The role of [68 Ga]Ga-FAPI-04 PET/CT in renal cell carcinoma: a preliminary study.

PURPOSE: We aimed to investigate the role of [68 Ga]Ga-FAPI-04 PET/CT and uptake patterns of primary and metastatic lesions in patients with renal cell carcinoma (RCC). METHODS: Twenty patients with a suspicious lesion considered primary renal malignancy or a history of RCC were included in our study. Two patients were excluded from further analyses due to other confirmed malignancies. Six patients were newly diagnosed, while the indication of 12 patients was restaging. All patients underwent [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT. SUVmax and tumor-to-background ratio (TBR) of primary (n = 7) and local recurrent lesions (n = 6) and lymph node (n = 26), lung (n = 32), bone (n = 5), and other metastases (n = 14) were compared between the two tracers. RESULTS: We detected 90 lesions in 18 patients with varying FAPI and FDG uptake values on both PET/CT. The median TBR of FAPI-PET/CT of all lesions was higher than TBR of FDG-PET/CT with statistically significance (5.6 vs. 2.1, p < 0.001). In primary and recurrent lesions, the median SUVmax, TBR, and tumor volume on FAPI-PET/CT were higher than FDG-PET/CT. The median SUVmax of lung lesions on FAPI-PET/CT was statistical significantly higher than FDG-SUVmax (3.8 vs. 1.8, p = 0.02). The median of FAPI-SUVmax on primary lesions was lower in the early stage based on TNM compared to the advanced stage. FAPI-SUVmax in 49% of all lesions were SUVmax ≥ 6, and 13% were SUVmax ≥ 10. In patient-based analyses, seven patients (39%) had at least one lesion with FAPI-SUVmax ≥ 10; 12 patients (67%) had at least one lesion with FAPI-SUVmax ≥ 6. CONCLUSION: This study showed the potential utility of [68 Ga]Ga-FAPI-04 PET/CT showing promising results in RCC. We have presumed that FAPI-PET/CT may be performed for complementary imaging modality providing prognosis and possibility of theranostic application in selected patients.

Detection of metastases in newly diagnosed prostate cancer by using 68Ga-PSMA PET/CT and its relationship with modified D'Amico risk classification.

PURPOSE: We aimed to investigate the diagnostic power of 68Ga-PSMA PET/CT in the detection of metastatic spread of newly diagnosed PCa, and evaluate the relationship with modified D'Amico risk classification. METHODS: We evaluated newly diagnosed PCa patients who underwent 68Ga-PSMA PET/CT prior to therapy. All images were interpreted retrospectively and areas of abnormally increased tracer uptake were documented according to PSMA-RADS version 1.0 system. Patients were divided into risk groups as low, intermediate, or high risk, according to a modification in D'Amico classification system as ISUP grade 3 tumors were included to high-risk group. 68Ga-PSMA PET/CT findings were compared among risk groups as well as PSA levels, clinical T stages, and ISUP grades. RESULTS: A total of 356 patients were included to the study with a median PSA level was 16.42 (1.29-7013) ng/ml and median Gleason score was 8 (range: 6-10). Of these, 13(3.7%), 54 (15.1%), and 289 (81.2%) were in the low-, intermediate-, and high-risk groups, respectively. Lymph node metastases were detected in 125 (35.1%) patients, and in 48 of them, metastasis was limited to pelvic lymph nodes (PLN). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated as 71.4%, 100%, 95.9%, 100%, and 95.4%, respectively for the detection of PLN, based on histopathological results of 49 patients. Overall, any metastasis was detected in 47.7% of high-risk patients, while only PLN metastases were defined in 3.7% intermediate-risk patients and none of low-risk patients had any kind of metastasis. CONCLUSION: This study revealed that 68Ga-PSMA PET/CT should be routinely used in newly diagnosed high-risk PCa patients; whereas it seems to be of limited use for intermediate-risk group and useless for the low-risk group.

