Small cell variant of chromophobe renal cell carcinoma: Clinicopathologic and molecular-genetic analysis of 10 cases.

The morphologic diversity of chromophobe renal cell carcinoma (ChRCC) is well-known. Aside from typical morphology, pigmented adenomatoid, multicystic and papillary patterns have been described. Ten cases of CHRCC composed of small cell population in various percentages were analysed, using morphologic parameters, immunohistochemistry and next-generation sequencing (NGS) testing. Patients were five males and five females, with age ranging from 40 to 78years. The size of tumors ranged from 2.2 cm to 11 cm (mean 5.17 cm). Small cell component comprised 10 to 80% of the tumor volume, while the remaining was formed by cells with classic ChRCC morphology. The immunohistochemical profile of the small cell component was consistent with typical ChRCC immunophenotype, with CD117 and CK7 positivity. Neuroendocrine markers were negative. Mutations of 13 genes were found: DCIER1, FGFR3, JAK3, SUFO, FAM46C, FANCG, MET, PLCG2, APC, POLE, EPICAM, MUTYH and AR. However, only the PLCG2 mutation is considered pathogenic.The small cell variant of ChRCC further highlights and expand upon existing morphologic heterogeneity spectrum. Recognition of small cell variant of CHRCC is not problematic in tumors, where the "classic" CHRCC component is present. However, in limited material (i.e., core biopsy), this may present a diagnostic challenge. Based on the limited follow-up data available, it appears that the small cell tumor component had no impact on prognosis, since there was no aggressive behavior documented.   Awareness of this unusual pattern and applying additional sections to find classic morphology of ChRCC, as well as excluding neuroendocrine nature by immunohistochemistry, may help resolve difficult cases.

Prostate Cancer Diagnostic Algorithm as a "Road Map" from the First Stratification of the Patient to the Final Treatment Decision.

The diagnostics of prostate cancer are currently based on three pillars: prostate biomarker panel, imaging techniques, and histological verification. This paper presents a diagnostic algorithm that can serve as a "road map": from initial patient stratification to the final decision regarding treatment. The algorithm is based on a review of the current literature combined with our own experience. Diagnostic algorithms are a feature of an advanced healthcare system in which all steps are consciously coordinated and optimized to ensure the proper individualization of the treatment process. The prostate cancer diagnostic algorithm was created using the prostate specific antigen and in particular the Prostate Health Index in the first line of patient stratification. It then continued on the diagnostic pathway via imaging techniques, biopsy, or active surveillance, and then on to the treatment decision itself. In conclusion, the prostate cancer diagnostic algorithm presented here is a functional tool for initial patient stratification, comprehensive staging, and aggressiveness assessment. Above all, emphasis is placed on the use of the Prostate Health Index (PHI) in the first stratification of the patients as a predictor of aggressiveness and clinical stage of prostrate cancer (PCa). The inclusion of PHI in the algorithm significantly increases the accuracy and speed of the diagnostic procedure and allows to choose the optimal pathway just from the beginning. The use of advanced diagnostic techniques allows us to move towards to a more advanced level of cancer care. This diagnostics algorithm has become a standard of care in our hospital. The algorithm is continuously validated and modified based on our results.

The predictive value of the prostate health index vs. multiparametric magnetic resonance imaging for prostate cancer diagnosis in prostate biopsy.

