Matthias Waldert

Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study.

PURPOSE We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. MATERIALS AND METHODS In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. RESULTS Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. CONCLUSIONS Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.

Comparison of Oncologic Outcomes for Open and Laparoscopic Nephroureterectomy: A Multi-Institutional Analysis of 1249 Cases

BACKGROUND Data regarding the oncologic efficacy of laparoscopic nephroureterectomy (LNU) compared to open nephroureterectomy (ONU) are scarce. OBJECTIVE We compared recurrence and cause-specific mortality rates of ONU and LNU. DESIGN, SETTING, AND PARTICIPANTS Thirteen centers from three continents contributed data on 1249 patients with nonmetastatic upper tract urothelial carcinoma (UTUC). MEASUREMENTS Univariable and multivariable survival models tested the effect of procedure type (ONU [n=979] vs LNU [n=270]) on cancer recurrence and cancer-specific mortality. Covariables consisted of institution, age, Eastern Cooperative Oncology Group (ECOG) performance status score, pT stage, pN stage, tumor grade, lymphovascular invasion, tumor location, concomitant carcinoma in situ, ureteral cuff management, previous urothelial bladder cancer, and previous endoscopic treatment. RESULTS AND LIMITATIONS Median follow-up for censored cases was 49 mo (mean: 62). Relative to ONU, LNU patients had more favorable pathologic stages (pT0/Ta/Tis: 38.1% vs 20.8%, p<0.001) and less lymphovascular invasion (14.8% vs 21.3%, p=0.02) and less frequently had tumors located in the ureter (64.5 vs 71.1%, p=0.04). In univariable recurrence and cancer-specific mortality models, ONU was associated with higher cancer recurrence and mortality rates compared to LNU (hazard ratio [HR]: 2.1 [p<0.001] and 2.0 [p=0.008], respectively). After adjustment for all covariates, ONU and LNU had no residual effect on cancer recurrence and mortality (p=0.1 for both). CONCLUSIONS Short-term oncologic data on LNU are comparable to ONU. Since LNU was selectively performed in favorable-risk patients, we cannot state with certainty that ONU and LNU have the same oncologic efficacy in poor-risk patients. Long-term follow-up data and morbidity data are necessary before LNU can be considered as the standard of care in patients with muscle-invasive or high-grade UTUC.

Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi‐institutional analysis of 1363 patients

To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive.

Insulin-like growth factors and prostate cancer

Prostate cancer is one of the most common malignant tumors in Western countries. The etiology of prostate cancer is currently unknown, but it has been suggested that growth factor abnormalities may be involved in initiation and progression of this disease. Insulin-like growth factors (IGFs), including IGF-1 and IGF-2, are mitogenic peptides involved in the regulation of cell proliferation, differentiation and apoptosis. Studies have shown that IGFs are potent mitogens for a variety of cancer cells including prostate cancer since they stimulate cancer cell growth and suppress programmed cell death. This review outlines elements of IGF pathophysiology, reviews recent evidence that circulating IGF-1 levels are related to prostate cancer risk and discusses the clinical implications of these lines of research with respect to prevention and treatment.

Renal tumour size measured radiologically before surgery is an unreliable variable for predicting histopathological features: benign tumours are not necessarily small

To compare histopathological findings as a function of radiological tumour size, as published data suggest that small renal tumours are often benign and large tumours are renal cell cancer (RCC).

Laparoscopic Cryoablation Versus Partial Nephrectomy for the Treatment of Small Renal Masses: Systematic Review and Cumulative Analysis of Observational Studies

CONTEXT For small renal masses (SRMs), partial nephrectomy (PN) represents the therapeutic standard of care. Laparoscopic cryoablation (LCA) could be regarded as an alternative to surgical excision in selected patients, if perioperative complication rates and oncologic results are comparable. OBJECTIVE To perform a cumulative analysis of observational studies regarding oncologic outcomes and perioperative complications of both procedures. EVIDENCE ACQUISITION Medline, Embase, and Web of Science searches were performed for clinically localized sporadic SRMs that were treated with PN or LCA. A total of 6785 lesions were analyzed for local and metastatic tumor progression and 10 906 procedures for perioperative complications. EVIDENCE SYNTHESIS Patients undergoing LCA were significantly older, mean tumor sizes were lower, and mean follow-up duration was shorter (each p<0.001). Following LCA and PN, 8.5% and 1.9% developed local tumor progression, respectively (p<0.001). In multivariable analysis, the relative risk for local tumor progression of LCA versus PN was 5.24-fold increased (p<0.001); the risk of metastatic progression was similar. The overall complication rate was higher following PN (23.5% vs 17.0%; p<0.001), especially the rate of major complications (19.2% vs 10.2%; p<0.001). In multivariable analysis, the total risk for complications and major complications for PN versus LCA was 4.6-fold (p=0.004) and 9.71-fold (p<0.001) increased, respectively. Limitations of this analysis include follow-up and selection bias, and lack of standardization reporting complications and outcomes. CONCLUSIONS Both PN and LCA are viable options for the management of SRMs. Compared with PN, LCA results in a higher risk of local tumor progression. The risk of perioperative complications appears to be lower following LCA; however, this difference is strongly influenced by selection bias, and thus limited conclusions can be made regarding true differences in complications. Therefore, PN is the gold standard for SRMs, but LCA may be indicated in selected patients with significant comorbidity.

Hybrid renal cell carcinomas containing histopathologic features of chromophobe renal cell carcinomas and oncocytomas have excellent oncologic outcomes.

