German evidence and consensus-based (S3) guideline: Vaccination recommendations for the prevention of HPV-associated lesions.

Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view.

[Improvement of vaccination activities in urology]. / Verbesserung der Impftätigkeiten in der Urologie.

Effective vaccines against various urologically important diseases have been established for a long time, nevertheless, vaccination activities are generally underperformed in urology. Consistently low vaccination rates, e.g. for human papillomavirus (HPV) vaccines and a widespread vaccination hesitancy characterize the situation especially in men. This article highlights the importance of various aspects of vaccinations in urology and focuses on the improvement of consultation techniques for vaccinations to increase the vaccination rate and acceptance in the future.

The Role of Human Papilloma Virus in Penile Cancer Prevention and New Therapeutic Agents.

Penile cancer remains an aggressive disease with poor prognosis in advanced stages. Another specific problem of any rare disease is that the population is not aware of prevention strategies and higher chances for curation by early diagnosis. In penile carcinogenesis, two major pathways are known. Besides a non-human papilloma virus (HPV)-related pathway (mainly caused by phimosis and chronic inflammation), up to 50% of penile carcinomas are HPV-related (HPV high-risk types). Prophylactic HPV vaccination has proven its efficacy against cervical cancer; its B-cell-mediated immunity against HPV capsid proteins provides probably lifelong protection against specific HPV subtypes covered by the vaccine. Therefore, a consequent HPV vaccination program for children of both sexes might dramatically reduce the incidence of not only cervical cancer but also partially prevent penile cancer. However, for the treatment of already existing intracellular HPV infections, an antigen-specific T-cell immunity is necessary. Appropriate therapeutic HPV vaccines are under investigation. This article gives an overview about different levels of prevention of the HPV-related penile cancer.

Detection of inguinal lymph node involvement in penile squamous cell carcinoma by 18F-fluorodeoxyglucose PET/CT: a prospective single-center study.

BACKGROUND: The extent of lymph node involvement is the most relevant prognostic factor in patients with penile cancer. OBJECTIVE: To prospectively analyze the diagnostic accuracy of 18F-FDG-PET/CT-scan in the assessment of inguinal lymph node involvement in patients with invasive penile carcinoma. PATIENTS AND METHODS: Thirty-five patients with invasive penile carcinoma were staged prospectively by 18F-FDG-PET/CT-scan, and blindly evaluated by 2 nuclear medicine physicians. In total, lymph node involvement was assessed in 70 inguinal groins. Reference standard was either histology or clinical follow-up with a minimum of 31 months (mean: 48.4 months; range: 31-68 months). RESULTS: 18-FDG-PET/CT showed a sensitivity of 88.2% and a specificity of 98.1%. Positive predictive value (PPV) was 93.8%, while negative predictive value (NPV) was 96.3%. In two groins, metastasis of 5 and 7 mm were missed by PET/CT scan. CONCLUSION: 18F-FDG-PET/CT is a promising staging tool in assessing the inguinal lymph node involvement of patients with penile carcinoma. Integration of PET/CT scanning into preoperative staging algorithms may avoid surgical staging in selected patients.

Fluorescence-guided laser therapy for penile carcinoma and precancerous lesions: long-term follow-up.

