Evaluation Of Renal Cell Carcinoma Research Articles

The lack of correlation between mast cells and microvessel density with pathologic feature of renal cell carcinoma

The growth of solid tumors requires angiogenesis. Evidence indicates that mast cells (MCs) play an important role in tumor angiogenesis but results are not definitive. The aim of this study is to investigate the possible effects of angiogenesis and the presence of MCs on the prognosis of renal cell carcinoma (RCC). The study involved 40 patients with RCC (24 men and 16 women who were treated with radical nephrectomy between 1995 and 2006, at our institution. The routine mast cell tryptase staining method was used to assess the MCs in both normal tissue and tumoral tissue. The immunohistochemical staining for CD34 antigen was used for determination of microvessel density. The relation between MC count and tumor status such as tumor stage, size, grade, and other clinicopathologic parameters in RCC were evaluated in this study. We found no relationship between the number of MCs and patient age, sex, tumor stage, grade, size. No association was noted between angiogenesis and either patient sex or age, tumor size, stage, and grade. No statistically significant correlation was found between the number of MCs and microvessel density in RCC (P-value = 0.45) but the max value of MCs and MVD were in clear cell carcinoma. The MC count was not associated with tumor status such as tumor stage, size, grade, and other clinicopathologic parameters, however, MCs may be related to tumor angiogenesis and acceleration of tumor growth in RCC and therefore need further evaluation in RCC.

11C-Acetate PET imaging for renal cell carcinoma

In this study, we investigated the effectiveness of positron emission tomography (PET) with (11)C-acetate (AC) for evaluation of renal cell carcinoma. Enrolled in the study were 20 patients with suspected renal tumour, one of whom had three renal lesions. In all, 22 renal lesions were evaluated. Following administration of 350 MBq (10 mCi) of AC, whole-body PET images were obtained. Based on these PET findings, kidney lesions were scored as positive or negative. The PET results were correlated with the CT findings and histological diagnosis after surgery. In 18 patients, 20 tumours were diagnosed as renal cell carcinoma. Lesions in the remaining two patients were diagnosed as complicated cyst without malignant tissue. Of the 20 renal cell carcinomas. 14 (70%) showed positive AC PET findings; 6 were negative. The two patients with complicated cyst had negative AC PET findings. Of the 20 renal cell carcinomas, 19 were clear-cell carcinoma and 1 was a papillary cell carcinoma. This papillary cell carcinoma showed high AC uptake. AC demonstrates marked uptake in renal cell carcinoma. These preliminary data show that AC is a possible PET tracer for detection of renal cancer.

Renal Cell Carcinoma: Diagnosis, Staging, and Surveillance

This educational review focuses on the staging and radiologic evaluation of renal cell carcinoma. It includes discussion of the epidemiology, pathology, and therapeutic options of renal cell carcinoma and the implications for radiologic follow-up. The incidence of renal cell carcinoma has been increasing. Imaging plays a central role in its detection, staging, and treatment evaluation and follow-up.

Microvascular Tumor Invasion, Tumor Size and Fuhrman Grade: A Pathological Triad for Prognostic Evaluation of Renal Cell Carcinoma

The biological behavior and clinical outcome of renal cell carcinoma are difficult to predict. We investigated the prognostic impact of clinicopathological variables to establish a risk stratification model to predict recurrence and survival rates. We studied 230 patients with renal cell carcinoma (stages T(1-4) N(x) M(0)) who underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 48 months (range 3 to 140). Univariate and multivariate analyses were performed, and the influence of clinical presentation, histological tumor size, tumor grade, lymph node involvement and microvascular tumor invasion on disease-free and cancer specific survival curves was determined. A composition model based on independent prognostic variables was then created to stratify tumors into low, intermediate and high risk of progression. The tumor recurrence rate was 17% (39 of 230) and the cancer specific mortality rate was 13% (31 of 230). Multivariate analyses determined that microvascular tumor invasion, tumor grade and tumor size were the only independent prognostic factors. Disease-free survival rates for low, intermediate and high risk tumors were 94.7%, 56.8% and 13.1%, respectively. Cancer specific survival rates were 94.7%, 61.7% and 32.0%, respectively. Tumor size, Fuhrman grade and microvascular tumor invasion are strong and independent predictors of survival of patients with renal cell carcinoma. Risk assessment and stratification based on this triad of pathological features may allow better individualization of followup schedules and trials of adjuvant treatment for patients with renal cell carcinoma.

