Oliver W. Hakenberg

Assessing the Impact of Ischaemia Time During Partial Nephrectomy

CONTEXT The impact of applying renal ischaemia during nephron-sparing surgery to avoid renal damage in the treated kidney has gained importance in different surgical techniques. OBJECTIVE The main objective of the present study is to point out the limit of renal ischaemia times for warm and cold ischaemia approaches. Important results of research on renal ischaemia and different surgical techniques as well as results of clinical studies concerning renal function after renal ischaemia in partial nephrectomy are highlighted. EVIDENCE ACQUISITION A Medline literature research was performed, combining queries on the keywords nephron-sparing surgery, partial nephrectomy, and ischemia. Links to related articles and cross-reading of citations in related articles were surveyed, as were reviews, letters to editors, and information collected from urologic textbooks. The references formed the basis of this review article, with selection and deletion based on the relevance and importance of the content. In a final step, interactive peer review by the expert panel of coauthors completed the review. EVIDENCE SYNTHESIS Renal ischaemia research showed an increasing renal damage proportional to ischemic time. Current clinical data support safe ischaemia times, within 20 min of warm ischaemia and up to 2 h of cold ischaemia, to minimise renal ischemic damage. To date, no ischaemia dose-response curve or algorithm is available to predict the risk of acute kidney injury and chronic kidney disease in patients undergoing intraoperative ischaemia. In general, there seems to be a higher risk for comorbidity caused by renal damage in patients suffering from kidney tumour. CONCLUSIONS If ischaemia is required, the tumour should be removed within 20 min of warm ischaemia, regardless of surgical approach. Efforts should be made to start immediately with cold ischaemia, if the feasibility within this span of time seems to be jeopardised. Thus, cold ischaemia times up to 2 h can be tolerated by the kidney, depending on the individual method. Nevertheless, cold ischaemia with ice slush should be kept as short as possible--at best within 35 min. In ischemic nephron-sparing surgery, one of the surgeons main aims should be to avoid loss of renal function. Only after optimal preoperative appraisal and planning can the best postoperative outcomes for renal function be achieved.

EAU Guidelines on Penile Cancer: 2014 Update

CONTEXT Penile cancer has high mortality once metastatic spread has occurred. Local treatment can be mutilating and devastating for the patient. Progress has been made in organ-preserving local treatment, lymph node management, and multimodal treatment of lymphatic metastases, requiring an update of the European Association of Urology guidelines. OBJECTIVE To provide an evidence-based update of treatment recommendations based on the literature published since 2008. EVIDENCE ACQUISITION A PubMed search covering the period from August 2008 to November 2013 was performed, and 352 full-text papers were reviewed. Levels of evidence were assessed and recommendations graded. Because there is a lack of controlled trials or large series, the levels of evidence and grades of recommendation are low compared with those for more common diseases. EVIDENCE SYNTHESIS Penile squamous cell carcinoma occurs in distinct histologic variants, some of which are related to human papilloma virus infection; others are not. Primary local treatment should be organ preserving, if possible. There are no outcome differences between local treatment modes in superficial and T1 disease. Management of inguinal lymph nodes is crucial for prognosis. In impalpable nodes, invasive staging should be done depending on the risk factors of the primary tumour. Lymph node metastases should be treated by surgery and adjuvant chemotherapy in N2/N3 disease. CONCLUSIONS Organ preservation has become the standard approach to low-stage penile cancer, whereas in lymphatic disease, it is recognised that multimodal treatment with radical inguinal node surgery and adjuvant chemotherapy improves outcome. PATIENT SUMMARY Approximately 80% of penile cancer patients of all stages can be cured. With increasing experience in the management of penile cancer, it is recognized that organ-preserving treatment allows for better quality of life and sexual function and should be offered to all patients whenever feasible. Referral to centres with experience is recommended.

Urine Markers for Detection and Surveillance of Non-Muscle-Invasive Bladder Cancer