BACKGROUND Modern histopathology is able to differentiate chromophobe renal cell carcinomas (cRCCs), oncocytomas, and chromophobe-oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear. OBJECTIVE To determine the clinical course of hybrid RCC. DESIGN, SETTING, AND PARTICIPANTS Ninety-one surgically treated tumors, originally classified as oncocytoma or cRCC, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells). INTERVENTIONS Radical tumor nephrectomy or nephron-sparing surgery. MEASUREMENTS Recurrence-free and tumor-specific survival. RESULTS AND LIMITATIONS Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were cRCCs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pT3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for cRCC was pT1 in 50% of tumors (n=17), pT2 in 23.5% of tumors (n=8), and pT3a in 26.5% of tumors (n=9). Low-grade RCC was found in 76.5% of tumors (n=26), and vascular invasion was found in 11.8% of tumors (n=4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two cRCCs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and cRCC were 100%, 100%, and 97%, respectively. CONCLUSIONS Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses.

Fluorescence Cystoscopy with High-Resolution Optical Coherence Tomography Imaging as an Adjunct Reduces False-Positive Findings in the Diagnosis of Urothelial Carcinoma of the Bladder

BACKGROUND The advantage of photodynamic diagnosis in detecting urothelial cell carcinoma (UCC) of the bladder has been demonstrated clearly, but it comes at the price of a higher false-positive rate. Optical coherence tomography (OCT) is a noninvasive, real-time, microstructural imaging modality that uses near-infrared light for a point analysis of the bladder-wall microstructure. OBJECTIVE To evaluate whether adding targeted OCT analysis of lesions that are suspicious at white-light (WL) and hexaminolevulinate (HAL) fluorescence cystoscopy improves diagnostic accuracy in the detection of UCC. DESIGN, SETTING, AND PARTICIPANTS In this prospective single-center study with same-patient comparison, patients with suspected UCC first received an intravesical instillation of HAL. Cystoscopy was performed in WL, followed by blue-light inspection and OCT scanning. INTERVENTION Suspicious lesions identified by WL or HAL were evaluated by OCT and were subsequently resected or biopsied. MEASUREMENTS We measured changes in sensitivity and specificity in detecting UCC using WL, HAL, and targeted OCT. RESULTS AND LIMITATIONS In 66 patients studied, 232 lesions were detected, were scanned by OCT, and were subsequently resected or biopsied. Additionally, 132 areas of normal-appearing urothelium were investigated by all three methods and biopsied. On a per-lesion basis, sensitivity and specificity were respectively 69.3% and 83.7% for WL, 97.5% and 78.6% for HAL, and 97.5% and 97.9% for HAL combined with OCT. Overall, UCC was diagnosed in 58 patients (87.9%), with a per-patient sensitivity of 89.7% for WL and 100% for both HAL alone and HAL with targeted OCT. Per-patient specificity for HAL alone and targeted HAL was 62.5% and 87.5%, respectively. The limitation of OCT results from poor visualization of flat lesions in WL, making scanning a time-consuming procedure. CONCLUSIONS Combining fluorescence cystoscopy with targeted OCT increases the specificity of fluorescence cystoscopy significantly, with no added morbidity, and reduces the need for unnecessary (false-positive) biopsies.

The oncological results of laparoscopic nephroureterectomy for upper urinary tract transitional cell cancer are equal to those of open nephroureterectomy

To compare the overall, tumour‐specific, recurrence‐free, and progression‐ free survival of patients with upper urinary tract transitional cell carcinoma (UUT‐TCC) treated with laparoscopic nephroureterectomy (LNU) or standard open NU (ONU).

Does preoperative symptom classification impact prognosis in patients with clinically localized upper-tract urothelial carcinoma managed by radical nephroureterectomy?

OBJECTIVES To evaluate if preoperative symptom classification could refine prediction of outcomes for patients with clinically localized upper-tract urothelial carcinoma (UTUC) managed by radical nephroureterectomy (RNU). METHODS Data on 654 patients with localized UTUC who underwent RNU were reviewed. Preoperative symptoms were classified as incidental (S1), local (S2), and systemic (S3). Clinical and pathologic data were compared between the cohorts. Kaplan-Meier analyses and Cox proportional hazard modeling were used to determine recurrence-free and cancer-specific survival amongst the symptom cohorts. RESULTS Symptom classification was S1 in 213 (33%) patients, S2 in 402 (61%), and S3 in 39 (6%). S3 symptoms were associated with advanced pathology, including higher stage, grade, and lymph node (LN) positivity. Five and 10-year recurrence-free and cancer-specific survival estimates were similar for patients with S1 and S2 symptoms (P = 0.75 and 0.58, respectively), but was worse for patients with S3 symptoms (P < 0.001 for both). On multivariate analysis adjusting for final pathologic stage, grade, and LN status, S3 symptoms were not an independent predictor of recurrence (HR 1.44, P = 0.19) or death due to disease (HR 1.66, P = 0.07). Addition of symptom classification, however, increased the accuracy of a model consisting of stage, grade, and LNs for prediction of recurrence-free and cancer-specific survival by 1.4% and 1.3%, respectively (P < 0.001 for both). CONCLUSIONS Local symptoms do not confer worse prognosis compared with patients with incidentally detected UTUC. However, systemic symptoms are associated with worse outcomes despite apparently effective RNU. Patients with systemic symptoms may harbor micrometastatic disease and could potentially benefit from a more rigorous metastatic evaluation or perioperative chemotherapy regimens.