSPC, and further investigations are warranted.

Development and Evaluation of a Nomogram to Predict Inguinal Lymph Node Metastasis in Patients With Penile Cancer and Clinically Negative Lymph Nodes

PURPOSE Optimal management for penile cancer in patients with clinically negative lymph nodes is still under debate. We developed and evaluated a nomogram to stratify patients who are suitable candidates for further treatment. MATERIALS AND METHODS This study included 110 men with penile cancer and clinically negative lymph nodes from 1990 to 2008. All patients underwent primary tumor resection and regional lymphadenectomy. We retrospectively reviewed medical records and tumor slides. Statistical analysis was done in R with library rms. RESULTS The lymph node metastasis rate in the entire cohort was 23.6%. The final model, presented as a nomogram, included T stage, grade, lymphovascular invasion and p53 expression. Only lymphovascular invasion showed independent prognostic value on multivariate analysis (p = 0.024). The model also showed good calibration (bootstrap corrected concordance index 0.79). To determine the clinical usefulness of the nomogram we compared it with the European Association of Urology risk classification using decision curve analysis. At a 10% probability threshold our nomogram led to 1 positive result per 100 patients without an increase in the number of false-positive results. At this probability threshold the model also decreased 13 unnecessary interventions per 100 patients without missing more metastatic disease. CONCLUSIONS We generated a nomogram in patients with clinically node negative penile cancer based on readily available pathological factors. The clinical usefulness of the nomogram was evidenced by decision curve analysis.

Organ-sparing surgery for penile cancer: Complications and outcomes

OBJECTIVE To evaluate the complications and outcomes of organ-sparing surgery in penile cancer. METHODS Thirty-two penile cancer patients had undergone organ-sparing surgery between 2006 and 2010 in Fudan University Shanghai Cancer Center. Applied surgical techniques included radical circumcision and/or wide local excision. Intraoperative frozen section analyses of circumference and deep margins were performed to guarantee complete removal of cancerous tissue. Complications and oncological and functional outcomes were recorded prospectively. Bilateral inguinal lymphadenectomy was routinely performed in patients with invasive penile cancer. RESULTS Of 32 patients, 8 underwent radical circumcision, 18 were treated with wide local excision, and 6 received wide local excision and circumcision. Postoperatively, only 3 (9.4%) patients had minor complications. With a median follow-up of 26.5 months, local control was achieved in 29 (90.6%) patients, and 3 patients (9.4%) with positive lymph nodes died of disseminated disease. Of 29 patients who completed follow-up surveys of functional outcome, only 1 (4.5%) claimed decreased sexual function and all reported satisfied urination. CONCLUSION Organ-sparing surgery, such as radical circumcision and wide local excision is an appropriate treatment option for selected penile cancer patients. It preserves sexual and urination function without significantly increasing the risk of recurrence.

New N Staging System of Penile Cancer Provides a Better Reflection of Prognosis

PURPOSE We determined whether the new N staging system, which was introduced in 2009, leads to more specific prediction of survival in patients with penile squamous cell carcinoma. MATERIALS AND METHODS We analyzed the records of 60 patients in whom node positive penile cancer was surgically resected from 1990 to 2008. All cases were staged according the 6th and 7th N staging system after pathological review. Histopathological information on the number of positive lymph nodes, lymph node metastasis laterality, extranodal extension, pelvic lymph node metastasis and lymph node ratio were also recorded. We evaluated the added information on these nodal related prognostic factors to the current N classification. Recurrence-free survival was calculated. Predictive accuracy was assessed by the concordance index. RESULTS Disease recurred in 27 of the 60 patients (42.4%) at a median of 10 months. In the 33 patients without recurrence at the last visit median followup was 53 months. Using the 6th N classification the 3-year recurrence-free survival rate was 69.8%, 48.2% and 33.3% for the N1, N2 and N3 categories, respectively. Log rank survival analysis failed to show a statistical difference (p=0.054). For the new 7th N categories the 3-year recurrence-free survival rate was 87.5%, 57% and 31.8% in the corresponding N1 to N3 groups. Better survival stratification was observed on analysis (p<0.001). Adding lymph node metastasis laterality or lymph node ratio significantly increased the accuracy of the 7th N category to predict recurrence-free survival. CONCLUSIONS The new N staging system better reflects the prognosis in patients with penile cancer.

Low pretreatment serum total testosterone is associated with a high incidence of Gleason score 8 - 10 disease in prostatectomy specimens: Data from ethnic Chinese patients with localized prostate cancer

Study Type – Prognosis (prospective cohort)