CONTEXT Bladder cancer diagnosis and surveillance includes cystoscopy and cytology. The limitation of urinary cytology is its low sensitivity for low-grade recurrences. As of now, six urine markers are commercially available to complement cystoscopy in the detection of bladder cancer. Several promising tests are under investigation. OBJECTIVE In this nonsystematic review, we summarize the existing data on commercially available and promising investigational urine markers for the detection of bladder cancer. EVIDENCE ACQUISITION A PubMed search was carried out. We reviewed the recent literature on urine-based markers for bladder cancer. Articles were considered between 1997 and 2011. Older studies were included selectively if historically relevant. EVIDENCE SYNTHESIS Although different studies have shown the superiority of urine markers regarding sensitivity for bladder cancer detection as compared with cytology, none of these tests is ideal and can be recommended unrestrictedly. CONCLUSIONS Urine markers have been studied extensively to help diagnose bladder cancer and thereby decrease the need for cystoscopy. However, no marker is available at present that can sufficiently warrant this. Several urinary markers have higher but still insufficient sensitivity compared with cytology. Urinary cytology or markers cannot safely replace cystoscopy in this setting. To identify an optimal marker that can delay cystoscopy in the diagnosis of bladder cancer, large prospective and standardized studies are needed.

Lymphadenectomy in the Surgical Management of Penile Cancer

CONTEXT Uncertainty remains about the extent and indications for inguinal lymphadenectomy in penile cancer, a procedure known for relatively high morbidity. Several attempts have been made to develop strategies which can improve the diagnostic quality and reduce the morbidity of the management of inguinal lymph nodes in penile cancer. OBJECTIVE To analyse the existing published data on the surgical management of inguinal nodes in penile cancer regarding morbidity and survival. EVIDENCE ACQUISITION A Medline search was performed of the English-language literature (1966-September 2008) using the MeSH terms penile carcinoma, lymph node dissection, lymphadenectomy, and complications. EVIDENCE SYNTHESIS Lymph node metastases are frequent in penile cancer, even in early pT1G2 stages. Since the results of systemic treatment of advanced penile cancer are disappointing, complete dissection of all involved lymph nodes is highly recommended. The extent of lymph node dissection should be adapted to clinical stage, as this corresponds to metastatic spread. For low-risk patients (pTis, pTa, and pT1G1) without palpable lymph nodes and with good compliance, a surveillance strategy may be chosen. For all other patients without palpable lymph nodes (including intermediate risk pT1G2 disease), a modified bilateral lymphadenectomy is recommended. An alternative to this is a dynamic sentinel lymph node biopsy in specialised centres. All patients with histologically proven lymph node metastases should undergo radical inguinal lymphadenectomy. Pelvic lymph node dissection should be done in all patients with more than two metastatic inguinal lymph nodes. In case of fixed inguinal lymph nodes, neoadjuvant chemotherapy is recommended, followed by node resection. CONCLUSIONS Lymphadenectomy is an integral part of the management of penile cancer, since early dissection of involved lymph nodes improves survival.

Bladder wall thickness in normal adults and men with mild lower urinary tract symptoms and benign prostatic enlargement.

There is evidence that increased bladder wall thickness can be a useful parameter in the evaluation of men with clinical benign prostatic hyperplasia (BPH). However, normal values for bladder wall thickness (BWT) in adults have not been established.

Incidence, Prevention, and Management of Complications Following Percutaneous Nephrolitholapaxy

CONTEXT Incidence, prevention, and management of complications of percutaneous nephrolitholapaxy (PNL) still lack consensus. OBJECTIVE To review the epidemiology of complications and their prevention and management. EVIDENCE ACQUISITION A literature review was performed using the PubMed database between 2001 and May 1, 2011, restricted to human species, adults, and the English language. The Medline search used a strategy including medical subject headings (MeSH) and free-text protocols with the keywords percutaneous, nephrolithotomy, PCNL, PNL, urolithiasis, complications, and Clavien, and the MeSH terms nephrostomy, percutaneous/adverse effects, and intraoperative complications or postoperative complications. EVIDENCE SYNTHESIS Assessing the epidemiology of complications is difficult because definitions of complications and their management still lack consensus. For a reproducible quality assessment, data should be obtained in a standardized manner, allowing for comparison. An approach is the validated Dindo-modified Clavien system, which was originally reported by seven studies. No deviation from the normal postoperative course (Clavien 0) was observed in 76.7% of PNL procedures. Including deviations from the normal postoperative course without the need for pharmacologic treatment or interventions (Clavien 1) would add up to 88.1%. Clavien 2 complications including blood transfusion and parenteral nutrition occurred in 7%; Clavien 3 complications requiring intervention in 4.1.%; Clavien 4, life-threatening complications, in 0.6%; and Clavien 5, mortality, in 0.04%. High-quality data on complication management of rare but potentially debilitating complications are scarce and consist mainly of case reports. CONCLUSIONS Complications after PNL can be kept to a minimum in experienced hands with the development of new techniques and improved technology. A modified procedure-specific Clavien classification should be established that would need to be validated in prospective trials.

