Should hilar lymph nodes be expected in radical nephrectomy specimens?

Lymph node (LN) status is essential in staging both renal cell carcinoma (RCC) and pelvic urothelial carcinoma (PUC). The rate of regional LN involvement is influenced by pathologic tumor stage, extent of the surgical resection, and accuracy of pathologic gross examination. In this study, we assess the presence of hilar LNs in radical nephrectomies (RN) by entirely submitting the hilar fat region (HFR) for microscopic evaluation (ME). Fifty consecutive RNs from 2006 to 2008 were evaluated by a standard gross examination protocol (SGEP) which consisted of palpation and sectioning of the HFR with submission of grossly identified LNs. Subsequently, the entire HFR was re-evaluated and submitted as study's total submission protocol (TSP). The number and disease status of hilar LNs identified by the SGEP and TSP were compared. Fifty RNs (37 clear cell RCC, 6 papillary RCC, 7 PUC) were studied prospectively. Ten of the 50 RNs had LNs identified (20%) with both protocols. Four of the 50 RNs had nodal metastases (8%) with the LN sizes ranging between 1.3 and 2.5 cm (mean 1.8 cm). All nodal metastases were identified by the SGEP. In three RNs (6%), additional minute (mean 0.12 cm) negative LNs not seen by the SGEP were identified by the TSP. LNs are present in only 20% of RNs, even after complete ME of the HFR. The SGEP for identifying hilar LNs in RNs is sufficient for staging and did not lead to underreporting of LN metastases.

Local tumor control with salvage cryotherapy for locally recurrent prostate cancer after external beam radiotherapy.

PURPOSE: We identified variables associated with a positive prostate biopsy after salvage cryotherapy in patients in whom initial external beam radiotherapy for prostate cancer failed to improve our cryotherapy technique, optimize local control and improve our patient selection criteria for salvage cryotherapy. MATERIALS AND METHODS: Between July 1992 and January 1995, 145 patients underwent salvage cryotherapy. Post-cryotherapy sextant prostate biopsies were performed in 107 cases. We evaluated certain variables on univariate and multivariate analysis as predictors of a positive biopsy after cryotherapy, including the type of previous therapy, tumor stage and grade at initial diagnosis, prostate volume, pre-cryotherapy prostate specific antigen (PSA), number of positive biopsy cores before cryotherapy, PSA nadir after cryotherapy, stage and grade of local recurrence, number of cryoprobes, number of freeze-thaw cycles and use of a urethral warming catheter during cryotherapy. RESULTS: Biopsies were positive in 23 cases (21%) after salvage cryotherapy. Variables associated with a positive biopsy on univariate analysis were initial stage, precryotherapy PSA, PSA nadir after cryotherapy, number of cryoprobes, number of freeze-thaw cycles and a history of chemotherapy (p = 0.005, 0.027, 0.001, 0.009, 0.018 and 0.008, respectively). Variables that remained associated with a positive biopsy on multivariate analysis were the number of probes used and post-cryotherapy PSA nadir (p = 0.013 and 0.019, respectively). CONCLUSIONS: Patients with initial clinical stage T1-2N0M0 disease and PSA no more than 10 ng./ml. have a higher rate of negative biopsies after salvage cryotherapy. Therefore, they are better candidates for salvage cryotherapy for locally recurrent prostate adenocarcinoma after external beam radiotherapy. To optimize the potential for local control the technique of salvage cryotherapy should include 2 freeze-thaw cycles and a minimum of 5 cryoprobes. Detectable PSA after salvage cryotherapy is a strong predictor of local failure.

Renal sinus involvement in renal cell carcinomas.

