ABSTRACT
BACKGROUND: Upper-tract-urothelial-carcinoma (UTUC) represents 5-10% of all urothelial-neoplasms with increasing incidence in the last decades. Current standard tools for diagnosis of UTUC include cytology, computed tomography (CT) urography and ureterorenoscopy (URS). The aim of this study was to evaluate the impact of Bladder Epicheck® Test as diagnostic tool for UTUC diagnosis and recurrence. METHODS: Overall, 136 urine samples, selective collected from upper-urinary-tract before URS for suspicion of UTUC were analyzed with cytology and Bladder Epicheck® Test. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of both markers were calculated and compared to URS and/or histology as reference. RESULTS: UTUC was detected in 40 cases (33.3%), among them 30 were classified as low-grade (LG) and 10 as high-grade (HG). Overall sensitivity of Bladder Epicheck® for UTUC detection was 65% compared to 42.5% for cytology, increasing to 100% for Bladder Epicheck® and 90% for cytology if considering only HG tumors. Overall specificity of Bladder Epicheck® was 81.2% and of cytology 93.7%. PPV and NPV were 63.4% and 82.2% for Bladder Epicheck® and 77.2% and 76.5% for cytology. Considering an EpiScore cut-off >75, instead of 60, specificity of Bladder Epicheck® improves to 89% and PPV to 74.2%. Limitations include the use of a marker validated only for bladder-cancer and the relatively small number of cases. CONCLUSIONS: Due to its high sensitivity for HG tumors, the Bladder Epicheck® Test can be used in diagnosis and treatment decision-making of UTUC. Furthermore, it could be very useful in follow-up of UTUC, after endoscopic treatment to postpone or avoid unnecessary endoscopic exploration. Even if further studies are needed to validate these findings, Bladder Epicheck® could be a promising clinical tool for detection of UTUC.
Subject(s)
Biomarkers, Tumor , Humans , Female , Male , Aged , Prospective Studies , Middle Aged , Biomarkers, Tumor/urine , Kidney Neoplasms/urine , Kidney Neoplasms/diagnosis , Ureteral Neoplasms/diagnosis , Ureteral Neoplasms/urine , Sensitivity and Specificity , Aged, 80 and over , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/urine , Predictive Value of Tests , Adult , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/urineABSTRACT
BACKGROUND/AIM: The aim of the study was to establish the performance of the M371-Test on the Thermocycler Rotor-GeneQ (Qiagen) platform for diagnosis and follow-up of testicular tumors and to evaluate the test under real-life conditions in comparison to the classical markers alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (ß-HCG) and lactate dehydrogenase (LDH). PATIENTS AND METHODS: Forty-four patients, of median age 29 years (range=24-84) were included in this prospective study at our institution between March 2021 and September 2022. Of the 44 patients, 23 had a suspicion of testicular cancer (TC) and 21 were under follow-up for TC. In total, 96 M371-Tests were performed and compared with AFP, ß-HCG, LDH using histological diagnosis and/or computer tomography (CT) scan as the gold standard. RESULTS: In the patients with suspicion of TC, the M371-Test showed a sensitivity of 73.7%, AFP of 21%, LDH of 31.6% and ß-HCG of 42.1%. In the patients under follow-up for TC, the M371-Test showed a sensitivity of 86.4%, AFP of 50%, LDH of 31.8% and ß-HCG of 63.6%. In germ cell tumours (GCT)/non-seminomas, M371-Test had a sensitivity of 83.3%, AFP of 77.8%, LDH of 38.9% and ß-HCG of 66.7%. In GCT/seminomas, M371-Test had a sensitivity of 85%, AFP of 5%, LDH of 30% and ß-HCG of 50%. CONCLUSION: Under real life conditions performed on the real-time Thermocycler Rotor-GeneQ (Qiagen) platform, the M371-Test shows an outstanding performance and is far beyond the sensitivity of the classical markers for detecting GCTs and in the follow-up of patients after GCT, especially in seminomas.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Seminoma , Testicular Neoplasms , Male , Humans , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Testicular Neoplasms/diagnosis , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , alpha-Fetoproteins , Follow-Up Studies , Biomarkers, Tumor/genetics , Prospective Studies , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/genetics , Seminoma/diagnosis , Seminoma/pathology , Chorionic GonadotropinABSTRACT
