The role of primary inguinal surgical debulking for locally advanced penile cancer followed by reconstruction with myocutaneous flap

ABSTRACT Purpose: To evaluate surgical complications and oncological outcomes of patients submitted to primary radical inguinal surgical debulking (PRISD) and myocutaneous pediculate flap reconstruction (MPFR) for locally advanced penile cancer (PC). Materials and Methods: Forty-two patients with ulcerated and/or fixed bulky inguinal masses underwent unilateral or bilateral PRISD with MPFR. Tensor fascia lata flap (TFL) was the standard of care for all patients. Additional use of the gracilis flap (GF) was carried out when necessary. Contra-lateral radical inguinal lymphadenectomy (RIL) was conduced when PRISD was performed unilaterally. Surgical complications were analyzed and stratified into minor and major according to the Bevan-Thomas classification. Adjunctive treatments were assessed and oncological outcomes analyzed. Results: Of the 42 patients evaluated, 10 (23.8%) underwent bilateral PRISD and 32 (76.2%) unilateral PRISD with contra-lateral RIL, totaling 84 lymphadenectomies. A total of 62 MPFRs were performed, 52 with TFL and 10 with GF. A total of 53 complications were identified, 49 related to PRISD with MPFR and 4 to RIL. Adjuvant chemotherapy was carried out in 16 patients. Median follow-up was 10.8 months with a median overall survival (OS) of 14.0 months against 6.0 months (p=0.006) for patients submitted to PRISD with adjuvant chemotherapy in relation to surgery alone. Conclusions: PRISD alone for advanced loco-regional PC is unlikely to promote long-term survival, although it can lead to temporary local control of the disease. Despite the feasibility of the procedure, it is related to high incidence of complications. Surgical treatment with adjuvant chemotherapy is associated with improved OS.

Treatment options and outcomes of penile constriction devices

ABSTRACT Purpose: To study the effect of penile constriction devices used on a large series of patients who presented at our emergency facility. We explored treatment options to prevent a wide range of vascular and mechanical injuries occurring due to penile entrapment. Materials and Methods: Between January 2001 and March 2016, 26 patients with penile entrapment were admitted to our facility and prospectively evaluated. Results: The time that elapsed from penile constrictor application to hospital admission varied from 10 hours to 6 weeks (mean: 22.8 hours). Non-metallic devices were used by 18 patients (66.6%) while the other nine (33.4%) had used metallic objects. Acute urinary retention was present in six (23%) patients, of whom four (66.6%) underwent percutaneous surgical cystotomy and two (33.4%) underwent simple bladder catheterization. The main reason for penile constrictor placement was erectile dysfunction, accounting for 15 (55.5%) cases. Autoerotic intention, psychiatric disorders, and sexual violence were responsible in five (18.5%), five (18.5%), and two (7.4%) cases, respectively. The mean hospital stay was 18 hours (range, 6 hours to 3 weeks). Conclusion: Penile strangulation treatment must be immediate through the extraction of the foreign body, avoiding vascular impairments that can lead to serious complications. Most patients present with low-grade injuries and use penile constrictors due to erectile dysfunction. Removal of constrictor device can be challenging. The use of specific tools for achieving penile release from constrictors is a fast, safe and effective method. Patients with urinary retention may require urinary diversion.

Relationship between XPD, RAD51, and APEX1 DNA repair genotypes and prostate cancer risk in the male population of Rio de Janeiro, Brazil

Abstract Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19-428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.

Myiasis associated with penile carcinoma: a new trend in developing countries?

ABSTRACT Objectives The aim of this study is to report an unusual form of penile cancer presentation associated with myiasis infestation, treatment options and outcomes. Materials and Methods We studied 10 patients with suspected malignant neoplasm of the penis associated with genital myiasis infestation. Diagnostic assessment was conducted through clinical history, physical examination, penile biopsy, larvae identification and computerized tomography scan of the chest, abdomen and pelvis. Clinical and pathological staging was done according to 2002 TNM classification system. Radical inguinal lymphadenectomy was conducted according to the primary penile tumor pathology and clinical lymph nodes status. Results Patients age ranged from 41 to 77 years (mean=62.4). All patients presented squamous cell carcinoma of the penis in association with myiasis infestation caused by Psychoda albipennis. Tumor size ranged from 4cm to 12cm (mean=5.3). Circumcision was conducted in 1 (10%) patient, while penile partial penectomy was performed in 5 (50%). Total penectomy was conducted in 2 (20%) patients, while emasculation was the treatment option for 2 (20%). All patients underwent radical inguinal lymphadenectomy. Prophylactic lymphadenectomy was performed on 3 (30%) patients, therapeutic on 5 (50%), and palliative lymphadenectomy on 2 (20%) patients. Time elapsed from primary tumor treatment to radical inguinal lymphadenectomy was 2 to 6 weeks. The mean follow-up was 34.3 months. Conclusion The occurrence of myiasis in the genitalia is more common in patients with precarious hygienic practices and low socio-economic level. The treatment option varied according to the primary tumor presentation and clinical lymph node status.