Can serum matrix metalloproteinase-9 and SMAD-2 levels predict lamina propria invasion in bladder urothelial carcinoma?

INTRODUCTION: Matrix metalloproteinase-9 (MMP-9) has a role in the destruction of lamina propria (LP) of the bladder wall and SMAD-2 promotes cell-to-cell adhesion. This study aimed to investigate the association between LP invasion and serum protein and mRNA expression levels of MMP-9 and SMAD-2 in bladder cancer (BC) patients. METHODS: Serum samples were taken from 57 patients with suspicious BC before TUR-BT (Group 1) and 20 patients with benign diseases as control (Group 2). The mRNA expression and serum protein levels of MMP-9 and SMAD-2 were analyzed using Real-Time PCR and ELISA methods, respectively. The comparison of protein and mRNA expression levels of MMP-9 and SMAD-2 were done statistically between Group 1 and 2, as well as for different T stages of BC. RESULTS: The protein levels of MMP-9 (2448 vs 637.5 pg/mL, P = .0001) and SMAD-2 (6.85 vs 1.61 P = .0001) were significantly higher in Group 1 compared to Group 2. The mRNA expression levels of MMP-9 (P = .89) and SMAD-2 (P = .99) did not significantly differ between the groups. The protein levels of MMP-9 in T1 patients were significantly higher from both of pTa patients (P = .018) and pT2 (P = .02). The protein levels of SMAD-2 were not statistically different between T stages. Similarly, the mRNA expression levels of MMP-9 and SMAD-2 were not different between T stages. CONCLUSIONS: The protein levels of MMP-9 and SMAD-2 were increased in BC patients while mRNA expressions were not different. Furthermore, the increased protein level of MMP-9 in T1 patients was more pronounced which may be related to LP invasion of the tumor.

The clinical predictive factors and postoperative histopathological parameters associated with upgrading after radical prostatectomy: A contemporary analysis with grade groups.

BACKGROUND AND AIM: Upgrading after radical prostatectomy (RP) is an ongoing problem since first description of Gleason score. In this retrospective study, our aim is to investigate upgrading after RP in grade groups (GG) and clinical predictive, and postoperative histopathological factors associated with GG upgrading (GGU). PATIENTS AND METHODS: A total of 753 patients undergoing RP between January 2006 and June 2019 at our institution were investigated. Overall cohort were divided into two groups according to GGU status after RP as nonupgrading and upgrading. Retrospectively documented preoperative clinical and postoperative histopathological parameters were compared between two groups. Furthermore, we investigated a subgroup of institutional cohort (n = 398) whose prostate biopsy (Pbx) and RP were performed in our institution and we also divided this cohort into two groups according to GGU status. χ2 and Mann-Whitney U tests were used for comparative analyses. The independent preoperative predictive and postoperative histopathological factors associated with GGU were investigated using multivariate logistic regression analysis. RESULTS: The total GGU was 55.8% in overall cohort and 45.2% in institutional cohort. The GGU was found as the most common in bioptic GG1 group in both overall (64.0%), and institutional (54.5%) cohorts. In multivariate analyses, the noninstitutional Pbx (odds ratio [OR] = 2.56; 95% confidence interval [CI]: 1.86-3.51; P < .001), tumor positive core numbers in Pbx (OR = 1.11; 95%CI: 1.04-1.19; P = .003), increased prostate specific antigen (PSA) density (OR = 3.59; 95%CI: 1.03-12.52, P = .045) and age (OR = 1.03; 95%CI: 1.00-1.05, P = .046) were independent clinical predictors of GGU in overall cohort whereas only increased PSA density (OR = 5.94; 95%CI: 1.28-27.50; P = .023) was independent predictor in institutional cohort. Among postoperative histopathological factors, perineural invasion (OR = 1.57; 95%CI: 1.70-3.87; P < .001 and OR = 2.53; 95%CI: 1.46-4.40; P = .001, respectively), increased maximum tumor diameter (OR = 1.46; 95%CI: 1.23-1.73; P < .001 and OR = 1.33; 95%CI: 1.07-1.66; P = .010, respectively), and high-grade prostatic intraepithelial neoplasia (HGPIN) existence at tumor surrounding tissue (OR = 1.96; 95%CI: 1.32-2.90; P = .001 and OR = 1.87; 95%CI: 1.10-3.21; P = .022, respectively) were independently associated with GGU after RP, in both of overall and institutional cohorts. CONCLUSIONS: Noninstitutional prostate biopsy, increased PSA density, higher tumor positive cores in Pbx and older age are the clinical predictors of upgrading after RP in contemporary GG. Perineural invasion, increased maximum tumor diameter, and HGPIN existence at tumor surrounding tissue are postoperative histopathological factors associated with GGU.