OBJECTIVES AND AIMS: Laser therapy for penile carcinoma is commonly used despite high recurrence rates of up to 48%. The aim of our study was to investigate the long-term recurrence rate of patients treated by fluorescence-guided laser therapy for penile carcinoma and its impact on oncologic outcome. PATIENTS AND METHODS: Between 1999 and 2005, a total of 26 patients with premalignant carcinoma in situ (Tis) (n = 11) or invasive penile carcinoma (n = 15) were treated by fluorescence-guided laser therapy in our center. The mean follow-up was 71.1 months (range 41-104 months). Recurrence rate, time to recurrence, and impact on survival was investigated for Tis patients and penile carcinoma patients separately. RESULTS: No patient died tumor-associated recurrence during follow-up. No local progression of T stage was observed in patients with Tis tumor. In the group with invasive penile cancer, there were 4 (15.4%) local recurrences. However, 3 of them occurred after more than 3 years and, therefore, are more likely to be considered as "de novo" carcinoma. No intra- or perioperative side effects of photodynamic diagnosis (PDD) were observed. CONCLUSIONS: Local recurrence rate of laser therapy can be reduced by fluorescence guidance without impairing cosmetic or functional results. The necessary equipment is available in many centers that perform PDD for urothelial bladder cancer. PDD, therefore, can be considered to be cost-effective and easy to perform. Prospective multi-center studies to directly compare recurrence rates between white light and fluorescence-guided laser therapy for penile carcinoma are required.

Intermediate-differentiated invasive (pT1 G2) penile cancer--oncological outcome and follow-up.

OBJECTIVES AND AIMS: Due to the low prevalence of penile cancer, little evidence exists on the metastatic potential and the ideal treatment strategies in intermediate-differentiated invasive (pT1 G2) penile cancer. The current study aimed to analyze the oncologic outcome of patients with penile carcinoma with long-term follow-up in a single-center study. PATIENTS AND METHODS: In this retrospective study, 38 patients with histologically proven T1 G2 squamous cell carcinoma of the penis were included. Only the 'classic' subtype was analyzed. Treatment of the primary tumor was Nd:YAG laser-therapy, excision, or partial amputation. Follow-up was performed according to EAU guidelines (2004). RESULTS: Mean follow-up was 78.1 months (range: 9-285 months). Local recurrence was seen in 12 patients (31.6%), but was not correlated with disease related death (P = 0.7944). Rate of local recurrence was not dependent on treatment modality (P = 0.3481); 13 patients died, accounting for a disease related survival rate of 81.6% during observation period. Positive lymph nodes were seen in 28.9% of patients and were significantly correlated with disease related death (P = 0.00004). Clinically enlarged inguinal lymph nodes were not correlated with histologically confirmed positive lymph nodes (P = 0.5785). CONCLUSIONS: For patients with T1 G2 penile cancer, organ preserving therapy appears to be a suitable treatment option. In our series, nearly one third of patients developed inguinal lymph node metastases, which highlights the potential benefit of surgical staging. Larger prospective multicenter studies are needed to define the best treatment strategy for intermediate-differentiated invasive penile cancer.

Organ-preserving neodymium-yttrium-aluminium-garnet laser therapy for penile carcinoma: a long-term follow-up.

OBJECTIVE: To retrospectively analyse the long-term follow-up of 54 patients treated with organ-preserving laser therapy for penile carcinoma, as such therapy provides excellent cosmetic and functional results, but recurrence rates are high, which might impair the oncological outcome and worsen tumour-related survival. PATIENTS AND METHODS: Between 1979 and 2008, 54 patients with penile carcinoma were treated with the neodymium-doped yttrium-aluminium-garnet (Nd:YAG) laser at our institution; 11 were classified as having carcinoma in situ (Tis), 39 as T1 and four as T2. RESULTS: There was local recurrence in 16 patients (42%); the mean (range) time to local recurrence was 53 (9-132) months. In half the patients the time to local recurrence was >53 months, with the latest recurrence at 132 months after initial therapy of primary tumour. There was no statistically significant difference in recurrence rates with Tis or invasive penile carcinoma. In lymph-node-negative patients at initial presentation, there were no newly developed positive lymph nodes during the follow-up. CONCLUSIONS: Organ-preserving laser therapy showed a relatively high recurrence rate in patients with a long-term follow up, but the oncological outcome and survival were not compromised by local recurrence. Therefore, laser therapy appears to be appropriate for treating premalignant lesions and early stages of penile carcinoma. Patients should be informed about the potential for late recurrence.

Squamous cell carcinoma antigen correlates with tumor burden but lacks prognostic potential for occult lymph node metastases in penile cancer.