PURPOSE: Following the current guidelines, diagnosis and staging for upper urinary tract tumours (UTUC) can be performed with Computed Tomography, urography, ureterorenoscopy (URS) and selective cytology. The aim of the study was to evaluate the performance of the Xpert®-BC-Detection and the Bladder-Epicheck®-test in the detection of UTUC and compare it with cytology and the Urovysion®-FISH test using histology and URS as gold standard. METHODS: A total of 97 analyses were collected through selective catheterization of the ureter before URS to test for cytology, Xpert®-BC-Detection, Bladder-Epicheck® and Urovysion®-FISH. Sensitivity, specificity, and predictive values were calculated using histology results/URS as reference. RESULTS: Overall sensitivity was 100% for Xpert®-BC-Detection, 41.9% for cytology, 64.5% for Bladder-Epicheck® and 87.1% for Urovysion®-FISH. The sensitivity of Xpert®-BC-Detection was 100% in both, LG and HG tumours, sensitivity of cytology increased from 30.8% in LG to 100% in HG, for Bladder-Epicheck® from 57.7% in LG to 100% in HG and of Urovysion®-FISH from 84.6% in LG to 100% in HG tumours. Specificity was 4.5% for Xpert®-BC-Detection, 93.9% for cytology, 78.8% for Bladder-Epicheck® and 81.8% for Urovysion®-FISH. PPV was 33% for Xpert®-BC-Detection, 76.5% for cytology, 58.8% for Bladder-Epicheck® and 69.2% for Urovysion®FISH. NPV was 100% for Xpert®-BC-Detection, 77.5% for cytology, 82.5% for Bladder-Epicheck® and 93.1% for Urovysion®FISH. CONCLUSION: Bladder-Epicheck® and Urovysion®FISH along with cytology could be a helpful ancillary method in the diagnosis and follow-up of UTUC while due to its low specificity Xpert®-BC Detection seems to be of limited usefulness.
Subject(s)
Carcinoma, Transitional Cell , Kidney Neoplasms , Ureteral Neoplasms , Urinary Bladder Neoplasms , Urologic Neoplasms , Humans , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/pathology , Urinary Bladder/pathology , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Predictive Value of Tests , Cytodiagnosis/methods , Urologic Neoplasms/pathology , Ureteral Neoplasms/diagnosis , Ureteral Neoplasms/pathology , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Sensitivity and SpecificityABSTRACT
Objectives: Upper urinary tract urothelial carcinoma (UTUC) represents about 5-10% of all urothelial malignancies with an increasing incidence. The standard diagnostic tools for the detection of UTUC are cytology, computed tomography (CT) urography, and ureterorenoscopy (URS). No biomarker to be included in the daily clinical practice has yet been identified. The aim of our study was to evaluate the potential role of Xpert® Bladder-Cancer (BC)-Detection in the diagnosis of UTUC. Methods: Eighty-two patients underwent 111 URS with Xpert® BC-Detection, cytology, or Urovysion® analysis of UT for suspicion of UTUC. Twenty-four cases were excluded from the analysis due to a non-diagnostic Xpert® BC-Detection, cytology, or Urovysion®. Samples were analyzed with upper tract (UT) urinary cytology, with Xpert® BC-Detection on UT urines, and with Urovysion® Fluorescence in situ hybridization (FISH) test. After urine collection, the patients underwent retrograde pyelography and/or URS, and if positive a UT biopsy. The Xpert® BC-Detection was reported by the software as negative or positive [cut-off total Linear Discriminant Analysis (LDA) = 0.45]. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cytology, Xpert® BC-Detection and Urovysion-FISH were calculated using URS and/or histology results as reference. Results: In all, 27 (31%) of 87 URS resulted positive, with 20 low-grade (LG) and 7 high-grade (HG) tumors. Overall sensitivity was 51.9% for cytology, 100% for Xpert® BC-Detection, and 92.6% for Urovysion. The sensitivity of cytology increased from 26% in LG to 100% in HG tumors. For Xpert® BC-Detection, sensitivity was 100% both in LG and in HG, and for Urovysion-FISH, it increased from 90% in LG to 100% in HG tumors. PPV was 82.4% for cytology, 35% for Xpert® BC-Detection, and 73.5% for Urovysion. NPV was 81.4% for cytology, 100% for Xpert® BC-Detection, and 96.2% for Urovysion. Conclusion: The excellent NPV of Xpert® BC-Detection allows to avoid unnecessary endoscopic exploration of the UT, reducing invasiveness and URS complications in the follow-up of UTUC.