Proteomics analysis of tissue samples from patients with squamous cell carcinoma of the penis and positive to human papillomavirus

ABSTRACTPurpose:The aim of this study was to identify possible protein biomarkers and/or candidates for therapeutic targets in tissues of patients with SCCP, infected by HPV, applying one dimensional electrophoresis (1DE), followed by direct mass spectrometry (MS) analysis.Materials and Methods:Tissues from 10 HPV positive patients with SCCP and from 10 patients with HPV negative non-tumorous penile foreskins were analyzed applying 1D electrophoresis, followed by analysis with direct mass spectrometry (MS).Results:Sixty-three different proteins were identified in the first group and 50 in the second group. Recognition was possible for 28 proteins exclusively detected in Group 1 and 21 proteins presented only in Group 2.Conclusion:Some proteins in the first group are directly involved in the development of other types of cancer, and therefore, suitable for analysis. Complement C3 protein is a strong candidate for evaluating SCCP patients.

Human glutathione S-transferase polymorphisms associated with prostate cancer in the Brazilian population

Objective To evaluate the influence of polymorphisms in GSTA1, GSTM1, GSTT1, and GSTP1 in the risk of developing Prostate Cancer (PCa) in a population of Rio de Janeiro and compare the distribution of allele and genotype frequencies of the polymorphisms analyzed in the present study population with other regions in the country and different ethnic groups. Materials and Methods We analyzed a sample of the Brazilian population, comprising 196 patients with PCa treated by the urology services of the Brazilian National Cancer Institute (INCA) and Mario Kroeff Hospital (HMK), and 208 male blood donors from the Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro (UFRJ). The polymorphisms were determined in DNA, extracted from peripheral blood leucocytes using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). Results Our results showed that the distribution of polymorphisms can vary significantly according to the Brazilian region and ethnic groups. The distribution of allele and genotype frequencies of the polymorphism GSTA1 was statistically different between cases and controls. Genotypes (A / B + B / B) were associated with protection (OR = 0.61, 95 % CI = 0.40-0.92) for PCa in comparison to genotype A / A. Conclusion The distribution of genotype frequencies of the polymorphism GSTA1 was statistically different between the case and control groups (p = 0.023), and the presence of genotypes A / B and B / B suggests a protective role against the risk of PCa compared to genotype A / A. This is the first study that reports the genotypic frequency of this polymorphism and its association with PCa in a Brazilian population sample. .

Penile primary melanoma: analysis of 6 patients treated at Brazilian national cancer institute in the last eight years

Purpose To describe our experience in treating penile melanoma in 06 patients followed at our institution. Materials and Methods Between 2004 and 2012 six consecutive patients with penile melanoma were treated at our Institution. Stage of the disease was classified according to the 2002 AJCC pathologic system. Melanoma in situ (TIS) was diagnosed in one patient. One patient was staged as T1b, two patients as T2b and two patients as T4b. The clinical and pathological findings were evaluated. Immunohistochemical tests were performed for Melan-A, HNB-45, S-100 and C-KIT. All histological specimens were examined by the same pathologist (ABSS). The patients with Cis, stages T1b and one patient T2b underwent only local excision. One patient T2b underwent local excision and sentinel lymph node dissection. Two patients with melanoma stage T4b underwent partial penile amputation. One of these last patients had palpable inguinal lymph nodes at diagnosis and underwent bilateral inguinal lymphadenectomy and received systemic chemotherapy (dacarbazine, 30 cycles). Results Mean follow-up was 36.3 months. One patient, with stage T2b, died after 12 months due to disease recurrence with bilateral inguinal involvement. The patient who underwent chemotherapy progressed with lung metastases and died after 14 months of follow up. The disease-free survival at five years was 33.3%. Conclusion: Penile melanoma is a disease with poor prognosis in most cases. Local excision or partial penile amputation may have effective control for stages T1 and T2 lesions. Patients who have clinically proven metastases died despite surgical and adjuvant chemotherapy. .

