Shilajit Kundu

Tumor size is associated with malignant potential in renal cell carcinoma cases.

PURPOSE We evaluated our experience with renal cortical tumors to determine whether tumor size is associated with malignant histology and/or nuclear grade. MATERIALS AND METHODS We identified 2,675 patients treated surgically at our institution for renal cell carcinoma or a benign tumor between 1989 and 2007. Histological subtype and tumor size were obtained from our kidney cancer database and logistic regression analysis was performed. RESULTS Of the 2,675 tumors 311 (12%) were benign and 2,364 (88%) were renal cell carcinoma. The OR for the association of malignancy with tumor size was 1.16 (95% CI 1.11-1.22, p <0.001), indicating that each 1 cm increase in tumor size was associated with a 16% increase in the odds of malignancy. The incidence of benign tumors decreased from 38% for tumors less than 1 cm to 7% for tumors 7 cm or greater. In patients with clear cell renal cell carcinoma each 1 cm increase in tumor size increased the odds of high grade disease (Fuhrman grade 3-4) compared with low grade disease (Fuhrman grade 1-2) by 25% (OR 1.25, 95% CI 1.21-1.30, p <0.001). In this subset the incidence of high grade lesions increased from 0% for tumors less than 1 cm to 59% for tumors greater than 7 cm. CONCLUSIONS Our results confirm previous observations suggesting that the risks of malignancy and high grade tumors increase with tumor size. Patients with small renal masses are at low risk for harboring a high grade clear cell malignancy, which may be useful during initial consultation.

Transforming growth factor-β in benign and malignant prostate

The present review summarizes the cellular action of TGF‐β in benign and malignant growth of the prostate.

Contemporary Use of Partial Nephrectomy at a Tertiary Care Center in the United States

PURPOSE The use of partial nephrectomy for renal cortical tumors appears unacceptably low in the United States according to population based data. We examined the use of partial nephrectomy at our tertiary care facility in the contemporary era. MATERIALS AND METHODS Using our prospectively maintained nephrectomy database we identified 1,533 patients who were treated for a sporadic and localized renal cortical tumor between 2000 and 2007. Patients with bilateral disease or solitary kidneys were excluded from study and elective operation required an estimated glomerular filtration rate of 45 ml per minute per 1.73 m(2) or greater. Predictors of partial nephrectomy were evaluated using logistic regression models. RESULTS Overall 854 (56%) and 679 patients (44%) were treated with partial and radical nephrectomy, respectively. In the 820 patients treated electively for a tumor 4 cm or less the frequency of partial nephrectomy steadily increased from 69% in 2000 to 89% in 2007. In the 365 patients treated electively for a 4 to 7 cm tumor the frequency of partial nephrectomy also steadily increased from 20% in 2000 to 60% in 2007. On multivariate analysis male gender (p = 0.025), later surgery year (p <0.001), younger patient age (p = 0.005), smaller tumor (p <0.001) and open surgery (p <0.001) were significant predictors of partial nephrectomy. American Society of Anesthesiologists score, race and body mass index were not significantly associated with treatment type. CONCLUSIONS The use of partial nephrectomy is increasing and it is now performed in approximately 90% of patients with T1a tumors at our institution. For reasons that remain unclear certain groups of patients are less likely to be treated with partial nephrectomy.

Metastatic Renal Cell Carcinoma Risk According to Tumor Size

PURPOSE Recent evidence suggests significantly discordant findings regarding tumor size and the metastasis risk in renal cell carcinoma cases. We present our experience with renal cell carcinoma. We evaluated the association between tumor size and the metastasis risk in a large patient cohort. MATERIALS AND METHODS Using our prospectively maintained nephrectomy database we identified 2,691 patients who were treated surgically for a sporadic renal cortical tumor between 1989 and 2008. Associations between tumor size and synchronous metastasis at presentation (M1 renal cell carcinoma) were evaluated with logistic regression models. Metastasis-free survival after surgery was estimated using the Kaplan-Meier method in 2,367 patients who did not present with M1 renal cell carcinoma and were followed postoperatively. RESULTS Of the 2,691 patients 162 presented with metastatic renal cell carcinoma. Only 1 of 781 patients with a tumor less than 3 cm had M1 renal cell carcinoma at presentation and tumor size was significantly associated with metastasis at presentation (for each 1 cm increase OR 1.25, p <0.001). Of the 2,367 patients who did not present with metastasis metastatic disease developed in 171 during a median 2.8-year followup. In this group only 1 of the 720 patients with renal cell carcinoma less than 3 cm showed de novo metastasis during followup. Metastasis-free survival was significantly associated with tumor size (for each 1 cm increase HR 1.24, p <0.001). CONCLUSIONS In our experience tumor size is significantly associated with synchronous and asynchronous metastases after nephrectomy. Our results suggest that the risk of metastatic disease is negligible in patients with tumors less than 3 cm.

Risk score and metastasectomy independently impact prognosis of patients with recurrent renal cell carcinoma.