OBJECTIVES: In penile cancer, radical groin dissection is the reference standard for lymph node staging, but it is associated with high morbidity. Prognostic markers for lymphatic spread would be helpful to select patients for a surveillance program. Squamous cell carcinoma (SCC) antigen is a well-known marker for various carcinomas. Our aim was to evaluate the value of the SCC antigen in terms of lymph node staging and treatment control. METHODS: From 1994 to 2004, the serum levels of SCC antigen were analyzed in 54 men with penile carcinoma at different disease stages. The SCC antigen values were compared in patients without evidence of tumor, with a primary tumor only, with nodal metastases, and with progressive metastatic disease. In 13 patients, repeated SCC antigen measurements correlated with the treatment effects. RESULTS: Once lymph node metastases occurred, a trend was found toward increased SCC antigen levels and at the stage of organ metastases, the SCC antigen levels had risen significantly (P <0.01). In cases of repeated measurements, a correlation was found between SCC antigen values and treatment effect. A response to treatment occurred, even if the values were within normal limits. CONCLUSIONS: The SCC antigen levels seemed to correlate with tumor burden in patients with penile carcinoma. However, it is of limited value in the primary prediction of occult lymph node metastases because the SCC antigen levels increased significantly only after massive lymph node involvement or metastatic disease has occurred. However, the SCC antigen could be used as a marker for treatment control in penile carcinoma.

Multidetector-row computed tomography (MDCT) in patients with a history of previous urothelial cancer or painless macroscopic haematuria.

The sensitivity and specificity of MDCT for depiction and localization of urothelial carcinoma (UC) was determined retrospectively. Axial and coronal four-row MDCT of the urinary tract (unenhanced, contrast-enhanced nephrographic, CT urography) was independently reviewed for UC by a radiologist (R1) and a urologist (R2), without other patient information, in 27 patients (22 male, five female; age, 72 +/- 11 years) with previous UC and/or painless macroscopic haematuria. Urinary tract segments included bladder, right and left upper, middle, and lower caliceal groups, renal pelvis, uretero-pelvic junction, upper, middle, and lower ureter. MDCT findings were corroborated by surgery, other invasive procedures, and 1-year follow-up, including MDCT, intravenous urography, and cystoscopy. Receiver-operating characteristic analysis was undertaken and the the area under the curve (AUC) calculated. Eighteen of 27 patients had evidence of UC (pTa, n = 3; pT1-pT3, n = 15; TNM 2002). Tumor was correctly located by both R1 and R2 in 17 patients (sensitivity, 94%; 95% confidence interval, 84-100%) and ruled out in seven (specificity, 78%; 95% confidence interval, 51-100%), with complete agreement. Each detected ten of 11 upper urinary tracts affected by UC. For 35 urinary tract segments with UC and 308 without, the AUC was 0.910 +/- 0.035 (R1) and 0.74 +/- 0.055 (R2), z = 2.4772, Bonferroni-corrected P = 0.022. MDCT depicts urinary tracts affected by UC with high sensitivity and substantial agreement between readers with different training.

Risk stratification in penile carcinoma: 25-year experience with surgical inguinal lymph node staging.

OBJECTIVES: In penile carcinoma, the most reliable staging method for lymph node involvement remains radical dissection with its associated high morbidity. However, the patient's prognosis is closely associated with lymph node status, and radical dissection is potentially curative. We report our experience with surgical lymph node staging and evaluate which group of patients could be assigned to a wait-and-see strategy or dynamic sentinel node biopsy and which group should undergo groin dissection. METHODS: From 1979 to 2004, 56 consecutive patients with penile cancer underwent surgical inguinal lymph node staging. On the basis of the histopathologic results, we defined risk stratification into low, high, and intermediate-risk groups according to the clinical examination findings, stage, and grade. RESULTS: Tumor stage (P = 0.019) and tumor grade (P <0.001) correlated significantly with lymph node status. Stratification into low (pT1G1, pT1G2), high (all G3 tumors), and intermediate-risk (all others) groups found 7.7% of low-risk patients with metastases. In the intermediate and high-risk groups, 28.6% and 75.0% had nodal metastases, respectively. Correlation with nodal involvement according to risk group was R2 = 0.608 (P <0.001). CONCLUSIONS: Risk stratification might enable a modified staging strategy for lymph node status according to stage, grade, and clinical examination findings. Highly motivated low-risk patients could be included in a surveillance program; however, high-risk patients should undergo bilateral inguinal dissection. Dynamic sentinel lymph node biopsy might be encouraged for intermediate-risk patients in the future.