Differencial proteome of clear-cell renal cell carcinoma (ccRCC) tissues

Purpose We attempted to detect, for the first time in a Brazilian cohort, differences in protein expression between clear-cell renal cell carcinoma (ccRCC) and their normal adjacent tissues, aiming to identify biomarkers and/or therapeutic target candidates for this disease. Material and Methods Twenty-four ccRCC and adjacent normal tissues were collected after surgery and their protein extracts were quantified, pooled and separated by two-dimensional polyacrylamide gel electrophoresis (2DE), followed by statistical analysis of the stained gels. Spots of interest were excised from the gels, digested with trypsin and identified by MALDI-TOF-TOF mass spectrometry. Results Twenty-six differential spots were detected between the two classes of tissues, among which twenty were identified by mass spectrometry and sixteen were found to be non-redundant. Eleven proteins were either underexpressed or undetected in the ccRCC extracts, such as prohibitin and peroxiredoxin-3, whereas five were found to be overexpressed or exclusively detected in the ccRCC extract, including αβ crystalin and heat shock protein 27. CONCLUSIONS Several proteins were detected at differential levels when compared to normal adjacent tissues, and, moreover, many have been previously described by their relationship with RCC. Therefore, this work corroborates previous reports on the search for biomarkers for ccRCC, as well as it points out new candidates that may be validated in future studies. .

Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

To investigate the use of ClinProt technique to identify cancer markers in plasma of patients suffering from squamous cell carcinoma of the penis (SCCP).

Plasma of 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment between June 2010 and June 2011 was collected and analyzed by the ClinProt/MALDI/ToF technique. Then the peptides were identified from the C8 MB eluted fraction of patients' and control subjects' plasma by LIFT MS/MS.

A cluster of 2 peptides (A=m/z 1897.22 ± 9 Da and B=m/z 2021.99 ± 9 Da) was able to discriminate patients from control subjects. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% sensitivity and specificity, respectively. The cluster also showed very high sensitivity (100%) and specificity (97%) for SCCP patients that died due to the disease. Furthermore, patients with lymph node involvement presented sensitivity and specificity of 80% and 97%, respectively. These two peptides were identified by the proteomic approach based on a MALDI-TOF/TOF as fragments of C3 (m/z 1896.17) and C4a/b (m/z 2021.26) complement proteins.

The results showed that as the disease progresses, the fragments C3 and C4 A/B are less expressed in comparison with healthy subjects. These results may be useful as prognostic tools. .

Prevalence of human papillomavirus and Epstein-Barr virus DNA in penile cancer cases from Brazil

Penile cancer is a potentially mutilating disease. Although its occurrence is relatively rare worldwide, penile cancer rates can be high in developing countries. A few studies have been conducted on the involvement of human papillomavirus (HPV) in penile carcinoma, which have found HPV present in 30-70 percent of penile malignant lesions, with a higher prevalence of HPV 16 and 18. It has been assumed that cofactors, such as Epstein-Barr virus (EBV) infections, may play a role in the progression of penile neoplasia. The aim of this study was to determine HPV and EBV prevalence in 135 penile malignant lesions from Brazilian men through the use of MY09/11 polymerase chain reaction (PCR), type-specific PCR and restriction fragment length polymorphism analysis. HPV prevalence among the men tested was 60.7 percent. Of the men who tested positive, 27 presented with HPV 16 (29.7 percent), five with HPV 18 (5.5 percent), 21 with HPV 45 (23.1 percent) and nine with HPV 6 (9.9 percent). Seven mixed infections were detected (9.2 percent), while 11 cases remained untyped (13.4 percent). Regarding EBV positivity, 46.7 percent of the samples contained EBV DNA with EBV-1 as the most prevalent type (74.6 percent). More than 23 percent of the men were co-infected with both HPV and EBV, while 35 percent presented exclusively with HPV DNA and 20 percent presented only with EBV DNA. Penile carcinoma aetiology has not been fully elucidated and the role of HPV and EBV infections individually or synergistically is still controversial. Hence, more studies are needed to determine their possible role in carcinogenesis.

Conservative treatment of penile melanoma: case report and literature review

Melanomas do pênis são tumores malignos muito agressivos. Descrevemos o caso de um paciente com uma lesão confinada ao prepúcio e com linfonodos inguinais clinicamente negativos, tratados conservadoramente. O pacientesubmeteu-se à ressecção alargada da lesão para tratamento e diagnóstico. O tratamento das regiões inguinais em pacientes com melanoma de pênis permanece controvertido, uma vez que a incidência de doença metastática é significativamente mais baixa nos pacientes com estádios patológicos iniciais. Como nesse paciente o estádio patológico do melanoma de pênis era T2a (profundidade 1,9 mm, sem ulceração), decidimos usar linfocintigrafia pré-operatória, mapeamento intra-operatório dos linfonodos e biópsia do linfonodo sentinela para avaliar o comprometimento metastático inguinal. Cortes de congelação do linfonodo sentinela direito retirado foram negativos para malignidade e nenhum tratamento adjuvante foi realizado. A ressecção alargada da lesão permitiu efetivocontrole local do tumor peniano e o paciente é mantido em acompanhamento clínico pós-operatório.