Outcome Of Surgical Treatment Of Isolated Local Recurrence After Radical Nephrectomy For Renal Cell Carcinoma

PURPOSE Isolated local recurrences after radical nephrectomy for renal cell carcinoma occur in 2% to 3% of cases. Today local recurrences can be detected at an early stage due to modern imaging techniques. It remains controversial whether an aggressive surgical approach to this problem can prolong survival. MATERIALS AND METHODS We retrospectively analyzed 16 patients who were treated surgically at our institution for suspected isolated local renal cell carcinoma recurrence during the last 10 years. All patients had undergone extensive staging and had no evidence of distant metastases with the local recurrence. Surgical exploration confirmed carcinoma recurrence in 13 of the 16 cases and all 13 patients underwent complete resection of the local recurrence. Three patients were found to have had false-positive computerized tomography findings on surgical exploration. RESULTS Mean time to recurrence was 45.5 months (range 7 to 224). Only 2 patients were symptomatic, while in 11 disease had been detected at routine followup. Mean size of the recurrent tumor was 5.92 cm. (range 2 to 10). All patients survived surgery without major complications. Of the patients 7 died of metastatic disease after a mean survival of 23.1 months (range 4 to 68) following recurrence removal and 6 are alive with a mean survival of 53.0 months (range 18 to 101) (p = 0.09). Time to recurrence after nephrectomy was significantly longer (p <0.05) and size of recurrence significantly smaller (p <0.04) in the patients still alive. In 1 surviving patient evidence of metastatic disease developed 9 months after surgery for recurrence. CONCLUSIONS Careful followup after radical nephrectomy for renal cell carcinoma allows the diagnosis of small local recurrences before they become symptomatic in the majority of cases. Although most of these patients will eventually have and die of metastatic disease, an aggressive surgical approach is justified and can result in prolonged survival.

Role of Human Papillomavirus in Penile Carcinomas Worldwide

BACKGROUND Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. OBJECTIVE To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. DESIGN, SETTING, AND PARTICIPANTS After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS HPV DNA prevalence and type distributions were estimated. RESULTS AND LIMITATIONS HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. CONCLUSIONS About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. PATIENT SUMMARY About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions.

Cisplatin, methotrexate and bleomycin for treating advanced penile carcinoma

To retrospectively evaluate the efficacy and toxicity of chemotherapy with cisplatinum, methotrexate and bleomycin (CMB) in the adjuvant and palliative setting, and its effect on survival in patients with locally advanced or metastatic penile carcinoma, which carries a very poor prognosis.

Follow-up After Surgical Treatment of Bladder Cancer: A Critical Analysis of the Literature

CONTEXT Follow-up of patients treated for bladder cancer (BCa) is of great importance for both non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) because of the high incidence of recurrence and progression. The schedule and methods of follow-up should reflect the individual clinical situation. OBJECTIVE To evaluate the existing evidence for intensity and duration of follow-up recommendations in patients after surgical treatment of BCa. EVIDENCE ACQUISITION We searched the Medline, Embase, and Cochrane databases for published data on the follow-up of patients with NMIBC and MIBC after radical cystectomy (RC). EVIDENCE SYNTHESIS Follow-up in patients with NMIBC is necessary because of the high probability of tumour recurrence and the risk of progression. Cystoscopy plus cytology are the standard methods for follow-up. Cystoscopy should be done 3 mo after the transurethral resection in every patient, and the frequency after that depends on the individual recurrence/progression risk. Cytology should be used as an adjunctive method to cystoscopy in intermediate- and high-risk patients. None of the currently available urinary markers or imaging methods can substitute for cystoscopy-based follow-up. High-risk NMIBC patients require regular lifelong upper urinary tract monitoring. Follow-up in MIBC is based on the fact that early detection of recurrence after RC allows for timely treatment with the aim of improving outcomes. Patients with extravesical and lymph node-positive disease should have the most intensive follow-up because of the highest recurrence risk. Routine upper urinary tract imaging is advisable for all patients and should continue in the long term. Follow-up also allows for early detection of urinary diversion-related complications, the rate of which increases with time. CONCLUSIONS Follow-up in BCa is necessary for diagnosing recurrence and progression, as well as for evaluating complications after radical treatment. Since randomised studies investigating the most appropriate follow-up schedule are lacking, most recommendations are based on only the retrospective experience. Nonetheless, reasonable recommendations can be made until further prospective randomised studies testing different follow-up schedules have been performed.