ABSTRACT
AIMS: Xpert® Bladder Cancer Monitor is a urinary marker based on the evaluation of five target mRNAs overexpressed in patients with bladder cancer (BC). The aim of our study is to update our results regarding the diagnostic accuracy of the Xpert® Bladder Cancer Monitor test in the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: We conducted a prospective study on 1015 samples of 416 patients (mean age 72.2 ± 10.3 years) under follow-up for NMIBC. Patients underwent voided urinary cytology, the Xpert® Bladder Cancer Monitor test and cystoscopy and, if positive, a transurethral resection of the bladder. Xpert® Bladder Cancer Monitor was reported as negative or positive: cut-off total Linear Discriminant Analysis (LDA) = 0.5. RESULTS: We identified 168 recurrent tumours: 126 (75%) were low-grade (LG) and 42 (25%) high-grade (HG). Overall sensitivity was 17.9% for cytology, 52.4% for Xpert® Bladder Cancer Monitor and 54.2% for the two tests combined. The sensitivity of cytology increased from 6.3% in LG to 52.4% in HG tumours whereas Xpert® Bladder Cancer Monitor showed a sensitivity ranging from 42.9% in LG to 80.9% in HG tumours. Combined cytology and Xpert® Bladder Cancer Monitor yielded an overall sensitivity of 45.2% for LG and 80.9% for HG tumours. Overall specificity was 98.5% for cytology and 78.4% for Xpert® Bladder Cancer Monitor and 78.2% for the two tests combined. The area under the curve (AUC) for Xpert® Bladder Cancer Monitor was 0.71; stratifying the patients according to the European Association of Urology risk groups, the AUC was 0.69, 0.67 and 0.85 for low, intermediate and high risk, respectively (p = 0.0003). CONCLUSION: Our data confirm a significantly higher sensitivity of Xpert® Bladder Cancer Monitor than for cytology in a larger patient cohort. The test performed very well in terms of specificity but could not reach the high value of cytology. Along with voided urinary cytology the test could allow to reduce cystoscopies in follow-up patients, reducing discomfort to the patients and costs.
ABSTRACT
BACKGROUND: The objective of the current study was to compare the diagnostic accuracy of 2 new real-time polymerase chain reaction-based urinary markers with each other and with urinary cytology, cystoscopy, and/or histology in patients being followed for non-muscle-invasive bladder cancer. METHODS: A total of 487 patients were enrolled in the study. Patients were evaluated using voided urine cytology, the Xpert Bladder Cancer Monitor, the Bladder EpiCheck test, and white light cystoscopy. RESULTS: The overall sensitivity was 27.17% for cytology, 64.13% for the Bladder EpiCheck test, and 66.3% for the Xpert Bladder Cancer Monitor. The overall specificity was 98.82% for cytology, 82.06% for the Bladder EpiCheck test, and 76.47% for the Xpert Bladder Cancer Monitor. The negative predictive value was very similar for the 3 tests at 83.56% for cytology, 89.42% for the Bladder EpiCheck test, and 89.35% for the Xpert Bladder Cancer Monitor. When combined, the Bladder EpiCheck test and Xpert Bladder Cancer Monitor detected overall 79.35% of the tumors: 70.37% in low-grade and 92.11% in high-grade tumors. CONCLUSIONS: The Xpert Bladder Cancer Monitor and Bladder EpiCheck test were found to perform very well in terms of sensitivity. Together, the 2 tests detected approximately 92.11% of high-grade tumors. Their specificity was high but could not reach the excellent value of cytology. The negative predictive value was the same for both tests and was higher than that for cytology, especially when the tests were used together (92.24%). These 2 new tests hold promise as urinary biomarkers. They may be used in combination to maximize sensitivity in a less invasive way, thereby reducing invasiveness in the follow-up of patients with non-muscle-invasive bladder cancer and decreasing discomfort for the patients as well as complications and costs.
