John A. Libertino

Long-term Results of Resection of Renal Cell Cancer with Extension into Inferior Vena Cava

From July 2, 1971 to April 1, 1985, 47 patients (median age 63 years) with renal cell cancer extending into the renal vein or inferior vena cava were evaluated and treated. Two-thirds of the tumors occurred in men and three-fourths were found in the right kidney. Of the 44 patients operated on 35 had no evidence of preoperative metastatic disease at operation. The patients were divided into ideal, favorable and unfavorable subgroups. The adjusted 5 and 10-year survival rates in the former 2 groups (32 patients) were 68.8 and 60.2 per cent, respectively. In contrast, 12 patients with nodal involvement or metastases had an adjusted median survival time of 1.2 years with no survival extending beyond 4.8 years. We believe that an extended operation for renal cell cancer with involvement of the vena cava is warranted and provides reasonable long-term survival in properly selected patients.

Total reconstruction of the vesico-urethral junction

We describe a novel technique of total vesico‐urethral reconstruction, which combines the tactics of previous surgeons, and compare the outcome of our innovative changes for return to early continence with prostatectomies with no or partial reconstruction of the vesico‐urethral junction.

Coronary Angiography and Acute Renal Failure in Diabetic Azotemic Nephropathy

Thirteen juvenile-onset diabetics with azotemic diabetic nephropathy (mean serum creatinine level, 6.8 mg/dl) being evaluated fro renal transplantation underwent cardiac catheterization with angiography. All were followed for development of acute renal failure. Twelve (92%) developed some evidence of acute renal failure. Two required potassium exchange resin therapy. Six required dialysis acutely. There were no deaths. All patients who received greater than 65 ml/m2 of iodinated contrast developed acute renal failure. No patient with a hemoglobin value greater than 9.9 g/dl required dialysis or potassium exchange resin. The single patients without acute renal failure received less than 50 ml/m2 of iodinated contrast and had the highest hemoglobin value (12.0 g/dl). No cardiac or angiographic variables were predictive of acute renal failure. In this group at high risk for acute renal failure, radiographic contrast procedures should only be done if the information to be obtained is weighed against the potential for injury.

Face, Content, and Construct Validity of dV-Trainer, a Novel Virtual Reality Simulator for Robotic Surgery

OBJECTIVES To assess the face, content, and construct validity of the dV-Trainer. The dV-Trainer is a virtual reality simulator for the da Vinci Surgical System that is in beta development. METHODS Medical students, residents, and attending surgeons were enrolled in a prospective, institutional review board-approved study. The subjects were prospectively categorized as novice or experienced. Each subject completed 2 EndoWrist modules and 2 needle-driving modules. The performance was recorded using a built-in scoring algorithm. Each subject completed a questionnaire after finishing the modules. RESULTS The novice group (n = 19) consisted of 3 students (16%), 11 residents (58%), and 5 attending surgeons (26%). The novices had operated an average of 1.3 +/- 2.2 hours at the da Vinci console before using the simulator. The experienced subjects (n = 7) had performed an average of 140 robotic cases (range 30-320). Experienced robotic surgeons outperformed novices in nearly all variables, including total score, total task time, total instrument motion, and number of instrument collisions (P < .01). All experienced surgeons ranked the simulator as useful for training and agreed with incorporating the simulator into a residency curriculum. The virtual reality and instrumentation achieved acceptability. The needle-driving modules did not exceed the acceptability threshold. CONCLUSIONS The results of the present study have shown that the dV-Trainer has face, content, and construct validity as a virtual reality simulator for the da Vinci Surgical System. The needle-driving modules need to be refined. Studies are underway to assess the concurrent and predictive criterion validity. The dV-Trainer could become a beneficial training simulator for robotic surgery.