The pathological upgrading after radical prostatectomy in low-risk prostate cancer patients who are eligible for active surveillance: How safe is it to depend on bioptic pathology?

BACKGROUND: Active surveillance (AS) is one of the treatment alternatives in low-risk prostate cancer (PCa). The pathological upgrading after radical prostatectomy (RP) were investigated in patients who were eligible for AS in the present study. METHODS: Between August 2006 and July 2017, 627 patients underwent RP in our institution. One hundred and thirty-six patients who were eligible for AS at the time of RP were included in this study. The previously defined AS criteria Gleason 3 + 3=6 adenocarcinoma at maximum two biopsy cores, prostate-specific antigen (PSA) < 10 ng/mL and clinical T stage ≤ 2a were used in the study. The demographics, clinical, and histopathological outcomes were retrospectively compared between two groups, which were divided in accordance with the upgrading status at final pathology as Group 1 (n = 67, upgrading) and Group 2 (n = 69, nonupgrading). RESULTS: Gleason upgrading (GU) was found in 67 (49.3%) patients, and 17 patients (12.5%) were upstaged to pT3a. The upgrading to Gleason 3 + 4 was reported in 38.7% of patients, however, 7.4%, and 3.7% of the patients were upgraded to Gleason 4 + 3, and Gleason 4 + 4, respectively. The 10.3% of the patients had extraprostatic involvement, and the rate (19.4% vs 1.4%, P = .002) was significantly higher in Group 1. PSA density (P = .001), tumor size (P < .001), tumor percentage (P < .001), apical involvement (P = .013), and perineural invasion (P < .001) in RP specimen were higher in Group 1. Multivariate analysis showed that perineural invasion (OR = 4.26; 95%CI: 1.76-10.33; P = .001) and pathologic T stage (OR = 5.45; 95%CI: 1.08-27.4; P = .04) were independently associated with GU. CONCLUSIONS: Since 12.5% of the patients upstaged to pT3a disease, and there is a possible risk of Gleason 4 pattern, upgrading of the tumor should carefully be kept in mind before offering AS to low-risk patients with PCa.

Validating the predictors of outcomes after radical cystectomy for bladder cancer.

BACKGROUND: An assessment of surgical risk is essential for patient counseling and decision making, and it can provide rationale adjustment for patient populations as health care moves from a fee-for-service to a value-based reimbursement model. The modified Frailty Index (mFI) has been proposed as a risk-stratification tool for radical cystectomy (RC), and the objective of the current study was to validate this potential use of the mFI using an institutional cohort. METHODS: A retrospective review of all patients who underwent RC for bladder cancer was conducted at the authors' institution from 2012 to 2016. In addition to detailed clinicopathologic and treatment parameters, patients were categorized according to the mFI, the Charlson Comorbidity Index (CCI), and the American Society of Anesthesiologists (ASA) classification. Covariates were analyzed to determine associations with 1-month complication rates (according to the Clavien-Dindo system), 3-month readmission rates, hospitalization length, and hospitalization costs. RESULTS: In total, 346 patients were included in the analysis. The overall complication rate was 56.6%, the major (Clavien grade ≥3) complication rate was 19.4%, and the readmission rate was 27.9%. Receiver operating curve analysis demonstrated a weak association of all indices with major complications after RC: the area under the curve was 0.535 (95% confidence interval [CI], 0.460-0.611) for the ASA classification; 0.565 (95% CI, 0.485-0.645) for the CCI score; and 0.551 (95% CI, 0.471-0.631) for the mFI. There were no significant differences in the rate of major complications when stratifying the results according to the mFI, CCI, or ASA class. Length of hospitalization and associated costs were correlated with mFI. CONCLUSIONS: Frailty was not associated with postoperative complications and provided little additional predictive ability over the ASA classification and the CCI score. Further research is required to identify patients who are likely to suffer significant complications after RC.