PURPOSE: To compare the ability of Prostate Health Index (PHI) to diagnose csPCa, with that of total PSA, PSA density (PSAD) and the multiparametric magnetic resonance (mpMRI) of the prostate. METHODS: We analysed a group of 395 men planned for a prostate biopsy who underwent a mpMRI of the prostate evaluated using the PIRADS v1 criteria. All patients had their PHI measured before prostate biopsy. In patients with an mpMRI suspicious lesions, an mpMRI/ultrasound software fusion-guided biopsy was performed first, with 12 core systematic biopsy performed in all patients. A ROC analysis was performed for PCa detection for total PSA, PSAD, PIRADS score and PHI; with an AUC curve calculated for all criteria and a combination of PIRADS score and PHI. Subsequent sub-analyses included patients undergoing first and repeat biopsy. RESULTS: The AUC for predicting the presence of csPCa in all patients was 59.5 for total PSA, 69.7 for PHI, 64.9 for PSAD and 62.5 for PIRADS. In biopsy naive patients it was 61.6 for total PSA, 68.9 for PHI, 64.6 for PSAD and 63.1 for PIRADS. In patients with previous negative biopsy the AUC for total PSA, PHI, PSAD and PIRADS was 55.4, 71.2, 64.4 and 69.3, respectively. Adding of PHI to PIRADS increased significantly (p = 0.007) the accuracy for prediction of csPCa. CONCLUSION: Prostate Health Index could serve as a tool in predicting csPCa. When compared to the mpMRI, it shows comparable results. The PHI cannot, however, help us guide prostate biopsies in any way, and its main use may, therefore, be in pre-MRI or pre-biopsy triage.

Preoperative prostate health index predicts adverse pathology and Gleason score upgrading after radical prostatectomy for prostate cancer.

BACKGROUND: We aimed to explore the utility of prostate specific antigen (PSA) isoform [- 2] proPSA and its derivatives for prediction of pathological outcome after radical prostatectomy (RP). METHODS: Preoperative blood samples were prospectively and consecutivelyanalyzed from 472 patients treated with RP for clinically localized prostate cancerat four medical centers. Measured parameters were PSA, free PSA (fPSA), fPSA/PSA ratio, [- 2] proPSA (p2PSA), p2PSA/fPSA ratio and Prostate Health Index (PHI)(p2PSA/fPSA)*√PSA]. Logistic regression models were fitted to determine the accuracy of markers for prediction of pathological Gleason score (GS) ≥7, Gleason score upgrading, extracapsular extension of the tumor (pT3) and the presence of positive surgical margin (PSM). The accuracy of predictive models was compared using area under the receiver operating curve (AUC). RESULTS: Of 472 patients undergoing RP, 339 (72%) were found to have pathologic GS ≥ 7, out of them 178 (53%) experienced an upgrade from their preoperative GS = 6. The findings of pT3 and PSM were present in 132 (28%) and 133 (28%) cases, respectively. At univariable analysis of all the preoperative parameters, PHI was the most accurate predictor of pathological GS ≥7 (OR 1.02, 95% CI 1.01-1.03, p<0.001), GS upgrading (OR 1.02, 95% CI 1.01-1.03, p<0.003), pT3 disease (OR 1.01, 95% CI 1.00-1.02, p<0.007) and the presence of PSM (OR 1.01, 95% CI 1.00-1.02, p<0.002). Adding of PHI into the base multivariable model increased significantly the accuracy for prediction of pathological GS by 4.4% to AUC = 66.6 (p = 0.015) and GS upgrading by 5.0% to AUC = 65.9 (p = 0.025), respectively. CONCLUSIONS: Preoperative PHI levels may contribute significantly to prediction of prostate cancer aggressiveness and expansion of the tumor detected at final pathology.

Stability of total prostate-specific antigen and free prostate-specific antigen after 10 years' storage.

