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.

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

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.

Identifying an optimal lymph node yield for penile squamous cell carcinoma: prognostic impact of surgical dissection.

OBJECTIVE: To evaluate the prognostic impact of lymph node yield (LNY) on survival outcomes for penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: In all, 532 patients who underwent inguinal LN dissection (ILND) across tertiary referral centres from Europe, China, Brazil and North America were retrospectively evaluated. From this cohort, 198 patients received pelvic LND (PLND).We identified threshold values for ILND and PLND using receiver operating characteristic curves. We tested prognostic value of LNY for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) using the Kaplan-Meir method and Cox proportional hazard regression models. RESULTS: The median (interquartile [IQR]) age was 59 (49-68) years and the median (IQR) follow-up after ILND was 28 (12-68.2) months. Overall, 85% of the patients had bilateral dissections. The median (IQR) number of inguinal LNs removed was 15 (10-22). Of those receiving PLND, The median (IQR) number of LNs was 13 (8-19). A LNY of ≥15 was used for dichotomisation of ILND patients, and a LNY of ≥9 was used in the PLND cohort. Patients with a LNY ≥15 had significantly better 5-year OS vs patients with a LNY <15 (70.1% vs 58.7%). On multivariable analyses, a LNY ≥15 was a predictor of OS (hazard ratio [HR] 0.68, P = 0.029). For cN0 patients, a LNY ≥15 was an independent predictor of RFS (HR 0.52, P = 0.043) and OS (HR 0.53, P = 0.021). In the PLND cohort, a LNY ≥9 was a predictor of RFS (HR 0.53, P = 0.032). CONCLUSIONS: Using one of the largest LND datasets to date, we found LNY to be a significant predictor of outcomes after lymphatic staging for penile SCC. Prospective validation is warranted.

Impact of Surgical Treatment of Penile Fracture on Sexual Function.

OBJECTIVE: To conduct a comprehensive assessment of sexual function of patients undergoing surgical treatment of penile fracture (PF), covering psychological aspects related to trauma. METHODS: Patients undergoing surgical treatment of PF from January 2014 to August 2017 were followed-up in our department for at least 6 months. The patients underwent a detailed clinical follow-up, including physical examination and were interviewed about any evidence of erectile dysfunction, penile nodules, or curvature acquired after surgery, besides psychological sexual problems. RESULTS: A total of 58 patients conducted the follow-up. The mean age was 38.5 years (range: 18-66 years). Eight (13.7%) patients complained of penile curvature after surgery. Postoperative erectile function was recovered after 6 months in 50 (86.2%) cases. After the last evaluation at 18 months, only 1 patient developed persistent erectile dysfunction (ED) and color duplex Doppler ultrasound excluded a vascular etiology. Psycho-sexual evaluations showed that 45 (77.5%) patients feared a new episode of PF. Changes in sexual habits, such as avoiding vigorous sexual intercourse, was reported by 40 (68.9%) patients. Finally, patients with performance anxiety and those who reported a negative impact on sexual life were more susceptible to the development of ED (P = .0337 and P = .0418, respectively). CONCLUSION: Sexual complications after surgical treatment of PF are unusual but may occur in the late postoperative period and should be treated. Psychological sequela is very common, causing fear of recurrence and psychogenic ED, resulting in negative impact on the sexual life of these patients, which should be monitored closely.

