PubMed Health⌕ Search

Biomedical subjects

Martin Susani

Publications and source records attributed to Martin Susani.

13 recordsLinked to original sources
PubMed2006

Are small renal tumors harmless? Analysis of histopathological features according to tumors 4 cm or less in diameter.

PURPOSE: Small renal tumors detected incidentally are considered to have less aggressive potential. This assumption is mainly based on the low tendency to increase in size on serial imaging studies, but histopathological parameters of progression in larger patient series are scant. MATERIALS AND METHODS: We reviewed data of 287 tumor bearing kidneys in which solid tumors 4 cm or less in diameter were detected by cross-sectional imaging and subsequently removed surgically. Tumor size as documented by preoperative computerized tomography was correlated to histological diagnosis, and in cases of malignancy correlated to tumor type, pathological TNM stage and nuclear (Fuhrman) grade. With multifocal lesions the largest single tumor was considered the reference lesion but multifocality was also considered a separate parameter. RESULTS: At a mean tumor diameter of 2.94 +/- 0.87 cm 65 (22.6%) tumors were 2 cm or less, 103 (35.9%) were 2.1 to 3.0 cm and 119 (41.5%) were 3.1 to 4 cm in diameter. A total of 56 (19.5%) tumors were benign with no correlation to tumor size (Pearson test p = 0.660). Renal cell cancer was found in 227 (79.1%) patients with 159 (70.0%) clear cell, 47 (20.7%) papillary, 11 (4.8%) chromophobe and 10 others with no correlation to tumor diameter. Of the kidneys 31 (13.6%) had multifocal renal cell carcinoma, with a significant correlation to larger tumor diameter (linear regression p = 0.048) and papillary renal cell carcinoma subtype (linear regression p = 0.018). Two (4.2%), 4 (5%) and 25 (25.5%) cases of renal cell carcinoma 2 cm or less, 2.1 to 3 cm and 3.1 to 4 cm in diameter had Fuhrman grade G3/4, respectively (Pearson p = 0.0007). Advanced stage (pT3a or greater) was documented in 2 (4.2%), 12 (14.9%) and 35 (35.7%) cases for the same categories, respectively (p = 0.0023). Whereas distant metastases were diagnosed in only 4 patients with renal cell carcinoma with tumors 3 cm or less, distant metastases were in 10 (8.4%) patients with tumors 3.1 to 4 cm (p = 0.045). CONCLUSIONS: The aggressive potential of small renal cell carcinoma increases dramatically beyond a tumor diameter of 3 cm. Given the difficulty in measuring tumor diameters reliably with sequential imaging studies, the threshold for selecting patients for a surveillance strategy should be set well under this parameter.

Carcinoma, Renal Cell↗
PubMed2006

Prostate cancer detected by uPM3: radical prostatectomy findings.

uPM3 is the first urine-based genetic test that is highly specific for detecting prostate cancer. The histopathologic characteristics of uPM3-detected cancer in radical prostatectomy specimens have not been previously described. We evaluated a consecutive series of radical prostatectomies to determine the extent, zonal distribution and other features of prostate cancer following uPM3 detection. A total of 24 whole-mounted, totally embedded radical prostatectomy specimens were evaluated. All patients had clinically localized cancer and none received preoperative therapy. Zonal location of cancer, distance to the urethra, cancer volume, Gleason grade and multicentricity were recorded; volume of cancer was measured using the grid-counting method. Patients ranged in age from 43 to 75 years (mean 65 years). In 21/24 cases, cancer involved the transition and peripheral zones and was multicentric (87%). Mean cancer volume was 3.96 cm3 (range 0.08-16.86 cm3). Mean distance to the urethra was 0.50 cm for the closest cancer and 0.61 cm for the most distant cancer. Mean Gleason score was 7 (range 5-9); pathologic stage was pT2 for 17 cases and pT3 for seven cases. The uPM3 is an independent and specific biomarker that detects prostate cancers of similar volume, location, extent and grade as other tests for early detection. uPM3 does not preferentially identify large or aggressive prostate cancers.

Adult↗
PubMed2005

Are repeat biopsies required in men with PSA levels < or =4 ng/ml? A Multiinstitutional Prospective European Study.