INTRODUCTION: PSA is a serine protease composed of 240 amino acids in a single polypeptide chain and is a routine parameter in prostate cancer diagnostics. The aim of our study was to test the long-term stability of tPSA and fPSA after 10 years' storage at -80°C. MATERIALS AND METHODS: We analyzed two aliquots from 55 serum samples. The first was assayed in routine testing at the time of establishing the diagnosis. The second was thawed for further testing after approximately 10 years' storage at -80°C. The mean of storage time was 10.41 years (min-max: 9.35-11.40 years). We compared the results of tPSA and fPSA. We calculated the fPSA/tPSA ratio and compared the results of clinical evaluation. Serum tPSA and fPSA levels were assayed using chemiluminescent kits Access Hybritech PSA and free PSA. All measurements were performed using the instrument UniCel® DxI 800. RESULTS: tPSA decreased 3.59% on average with a correlation r=0.9213, and fPSA increased at an average of 2.41% with a correlation r=0.9338. The fPSA/tPSA ratio increased 0.80% on average with a correlation r=0.9174. On clinical evaluation, five samples had fallen to a less malignant category and three samples had risen to a higher malignant category compared with the original results. CONCLUSION: The stability of tPSA and fPSA levels in serum is sufficient after 10 years' storage at -80°C. Calculation of the fPSA/tPSA ratio is not recommended due to the change in the category of malignancy of 15% of the samples.

The Ability of Prostate Health Index (PHI) to Predict Gleason Score in Patients With Prostate Cancer and Discriminate Patients Between Gleason Score 6 and Gleason Score Higher Than 6-A Study on 320 Patients After Radical Prostatectomy.

AIM: The purpose of this study was to investigate the Prostate Health Index as a marker for tumor aggressiveness in prostate biopsy and the optimization of indication for treatment options. METHODS: Our cohort consisted of 320 patients indicated for radical prostatectomy with preoperative measurements of total prostate-specific antigen, free prostate-specific antigen, [-2]proPSA, calculated %freePSA, and Prostate Health Index. The Gleason score was determined during biopsy and after radical prostatectomy. Using the Gleason score, we divided the group of patients into the 2 subgroups: Gleason score ≤6 and Gleason score >6. This division was performed according to the biopsy Gleason score and according to the postoperative Gleason score. We compared total prostate-specific antigen, [-2]proPSA, %freePSA, and Prostate Health Index in the subgroups Gleason score ≤6 and Gleason score >6 after biopsy and the definitive score. RESULTS: On evaluation of the subgroups created by Gleason score ≤6 and Gleason score >6, we observed agreement between biopsy Gleason score and definitive Gleason score in only 45.3% of cases. Of the calculated biopsy, Gleason score ≤6 and Gleason score >6 subgroups, [-2]proPSA, and Prostate Health Index ( P = .0003 and P = .0005) were statistically significant. Of the definitive Gleason score ≤6 and Gleason score >6 subgroups, Prostate Health Index, [-2]proPSA, %freePSA, and PSA ( P < .0001, P < .0001, P = .0003, and P = .0043) were statistically significant. The best area under the curve value (0.7496) was achieved by Prostate Health Index when the subgroups were established according to the postoperative Gleason score. CONCLUSION: Prostate Health Index is the best of the tested markers for the categorization of Gleason score 6 tumors and for facilitating the management of patients with prostate cancer. Prostate Health Index can be a helpful marker for indication of active surveillance or radical prostatectomy. Prostate health index can also simplify the decision of whether to perform nerve-sparing radical prostatectomy.

Surgical treatment of kidney tumors - contemporary trends in clinical practice.

INTRODUCTION: The aim of this article is to generally describe the roles of main surgical modalities in treatment of renal tumors, especially in the CT1a category in clinical practice. Surgical modalities include the following: laparoscopic or open resection (LR, OR) and laparoscopic or open nephrectomy (LN, ON). Representation of these methods has been changing over years due to improved operative skills and equipment and due to a shift of tumors to the lower T categories. MATERIAL AND METHODS: The sources of data were surgeries performed for renal tumors at the institution of the main author during the period 2002 to III/2016, reaching a total of 2204 cases (546 ONs, 647 LNs, 668 ORs and 343 LRs). Patients indicated for percutaneous ablative therapy or active surveillance were not included. RESULTS: During the whole period, the proportions of methods were: ONs 24.8%, LNs 29.4%, ORs 30.3%, LRs 15.6%. But during the years 2014 - III/2016, these changed to 12.6%:26.3%:31.6%:29.4% (in cT1a 1.7%:8.3%:37.8%:52.2%). Category cT1a constitutes in the years 2007 - III/2016 41.3%, in 2014 - III/2016 50.9%. CONCLUSIONS: Resections and minimally invasive approaches are being performed more frequently and are the preferred methods in surgical treatment of kidney tumors. Resection is now indicated in about 60% of cases (open vs. laparoscopic resection are used nearly equally with a slight tendency for laparascopic predomination). In the cT1a category (amounting to approximately 50% of all surgically treated tumors), resection is possible in about 85-90% of cases.