Subject(s)
Biomarkers, Tumor/urine , Cytodiagnosis/methods , Real-Time Polymerase Chain Reaction/methods , Urinary Bladder Neoplasms/diagnosis , Aged , Biomarkers, Tumor/genetics , Female , Follow-Up Studies , Humans , Male , Muscle, Skeletal , Predictive Value of Tests , ROC Curve , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/urineABSTRACT
PURPOSE: Prostate biopsy is the gold standard for prostate cancer diagnosis; unfortunately, this procedure is not free from complications. Recent studies have shown an increase in antibiotic resistance. The aim of our prospective randomized study was to evaluate the efficacy and safety of a prostate biopsy prophylaxis protocol using 2 vs. 3 fosfomycin doses. METHODS: Two hundred and ninety-seven patients undergoing transrectal systematic ultrasound (US)-guided (n = 277) or transrectal fusion prostate biopsy (n = 20) were prospectively evaluated and randomized by date of birth, to receive 2 (even years, group A) versus 3 doses of fosfomycin (odd years, group B), and prospectively evaluated. RESULTS: Two hundred and ninety-seven patients were randomized to group A (n = 162) or group B (n = 135). The 2 groups were comparable with respect to age, comorbidity, PSA value, prostate volume, operative time and urine culture results. Out of 297 patients, 44 (14.8%) developed complications after the procedure; 2.7% (8/297) of patients developed fever >38° requiring hospitalization (6 [3.7%] in group A and 2 [1.5%] in group B, p = 0.29). Patients who underwent fusion biopsy were more frequently readmitted in comparison with patients undergoing US-guided prostate biopsy (p = 0.000). CONCLUSION: The low fever and prostatitis rate suggest that fosfomycin prophylaxis is safe and efficient. There is no significant difference in clinical outcome between the 2 dosage regimens.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Antibiotic Prophylaxis , Bacterial Infections/prevention & control , Fosfomycin/administration & dosage , Postoperative Complications/prevention & control , Prostate/pathology , Prostatic Neoplasms/pathology , Aged , Anti-Bacterial Agents/adverse effects , Antibiotic Prophylaxis/adverse effects , Antibiotic Prophylaxis/methods , Clinical Protocols , Fosfomycin/adverse effects , Humans , Image-Guided Biopsy/methods , Male , Middle Aged , Prospective Studies , Rectum , Treatment OutcomeABSTRACT
BACKGROUND: The objective of this study was to evaluate the diagnostic accuracy of the Bladder EpiCheck test in the follow-up of patients with non-muscle-invasive bladder cancer (NMIBC) and to compare it with the accuracy of urinary cytology, cystoscopy, and/or histology. METHODS: In total, 243 patients were enrolled in the current study. Patients were evaluated by voided urine cytology, by the Bladder EpiCheck test, and by white-light cystoscopy. RESULTS: Overall sensitivity was 33.3% for cytology, 62.3% for Bladder EpiCheck, and 66.7% for the 2 tests combined. The sensitivity of cytology increased from 7.7% in low-grade (LG) tumors to 66.6% in high-grade (HG) tumors; whereas, for the Bladder EpiCheck test, the sensitivity was 46.1% in LG tumors and 83.3% in HG tumors. Combined cytology and Bladder EpiCheck testing yielded an overall sensitivity of 56.4% for LG tumors and 90% for HG tumors. Overall specificity was 98.6% for cytology, 86.3% for Bladder EpiCheck, and 85.6% for the 2 tests combined. The positive predictive value was 92% for cytology and 68.2% for Bladder EpiCheck. For the 2 tests combined, it was 68.6%. The negative predictive value was similar for the 2 tests: 75.8% for cytology, 82.9% for Bladder EpiCheck, and 84.5% for the 2 tests combined. CONCLUSIONS: The sensitivity of the Bladder EpiCheck test was significantly higher than that of cytology. The test performed very well in terms of specificity but could not reach the high value of cytology. The positive predictive value was higher for Bladder EpiCheck, whereas the negative predictive value was approximately the same for both tests.