Sexual complications of penile frature in men who have sex with men

ABSTRACT Objectives: Evaluate the demographic data, etiology, operative findings and results of surgical treatment of penile fracture (PF) in men who have sex with men(MSM) with emphasis on sexual complications. Materials and Methods: We studied 216 patients underwent surgical correction of PF at our hospital. Patients self-identified as MSM were followed for at least 6 months. Demographic data, presentation, operative findings, International Index of Erection Function - 5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool. Results: Of 216 PF cases, 4 (1.8%) were MSM. All cases resulted from sexual activity and all patients reported using the "doggy style" position during anal intercourse. Unilateral or bilateral injury of corpus cavernosum was found in 2 patients each. One (25%) patient had complete urethral injury associated with bilateral corpus cavernosum lesion. During the follow-up period, all patients developed some type of sexual complication. One patient reported penile pain during intercourse. Another patient experienced low sexual desire and premature ejaculation. This patient was also dissatisfied with the aesthetic result of the surgical scar and complained about decreased penis size after surgery. The third case developed delayed ejaculation. The fourth patient experienced mild to moderate erectile dysfunction. This same patient presented with penile curvature. Finally, palpable fibrotic nodules in the operative area were observed in all cases. Conclusions: Sexual activity in the "doggy style" position was the commonest cause of PF in MSM. Sexual dysfunction is always present in gay man after surgery for PF. However, additional studies with larger samples should be coinducted.

Sexual complications of penile frature in men who have sex with men.

OBJECTIVES: Evaluate the demographic data, etiology, operative findings and results of surgical treatment of penile fracture (PF) in men who have sex with men(MSM) with emphasis on sexual complications. MATERIALS AND METHODS: We studied 216 patients underwent surgical correction of PF at our hospital. Patients self-identified as MSM were followed for at least 6 months. Demographic data, presentation, operative findings, International Index of Erection Function - 5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool. RESULTS: Of 216 PF cases, 4 (1.8%) were MSM. All cases resulted from sexual activity and all patients reported using the "doggy style" position during anal intercourse. Unilateral or bilateral injury of corpus cavernosum was found in 2 patients each. One (25%) patient had complete urethral injury associated with bilateral corpus cavernosum lesion. During the follow-up period, all patients developed some type of sexual complication. One patient reported penile pain during intercourse. Another patient experienced low sexual desire and premature ejaculation. This patient was also dissatisfied with the aesthetic result of the surgical scar and complained about decreased penis size after surgery. The third case developed delayed ejaculation. The fourth patient experienced mild to moderate erectile dysfunction. This same patient presented with penile curvature. Finally, palpable fibrotic nodules in the operative area were observed in all cases. CONCLUSIONS: Sexual activity in the "doggy style" position was the commonest cause of PF in MSM. Sexual dysfunction is always present in gay man after surgery for PF. However, additional studies with larger samples should be coinducted.

Experimental validation of the complement protein C3a down expression in the plasma of patients with squamous cell carcinoma of the penis.

OBJECTIVES: We have previously shown the importance of the complement system in differentiating between patients with squamous cell carcinoma of the penis (SCCP) and controls. These patients had low expression of C3a and C4 fragments. Therefore, in this study, we investigated the complement protein C3a as a potential circulating biomarker in these patients by a commercially available enzyme-linked immunosorbent assay (ELISA) test. PATIENTS AND METHODS: Plasma samples from 39 patients with SCCP, 15 patients with prostate cancer, and 50 healthy male subjects were evaluated using the ELISA-Bioscience OptEIA Kit human anti-C3a (BD). The nonparametric Mann-Whitney test was used for comparison of means among the groups. RESULTS: The complement protein C3a was found down expressed in patients with SCCP (P<0.05) in comparison to either subjects with good health or subjects with prostate cancer. CONCLUSION: Experimental validation of the down expression of C3a was well succeeded using a commercial ELISA kit. Complement system fragment C3a is down expressed in patients with SCCP. Besides, C3a is also low expressed in the plasma of patients with initial prostate cancer when compared to healthy subjects. These results suggest that the innate immune response might be suppressed in patients with these malignancies.

Human papillomavirus, Epstein-Barr virus, and methylation status of p16ink4a in penile cancer.