OBJECTIVES: Pathological and biochemical features of prostate cancers detected on repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were evaluated and compared to those cancers detected on first biopsy. METHODS: 315 men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound guided sextant biopsy and two additional transition zone biopsies (Octant Biopsy). All subjects whose biopsy samples were negative for prostate cancer underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers were offered surgery or radiation therapy. Pathological and clinical features of patients diagnosed with prostate cancer on initial and repeat biopsy were compared. RESULTS: Cancer detection rates on first and second biopsy were 24% (75/315) and 13% (29/224), respectively. Overall, of patients with clinically localized disease (83% of cancers detected), 87% underwent radical prostatectomy, 11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found in the first biopsy group were more multifocal (p = 0.01) while cancers found on second biopsy were more located in the apical-dorsal region (p = 0.003). No significant differences were noted with respect to extracapsular extension, seminal vesical invasion, positive margins, final pathological stage, Gleason score, percentage Gleason grade 4/5, serum PSA and patient age between first and second biopsy. CONCLUSIONS: With an octant biopsy regime, biochemical and pathological features of cancers detected on initial and repeat biopsy in the PSA range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer volume suggesting identical cancer characteristics, thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy.

Aged↗
PubMed2005

Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma.

Distinguishing renal oncocytoma from chromophobe and other renal carcinomas is essential, considering their differing biological potentials. Although renal oncocytoma is considered a benign tumor, chromophobe renal cell carcinoma has potentially malignant biological behavior. The numerous reported studies on distinguishing these 2 entities have been based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. But none of these features has proven to be reliably specific, especially in tumors with overlapping phenotypes. We report a novel immunohistochemical approach based on the expression of a recently described kidney-specific cadherin (Ksp-cadherin) for the differential diagnosis of these 2 tumors. We compared Ksp-cadherin expression in 212 renal tumors, including 102 clear cell renal carcinomas, 46 papillary renal cell carcinomas, 30 chromophobe carcinomas, 3 collecting duct carcinomas, and 31 oncocytomas. In addition, we examined the expression of epithelial membrane antigen, vimentin, CK7, and Hale's colloidal iron staining. We found that chromophobe renal cell carcinomas consistently (96.7% of cases) demonstrated a distinctive membrane pattern of Ksp-cadherin expression, whereas renal oncocytomas (3.2%), clear cell renal cell carcinomas (0%), papillary renal cell carcinomas (2.2%), and collecting duct carcinomas (0%) usually did not express Ksp-cadherin. CK7 expression was found in 90.0%, 6.5%, 7.8%, 76.1%, and 33.3% of these tumor cases, respectively. Whereas CK7 was detected in different types of renal cell carcinomas, Ksp-cadherin was expressed almost exclusively in chromophobe renal cell carcinomas. Immunohistochemical analysis of Ksp-cadherin offers a fast, reliable approach for the distinguishing between renal oncocytoma and chromophobe renal cell carcinoma that is applicable for routine pathology laboratory studies without the need for time-consuming and costly ancillary studies.

Adenocarcinoma↗
PubMed2005

Diagnostic significance of aquaporin-1 in liver tumors.

The diagnostic utility of aquaporin (AQP)-1 in liver tumors was tested and compared with other well-established markers. In 30 cholangiocarcinomas (CCs), 20 hepatocellular carcinomas (HCCs), and 10 metastatic colorectal carcinomas (MCCs) of the liver, expression of AQP-1, CD10, cytokeratin (CK) 7, CK20, and polyclonal carcinoembryonic antigen (pCEA) was tested. In addition, staining patterns of CD10 and pCEA were analyzed. To compare the selectivity of AQP-1 and CK7 as possible markers for differentiated cholangiocytes, liver biopsies of cholestatic disease were also analyzed. Aquaporin-1 expression was found in 93% of all CCs compared with 0% of HCC (P < .000001) and with 30% of MCC (P < .01). CD10 was positive in 16.7% of CC compared with 40% of HCC (P < .04) and to 20% of MCC (not significant). Cytokeratin 7 was positive in 90% of CC compared with 10% of HCC (P < .00001) and with 20% of MCC (P < .0001). Cytokeratin 20 was positive in 90% of MCC compared with 16.7% of CC (P < .0001) and with 20% of HCC (P < .00001). Canalicular staining patterns of CD10 and pCEA were observed in HCC (100% and 89.5%, respectively) but typically not in CC (0% and 6.7%, respectively) and never in MCC. In cholestatic disease, AQP-1 was expressed in differentiated epithelial cells of the bile ducts, whereas CK7-positive hepatocytes of Rappaport zone 1 did not show any AQP-1 reactivity. Therefore, AQP-1 seems to be a highly selective marker for differentiated cholangiocytes and can be very helpful in the differential diagnosis of liver tumors.

Adult↗
PubMed2005

Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study.