Modelling cost-effectiveness of a biomarker-based approach to neoadjuvant chemotherapy for muscle-invasive bladder cancer.

OBJECTIVES: To model the cost-effectiveness of a biomarker-based approach to select patients for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: We obtained data from the most recent clinical studies on patients with locally advanced MIBC treated by RC, including stage distributions, overall survival (OS) estimates, associated costs, and utilisation/response to NAC. Additionally, we estimated the putative efficacy of three biomarkers to select patients for NAC: DNA-repair gene panel [ataxia telangiectasia mutated (ATM), retinoblastoma 1 (RB1), and Fanconi anaemia complementation group C (FANCC)], excision repair cross-complementation group 2 (ERCC2), and ribonucleic acid (RNA) subtypes. A decision analysis model was developed to evaluate the cost-effectiveness of biomarker-based approaches to select patients with MIBC for NAC. Comparison of cost-effectiveness included RC alone, unselected NAC plus RC, and NAC based on the three aforementioned biomarkers. RESULTS: The DNA-repair gene panel-based approach to NAC was the most cost-effective strategy (mean OS of 3.14 years, $31 482/life year). Under this approach, 38% would undergo NAC, about twice the number of patients who are currently receiving NAC for MIBC. Such an approach would improve mean OS by 5.2, 1.6, and 4.4 months compared to RC alone, a hypothetical scenario where all patients received NAC, and compared to current estimates of NAC utilisation, respectively. CONCLUSIONS: A biomarker-based strategy to identify patients with MIBC who should undergo NAC was more cost-effective than unselected use of NAC or RC alone. As further data becomes available, such a model may serve as a basis for incorporating biomarkers into clinical decision making.

Prospective evaluation of complications in laparoscopic urology at a mid-volume institution using standardized criteria: Experience of 1023 cases including learning curve in 9 years.

AIM: To evaluate the laparoscopic operations performed in our department according to the modified Clavien classification system of complications. MATERIALS AND METHODS: Between September, 2005 and February, 2014, a total of 1023 laparoscopic cases were performed. This period was divided into three terms (Terms 1, 2 and 3 consisting of 38, 32 and 32 months, respectively). According to the European Scoring System (ESS), easy (E), slightly difficult (SD), fairly difficult (FD), difficult (D), very difficult (VD) and extremely difficult (ED) cases were 35, 88, 170, 390, 203 and 137, respectively. The perioperative complications were evaluated based on the 3 time periods, with a specific emphasis on determining the learning curve according to the modified Clavien classification system of complications. RESULTS: A total of 236 (23.1%) complications were observed according to the modified Clavien classification. The minor (Clavien I-II) and major (Clavien III, IV and V) complication rates were 20.5% (n = 210) and 2.4% (n = 26), respectively. Clavien I was the most frequently encountered type of complication (n = 120, %11.7). No significant difference was observed among all 3 time periods regarding total complication rates. The D cases had the highest complication rate compared to E, SD, FD, VD and ED cases among all three terms. The total number of complications increased significantly with increasing grade of technical difficulty according to the ESS. CONCLUSION: Complications encountered in our laparoscopic surgery experience were predominantly minor, and the rate of complications was not significantly increased during the learning curve. The present data can provide guidance and manage expectations for surgeons introducing laparoscopy into their practice.