Pharmacokinetic/pharmacodynamic (PK/PD) modeling and trial simulations to guide dose selection with CNTO 328, a chimeric anti-IL-6 monoclonal antibody (MAb), in patients with renal cell carcinoma (RCC)

2608 Background: PK/PD modeling and trial simulation were employed to guide dose selection for a Phase I/II clinical study with CNTO 328 in patients with RCC. Methods: Modeling and simulations were conducted using WinNonlin and Trial Simulator software. The PK model was developed using published data from patients with advanced multiple myeloma (van Zaanen, 1996). It was further refined following the availability of single dose PK data from the current study in RCC. The PK properties of CNTO 328 after IV infusion were best described using a two-compartment model. A PK/PD inhibitory effect of sigmoidal Emax model was developed for characterization of the relationship between serum CNTO 328 concentration and the concentration of the biomarker, C-reactive protein (CRP). Trial simulations were performed to guide the selection of a multiple dosing regimen for further clinical evaluation in RCC. Results: The PK/PD modeling and simulations predicted that 3 and 6 mg/kg of CNTO 328 administered at weeks 0, 3, 6, and 9 would suppress the CRP values to below 4 μg/mL (lower limit of quantification) for approximately 9 and 14 weeks, respectively. Conclusions: This PK/PD modeling and trial simulation approach has been used to rationally select an optimal dosing regimen for CNTO 328 to expedite the further clinical evaluation of this agent in the treatment of RCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor Centocor Centocor

Pharmacokinetic/pharmacodynamic (PK/PD) modeling and trial simulations to guide dose selection with CNTO 328, a chimeric anti-IL-6 monoclonal antibody (MAb), in patients with renal cell carcinoma (RCC)

2608 Background: PK/PD modeling and trial simulation were employed to guide dose selection for a Phase I/II clinical study with CNTO 328 in patients with RCC. Methods: Modeling and simulations were conducted using WinNonlin and Trial Simulator software. The PK model was developed using published data from patients with advanced multiple myeloma (van Zaanen, 1996). It was further refined following the availability of single dose PK data from the current study in RCC. The PK properties of CNTO 328 after IV infusion were best described using a two-compartment model. A PK/PD inhibitory effect of sigmoidal Emax model was developed for characterization of the relationship between serum CNTO 328 concentration and the concentration of the biomarker, C-reactive protein (CRP). Trial simulations were performed to guide the selection of a multiple dosing regimen for further clinical evaluation in RCC. Results: The PK/PD modeling and simulations predicted that 3 and 6 mg/kg of CNTO 328 administered at weeks 0, 3, 6, and 9 would suppress the CRP values to below 4 μg/mL (lower limit of quantification) for approximately 9 and 14 weeks, respectively. Conclusions: This PK/PD modeling and trial simulation approach has been used to rationally select an optimal dosing regimen for CNTO 328 to expedite the further clinical evaluation of this agent in the treatment of RCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor Centocor Centocor

Uropathology

The close interaction between the pathologist and the urologist is essential for accurate pathological diagnosis of several urological cancers. The adoption of the new grading system in transitional cell carcinoma (TCC) of the bladder introduced by the World Health Organisation in 1998/1999, will improve the accuracy of pathological diagnosis of this cancer beyond the 61% already reported. Frozen section biopsy during cystectomy can be advocated in certain cases for urethral margin and lymph node biopsies, but not for ureteric margin biopsy. With regard to prostate cancer, this article describes in detail the careful steps required in the taking and handling of biopsy samples in order to maximise the histopathological diagnosis. These include a practice that has been advocated for some time—the separating of individual biopsy cores. Testicular cancer is discussed from the point of view of preserving the function of the testes, particularly with regard to intra-testicular and incidentally identified masses. Finally, partial nephrectomy for renal cell carcinoma (RCC) is discussed. Data suggest that multifocality is the main cause of local recurrence with this procedure. Consequently, preoperative and intraoperative evaluation in RCC are mandatory in order to identify multifocality.