18F-FDG PET/CT for staging of penile cancer.

UNLABELLED: The value of PET or PET/CT with (18)F-FDG for the staging of penile cancer has yet to be determined. The objective of this study was to investigate the pattern of (18)F-FDG uptake in the primary malignancy and its metastases and to determine the diagnostic value of (18)F-FDG PET/CT in the staging and restaging of penile cancer. METHODS: Thirteen patients (mean +/- SD age, 64 +/- 14.0 y) with suspected penile cancer or suspected recurrent disease were examined with a Gemini PET/CT system (200 MBq of (18)F-FDG). The reference standard was based on histopathologic findings obtained at biopsy or during surgery. RESULTS: Both the primary tumor and regional lymph node metastases exhibited a pattern of (18)F-FDG uptake typical for malignancy. Sensitivity in the detection of primary lesions was 75% (6/8), and specificity was 75% (3/4). On a per-patient basis, sensitivity in the detection of lymph node metastases was 80% (4/5), and specificity was 100% (8/8). On a nodal-group basis, PET/CT showed a sensitivity of 89% (8/9) in the detection of metastases in the superficial inguinal lymph node basins and a sensitivity of 100% (7/7) in the deep inguinal and obturator lymph node basins. The mean +/- SD maximum standardized uptake value for the 8 primary lesions was 5.3 +/- 3.7, and that for the 16 lymph node metastases was 4.6 +/- 2.0. CONCLUSION: According to our results, the main indication for (18)F-FDG PET in the primary staging or follow-up of penile cancer patients may be the prognostically crucial search for lymph node metastases. With the use of a PET/CT unit, the additional information provided by CT may be especially useful for planning surgery. Implementing (18)F-FDG PET and PET/CT in future staging algorithms may lead to a more precise and stage-appropriate therapeutic strategy. Furthermore, invasive procedures with a high morbidity rate, such as general bilateral lymphadenectomy, may be avoided.

Durability of probes for interstitial laser coagulation: impact of power setting and probe design.

BACKGROUND AND PURPOSE: Interstitial laser coagulation (ILC) is a well-established treatment option for patients suffering from benign prostatic hyperplasia (BPH). The vulnerability of the current fibers adds to the high cost of the procedure. The objective was to study the impact of different time-power modes and novel probe designs on tissue effects and fiber durability. MATERIALS AND METHODS: Standardized interstitial laser (Nd:YAG) applications utilizing different fiber types and power settings were performed in vitro on fresh bovine liver in a fluid medium. The resulting effects on tissue coagulation were evaluated. Additionally, the durability of contemporary probes as well as novel designs was examined. RESULTS: High-intensity application protocols of 1750 J within 60 seconds were significantly (p < 0.001) more effective in coagulating tissue (4.22 cm3) than the 90 seconds (3.68 cm3) and 120 seconds (3.06 cm3) time-power modes but significantly (p < 0.001) decreased the durability of fibers. Prototype probes significantly improved durability (p < 0.001), whereas efficacy remained unchanged (p > 0.5). CONCLUSIONS: Using a laboratory model, we could demonstrate that high-intensity time-power settings are more effective in creating tissue coagulation in ILC. The resulting deterioration of the probes can be reduced by applying new fiber designs.