Imaging Appearances of Paratesticular Fibrous Pseudotumor.

BACKGROUND: In this paper the clinical and radiological features of three cases with paratesticular fibrous pseudotumor were presented after a retrospective analysis of medical archives of our hospital. CASE REPORT: Each of the three cases had unilateral, multiple nodular lesions with smooth borders accompanied by a hydrocele. On sonographic examination, the lesions showed echogenicity similar to, or slightly lower than, the testis, and the two large lesions had posterior acoustic shadowing. Color Doppler ultrasound examination of two cases showed intralesional vascularity of mild-to-moderate degree. All lesions appeared hypointense compared to testicular tissue on T1W and T2W magnetic resonance images. Moderate-to-high enhancement was observed in the diffuse pattern after intravenous injection of contrast material. An intraoperative pathological examination was performed and local excision carried out in all three cases. CONCLUSIONS: Fibrous pseudotumor is a rare benign paratesticular lesion, which can be confused with malignant masses. Imaging procedures play an important role in correct diagnosis. Unfamiliarity with imaging findings of paratesticular fibrous pseudotumor may eventuate in an unnecessary orchiectomy.

The increased transglutaminase 2 expression levels during initial tumorigenesis predict increased risk of metastasis and decreased disease-free and cancer-specific survivals in renal cell carcinoma.

PURPOSE: The aim of this study was to investigate the role of transglutaminase 2(TG2) in renal cell carcinoma (RCC) by comparing the immunohistochemistry staining of primary and metastatic tumor tissues. METHODS: A total of 33 metastatic RCC(mRCC) and 33 non-metastatic RCC (nmRCC) patients who were matched as closely as possible based on gender, age, nuclear grade and pathologic T stage were retrospectively investigated. TG2 immunohistochemistry staining was performed on paraffin-embedded primary tumor tissues from both patient groups and on metastatic tissues from mRCC patients. The tissues were scored from 0 to 7 according to the TG2 staining. Furthermore, the patients were stratified into two groups using median primary tumor staining score as the cutoff value: Group 1 (high risk, n = 41) and Group 2(low risk, n = 22). The clinical, histopathological and survival outcomes were compared between these risk groups using Chi-square test, t test, Mann-Whitney U test and Kaplan-Meier survival analyses. RESULTS: The median TG2 score for primary tumor was 5 for the entire study population. The median primary tumor TG2 score of the mRCC patients was significantly higher compared to the nmRCC patients (6 vs. 4, p < 0.001). The TG2 score between the primary and metastatic tissues of mRCC patients was not significantly different (6 vs. 7, p = 0.086). The percentage of metastatic patients was significantly higher in Group 1 compared to Group 2 (68.3 vs. 18.2 %, p < 0.001). Kaplan-Meier analyses showed that 5-year disease-free (34.9 vs. 92.9 %, p = 0.001) and cancer-specific (47.4 vs. 86.5 %, p = 0.04) survival rates were significantly lower in high-risk group. CONCLUSIONS: The increased expression of TG2 in primary tumor predicts metastasis in RCC patients and is also associated with a decrease in disease-free and cancer-specific survival outcomes.

Novel mutations and role of the LKB1 gene as a tumor suppressor in renal cell carcinoma.