375. Immunohistochemical Evaluation of Renal Cell Carcinoma Treated with GM-CSF-Gene Transduced Lethally Irradiate Autologous Tumor Cell Vaccine (GVAX)

375. Immunohistochemical Evaluation of Renal Cell Carcinoma Treated with GM-CSF-Gene Transduced Lethally Irradiate Autologous Tumor Cell Vaccine (GVAX)

Preoperative radiologic evaluation of tumors of the renal parenchyma

Renal cell carcinoma is frequently a matter of urological interest. In recent years there were significant improvements regarding the earlier diagnosis, more precise preoperative staging and appropriate therapy. One hundred patients (42-78 years old) with the preoperative diagnosis of renal cell carcinoma were analyzed. Preoperative radiological evaluation included: transabdominal ultrasound, intravenous urography, computer-assisted tomography, and angiography. In all patients after radical nephrectomy pathohistological diagnosis was established and patients with the confirmed renal cell carcinoma tumour staging was performed. All histological findings were compared with the preoperative results of radiological examinations. Reliability of all of them is separately determined. Our results confirmed that the most efficient method of preoperative staging was computer-assisted tomography (accuracy 93%). Diagnostic methods that were previously used like intravenous urography and angiography, were not useful for routine diagnostic purposes. Ultrasound is a precise but not an enough informative diagnostic tool (accuracy 87%). Combine used of both ultrasound and contrast computer-assisted tomography is cost-effective, and an enough precise combination for everyday use.

Color Duplex Sonography vs. Computed Tomography: Accuracy in the Preoperative Evaluation of Renal Cell Carcinoma

Purpose: Accurate imaging is essential for correct operative planning and successful surgical intervention in renal cell carcinoma (RCC). Our objective was the comparison of color duplex sonography with spiral computed tomography (CT) and surgical–pathological findings in the evaluation of renal masses to determine tumor localization, size, tumor thrombus extent and lymph node metastases. Methods: We evaluated 60 patients with a renal mass in a prospective study. Both color duplex sonography and CT were performed by different investigators without knowledge of the supposed diagnosis. The color Doppler findings were compared to CT and surgical pathological findings. Results: The sensitivity of color duplex sonography in the detection of RCC and lymph node metastases is comparable to that of CT (100%). Color duplex sonography was superior in the detection of renal vein involvement. Color duplex sonography alone allowed correct planning of the surgical procedure without intraoperative changes in all patients. Conclusion: Duplex sonography provides exactly the same information as CT. Although duplex sonography is less expensive with lower exposure to radiation, most surgeons will still probably demand CT for diagnosis, especially as this method is unerring and duplex sonography highly depends on the expertise of the person using it.

Evaluation of Renal Cell Carcinoma detected by Ultrasonographic Examination in Human Dry Dock.

Evaluation of Renal Cell Carcinoma detected by Ultrasonographic Examination in Human Dry Dock.

Conference summary

This meeting was the first international multidisciplinary workshop on renal cell carcinoma held by the World Health Organization in collaboration with the Union Internationale Contre le Cancer (UICC), American Joint Committee on Cancer (AJCC), Mayo Clinic and Mayo Foundation, the Pacific Northwest Cancer Foundation, and other sponsoring groups. Its purpose was, in large measure, met successfully, as a result of the efforts of the distinguished faculty. We are especially grateful for the support this workshop received from the various foundation sources. Significant progress was documented for all aspects of the diagnosis and prediction of the outcome of renal cell carcinoma, but many issues remain unresolved. All workgroup reports were discussed and modified to some extent at the general session to reflect the collective understanding and concerns in each area. International agreement was reached on the histologic classification of renal cortical epithelial neoplasms. Papillary adenoma Renal oncocytoma Metanephric adenoma and adenofibroma Conventional (clear cell) renal carcinoma Papillary renal carcinoma Chromophobe renal carcinoma Collecting duct carcinoma Renal cell carcinoma, unclassified Information that is essential to patient management is contained in the report on grading. Nuclear grading is preferred, but the optimal system has not been described or tested. Grading remains subjective, but new methods, including computer-based morphometric studies, may improve objectivity. The current staging system for renal cell carcinoma has evolved and merits attention for future change. The AJCC and the UICC have published new manuals for staging in 1997, and those standards are reported herein. Issues of specimen handling by the pathologist are also discussed. Current prognostic factors for use in the evaluation of renal cell carcinoma are reviewed and prioritized on the basis of current available information. This consensus provides a basis for adoption. Use and testing in the clinic and in randomized trials are at three levels: prior to treatment, after nephrectomy, and in the presence of recurrent or metastatic cancer. There are numerous new and pending prognostic factors that merit serious consideration and examination. Such efforts should be supported for further investigation. In this report, future prognostic factors are critically evaluated, with emphasis on their practical relevance to renal cell carcinoma. This group addressed data regarding priorities for renal cell carcinoma funding, placing emphasis on clinical trials. Chemoprevention was noted to be an area of endeavor that merits attention, as does immunotherapy, gene therapy, and vaccine therapy. Molecular biology is providing a multitude of new targets for intervention, and these should be exploited in future studies. This report was meant to provide references as standards for timely and future assessments.