Incomplete Renal Tumor Destruction Using Radio Frequency Interstitial Ablation

PURPOSE We evaluate the efficacy of temperature based radio frequency ablation as a potential treatment modality for small (less than 3.5 cm.) renal tumors. MATERIALS AND METHODS We treated 15 patients with a total of 20 tumors with radio frequency ablation through an open surgical approach immediately before partial nephrectomy. All tumors were biopsied before radio frequency ablation treatment. Tumors were heated to 90 to 110C for 6 to 16 minutes (mean 9.1). Tumor ablation was monitored by direct vision and ultrasound. Partial nephrectomy was performed in standard fashion. All specimens were stained with hematoxylin and eosin, and 5 specimens were stained for nicotinamide adenine dinucleotide (NADH) diaphorase activity. RESULTS Tumors ranged from 1.5 to 3.5 cm. (mean 2.4) in greatest dimension. All 20 specimens had evidence of morphologically unchanged tumor and normal renal parenchyma on standard hematoxylin and eosin staining. Of the 5 specimens 4 stained positively for NADH in areas confirmed to be tumor in hematoxylin and eosin stained neighboring sections. There was 1 intraoperative renal pelvic thermal injury requiring pyeloplasty and 2 postoperative caliceal leaks requiring stent placement. CONCLUSIONS In our series radio frequency therapy did not result in total tumor destruction when specimens were examined with hematoxylin and eosin or NADH staining. We believe that radio frequency interstitial tumor ablation of renal cell carcinoma without subsequent tissue resection should continue to be an investigational treatment modality for those who would otherwise undergo partial or radical nephrectomy.

Radical nephrectomy in patients with renal cell carcinoma with venous, vena caval, and atrial extension

BACKGROUND From July 31, 1968, through August 31, 1992, 100 patients with renal cell carcinoma extending into the renal vein, vena cava, and right atrium were treated and evaluated at our institution. Each patient underwent radical nephrectomy with vena cavotomy and atriotomy as considered to be appropriate for each individual patients tumor thrombus. METHODS The charts were retrospectively analyzed, and surveys were sent to survivors or nearest of kin. RESULTS The median age was 61 years, and two thirds of the tumors occurred in men (67 cases). Of the 100 patients with renal cell carcinoma resected, 13 patients (13%) had atrial extension; 75 patients (75%) had vena caval extension; and 12 patients (12%) had extension only into the renal vein. Seventy-two patients (72%) had no evidence of metastatic disease at the time of surgery and have a median survival of 21.1 years. Five-year survival is 64%, and 10-year survival is 57%. Twenty-eight patients (28%) had evidence of metastatic intraoperative and/or pathologically proven metastatic disease and have a median survival of 2.5 years with a 5-year survival of 20% and no patient living beyond 7.8 years. CONCLUSION We believe that an extended operation for renal cell cancer with involvement of the renal vein, vena cava, and right atrium is warranted in properly selected patients and ensures reasonable long-term survival.

Prognostic Impact of the 2009 UICC/AJCC TNM Staging System for Renal Cell Carcinoma with Venous Extension

BACKGROUND The prognostic significance of venous involvement and tumour thrombus level in renal cell carcinoma (RCC) remains highly controversial. In 2010, the American Joint Committee on Cancer (AJCC) and the Union International Centre le Cancer (UICC) revised the RCC staging system (7th edition) based on tumour thrombus level, differentiating the T stage of tumours limited to renal-vein-only involvement. OBJECTIVE We aimed to evaluate the impact of tumour thrombus extension in a multi-institutional cohort of patients. DESIGN, SETTING, AND PARTICIPANTS An international consortium of 11 institutions was established to retrospectively review a combined cohort of 1215 patients undergoing radical nephrectomy and tumour thrombectomy for RCC, including 585 patients with inferior vena cava (IVC) involvement or higher. MEASUREMENTS Predictive factors of survival, including histology, tumour thrombus level, nodal status, Fuhrman grade, and tumour size, were analysed. RESULTS AND LIMITATIONS A total of 1122 patients with complete data were reviewed. The median follow-up for all patients was 24.7 mo, with a median survival of 33.8 mo. The 5-yr survival was 43.2% (renal vein involvement), 37% (IVC below the diaphragm), and 22% with caval involvement above the diaphragm. On multivariate analysis, tumour size (hazard ratio [HR]: 1.64 [range: 1.03-2.59]; p=0.036), Fuhrman grade (HR: 2.26 [range: 1.65-3.1]; p=0.000), nodal metastasis (HR: 1.32 [range: 1.09-1.67]; p=0.005), and tumour thrombus level (HR: 2.10 [range: 1.53-3.0]; p=0.00) correlated independently with survival. CONCLUSIONS Based on analysis of the largest known cohort of patients with RCC along with IVC and atrial thrombus involvement, tumour thrombus level is an independent predictor of survival. Our findings support the changes to the latest AJCC/UICC staging system.