Melanomas of the penis are highly aggressive malignant tumors. We report on a patient with a lesion confined tothe prepuce and with clinically negative inguinal lymph nodes, treated conservatively. The patient underwent wide local excision (WLE) for treatment and histological diagnosis. Treatment of the inguinal region in patients withpenile melanoma remains controversial, since the incidence of metastatic disease in those with early pathologicalstagedisease is significantly lower. Since our patient presented penile melanoma pathological stage T2a (depth 1.9mm, without ulceration), we chose to use pre-operative lymphoscintigraphy, intra-operative lymph node mapping,and sentinel node biopsy to evaluate inguinal metastatic involvement. Frozen sections in an excised right sentinelnode were negative, and no adjuvant treatment was performed. WLE provided effective local control of the peniletumor, and the patient remains under postoperative surveillance.

Incisäo de gibson na linfadenectomia ílio-inguinal / Gibson's incision for ilio-inguinal lymphadenectomy

Squamous cell carcinoma of the penis usually metastasizes to the inguinal and iliac regions through the lymphatic channels. Early prophylactic lymphadenectomy in patients with invasive penile carcinoma result in better survival when compared with delayed or therapeutic lymphadenectomy. Skin flap necrosis is the most common complication associated with ilio-inguinal limphadenectomy. The author describes the ilio-inguinal lymphadenectomy using the Gibson incision for patients with squamous cell carcinoma of penis. This incision of the abdominal wall provides excellent exposure of the iliac vessels when the peritoneum is retracted medially. After groin dissection, transplantation of the sartorius muscle is not necessary. When we use the Gibson incision the incidence of flap necrosis is low because the incision is performed in the superior margin of the dissection. The superior flap is always viable and we do not need to perform further complementary distal incision. In our experience, patients who underwent lymphadenectomy concomitantly with penile suegery had better prognosis than those who underwent delayed lymphadenectomy

Adenocarcinoma renal metastático para a uretra feminina. Estudo Imuno-histoquímico / Urethral metastasis from renal cell carcinoma in female patient. Immunohistochemical analysis

A case of urethral metastasis from renal cell carcinoma in a female patient is reported. The metastatic lesion appeared five months after radical nephrectomy. The patiet was referred to our institution with the diagnosis of primary urethra tumor. The pathologic examination and the immunohistochemical analysis of urethral lesion revealed metastatic renal cell carcinoma. To our knowledge, this is the second case of urethral metastasis from renal cell carcinoma described in the urological literature

Reservatório urinário continente: uma alternativa para a substituiçäo vesical / Contigent urinary reservoir: an alternative for vesical substitution

Um segmento de íleo e de cólon é utilizado para criar uma neobexiga, após cistectomia com uma anastomose ceco-uretal. Esta técnica cirúrgica denominada Mainz Pouch utiliza 15 cm de ceco e cólon ascendente e duas alças ileais do mesmo comprimento para a construçäo de um reservatório urinário. Esta neobexiga permite a continência urinária, um grande reservatório de baixa pressäo, o esvaziamento vesical voluntário e o reimplante uretral com técnica anti-refluxo. Quatro pacientes foram submetidos a este procedimento após a cistoprostatectomia, poupando-se, porém, a inervaçäo responsável pela ereçäo. O seguimento destes pacientes variou entre oito e 14 meses. Os quatro pacientes estäo continentes, durante os períodos diurno e noturno. Três esvaziam suas neobexigas espontaneamente, em intervalos normais. Um paciente tem ereçöes e relaçöes sexuais.

Carcinoma da uretra feminina / Carcinoma of the female urethra

O carcinoma da uretra feminina é uma neoplasia de grave prognóstico. Seu tratamento está relacionado ao estadiamento e à porçäo uretral comprometida. A experiência mundial é pequena com estes casos, mas os autores adiantam que possivelmente a melhor forma de tratamento, no momento seja a utilizaçäo de radioterapia para os tumores iniciais e radioterapia pré-operatória seguida de exenteraçäo pélvica nos casos mais avançados