The tumor suppressor LKB1 gene is a master kinase and inhibits mammalian target of rapamycin (mTOR) by activating AMP-activated protein kinase (AMPK) and AMPK-related kinases. LKB1 is a critical intermediate in the mTOR signaling pathway, and mutations of the LKB1 gene have been implicated in the development of different tumor types. Recent evidence indicates that LKB1 alterations contribute to cancer progression and metastasis by modulating vascular endothelial growth factor (VEGF) production. The Ras homolog enriched in brain (RHEB) protein is a component of the mTOR pathway and functions as a positive regulator of mTOR. However, the mechanisms and effectors of RHEB in mTOR signaling are not well known. In this study, we analyzed the expression of RHEB and HIF1α genes in correlation with LKB1 gene mutations. All coding exons and exon/intron boundaries of the LKB1 gene were analyzed by direct sequencing in 77 renal cell carcinoma (RCC) tumors and 62 matched noncancerous tissue samples. In 51.6 % of the patients, ten different mutations including four novel mutations in the coding sequences and six single nucleotide substitutions in the introns were observed. Rheb and HIF1α expression levels were not statistically different between the tumor and corresponding noncancerous tissue samples. However, expression of the Rheb gene was upregulated in the tumor samples carrying the intron 2 (+24 G→T) alteration. Association between the gene expression and tissue protein levels was also analyzed for HIF1α in a subgroup of patients, and a high correlation was confirmed. Our results indicate that the LKB1 gene is frequently altered in RCC and may play a role in RCC progression.

EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study.

Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question "whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods" and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p=0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found in total patients group (r=0.683, p=0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment.

LKB1 mutations and their correlation with LKB1 and Rheb expression in bladder cancer.

Although there are extensive studies on the genetics of bladder cancer, several questions remain unanswered. One of the pathways which are altered in bladder cancer is the mTOR signaling pathway. In the present study, we analyzed the expression of Rheb gene and genetic alterations in the LKB1 gene which are the key components of mTOR pathway. Nine exons of the LKB1 gene were analyzed by direct sequencing in 51 bladder cancer patients. To investigate the expression of Rheb and LKB1, real-time quantitative RT-PCR was performed in bladder tumor and normal bladder tissue samples. We did not observed a statistically significant difference in Rheb or LKB1 expression between the tumor and normal tissue samples. We detected a novel missense mutation creating stop codon in a high percent of the tumor samples. Five different single nucleotide substitutions were also observed in the introns. Our results indicate that LKB1 gene may play a role in the progression of bladder cancer.

Tunica albuginea decompression fails to alter the injury of prolonged arterial occlusion during testicular torsion.

PURPOSE: The correlation between intratesticular pressure during torsion/detorsion and subsequent testicular function and viability has been reported in several recent studies. We assessed the impact of tunica albuginea incision with tunica vaginalis flap coverage on intratesticular pressure and future histopathological parameters in a rat testicular torsion model. MATERIALS AND METHODS: A total of 21 rats were divided into 3 groups. Group 1 consisted of 7 controls undergoing a sham operation, group 2 consisted of 7 animals undergoing torsion-detorsion, and group 3 consisted of 7 animals undergoing testicular torsion-detorsion followed by tunica albuginea incision and tunica vaginalis flap coverage. Torsion was created by 720-degree counterclockwise rotation of the left testis for 2 hours. By using a compartment monitor, the intratesticular pressure of the torsed testes was measured before torsion (pre-torsion), immediately before torsion repair (pre-detorsion), 5 minutes after detorsion (post-detorsion), and after tunical incision and tunica vaginalis flap application. The correlations between intratesticular pressure values and testicular weight, modified Johnsen score and mean seminiferous tubule diameter were evaluated 4 weeks postoperatively. RESULTS: Median pre-detorsion intratesticular pressure was significantly decreased after detorsion in group 2 (21 vs 7 mm Hg, p <0.001) and group 3 (23 vs 7 mm Hg, p = 0.001). In addition, median intratesticular pressure after tunica albuginea incision and tunica vaginalis flap coverage in group 3 was significantly less compared to median post-detorsion intratesticular pressure in group 2 (5 vs 7 mm Hg, p = 0.025). Overall no significant difference was detected between groups 2 and 3 regarding median modified Johnsen score, mean seminiferous tubule diameter or median testicular weight. The significant reduction of intratesticular pressure in group 3 did not correlate with testicular weight (r = 0.500, p = 0.391), modified Johnsen score (r = -0.205, p = 0.741) or mean seminiferous tubule diameter (r = -0.200, p = 0.747). CONCLUSIONS: Tunica albuginea decompression with tunica vaginalis flap coverage is an effective technique for decreasing intratesticular pressure in torsed testes. However, this technique failed to alter the injury of prolonged arterial occlusion in testicular torsion.