Identification and Prognostic Significance of an Epithelial-Mesenchymal Transition Expression Profile in Human Bladder Tumors

Purpose: Epithelial to mesenchymal transition (EMT) is reportedly an important transition in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. In this study, we examined the expression pattern of EMT markers in vivo and determined the occurrence and clinical significance of these events in a series of bladder carcinomas. Experimental Design: Eight hundred and twenty-five tumor samples from 572 bladder cancer patients were assembled in 10 tissue microarrays. Paraffin sections from each tissue microarray were subjected to antigen retrieval and processed by immunohistochemistry for the expression of E-cadherin, plakoglobin, β-catenin, N-cadherin, and vimentin. Results: Pathologic expression of E-cadherin, β-catenin, plakoglobin, and vimentin were associated with the clinicopathologic variables of grade and stage with only the cytoplasmic localization of plakoglobin found associated with lymph node status. Associations between the aforementioned markers were found significant as determined by the Spearman correlation coefficient with N-cadherin showing no associations in this analysis. In univariate survival analysis involving patients who underwent cystectomy, the reduction or loss of plakoglobin significantly influenced overall survival (P = 0.02) in which the median time to death was 2 years compared with 4 years when a normal level of plakoglobin was recorded. When the analysis was done for cancer-specific survival, low levels of both plakoglobin (P = 0.02) and β-catenin (P = 0.02) significantly influenced survival. Conclusion: The putative markers of EMT defined within a panel of bladder carcinoma cell lines were recorded in vivo, frequently associated with tumors of high grade and stage. Although multivariate analysis showed no significant influence of the EMT biomarkers on survival, alterations associated with plakoglobin were identified as significant prognostic features in these tumors.

Radioimmunoscintigraphy with 111Indium Labeled Cyt-356 for the Detection of Occult Prostate Cancer Recurrence

We assessed the safety and ability of the 111indium labeled immunoconjugate 7E11-C5.3-glycyl-tyrosyl-(N,e-diethylenetriaminepentaacetic acid)-lysine (CYT-356) to detect sites of occult prostate cancer in 27 subjects who had undergone radical prostatectomy and whose only evidence of recurrent disease was an increasing (0.8 ng./ml. or greater) serum prostate specific antigen (PSA). All subjects underwent whole body scintigraphy between 2 and 4 days following the radiopharmaceutical injection. Routine blood work and human anti-mouse antibody titers were monitored. Scintigraphic findings were compared with clinical parameters, prostatic fossa biopsy results and conventional imaging techniques. Except for transient hypotension in 1 subject following the second infusion, no side effects or human anti-mouse antibody titers were detected. In 22 subjects 1 or more lesions were detected, of which 11 (50%) were confirmed by biopsy, computerized tomography or magnetic resonance imaging. Of 14 subjects with lesions in the prostatic fossa 13 had biopsies performed, 8 (62%) of which were positive. Magnetic resonance imaging confirmed tumor in the spine and chest computerized tomography findings were compatible with lesions seen in the mediastinum in 1 subject each. There was a statistically significant relationship between detecting a scan abnormality and the initial pathological stage of disease but not with the serum PSA. These data provide preliminary evidence that 111indium labeled CYT-356 can be safely administered and readministered, and it detects sites of occult prostate cancer recurrence in subjects whose PSA is increasing following radical prostatectomy.

Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.

OBJECTIVES No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. METHODS The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. RESULTS Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. CONCLUSIONS Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.