Experimental comparison of high power (80 W) potassium titanyl phosphate laser vaporization and transurethral resection of the prostate.

PURPOSE: Perioperative hemorrhage is still the major complication of standard transurethral prostate resection (TURP). Potassium titanyl phosphate (KTP) laser vaporization using 80 W is a novel technique that promises instant hemostatic tissue ablation. In this ex vivo investigation we compared the hemostatic properties of the 2 procedures. MATERIALS AND METHODS: Ex vivo, blood perfused porcine kidneys were used to verify the hemostatic efficacy of KTP laser vaporization and TURP-like tissue resection. Bleeding could be exactly quantified in relation to tissue ablation for the 2 techniques. In addition, specimens were examined microscopically. RESULTS: KTP laser vaporization demonstrated highly significantly decreased bleeding as compared to conventional tissue resection for a standardized ablation volume of 16 cm tissue (2.1 vs 23.3 ml per minute, p <0.0001). Tissue ablation was more rapid in the resection group (20 vs 100 seconds, p <0.001). Histological examinations revealed larger coagulation zones for the KTP group compared to conventional tissue resection (0.9 vs 0.6 mm, p <0.01). CONCLUSIONS: Ex vivo, 80 W KTP laser vaporization is a virtually bloodless ablative procedure, giving rise to hemostasis that is highly superior to conventional TURP-like tissue resection. However, the novel procedure is considerably more time-consuming.

Photodynamic therapy of prostate cancer by means of 5-aminolevulinic acid-induced protoporphyrin IX - in vivo experiments on the dunning rat tumor model.

OBJECTIVE: In order to expand the use of photodynamic therapy (PDT) in the treatment of prostate carcinoma (PCA), the aim of this study was to evaluate PDT by means of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) in an in vivo tumor model. METHODS: The model used was the Dunning R3327 tumor. First of all, the pharmacokinetics and the localization of PPIX were obtained using fluorescence measurement techniques. Thereafter, PDT using 150 mg 5-ALA/kg b.w. i.v. was performed by homogenous irradiation of the photosensitized tumor (diode laser lambda = 633 nm). The tumors were resected 2 days post-PDT and the extent of the necrosis was determined histopathologically. RESULTS: The kinetics of PPIX fluorescence revealed a maximum intensity in the tumor tissue within 3 and 4.5 h post-application of 5-ALA. At this time, specific PPIX fluorescence could be localized selectively in the tumor cells. The PDT-induced necrosis (n = 18) was determined to be 94 +/- 12% (range 60-100%), while the necrosis of the controls (n = 12) differs significantly (p < 0.01), being less than 10%. CONCLUSION: These first in vivo results demonstrate the effective potential of 5-ALA-mediated PDT on PCA in an animal model.

Use of argon plasma coagulation in endourology: in vitro experiments.

OBJECTIVES: To investigate different parameters influencing argon plasma coagulation (APC) in a fluid medium with regard to endourologic procedures. APC is a novel therapeutic modality of noncontact electrocoagulation that applies high-frequency current by way of ionized argon gas. Recent modifications for endoscopic application of APC have helped to establish new indication in various surgical fields. METHODS: Standardized experiments using an endoscopic APC device were performed on fresh bovine skeletal muscle in different fluid media. The effects of the power setting, gas flow rates, and treatment duration on the coagulation zones and tissue ablation were evaluated. RESULTS: The coagulation zones were remarkably uniform. The depths of coagulation increased significantly with augmented power settings and APC duration but were not dependent on gas flow rates. Likewise, tissue removal increased with greater power and longer application times but was not affected by flow rates. Tissue ablation in general was moderate. Different fluid media generated varying performances. CONCLUSIONS: Using a laboratory model, we demonstrated that APC performed in a fluid medium is feasible. The power setting, treatment duration, and different fluid media were interdependent factors affecting the performance of APC in a fluid milieu. However, before application of APC in endourologic procedures in humans, additional studies concerning safety issues are mandatory.