The renal sinus is the fatty compartment located within the confines of the kidney not delineated from the renal cortex by a fibrous capsule. Because it contains numerous veins and lymphatics, invasion into this compartment may permit dissemination of a tumor otherwise regarded as renal-limited. Thirty-one consecutive renal carcinomas were studied: 22 clear cell renal cell carcinomas (3 multilocular cystic renal cell carcinomas), 4 chromophobe renal carcinomas, and 5 papillary renal carcinomas. The entire interface between the neoplasm and the sinus was embedded. Seventeen carcinomas did not invade the renal sinus and 16 were pT1 or pT2 tumors. Fourteen carcinomas, 13 clear cell renal cell carcinoma and one chromophobe renal carcinoma, invaded the renal sinus fat, and 9 of 14 invaded the lumen of renal sinus veins (all clear cell renal carcinomas). Although 14 of 22 clear cell renal carcinomas appeared to be renal limited pT1 and pT2 cancers, 6 of 14 carcinomas invaded sinus fat and 4 invaded into the lumen of renal sinus veins. Compared with the nine sinus-negative clear cell renal cell carcinomas, the 13 sinus-positive cancers were larger, exhibited more frequent renal capsule and renal vein involvement, and had higher nuclear grades. Renal sinus invasion was most common in clear cell renal cell carcinomas but was uncommon (one in 12) in 3 more indolent renal cell carcinomas: multilocular cystic renal cell carcinoma, chromophobe renal carcinoma, and papillary renal carcinoma. The follow-up period was short (1-17 months), but metastases developed in four of 31 cases. In three cases with metastases, carcinoma had involved the lumen of sinus veins but not the main renal vein, although two of three had also invaded through the renal capsule. This study shows that in carcinomas which appear to be renal limited (pT1/pT2), seven of 23 (30.4%) had invaded sinus fat and four of 23 (17.4%) had invaded sinus veins. We conclude that renal sinus invasion, especially sinus vein invasion, could identify a patient at risk for metastases even in a putative renal limited tumor, and suggest that all cases be examined for this feature. Renal sinus invasion merits further investigation to establish its prognostic importance and possible incorporation into future revisions of the TNM staging system for renal cell carcinomas.

Patient selection for salvage cryotherapy for locally recurrent prostate cancer after radiation therapy.

PURPOSE: Our objective was to identify clinical pretreatment factors associated with early treatment failure after salvage cryotherapy. PATIENTS AND METHODS: Between 1992 and 1995, 145 patients underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Treatment failure was defined as an increasing postcryotherapy serial prostate-specific antigen (PSA) level of more than or equal to 2 ng/mL above the postcryotherapy nadir or as a positive posttreatment biopsy. We evaluated the following factors as predictors of treatment failure: tumor stage and grade at initial diagnosis, type of prior therapy, stage and grade of locally recurrent tumor, number of positive biopsy cores at recurrence, and precryotherapy PSA level. RESULTS: Among patients with a prior history of radiation therapy only, the 2-year actuarial disease-free survival (DFS) rates were 74% for patients with a precryotherapy PSA less than 10 ng/mL and 28% for patients with a precryotherapy PSA more than 10 ng/mL, P <.00001. The DFS rates were 58% for patients with a Gleason score of less than or equal to 8 recurrence and 29% for patients with a Gleason score greater than or equal to 9 recurrence, P <.004. Among patients with a precryotherapy PSA less than 10 ng/mL, DFS rates were 74% for patients with a prior history of radiation therapy only and 19% for patients with a history of prior hormonal therapy plus radiation therapy, P <.002. CONCLUSION: Patients failing initial radiation therapy with a PSA more than 10 ng/mL and Gleason score of the recurrent cancer more than or equal to 9 are unlikely to be successfully salvaged. Patients failing initial hormonal therapy and radiation therapy are less likely to be successfully salvaged than patients failing radiation therapy only.

Predictive value of prostate specific antigen nadir after salvage cryotherapy.

PURPOSE: We determined nadir prostate specific antigen (PSA) after salvage cryotherapy to distinguish patients who are potentially cured from those at risk for subsequent biochemical and biopsy proved failure. MATERIALS AND METHODS: A total of 146 patients who underwent salvage cryotherapy were followed a median of 21 months (range 3 to 47) with regular serum PSA analysis and digital rectal examination. Sextant biopsies were performed at 6 months or earlier when PSA increased greater than 2 ng./ml. from the nadir value (biochemical failure) or there was a palpable local recurrence. We compared the incidence of biochemical failure and biopsy specimens positive for cancer to pretreatment PSA and posttreatment nadir PSA. RESULTS: In 59 of the 146 patients (40%) PSA decreased to an undetectable level within a median of 3 months. In 85 of the 109 patients (78%) who underwent biopsy the specimens were negative for cancer. Low serum PSA nadir values were associated with low pretreatment PSA and a low incidence of biochemical failure. In 6 of 60 patients (10%) in whom PSA nadir was 0.5 ng./ml. or less and in 18 of 49 (37%) with a higher PSA nadir biopsy was positive for cancer. CONCLUSIONS: A PSA nadir of 0.5 ng./ml. or less should be achieved after salvage cryotherapy. Higher nadirs are more likely to be associated with increasing posttreatment PSA and positive biopsies. PSA nadir is a better prognostic indicator of biochemical and biopsy proved failure after salvage cryotherapy than pretreatment PSA.

Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells implanted in nude mice using an in situ messenger RNA hybridization technique.

The purpose of this study was to determine whether the expression level of several metastasis-regulating genes correlates with the metastatic potential of human prostate cancer cells implanted into the prostate of nude mice. The steady-state mRNA expression levels for epidermal growth factor receptor (EGFR; growth), basic fibroblast growth factor (bFGF) and interleukin (IL)-8 (angiogenesis), 72-kd and 92-kd type IV collagenase (invasion), E-cadherin (adhesion), and multidrug resistance (mdr-1; drug resistance) were measured by Northern blot and colorimetric in situ hybridization techniques in human PC-3M cells and selected cell variants with different metastatic potentials. Highly metastatic cells growing in culture constitutively and uniformly expressed higher levels of bFGF, IL-8, type IV collagenase, and mdr-1 mRNA transcripts than parental PC-3M cells or low metastatic cells, which displayed a heterogeneous pattern of gene expression. Human prostate cancer cells implanted in nude mice at an ectopic site (subcutaneous) expressed lower levels of EGFR, mdr-1, bFGF, IL-8, and collagenase type IV than those implanted in an orthotopic site (prostate), indicating that the expression of these genes was dependent on the organ environment. Highly metastatic cells growing in the prostate expressed higher levels of EGFR, bFGF, type IV collagenase, and mdr-1 mRNA than low metastatic parental cells in the same site. These data demonstrate a direct correlation between the expression of several metastasis-related genes and the metastatic potential of human prostate cancer cells in nude mice and suggest that multiparametric in situ hybridization analyses can be used to identify the metastatic potential of individual patients' prostate cancers.

Multiparametric in situ mRNA hybridization analysis to predict disease recurrence in patients with colon carcinoma.

We examined the expression level of several genes that regulate different steps of metastasis in formalin-fixed, paraffin-embedded archival specimens of primary human colon carcinomas from patients with at least 5 years of follow-up. The expression of epidermal growth factor receptor, basic fibroblast growth factor, type IV collagenase, E-cadherin, and multidrug resistance (mdr-1) was examined by a colorimetric in situ mRNA hybridization technique concentrating on reactivity at the periphery of the neoplasms. The in situ hybridization technique revealed inter- and intratumor heterogeneity for expression of the metastasis-related genes. The expression of basic fibroblast growth factor, collagenase type IV, epidermal growth factor receptor, and mdr-1 mRNA was higher in Dukes's stage D than in Dukes' stage B tumors. Among the 22 Dukes' stage B neoplasms, 5 specimens exhibited a high expression level of epidermal growth factor receptor, basic fibroblast growth factor, and collagenase type IV. Clinical outcome data (5-year follow-up) revealed that all 5 patients with Dukes' stage B tumors developed distant metastasis (recurrent disease), whereas the other 17 patients with Dukes' stage B tumors expressing low levels of the metastasis-related genes were disease-free. Multivariate analysis identified high levels of expression of collagenase type IV and low levels of expression of E-cadherin as independent factors significantly associated with metastasis or recurrent disease. More specifically, metastatic or recurrent disease was associated with a high ratio (> 1.35) of expression of collagenase type IV to E-cadherin (specificity of 95%). Collectively, the data show that multiparametric in situ hybridization analysis for several metastasis-related genes may predict the metastatic potential, and hence the clinical outcome, of individual lymph-node-negative human colon cancers.

Cystitis associated with tiaprofenic acid.

Ten patients with cystitis associated with tiaprofenic acid were reviewed. All patients displayed similar cystoscopic and histological features, and all failed a variety of initial therapies but achieved a dramatic improvement or resolution of symptoms with discontinuation of the tiaprofenic acid. Drug-induced cystitis may be more common than previously recognized.