Subject(s)
Biomarkers, Tumor/genetics , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder/pathology , Urine/cytology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/urine , Cystoscopy , DNA Methylation , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Predictive Value of Tests , Urinary Bladder/diagnostic imaging , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/urine , Urine/chemistryABSTRACT
Urachal carcinoma (UrC) is an exceedingly rare neoplasm that develops from the urachus, an embryologic remnant of the urogenital sinus and allantois. The most commonly encountered histologic subtype is adenocarcinoma. The aim of this study is to characterize a series of UrC by morphology, immunohistochemistry, and molecular analysis. We retrospectively investigated seven cases of UrCs and assessed patient symptoms, imaging, histologic features, immunohistochemical profile, molecular characteristics, pathologic stages, and type of treatment. Immunostaining for CK7, CK20, Muc-2, CDX2, GATA3, ß-catenin, and CK34ßE12 was carried out on each neoplasm and on seven non-neoplastic urachal remnants as the control group. Additionally, a mutational analysis was performed using the QIAact Actionable Insights Tumor Panel Kit, which analyzes KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1. Our cohort comprised five females and two males with a mean age of 64 years. UrCs consisted of two mucinous cystadenocarcinomas and five invasive, non-cystic adenocarcinomas. Carcinoma antigen expression profile was positive for CK20 and negative for CK34ßE12 and GATA3 in all cases. Five of seven cases stained positively for Muc-2 and CDX2. On the contrary, non-neoplastic urachal remnants were immunoreactive for CK34ßE12, CK7, and GATA3. Mutational analysis gave a positive result in four out of seven (57.1%) cases. All four positive tumors showed RAS mutation and one an additional mutation in PIK3CA. Urachal tumors exhibit peculiar morphologic, immunohistochemical, and molecular features. Due to the advanced stage at presentation, individualized treatment should be undertaken.
Subject(s)
Biomarkers, Tumor , Cystadenocarcinoma, Mucinous/diagnosis , DNA Mutational Analysis , Immunohistochemistry , Mutation , Urinary Bladder Neoplasms/diagnosis , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Biopsy , Cystadenocarcinoma, Mucinous/chemistry , Cystadenocarcinoma, Mucinous/genetics , Cystadenocarcinoma, Mucinous/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Urinary Bladder Neoplasms/chemistry , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
AIMS: Cystoscopy and urine cytology represent the gold standard for monitoring superficial bladder cancer (BC). Xpert BC Monitor is a new urinary marker based on the evaluation of five target mRNAs overexpressed in patients with bladder cancer. The aim of our study was to evaluate the diagnostic accuracy of Xpert BC Monitor in follow-up of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: 230 patients were included in this prospective study. Xpert BC Monitor cut-off was set to 0.5. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology, Xpert BC Monitor and their combination were calculated and compared with cystoscopy/histology. RESULTS: 52/230 patients showed a NMIBC recurrence, 45 low grade (LG) and 7 high grade (HG). Overall sensitivity was 11.5% for cytology, 46.2% for Xpert BC Monitor and 48.1% for the two tests combined. Sensitivity of cytology increased from 4.4% in LG to 57.1% in HG tumours whereas for the Xpert BC Monitor it was 40% in LG and 85.7% in HG tumours. Combined cytology and Xpert BC Monitor yielded an overall sensitivity of 42% for LG and 85.7% for HG. Overall specificity was 97.2% for cytology, 77% for Xpert BC Monitor and 75.8% for the two tests. CONCLUSIONS: Sensitivity for the Xpert BC Monitor Test was significantly higher than for cytology. The test performed very well in terms of specificity but could not reach the value of cytology, while PPV and NPV performed approximately the same for both tests.
Subject(s)
Biomarkers, Tumor/urine , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/urine , Adult , Aged , Aged, 80 and over , Area Under Curve , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/urine , Predictive Value of Tests , ROC CurveABSTRACT
Bladder carcinoma is the most common malignancy of the urinary tract and cystoscopy with cytology is currently considered the gold standard for the detection and surveillance of primary tumors and for the follow-up of patients after transurethral resection. Even if cytology has a low sensitivity especially in low-grade bladder carcinomas, the high specificity and the inexpensive nature of the equipment required, justify performing it. The greatest value of cytology for patients with low-grade, nonmuscle-invasive bladder cancer (NMIBC) is the detection of those lesions that may progress to high-grade urothelial carcinoma.