PHI in the Early Detection of Prostate Cancer.

AIM: To evaluate changes in the serum levels of prostate specific antigen (PSA), %free PSA and -2proPSA biomarkers, and prostate health index (PHI) in the diagnostic algorithm of early prostate cancer. PATIENTS AND METHODS: The Immunoanalytical Laboratory of the University Hospital in Pilsen examined sera from 263 patients being treated at the Hospital's Urology Department with suspected prostate cancer who had undergone biopsies and were divided into a benign and malignant group. The monitored biomarkers were measured using chemiluminescence. All statistical analyses were calculated using the SAS software. RESULTS: We found statistically significantly increased levels of -2proPSA, PHI and PSA and decreased levels of %freePSA in patients diagnosed with prostate cancer by prostate biopsy vs. patients with benign prostatic hypertrophy (median values: -2proPSA: 16 vs. 21 ng/l, PHI: 35 vs. 62, total PSA: 7.2 vs. 7.7 µg/l and %free PSA: 16.7 vs. 11.7%). Receiver operating characteristic curves showed the best performance for PHI compared to other markers. CONCLUSION: The assessment of -2proPSA and the calculation of PHI appear to be of great benefit for a more accurate differential diagnosis of benign hyperplasia and prostate cancer.

Laparoscopic urinary bladder diverticulectomy combined with photoselective vaporisation of the prostate.

INTRODUCTION: Pseudodiverticulum of the urinary bladder is mostly a complication of subvesical obstruction (SO). The gold standard of treatment was open diverticulectomy with adenectomy. A more contemporary resolution is endoscopic, in two steps: the first transurethral resection of the prostate (TURP), the second laparoscopic diverticulectomy (LD). AIM: To present a one-session procedure - photoselective vaporisation of the prostate (PVP) with LD. MATERIAL AND METHODS: From 1/2011 to 6/2014, 14 LDs were performed: 1 LD only, 1 with laparoscopic radical prostatectomy, 12 combined with treatment of benign prostatic hyperplasia (BPH), 4 cases of TURP and LD in the second period. In 8 cases, PVP and LD in one session were combined. These 8 cases are presented. 3D CT cystography was used as a gold standard for assessment of diverticulum. RESULTS: The mean age was 66.5 ±5.5 (57.3-75.1) years, the mean size of the diverticulum 61.8 ±22.1 (26-90) mm. The procedure starts in the lithotomy position. It includes PVP and stenting of the ureter(s). Changing of position and laparoscopy follows: four ports, transperitoneal extravesical approach. Photoselective vaporisation of the prostate was performed using the Green Light Laser HPS (1x) or XPS with cooled fibre MoXy (7x). The mean delivered energy in PVP was 205.1 ±106.4 (120-458) kJ. The mean time of operation was 165.0 ±48.5 (90-255) min. No postoperative complications were observed. One patient underwent TUR incision after 1 year for sclerosis of the bladder neck. CONCLUSIONS: Pseudodiverticulum of the urinary bladder (with or without SO) is a relatively rare disease. One session of PVP (Green Light Laser XPS, MoXy fibre) and laparoscopic (transperitoneal extravesical) diverticulectomy is the preferred method for treatment of subvesical obstruction due to BPH and bladder diverticulum at our institution.

Choriogonadotropin positive seminoma-a clinicopathological and molecular genetic study of 15 cases.