Diagnostic use of antibodies against aquaporin water channel proteins and PAX-2, a nuclear transcription factor in renal development, was tested in 202 renal neoplasms, using tissue microarray technique. Immunohistochemistry for aquaporin-1, aquaporin-2, PAX-2, CD10, and cytokeratin 7 was performed on 102 clear cell renal cell carcinomas, 44 papillary renal cell carcinomas (among them 34 type 1 and 10 type 2), 24 chromophobe renal cell carcinomas, three collecting duct carcinomas (carcinomas of the collecting ducts of Bellini), and 29 oncocytomas. Aquaporin-1 expression was found in clear cell renal cell carcinomas and papillary renal cell carcinomas of both types (78 and 73%, respectively), but not in chromophobe renal cell carcinomas, collecting duct carcinomas, and oncocytomas. Aquaporin-2 expression was not seen in any of the tested tumors. PAX-2 and CD10 was found in the majority of clear cell renal cell carcinomas (88 and 85%, respectively) but only in few papillary renal cell carcinomas, chromophobe renal cell carcinomas and oncocytomas. Decrease or loss of aquaporin-1 and PAX-2 was shown in higher grades compared to lower grades of clear cell renal cell carcinomas (P<0.0001 and <0.0245, respectively). Cytokeratin 7 was rarely seen in clear cell renal cell carcinomas, type 2 papillary renal cell carcinomas, and oncocytomas, but was found in the majority of type 1 papillary renal cell carcinomas (97.1%) and chromophobe renal cell carcinomas (88%). Aquaporin-1 and PAX-2 expression was found to correlate with nuclear grading for clear cell renal cell carcinomas but not for papillary renal cell carcinomas. No correlation of tumor stage and aquaporin-1 and PAX-2 expression was seen. Aquaporin-1 and PAX-2 are reliable markers for clear cell renal cell carcinomas of lower grades but not for higher grades. CD10 expression remains stable, independent of nuclear grading.

Adenocarcinoma, Clear Cell↗
PubMed2004

Response to sublethal heat treatment of prostatic tumor cells and of prostatic tumor infiltrating T-cells.

BACKGROUND: To investigate the possibilities offered by high intensity focused ultrasound (HIFU) in the field of tumor vaccination, we analyzed how prostatic cancer (CaP) cells react towards heat treatment and whether increased access to CaP cells by the immune system would be the result. METHODS: Heat/stress response of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry, Western blotting, and Atlas array. A heat-induced change in immune recognition was analyzed functionally using human T-helper (Th)1 and Th2-cytokine release with tumor infiltrating T-lymphocytes (TIL) as responder and autologous CaP cells either heated or untreated as stimulator cells. RESULTS: Transcription of 68 out of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells. Significantly upregulated stress protein (SP) expression (HSP-72, -73, GRP-75, -78) was seen at the border zone of HIFU treatment. Remarkably, even untreated benign prostatic hyperplasia (BPH) specimens revealed relative overexpression of heat shock protein (HSP)-72, -73 and glucose regulated protein (GRP)-75, -78. Heated CaP cells increased Th1-cytokine (IL-2, IFN-gamma, TNF-alpha) release but decreased Th2-cytokine (IL-4, -5, -10) release of TIL. CONCLUSIONS: HIFU treatment may alter the presentation of prostate tissue and tumor antigens and this presentation is most likely stimulatory. HSP-72/73 overexpression in untreated BPH may suggest a mechanism by which BPH can incite inflammation.

Antigens, Neoplasm↗
PubMed2004

Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy.

PURPOSE: In this European multicenter study we compared hexaminolevulinate (HAL) fluorescence cystoscopy and standard white light cystoscopy for the detection of carcinoma in situ (CIS) in patients suspected of having high risk bladder cancer. MATERIALS AND METHODS: This study was a prospective controlled, within-patient comparison of standard and HAL fluorescence cystoscopy. Eligible patients received an intravesical instillation of 50 ml HAL 8 mM solution. Cystoscopy was performed using a D light system, which provided white and blue light at 375 to 440 nm. The bladder wall was inspected and mapped, first under white light, followed by blue light. All tumors and suspicious areas identified under white light and by red fluorescence were resected or biopsied. Histological findings were assessed by an independent central pathologist blinded to the identity of the biopsies. RESULTS: Of 211 evaluable patients 83 (39%) had CIS, of whom 18 (22%) were detected by HAL cystoscopy only, 62 (75%) were detected by standard and HAL cystoscopy, 2 (2%) were detected by standard cystoscopy only and 1 (1%) was detected by nonguided biopsy. Therefore, HAL cystoscopy identified 28% more patients with CIS than standard cystoscopy. The side effects of HAL instillation were negligible and no unexpected events were reported. CONCLUSIONS: HAL fluorescence cystoscopy improves the detection of bladder CIS significantly, which has consequences for clinical management and may improve the patient prognosis. The procedure is easily implemented as an adjunct to standard cystoscopy and it adds no significant risk of complications.

Adult↗
PubMed2002

Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients.

