Uncontrolled donation after circulatory death: comparison of two kidney preservation protocols on graft outcomes.

BACKGROUND: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes. METHODS: The primary endpoint was the one-year measured graft filtration rate (mGFR). We collected retrospective data from 64 consecutive uDCD recipients transplanted over a seven-year period in a single centre. RESULTS: Thirty-two grafts were preserved by in situ perfusion and 32 by normothermic recirculation. The mean ± SD mGFR at 1 year post-transplantation was 43.0 ± 12.8 mL/min/1.73 m2 in the in situ perfusion group and 53.2 ± 12.8 mL/min/1.73 m2 in the normothermic recirculation group (p = 0.01). Estimated GFR levels were significantly higher in the normothermic recirculation group at 12 months (p = 0.01) and 24 months (p = 0.03) of follow-up. We did not find any difference between groups regarding patient and graft survival, delayed graft function, graft rejection, or interstitial fibrosis. CONCLUSIONS: Function of grafts preserved by normothermic recirculation was better at 1 year and the results suggest that this persists at 2 years, although no difference was found in short-term outcomes. Despite the retrospective design, this study provides an additional argument in favour of normothermic recirculation.

The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study.

University of Wisconsin (UW) solution is not optimal for preservation of marginal organs. Polyethylene glycol (PEG) could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on kidney endothelial cells, ex vivo on preserved kidneys, and in vivo in a pig kidney autograft model. In vitro, all PEGs provided superior preservation than UW in terms of cell survival, adenosine triphosphate (ATP) production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L).

Hypothermic pulsatile preservation of kidneys from uncontrolled deceased donors after cardiac arrest - a retrospective study.

Kidneys from uncontrolled donors after cardiac arrest (uDCD) suffer from a period of warm ischemia between cardiac arrest and cold flushing. Aim of the study was to evaluate renal outcomes of uDCD kidneys selected on the basis of renal Resistance Index (RI) and its influence on graft function and survival. The study included 44 kidneys procured from 26 uDCD starting 1.1.2006 until 12.31.2013. The donors (Maastricht category II) underwent cardiopulmonary resuscitation by assisted ventilation and chest compression; the organs were preserved with in situ cold perfusion or a normothermic regional perfusion. All kidneys were perfused on hypothermic (1-4 °C) pulsatile perfusion machine (RM3; Waters Medical System) and discarded when RI ≥0.5 mmHg/ml/min after 6 h of perfusion. There was one (2.2%) primary non function, while 37 recipients (84.1%) experienced delayed graft function. Graft survival was 97.6% at 1 and 3 post-transplantation years. Linear regression models showed that lower values of RI at the end of perfusion were associated with higher values of Modification of Diet in Renal Disease at 3 (P = 0.049) and 6 months after transplantation (P = 0.010) and with higher values of inulin clearance at 1 year (P = 0.030). RI showed to be a useful tool to select uDCD kidneys allowing to achieve good clinical results.

Influence of allograft weight to recipient bodyweight ratio on outcome of cadaveric renal transplantation.

AIM: One of the factors that may affect survival and function of kidney graft is its functional mass. METHODS: In a prospective study, we investigated the impact of the ratio between donor kidney weight in grams and recipient bodyweight in kilograms (DKW/RBW) on creatinine clearance, inulin clearance, and proteinuria: 154 kidneys from deceased donors were weighed and the mean kidney weight was 227 ± 59 g, the bodyweight of the recipients was 64 ± 19 kg. RESULTS: This study showed significant lower values of modification of diet in renal disease (MDRD) in patients with DKW/RBW ratio 2.5 g/kg and between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg as well as in patients with DKW/RBW ratio <3 g/kg and between 3 and 4 g/kg compared with those with DKW/RBW ratio >4 g/kg; moreover a random coefficient model showed a different time evolution in creatinine clearance values in patients with DKW/RBW ≤ 3 g/kg when compared with patients with DKW/RBW ratio >4 g/kg. There were significant lower values of inulin clearance in patients with DKW/RBW ratio between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg at 12 post-transplant months and a significantly greater occurrence and earlier appearance of proteinuria in the recipients with DKW/RBW ratio <2.5 g/kg. DKW/RBW ratio did not influence DGF incidence and graft survival. Donor and recipient gender, number of acute rejection episodes and donor age also significantly influenced MDRD values. CONCLUSIONS: Measurements of graft weight as well as donor kidney and recipient body matching should be recommended as influencing renal function.

Dual kidney transplantation from uncontrolled deceased donors after cardiac arrest: a possible option.

Organ shortage is a major problem in organ transplantation. For this reason, transplantation teams have found it necessary to revisit their organ acceptance criteria. Uncontrolled deceased donors after cardiac arrest could increase the donor pool by 20%, but at the same time there is a greater risk of delayed graft function and primary non-function. Dual kidney transplantation is an option when single kidney transplantation cannot be carried out because of lack of organ quality. We report for the first time our four first dual kidney transplantation from uncontrolled deceased donors after cardiac arrest with a follow up longer than 1 year. We described graft outcomes until 5 years, and histology at 3 and 12 months after transplantation. All organs were machine perfused in order to assess their quality leading to a single kidney transplantation or dual kidney transplantation decision. After 1 year of follow up, all grafts were functional with a mean estimated glomerular filtration rate of 44.5 ± 3.3 mL/min/1.73 m(2), and a mean inulin clearance of 43.7 ± 13.6 mL/mn/1.73 m(2). These findings suggest that dual kidney transplantation can represent a viable option for kidneys unsuitable for single kidney transplantation without increasing the rate of surgical complications. Successful transplantation is linked to histological, biological and donor clinical criteria, as well as perfusion parameters.