PURPOSE We evaluated the prognostic roles of metastasectomy and an established risk stratification system in patients with disease recurrence following nephrectomy for nonmetastatic renal cell carcinoma. MATERIALS AND METHODS A retrospective analysis was performed in 129 patients with localized renal cell carcinoma treated with partial or radical nephrectomy and subsequently diagnosed with disease recurrence. At recurrence a previously validated risk score based on Karnofsky performance status, interval from nephrectomy, and serum hemoglobin, calcium and lactate dehydrogenase was used to categorize patients as being at favorable, intermediate or poor risk. Survival from time of recurrence was assessed based on risk categorization and metastasectomy. RESULTS Median time from nephrectomy to recurrence was 16 months. The risk score was strongly associated with median survival and the 2-year survival rate, including 73 months and 81% for favorable risk, 28 months and 54% for intermediate risk, and 6 months and 11% for poor risk, respectively (log rank <0.001). Metastasectomy performed in 44 patients (34%) was found to be of clinical benefit across the various risk categories (interaction analysis p = 0.8). On multivariate analysis a better risk category and metastasectomy were each independently associated with more favorable survival (each p <0.001). When combined, they provided 6 risk categories with an estimated 2-year survival of 0% to 93%. CONCLUSIONS The clinical course in patients with recurrent renal cell carcinoma following nephrectomy can be variable. It is independently impacted by an objectively determined risk score and whether the patient undergoes metastasectomy.

Blockade of transforming growth factor-β signaling in tumor-reactive CD8+ T cells activates the antitumor immune response cycle

Transforming growth factor-β (TGF-β) is a potent immunosuppressant. Overproduction of TGF-β by tumor cells leads to evasion of host immune surveillance and tumor progression. Results of our early studies showed that adoptive transfer of tumor-reactive, TGF-β-insensitive CD8+ T cells into immunocompetent mice was able to eradicate lung metastasis of mouse prostate cancer. The present study was conducted with three objectives. (a) We tested if this technology could be applied to the treatment of solid xenograft tumors in allogeneic immunodeficient hosts. (b) We determined relevant variables in the tumor microenvironment with the treatment. (c) We tested if immune cells other than CD8+ T cells were required for the antitumor effect. Mouse prostate cancer cells, TRAMP-C2 of the C57BL/6 strain, grown in immunodeficient allogeneic hosts of BALB/c strain, were used as a xenograft model. Tumor-reactive CD8+ T cells from C57BL/6 mice were isolated, expanded ex vivo, and rendered insensitive to TGF-β by introducing a dominant-negative TGF-β type II receptor vector. Seven days following s.c. injection of TRAMP-C2 cells (5 × 105) into the flank of male BALB/c-Rag1−/− mice, tumor-reactive, TGF-β-insensitive CD8+ T cells (1.5 × 107) were transferred with and without the cotransfer of an equal number of CD8-depleted splenocytes from C57BL/6 donors. Naive CD8+ T cells or green fluorescent protein-empty vector–transfected tumor-reactive CD8+ T cells were transferred as controls. Forty days following the transfer, the average tumor weight in animals that received cotransfer of tumor-reactive, TGF-β-insensitive CD8+ T cells and CD8-depleted splenocytes was at least 50% less than that in animals of all other groups (P < 0.05). Tumors in animals of the former group showed a massive infiltration of CD8+ T cells. This was associated with secretion of relevant cytokines, decreased tumor proliferation, reduced angiogenesis, and increased tumor apoptosis. Based on these results, we postulated a concept of antitumor immune response cycle in tumor immunology. [Mol Cancer Ther 2006;5(7):1733-43]

Contemporary imaging of patients with a renal mass: does size on computed tomography equal pathological size?

To evaluate the difference between radiographic size on computed tomography (CT) and the pathological size of renal tumours, in contemporary patients.

Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(1)‐TGF‐β type II dominant negative receptor

Prostatic epithelial cells are sensitive to the inhibitory effects of TGF‐β. However, TGF‐β signaling in the prostate is dependent on androgenic status. Under the in vivo conditions, it is difficult to dissociate the effect of TGF‐β from that of androgen on the prostate.

Impact of resident involvement on urological surgery outcomes: An analysis of 40,000 patients from the ACS NSQIP database

PURPOSE In addition to excellent patient care, the focus of academic medicine has traditionally been resident training. The changing landscape of health care has placed increased focus on objective outcomes. As a result, the surgical training process has come under scrutiny for its influence on patient care. We elucidated the effect of resident involvement on patient outcomes. MATERIALS AND METHODS We retrospectively analyzed data from the 2005 to 2011 NSQIP® participant use database. Patients were separated into 2 cohorts by resident participation vs no participation. The cohorts were compared based on preoperative comorbidities, demographic characteristics and intraoperative factors. Confounders were adjusted for by propensity score modification and complications were analyzed using perioperative variables as predictors. RESULTS A total of 40,001 patients met study inclusion criteria. Raw data analysis revealed that cases with resident participation had a higher rate of overall complications. However, after propensity score modification there was no significant difference in overall, medical or surgical complications in cases with resident participation. Resident participation was associated with decreased odds of overall complications (0.85). Operative time was significantly longer in cases with resident participation (159 vs 98 minutes). CONCLUSIONS Urology resident involvement is not associated with increased overall and surgical complications. It may even be protective when adjusted for appropriate factors such as case mix, complexity and operative time.

Urinary fistulae after partial nephrectomy

Study Type – Therapy (case series)
Level of Evidence 4