Subject(s)
Urinary Bladder Neoplasms/pathology , Urine/cytology , HumansABSTRACT
AIM: To examine the long-term follow-up of patients with that previously underwent risk stratification based on multicolour FISH testing. PATIENTS AND METHODS: On 81 patients with intermediate-risk urothelial carcinoma, a multicolour-FISH was performed. Patients were sub-divided into low- and high-risk groups based on chromosomal patterns. Univariate analysis, using Mantel-Cox log-rank test for disease-free, progression-free survival and overall survival, was employed to determine the prognostic significance of FISH analysis. Survival times were calculated according to the Kaplan-Meier product-limit method and multivariate analysis using Cox proportional hazards regression model. RESULTS: The univariate Mantel-Cox log-rank test showed significant differences between the low-risk and the high-risk group for disease-free survival (p=0.005) and overall survival (p=0.038), but not for progression-free survival (p=0.129). CONCLUSION: Our long-term follow-up data appear to be able to divide tumors into low and high risk groups for recurrence based on molecular/genetic changes observed with FISH.
Subject(s)
Chromosome Aberrations , Chromosomes, Human/genetics , In Situ Hybridization, Fluorescence/methods , Urinary Bladder Neoplasms/classification , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Prospective Studies , Risk Factors , Survival Rate , Time Factors , Urinary Bladder Neoplasms/geneticsABSTRACT
OBJECTIVE: To test the prognostic value of multicolor fluorescence in situ hybridization analyses of tumor cells in urine for prediction of the recurrence and progression of tumor in patients with intermediate risk non-muscle invasive bladder cancer. METHODS: A total of 168 patients with non-muscle invasive bladder cancer were included in the study. Fluorescence in situ hybridization was carried out on the bladder wash urine collected before resection. Tumors were classified as low molecular grading if they had a diploid chromosomal pattern or only a loss of p16 or ch3 aneuploidy, and as high molecular grading if they showed aneuploidy of ch7 or 17. Cox regression models assessed the added prognostic value of fluorescence in situ hybridization for primary tumor recurrence or progression, respectively. RESULTS: Median follow up was 67 months. A total of 57% of tumors were classified as low molecular grading. The 2- and 5-year recurrence-free survival was 68% and 49% for low molecular grading, and 47% and 30% for high molecular grading, respectively. The 2- and 5-year progression-free survival was 95% and 84% for low molecular grading, and 79% and 58% for high molecular grading tumor patients, respectively. Molecular grading (hazard ratio 1.60; P = 0.03) was associated with recurrence, when also accounting for histopathology and a patient's characteristics. Both cancer severity score (hazard ratio 1.51; P < 0.01) and molecular grading (hazard ratio 2.53; P < 0.01) independently and positively predicted progression in multivariable models. The C-index for predicting recurrence increased from 0.58 to 0.61 when molecular grading fluorescence in situ hybridization was included in the model, and from 0.68 to 0.72 when predicting progression. CONCLUSIONS: Fluorescence in situ hybridization-based molecular grading increases the accuracy of a prognostic model, predicting both recurrence and progression in patients with intermediate risk non-muscle invasive bladder cancer.