Little is known about penile carcinogenesis. The aim of this study was to evaluate the prevalence of HPV and EBV, and the methylation status of p16ink4a in penile cancer samples, and to contribute to the understanding of the mechanisms responsible for penile cancer development. HPV DNA was detected in 63.6% of 122 cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%, with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in 27.3% of the cases. Hypermethylation in p16ink4a was detected in 64.5% of 110 tested cases. An association between the absence of HPV absence and p16ink4a hypermethylation was also found. Death and/or progressive disease was associated with grade (P = 0.001), T stage (P < 0.0001), and N stage (P < 0.0001). In the multivariable model, grade and N stage were independent risk factors for disease-free survival (P = 0.008 and P < 0.001, respectively). Patients without viral infection had a median age significantly lower than that of the HPV-infected patients. We suggest at least two pathways for penile carcinogenesis, one HPV-independent linked to epigenetic events, probably via p16ink4a inactivation; and another, dependent on HPV infection.

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

PURPOSE: 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.

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.

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. .

Prognostic factors in renal cell carcinoma: analysis of 227 patients treated at the Brazilian National Cancer Institute.

PURPOSE: We evaluated the role of several prognostic factors in predicting death and/or progressive disease in patients with renal cell carcinoma. MATERIALS AND METHODS: Between 2004 and 2010, 227 consecutive patients with renal cell carcinoma underwent radical nephrectomy at our Institute. All histological specimens were examined by the same pathologist. We considered certain histological parameters, including histological subtype, conventional Fuhrman grade, presence of sarcomatoid features, adrenal gland infiltration, invasion of the perinephric fat, vascular embolization, collecting system invasion, presence or absence of tumour necrosis (0 %, 1 % to 49 %, or 50 % or greater) and regional lymph node metastasis. RESULTS: Variables significantly associated with death and/or progressive disease on univariate analysis were histological subtype (p = 0.006), Fuhrman grade (p < 0.0001), tumor necrosis (p = 0.009), perinephric fat invasion (p = 0.002), vascular embolization (p = 0.0002), presence of lymph node involvement (p < 0.002), tumor size (p = 0.0006), TNM stage (p < 0.00001) and presence of metastasis (p < 0.00001). In the multivariable model histological subtype, tumor necrosis, lymph node involvement and presence of metastasis were independent risk factors for disease-free survival (p = 0.011, 0.042, 0.025 and p < 0.0001, respectively). CONCLUSION: Histological subtype, tumor necrosis, lymph node involvement and presence of metastasis proved to be independent prognostic factors for disease-free survival. Therefore, the presence and rate of tumor necrosis should always be informed by the pathologist and lymphadenectomy should be performed in all patients.

Prognostic factors in renal cell carcinoma: analysis of 227 patients treated at the Brazilian National Cancer Institute

PURPOSE: We evaluated the role of several prognostic factors in predicting death and/or progressive disease in patients with renal cell carcinoma. MATERIALS AND METHODS: Between 2004 and 2010, 227 consecutive patients with renal cell carcinoma underwent radical nephrectomy at our Institute. All histological specimens were examined by the same pathologist. We considered certain histological parameters, including histological subtype, conventional Fuhrman grade, presence of sarcomatoid features, adrenal gland infiltration, invasion of the perinephric fat, vascular embolization, collecting system invasion, presence or absence of tumour necrosis (0%, 1% to 49%, or 50% or greater) and regional lymph node metastasis. RESULTS: Variables significantly associated with death and/or progressive disease on univariate analysis were histological subtype (p = 0.006), Fuhrman grade (p < 0.0001), tumor necrosis (p = 0.009), perinephric fat invasion (p = 0.002), vascular embolization (p = 0.0002), presence of lymph node involvement (p < 0.002), tumor size (p = 0.0006), TNM stage (p < 0.00001) and presence of metastasis (p < 0.00001). In the multivariable model histological subtype, tumor necrosis, lymph node involvement and presence of metastasis were independent risk factors for disease-free survival (p = 0.011, 0.042, 0.025 and p < 0.0001, respectively). CONCLUSION: Histological subtype, tumor necrosis, lymph node involvement and presence of metastasis proved to be independent prognostic factors for disease-free survival. Therefore, the presence and rate of tumor necrosis should always be informed by the pathologist and lymphadenectomy should be performed in all patients.

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

PURPOSE: To investigate the use of ClinProt technique to identify cancer markers in plasma of patients suffering from squamous cell carcinoma of the penis (SCCP). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.