Manganese superoxide dismutase Ile58Thr, catalase C-262T and myeloperoxidase G-463A gene polymorphisms in patients with prostate cancer: relation to advanced and metastatic disease.

OBJECTIVE: To evaluate the relationship between manganese superoxide dismutase (MnSOD) Ile58Thr, catalase (CAT) C-262T and myeloperoxidase (MPO) G-463A gene polymorphisms and the susceptibility and clinicopathological characteristics of prostate cancer. PATIENTS AND METHODS: In all, 155 patients diagnosed with prostate cancer and 195 controls with negative digital rectal examinations and PSA levels of <4 ng/dL were enrolled in this study. MnSOD, CAT and MPO gene polymorphisms were identified by polymerase chain reaction restriction-fragment length polymorphism methods. RESULTS: The TT genotype in MnSOD Ile58Thr polymorphism, CC genotype in the CAT C-262T polymorphism and the GG genotype in the MPO G-463A polymorphism were the predominant genotypes amongst this Turkish male population. There was no association between MnSOD Ile58Thr polymorphism and prostate cancer. For the CAT C-262T polymorphism, the TT genotype had significantly increased prostate cancer risk compared with the CC genotype. Similarly, the TT genotype had a 1.94- and 3.83-fold increased risk for high-stage disease and metastasis, respectively, when compared with the CC genotype. For the MPO G-463A polymorphism, the GG genotype had 1.78-fold increased risk of prostate cancer compared with the AA genotype. However, no association was found regarding Gleason score, advanced and metastatic prostate cancer risk. CONCLUSIONS: It seems that there is no association of prostate cancer with MnSOD Ile58Thr polymorphism, whereas the TT genotype in the CAT C-262T polymorphism and the GG genotype in the MPO G-463A polymorphism may be associated with increased prostate cancer risk. The TT genotype in the CAT C-262T gene polymorphism may also be a risk factor in tumour progression and metastasis among Turkish men.

Use of a combined retroperitoneoscopic and transperitoneal laparoscopic technique for the management of renal cell carcinoma with level I tumor thrombi.

BACKGROUND: To report our initial experiences using a combined retroperitoneoscopic and transperitoneal laparoscopic technique for the management of renal cell carcinoma with level I tumor thrombi. MATERIALS AND METHODS: Two patients underwent this technique for tumors 11- and 13-cm in diameter. After transection of the renal artery with limited mobilization of the kidney using a retroperitoneoscopic approach, additional ports were placed, and the management of the tumor thrombus was performed in the large working space provided by the transperitoneoscopic approach. RESULTS: The technique was feasible in the present 2 cases. The total operative times were 170 and 200 min, respectively. The estimated blood loss was 450 cc in the first case and 200 cc in the second case. No complications were observed in either of the patients. CONCLUSIONS: Based on the initial clinical experience, we have presented a feasible surgical option for the laparoscopic management of renal cell carcinoma with level I thrombi.

Nitric oxide synthase (eNOS4a/b) gene polymorphism is associated with tumor recurrence and progression in superficial bladder cancer cases.