Subject(s)
Aneuploidy , Carcinoma/genetics , Carcinoma/pathology , In Situ Hybridization, Fluorescence , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Aged , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 3 , Chromosomes, Human, Pair 7 , Chromosomes, Human, Pair 9 , Color , Diploidy , Disease Progression , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Proportional Hazards Models , Urine/cytologyABSTRACT
OBJECTIVES: Bladder perforation is the second most common complication during transurethral resection of bladder tumours. It is unknown whether perforation affects the natural history of the tumour through cell seeding. The aim of this study was to study the impact of perforation on the oncologic outcomes of bladder carcinoma. MATERIALS AND METHODS: Between 2003 and 2007, 926 consecutive patients underwent transurethral resection of bladder tumours at our institution; 327 cases were staged ≥ pT2 and were treated immediately with cystectomy and/or multimodal therapy and therefore excluded from the study. An additional 34 cases without urothelial carcinoma were excluded. Of the remaining 565 patients with non-muscle invasive bladder cancer, 457 (80.8 %) were male and 108 (19.2 %) were female with a mean age of 69.5 years in men and 67.3 years in women. Thirty-seven patients (6.5 %) experienced bladder perforation at the time of tumour resection. This group of patients (Group 1) was compared to the remaining 528 patients (Group 2) who did not experience a bladder perforation. RESULTS: Patients with bladder wall perforation experienced a shorter disease-free survival in both univariate (p = 0.003) and multivariate analyses (p = 0.006). In addition, subsequent recurrences revealed stage progression of recurrent disease (p = 0.05) and trended to a higher number of cystectomies in the perforated group of patients (p = 0.06). Nevertheless, perforation did not appear to influence overall survival (p = 0.127) or cancer-specific survival (p = 0.141). CONCLUSION: The results indicate that bladder perforation during resection of superficial bladder tumours is burdened by a shortened disease-free survival and T-stage progression.
Subject(s)
Carcinoma, Transitional Cell/secondary , Carcinoma, Transitional Cell/surgery , Cystectomy/methods , Intraoperative Complications/etiology , Neoplasm Seeding , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Urinary Bladder/injuries , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , UrethraABSTRACT
AIMS: Epithelial cell adhesion molecule (EpCAM) is a widely used immunohistochemical marker for epithelial human malignancies. Antibodies to target EpCAM are usually directed against its ectodomain (EpEX), but do not detect the intracellular domain (EpICD). The aim of this study was to compare membranous EpEX versus EpICD expression by immunohistochemistry. METHODS AND RESULTS: Concurrent EpEX and EpICD expression was investigated retrospectively in cancerous and matched non-neoplastic tissue samples from patients with pancreatic adenocarcinoma. In total, 317 paired samples of pancreatic tissue from 88 patients were analysed and correlated with clinicopathological parameters. In non-cancerous tissue, a high concordance of membranous EpEX and EpICD expression was observed and defined as the expression of the full-length EpCAM (EpEX(+)/EpICD(+) phenotype, EpCAM(MF)), which was highly predominant. In contrast, while most tumour samples were EpEX positive, loss of membranous EpICD expression (EpEX(+)/EpICD(-) phenotype, EpCAM(MT)) was observed in one-third of cases, and these patients had a significantly shortened disease-free and overall survival. CONCLUSIONS: This study demonstrates for the first time that loss of membranous EpICD expression is a frequent event and predicts poor prognosis in patients with pancreatic cancer. Additional studies evaluating the predictive and prognostic value of the expression of different membranous EpCAM variants are warranted in epithelial cancers.
Subject(s)
Adenocarcinoma/metabolism , Antigens, Neoplasm/chemistry , Antigens, Neoplasm/metabolism , Cell Adhesion Molecules/chemistry , Cell Adhesion Molecules/metabolism , Pancreatic Neoplasms/metabolism , Adenocarcinoma/pathology , Aged , Antibody Specificity , Antigens, Neoplasm/immunology , Biomarkers, Tumor/chemistry , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Cell Adhesion Molecules/immunology , Epithelial Cell Adhesion Molecule , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Pancreatic Neoplasms/pathology , Prognosis , Protein Structure, Tertiary , Retrospective Studies , Tissue Array AnalysisABSTRACT
OBJECTIVE: To evaluate quick-staining cytology as an alternative method to intraoperative frozen sectioning after nephron-sparing nephrectomy. MATERIALS AND METHODS: Eighty-two partial nephrectomies were performed with intraoperative quick-staining cytology and frozen section evaluation. The results of both were compared with permanent histology as the gold standard. RESULTS: After partial nephrectomy, permanent histologic surgical margins were positive in 8 of 82 (9.7%), cytology in 10 of 82 (12%), and frozen sectioning in 4 of 82 (5%). In comparison with permanent histologic examination, sensitivity of the cytologic examination was 87.5%, positive predictive value 70%, specificity 95.9%, and negative predictive value 98.6%. Kappa values (κ) revealed a good level of agreement between intraoperative cytology and final histologic examination (κ = 0.751; P <.0001). In comparison with permanent histology, sensitivity of frozen sections was 50%, specificity 100%, positive predictive value 100%, and negative predictive value 95%. Of the 8 cases with positive margin on permanent histologic examination, 7 were cytologically positive and only 4 positive on frozen sectioning. Two patients had a local recurrence on follow-up, of which both were correctly identified on quick-staining cytology. The quick-staining cytologic evaluations were completed in <4 minutes. CONCLUSION: Quick-staining cytology is rapid, highly sensitive, and specific to evaluate intraoperative surgical margins at partial nephrectomy. It reduces diagnostic time, could be used as alternative to intraoperative frozen section, and warrants further investigation.