BACKGROUND: Nephrogenic adenomas are benign, tumor-like lesions within the urothelial mucosa of the urinary tract that are not uncommon in renal-transplant recipients. We investigated the origin of nephrogenic adenomas in renal-transplant recipients. METHODS: Tissue sections were analyzed by fluorescence in situ hybridization with the use of probes for the X and Y chromosomes, by immunohistochemical methods with the use of antibodies to renal tubular antigens, and by lectin histochemical methods. Forty-six nephrogenic adenomas from 29 patients were analyzed. RESULTS: All nephrogenic adenomas in 14 female recipients of transplants from male donors and 10 male recipients of transplants from female donors showed the same sex-chromosome status as the donor kidney, but not the same sex-chromosome status as the recipient's surrounding bladder tissue. The nephrogenic adenomas from all 6 female recipients of transplants from female donors showed female chromosomes, and those from the 16 male recipients of transplants from male donors showed male chromosomes. The presence of aquaporin 1, PAX2, and lectin-binding capacity for peanut agglutinin, Lotus tetragonolobus agglutinin, and Sophora japonica agglutinin in nephrogenic adenomas indicated an origin from renal tubular cells. CONCLUSIONS: Nephrogenic adenomas in renal-transplant recipients are derived from tubular cells of the renal transplants and are not metaplastic proliferations of the recipient's bladder urothelium.

Adenoma↗
PubMed2002

DNA profiles and numeric histogram classifiers in nephrogenic adenoma.

BACKGROUND: The malignant potential of nephrogenic adenoma is still a matter of controversy and therapeutic regimens of this morphologic entity range from partial, even total cystectomy to watchful waiting. The objective of the current study was to evaluate several robust image cytometry-DNA histogram classifiers and to search among those for factors that separate a biologically nonaggressive metaplastic lesion from lesions with increased malignant potential. METHODS: The study included bladder irrigation specimens, 23 preceding transurethral resection of nephrogenic adenoma and 24 preceding resection of papillary bladder carcinoma. Feulgen-stained nuclei were imported to a static image analysis system, and densitometric data were interpreted by two different software programs. Histograms were described numerically by DNA index, 2c deviation index, and by 5c/9c-exceeding and euploid polyploidy rates. In addition, an interpretation algorithm based on a dual parameter analysis with an integrated automatic threshold was used. RESULTS: The numeric classification of DNA histograms of patients suffering from nephrogenic adenoma resulted in DNA indices between 0.91 and 1.15. The 2c deviation indices ranged from 0.03 to 0.43, and the 5c exceeding rates ranged from 0.0 to 1.58. None of the measurements showed nuclei exceeding 9c. The p25-75 ranges of 2c deviation indices in nephrogenic adenoma and papillary urothelial carcinoma did not overlap. These findings might be explained by minor proliferative activity in nephrogenic adenoma. Euploid polyploidy rates less than 5% confirm this explanation. Risk analysis documented high risk only for those patients with nephrogenic adenomas who had proven transitional cell carcinoma in their history. CONCLUSIONS: DNA estimation by image cytometry of urinary bladder irrigation specimens appears able to separate papillary bladder lesions. The method detects those lesions with higher malignant potential but is limited in separating entities with low malignant potential. Comparison of the discriminative power of robust numeric DNA classifiers reveals the 2c deviation index superior to the widely used DNA index and the 5c exceeding rate in this material.

Adenoma↗
PubMedDate not supplied

Correlation of clinical outcome with p53 and p21 status in patients with advanced transitional-cell carcinoma treated with paclitaxel and carboplatin.

BACKGROUND: The purpose of the present study was to correlate the nuclear expression of p53 and p21 with response to paclitaxel and carboplatin, progression-free survival (PFS) as well as overall survival (OS), in patients with urothelial metastatic transitional-cell carcinoma (TCC). PATIENTS AND METHODS: Histological specimens of 23 patients with metastatic TCC, who were treated with paclitaxel and carboplatin, were investigated for p53 and p21 proteins and correlated with overall response (OR) to chemotherapy, PFS and OS. RESULTS: After a median follow-up of 33.2 months, the OR rate was 57%. Median PFS was 7.4 (range: 2.5-49.2) months while median OS was 13.2 (range: 4.2-49.5) months. The tumour specimens of 48% of patients were classified as p53-positive, whereas 57% were classified as p21-positive. Neither p53- nor p21-status were significantly associated with CR, CR and PR or CR, PR and SD. In addition, neither PFS nor OS were significantly influenced by p53- and p21-status. CONCLUSION: Previous findings on the efficacy of the combination of paclitaxel and carboplatin in metastatic TCC patients are thus re-confirmed even after a considerable duration of follow-up. Moroever, the clinically relevant results obtained were independent from p53- or p21-status thus suggesting the involvement of other, yet unidentified, pathways as prognostic indicators for the course of the disease under the present treatment.

Aged↗