PURPOSE: We investigated the relationship between the distribution of the eNOS4a/b polymorphism and the clinical features of superficial bladder cancer. MATERIALS AND METHODS: This study included 201 healthy controls with a mean ± SD age of 62.35 ± 7.96 years and 123 patients with a mean age of 64.03 ± 11.00 years diagnosed with histopathologically confirmed superficial bladder cancer. The eNOS4a/b polymorphism genotype (aa, bb or ab) was identified by polymerase chain reaction. Blood glutathione and plasma malondialdehyde levels were measured by spectrophotometry as an indicator of oxidative stress. We estimated total plasma levels of nitric oxide metabolites using a colorimetric assay kit. RESULTS: There were no significant differences in age or body mass index between patients and controls. Malondialdehyde and nitric oxide metabolite levels were statistically significantly increased (p = 0.000 and 0.024, respectively) and glutathione levels were decreased (p = 0.000) in patients with superficial bladder cancer. The bb genotype of the eNOS4a/b polymorphism is the most frequent one in the Turkish population and the aa genotype was significantly more common in patients with superficial bladder cancer (p = 0.000). Also, the aa plus ab genotype was significantly more common in patients with high grade tumors (p = 0.013) and in those with more progression to muscle invasive disease (p = 0.000). This genotype was also a significant independent risk factor for recurrence after adjusting for smoking status, stage, grade and the presence of carcinoma in situ on logistic regression analyses (OR 3.095, 95% CI 1.21-7.86, p = 0.018). CONCLUSIONS: The current study suggests that a genotype containing the a allele of the eNOS4a/b polymorphism may be a risk factor for bladder cancer. Additionally, patients harboring the aa plus ab genotype are more likely to experience tumor recurrence and progression.

Increased risk of advanced prostate cancer associated with MnSOD Ala-9-Val gene polymorphism.

We aimed to investigate the association between manganese superoxide dismutase (MnSOD) Ala-9-Val gene polymorphism and the initiation and/or progression of prostate cancer (PCa) as well as to evaluate its potential interactions with advanced age and smoking status. MnSOD Ala-9-Val gene polymorphism was carried out in 134 (mean age 64.1±7.48) PCa patients and 159 (mean age 62.5±7.53) healthy controls with serum prostate specific antigen (PSA) levels (<4 ng/ml) and normal digital rectal examination (DRE) findings in this prospectively designed study. PCa patients were classified as low stage disease (T1 or T2 and N0M0 stages) and high stage disease (T3 or T4 and N0M0 or N1 or M1 stages). Genotypes for MnSOD Ala-9-Val gene polymorphism were identified by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL). Despite lack of association between different genotypes of MnSOD Ala-9-Val gene polymorphism and the presence of PCa, patients with Ala/Ala genotype were at an increased risk of high stage disease compared with those with the Val/Val genotype [odds ratio (OR), 3.77; 95% CI, 1.30-10.94; P=0.012]. However, no significant difference was observed in the distribution of each genotype among PCa patients, with respect to tumor grade. On the other hand, smoking status and aging did not seem to change the association between genotypes and PCa risk. Ala/Ala genotype of MnSOD polymorphism may have an effect on adverse features of PCa such as high stage disease.

Association between SDF1-3'A or CXCR4 gene polymorphisms with predisposition to and clinicopathological characteristics of prostate cancer with or without metastases.

In the present study, we aimed to investigate the association between SDF1-3'A and CXCR4 gene polymorphisms and the susceptibility and clinicopathological development of prostate cancer. SDF1-3'A and CXCR4 gene polymorphisms were assessed by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) in 149 healthy subjects and 152 patients with prostate cancer. There were no significant differences in the distributions of SDF-1 and CXCR4 genotypes between controls and prostate cancer patients. However, the patients with AA genotype of SDF1-3'A gene presented a higher risk for developing an advanced disease status as compared to patients with GG homozygotes (aOR = 2.02; 95 % CI = 1.05-3.90; P = 0.035). In addition, the distribution of AA genotype of SDF1-3'A gene was found significantly increased in the patients with bone metastasis in comparison to those without bone metastasis (aOR = 2.94; 95 % CI = 1.26-6.82; P = 0.012). On the other hand, CXCR4 gene polymorphism was not associated with the clinicopathological characteristics of prostate cancer. Our results suggest that SDF1-3'A and CXCR4 gene polymorphisms may not be risk factors for the susceptibility to prostate cancer. However, SDF1-3'A gene polymorphism may be associated with the progression and bone metastasis of prostate cancer in a Turkish men population.