The Role of Gamma-Glutamyl Transpeptidase in the Preoperative Metastatic Evaluation of Renal Cell Carcinoma

The Role of Gamma-Glutamyl Transpeptidase in the Preoperative Metastatic Evaluation of Renal Cell Carcinoma

The Role of Gamma-Glutamyl Transpeptidase in the Preoperative Metastatic Evaluation of Renal Cell Carcinoma

We evaluated gamma-glutamyl transpeptidase as an indicator of metastatic disease in patients with renal cell carcinoma. We reviewed the records of 53 patients with metastatic renal cell carcinoma, and compared serum alkaline phosphatase and gamma-glutamyl transpeptidase with the site of metastases. These results were then compared to those in 29 patients with clinically localized renal cell carcinoma. Overall gamma-glutamyl transpeptidase was elevated in 37 patients (69.8%) with metastatic disease, while alkaline phosphatase was elevated in 16 (30.2%, p < 0.025). Gamma-glutamyl transpeptidase was increased in more patients with hepatic metastases only than alkaline phosphatase (p < 0.025) and in all groups it was a better predictor of metastases than alkaline phosphatase. Gamma-glutamyl transpeptidase was also increased in significantly more patients with metastatic renal cell carcinoma (37 of 53) compared to 1 of the 27 with localized renal cell carcinoma (p < 0.001). Gamma-glutamyl transpeptidase was increased in a large percent of patients with metastatic renal cell carcinoma, and it was normal in the majority with localized renal cell carcinoma. We conclude that gamma-glutamyl transpeptidase should be included as well as alkaline phosphatase in the preoperative metastatic evaluation of patients with renal cell carcinoma. Elevated gamma-glutamyl transpeptidase should prompt a search for bone as well as liver metastases.

MR imaging evaluation of renal cell carcinoma.

This study examines the minimally required imaging protocol needed for detection and staging of renal cell carcinoma (RCC). In 81 patients (21 women, 60 men; mean age = 62 years) with 85 RCCs, T1-weighted (T1WI), contrast-enhanced T1-weighted (Gd-T1WI), T2-weighted (T2WI), and gradient recalled echo-fast low flip angle shot (GRE/FLASH) images were evaluated alone and in combination. Surgical-pathological findings were available in all patients and were considered the standard of reference. Tumor detection for lesions smaller than 3 cm was better on Gd-T1WI than on any other sequence, but only the comparison with noncontrast T1WI and GRE/FLASH was statistically significant (detection: T1WI = 33%, Gd-TIWI = 80%, T2WI = 60%, GRE = 47%). The respective accuracies of T1WI, Gd-T1WI, T2WI, and GRE/FLASH images were 81%, 78%, 71%, and 62% for evaluating local tumor extension; 90%, 88%, 89%, and 85% for lymphadenopathy; and 89%, 81%, 91%, and 95% for renal vein thrombus. The combination of T1WI and GRE sequences rendered the highest overall staging accuracy. For tumor detection, contrast-enhanced T1WI is necessary for lesions smaller than 3 cm. For tumor staging, although the addition of GRE results in significant improvement in the evaluation of venous thrombus, any combination of two sequences will result in similar accuracy, and the use of multiple sequences is not necessary.

Cytofluorometric and cytogenetic evaluation of renal cell carcinoma: correlations with the clinical course.

The tumor specimens of 20 patients who underwent radical nephrectomy for nonfamiliar unifocal renal cell carcinoma were evaluated with conventional histopathology, cytogenetic analysis and evaluation of nuclear ploidy with cytofluorometry. The pathological stages were 1 T1N0M0, 10 T2N0M0, 1 T2N + M0, 6 T3N0M0 and 2 T3N + M0. Eleven tumors presented clonal chromosomal abnormalities, 2 had chromosomal instability and 7 normal karyotype. Rearrangement of chromosome 3 was documented in 2 cases only, in contrast with previous observations in the literature. Ten patients had a diploid or peridiploid DNA tumor content, 1 tetraploid, 4 triploid and 5 multiclonal. No correlation was found between nuclear ploidy and karyotype. Chromosomal abnormalities did not impact on survival, while a statistically significant correlation was found with diploid nuclear DNA content, since with a mean follow-up of 45.7 months, 9 out of 10 patients with diploid and peridiploid tumors are alive (p < 0.02), while 8 out of 10 nondiploid died of disease progression.