Subject(s)
Cytodiagnosis/methods , Frozen Sections/methods , Kidney Neoplasms/surgery , Nephrectomy/methods , Nephrons/surgery , Adult , Aged , Aged, 80 and over , Humans , Laparoscopy/methods , Middle Aged , Predictive Value of Tests , Prospective Studies , Recurrence , Sensitivity and SpecificityABSTRACT
In recent decades years, we have witnessed the propagation and marketing of numerous diagnostic tests capable of detecting, in the urine of patients, the presence of urothelial tumor markers. Among None of the different markers studied to date , no one has been able to meet all the requirements of the ideal marker. We present and discuss below we discuss the results reported in the literature of about two tests approved by the Food and Drug Administration [ImmunoCyt/uCyt+ and Fluorescence In Situ Hybridisation (FISH)], which have been and commercially available for about 10 years., ImmunoCyt/uCyt + and Fluorescence In Situ Hybridisation (FISH).
Subject(s)
Carcinoma, Transitional Cell/diagnosis , Urologic Neoplasms/diagnosis , Humans , Immunologic Tests , In Situ Hybridization, FluorescenceSubject(s)
Breast Neoplasms/metabolism , Capsid Proteins/metabolism , Cytoplasm/metabolism , Oncogene Proteins, Viral/metabolism , Paget Disease, Extramammary/metabolism , Paget's Disease, Mammary/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/virology , Female , Humans , Paget Disease, Extramammary/pathology , Paget Disease, Extramammary/virology , Paget's Disease, Mammary/pathology , Paget's Disease, Mammary/virologyABSTRACT
BACKGROUND: The aim of the current study was to report the results of 7422 uCyt+/ImmunoCyt and cytology analyses that were performed over the course of 9 years at the study institution for the evaluation and follow-up of patients with urothelial carcinoma. METHODS: Between January 2002 and March 2011, 2217 patients with a mean age of 69.5 years (range, 15 years-99 years) were enrolled in the current study. All patients seen for the follow-up of bladder and/or upper tract urothelial cancer as well as those with a history that was suspicious for bladder cancer were recruited. In all patients, a voided urinary cytology and uCyt+/ImmunoCyt test was performed. Patients underwent routine cystoscopy as well as cystoscopy when cytology and/or the uCyt+/ImmunoCyt test yielded positive results. Lesions that were detected cystoscopically were biopsied and removed transurethrally. A total of 7422 uCyt+/ImmunoCyt and cytology analyses were performed. RESULTS: Of the 7422 uCyt+/ImmunoCyt tests and cytologies that were performed, 7075 (95.3%) were considered adequate. A total of 578 patients (with 1156 analyses) underwent biopsy and 728 (63%) samples had a histologically proven urothelial carcinoma. Overall sensitivity was 34.5% for cytology, 68.1% for uCyt+/ImmunoCyt, and 72.8% for the 2 tests combined. Overall specificity was 97.9% for cytology, 72.3% for uCyt+/ImmunoCyt, and 71.9% for the 2 tests combined. Cytology and the uCyt+/ImmunoCyt test together had an overall sensitivity of 72.8%, with 59% for grade 1, 77% for grade 2, and 90% for grade 3 tumors (according to the 1973 World Health Organization grading classification system). CONCLUSIONS: On the basis of their 9-year experience, the authors confirm the value of uCyt+/ImmunoCyt and cytology analyses in the follow-up of patients with non-muscle-invasive urothelial cancer. This could potentially reduce the number and cost of routine cystoscopic examinations in patients who are followed for bladder carcinoma. Cancer (Cancer Cytopathol) 2013;121:392-397. © 2013 American Cancer Society.