The presence of human chorionic gonadotropin (hCG) positive syncytiotrophoblastic cells (STC) in classic seminoma (CS) is well documented. CS with extensive hCG positive, non-syncytiotrophoblastic tumour cells (without STC) is exceptionally rare. In this study, we present 15 such cases. 168 CSs were retrieved from the Plzen Tumor registry. Cases of mixed germ cell tumors (with CS) and CSs with typical STC were excluded. Cases with completely embedded tumor mass were selected for further study and immunohistochemically examined with anti-hCG. Positive cases were further analyzed by reverse transcriptase polymerase chain reaction. Two groups of hCG-positive CSs were identified. Group 1 comprised 10 patients with a mean patient age of 37.7 years and mean tumor size of 4.96 cm. Eight cases were pT1 (TMN 2009) and 2 cases pT3a. Blood levels of hCG were elevated in 6 of the 10 patients preoperatively. In 2 patients the blood level of hCG was not tested. Mean follow-up period was 6.1 years. No metastatic behavior was noted. All tumors were extensively immunoreactive for hCG in more than 60% of tumor cells. The expression of hCG beta subunit (CGB)-mRNA in tumor tissue was documented. Group 2: Comprised 5 patients with a mean age was 34 years. Mean tumor size was 4.7 cm. Four cases were stage pT1 and 1 case was pT2. The mean follow-up period was 3.1 years. No metastatic behavior was noted. Preoperative blood levels of hCG were elevated in 1/5 of the patient. Strong hCG positivity was limited to scattered single tumor cells distributed throughout the entire tumor. Only weak expression of CGB mRNA was detected. We can conclude that immunohistochemical detection of expression of hCG in CS is not limited to syncytiotrophoblastic cells. In this study, we report two immunohistochemical patterns of hCG expression in classic seminomas: diffuse hCG staining in the majority of tumor cells and scattered hCG-positive cells within the tumor.

Laparoendoscopic single-site surgery adrenalectomy - own experience and matched case-control study with standard laparoscopic adrenalectomy.

INTRODUCTION: At our institution, laparoendoscopic single-site surgery (LESS) has been established as a technique for laparoscopic nephrectomy since 2011, and since 2012 in selected cases for adrenalectomy (AE) as well. AIM: To compare LESS AE with standard laparoscopic AE (SLAE). MATERIAL AND METHODS: Between 3/2012 and 7/2014, 35 adrenalectomies were performed. In 18 (51.4%), a LESS approach was chosen. Indications were strictly non-complicated cases (body mass index (BMI) < 34 kg/m(2), tumour ≤ 7 cm, non-malignant aetiology, no previous surgery). All LESS procedures were done by one surgeon. Standard equipment was a 10 mm rigid 0° camera, Triport+, one pre-bent grasper, and a sealing instrument. The approach was pararectal in all cases except one (transumbilical in a slim man). Three patients with LESS were excluded (2 partial AEs only, one adrenal cancer converted to SLAE and then to open surgery). These 15 LESS AE procedures were compared to 15 SLAEs with similar characteristics chosen among 54 SLAEs performed in the period 1/2008-2/2012. RESULTS: In 8 cases (53.3%) of LESS AE, a 3 mm port was added to elevate the liver/spleen. Mean parameters of LESS AE vs. SLAE (Wilcoxon test): maximal tumour diameter 43.7 mm vs. 36.1 mm (p = 0.28), time of surgery 63.3 min vs. 55.3 min (p = 0.22), blood loss 38.0 ml vs. 38.0 ml (p = 0.38), BMI 26.9 kg/m(2) vs. 28.5 kg/m(2) (p = 0.13), discharge from hospital 5.4 days vs. 3.9 days (p = 0.038). There were no complications in either group. CONCLUSIONS: The LESS AE is feasible in selected cases, especially small left-sided tumours in thin patients with no history of previous abdominal operations, but requires an additional port in half of the cases.