Intraoperative Evaluation of Renal Cell Carcinoma: A Prospective Study of the Role of Ultrasonography and Histopathological Frozen Sections

Purpose Nephron sparing surgery is being performed increasingly for treatment of renal cell carcinoma, including in select patients with a normal contralateral kidney. The number of tumors in the involved kidney (single versus multiple) and presence or absence of perinephric fat involvement (pathological stage T1 to 2 versus T3A) are important prognostic factors. In a prospective study we evaluated the accuracy of intraoperative histopathological frozen section analysis of renal capsular biopsies for assessing local tumor stage, and the accuracy of intraoperative ultrasonography for assessing tumor focality. Materials and Methods Intraoperative frozen section biopsies and ultrasonography were compared with information obtained from preoperative computerized tomography (CT), intraoperative inspection of the kidney by the surgeon and permanent histopathological specimens. Results We evaluated 99 patients (102 kidneys) with localized solid renal masses undergoing either radical nephrectomy (48) or nephron sparing surgery (54). Final pathological analysis revealed 95 renal cell carcinomas (stage T3A in 24), 6 oncocytomas and 1 angiomyolipoma. Multiple tumors were detected in 18 of 102 kidneys overall. Frozen section analysis identified 87 percent of the stage T3A lesions with no false-positive results, compared to CT, which only identified 67 percent. Ultrasonography identified 14 of 18 multifocal tumors (78 percent) and was not more accurate than the combination of CT and intraoperative inspection. However, during nephron sparing surgery ultrasonography was useful to localize the intrarenal extent of tumors (17 cases). Conclusions Our results clarify the role of intraoperative ultrasonography and frozen section analysis in patients undergoing nephron sparing surgery for renal cell carcinoma. Frozen section analysis may be useful in select patients with small peripheral tumors who are under consideration for elective nephron sparing surgery.

Conservative Surgery of Renal Cell Tumors in 140 Patients: 21 Years of Experience

Operative method, course and complications were analyzed retrospectively in 140 patients who underwent a conservative operation for renal tumor between June 1969 and December 1990. In 53 patients (20 women and 33 men, mean age 61.2 years, range 38 to 77 years, with 49 renal cell carcinomas and 4 benign renal tumors) there was an imperative indication for an organ preserving operation because nephrectomy would have made dialysis obligatory. In 87 patients (29 women and 58 men, mean age 53.7 years, range 27 to 74 years, with 72 renal cell carcinomas and 15 benign renal tumors) the tumor was conservatively resected in the presence of a normal contralateral unit (elective indication) and 68 of these patients (78%) were symptom-free. In the imperative group 32 of 49 patients (65.3%) with renal cell carcinoma had no evidence of disease after a mean followup of 4.6 years. Known metastases were present in 4 of 7 patients who died of the tumors in this group. In 3 patients with an imperative indication for conservative surgery a second tumor occurred in the kidney: 2 were treated with further parenchyma sparing operations, while in 1 with poor physical condition no further measures were possible. Of 72 patients with renal cell carcinoma who underwent an elective operation 68 (94.4%) had no signs of tumor progression after a mean followup of 3.3 years. One patient died of tumor metastases, and 2 (2.7%) had tumor recurrence in the kidney requiring nephrectomy and enucleation, respectively. The 5-year cause-specific survival rates for the imperative and elective groups were 84% and 96%, respectively. Patients with a local stage T3 tumor were characterized by a significantly worse survival curve than those with a stage T1 or T2 tumor but no significant difference was noted among the various grades of differentiation.

Duplex Sonography and Doppler Evaluation of Renal Cell Carcinoma With Inferior Vena Cava Involvement

Duplex Sonography and Doppler Evaluation of Renal Cell Carcinoma With Inferior Vena Cava Involvement

Clinical Evaluation of Renal Cell Carcinoma

Clinical Evaluation of Renal Cell Carcinoma