Epidemiologic profile, sexual history, pathologic features, and human papillomavirus status of 103 patients with penile carcinoma.

PURPOSE: The incidence of penile cancer is four times higher in Paraguay than in the United States or Europe. There are no adequate scientific explanations for this geographical variation. The goal of this study was to evaluate the interplay among risk factors, morphology of the primary tumor, and HPV status. METHODS: Information on socioeconomic status, education level, habits, and sexual history was obtained in 103 Paraguayan patients with penile cancer. All patients were then treated by surgery, and specimens were evaluated histopathologically. RESULTS: Patients usually dwelled in rural/suburban areas (82%), lived in poverty (75%), had a low education level (91%), and were heavy smokers (76%). Phimosis (57%), moderate/poor hygienic habits (90%), and history of sexually transmitted diseases (74%) were frequently found. Patients with >10 lifetime female partners had an odds ratio of 3.8 (95% CI 1.1, 12.6; P-trend = .03) for presenting HPV-positive tumors when compared to patients with <6 partners. However, this trend was not significant when the number of sexual partners was adjusted for age of first coitus and antecedents of sexually transmitted diseases. HPV-related tumors (found in 36% of the samples) were characterized by a warty and/or basaloid morphology and high histological grade in most cases. CONCLUSIONS: In our series, patients with penile cancer presented a distinctive epidemiologic and pathologic profile. These data might help explaining the geographical differences in incidence and aid in the design of strategies for cancer control in Paraguay.

Chronic renoprotective effect of pulsatile perfusion machine RM3 and IGL-1 solution in a preclinical kidney transplantation model.

BACKGROUND: Machine perfusion (MP) of kidney graft provides benefits against preservation injury, however decreased graft quality requires optimization of the method. We examined the chronic benefits of MP on kidney grafts and the potential improvements provided by IGL-1 solution. METHOD: We used an established autotransplantation pig kidney model to study the effects of MP against the deleterious effects of warm ischemia (WI: 60 minutes) followed by 22 hours of cold ischemia in MP or static cold storage (CS) followed by autotransplantation. MPS and IGL-1 solutions were compared. RESULTS: Animal survival was higher in MPS-MP and both IGL groups. Creatinine measurement did not discriminate between the groups, however MPS-MP and both IGL groups showed decreased proteinuria. Chronic fibrosis level was equivalent between the groups. RTqPCR and immunohistofluorescent evaluation showed that MP and IGL-1 provided some protection against epithelial to mesenchymal transition and chronic lesions. IGL-1 was protective with both MP and CS, particularly against chronic inflammation, with only small differences between the groups. CONCLUSION: IGL-1 used in either machine or static preservation offers similar levels of protection than standard MP. The compatibility of IGL-1 with both machine perfusion and static storage could represent an advantage for clinical teams when choosing the correct solution to use for multi-organ collection. The path towards improving machine perfusion, and organ quality, may involve the optimization of the solution and the correct use of colloids.

Renoprotective effect of pulsatile perfusion machine RM3: pathophysiological and kidney injury biomarker characterization in a preclinical model of autotransplanted pig.

OBJECTIVES: To assess the effect of machine perfusion (MP) on renal function recovery vs kidney preservation in static cold storage (CS), in a large animal preclinical model. To assess whether MP benefits are dependent on the preservation solution used. METHODS: Using an established autotransplantation pig kidney model associated with a contralateral nephrectomy we studied the impact of MP against the deleterious effects of warm ischaemia (WI; 60 min), then 22 h of cold ischaemia using MP or static CS, followed by autotransplantation. We used Berzer MP solution (MPS), recommended for MP, and Institut Georges Lopez preservation solution (IGL-1), designed for CS. The pigs were divided into four study groups: MPS-CS: static CS with MPS (n = 7); MPS-MP: renal perfusion with MPS using the Waters Medical Systems (Rochester, MN, USA) RM3 pulsatile machine (n = 7); IGL-CS: static CS with IGL-1 solution (n = 7); IGL-MP: renal perfusion with IGL-1 solution (n = 7). The effect of ischaemia was determined using different variables: pig survival; plasma creatinine; proteinuria; oxidative stress; tubular sodium reabsorption rate; and tissue damage at 1 month. RESULTS: Pig survival was higher in MP and IGL groups compared to MPS-CS. Plasma creatinine levels did not differ among the groups, but proteinuria assay showed significant benefits for the MP vs static CS groups. Histological evaluation of kidney grafts showed more injury in the CS groups than in the MP groups. Urinary measurement of tubular enzyme activity differed substantially among the groups, highlighting the benefits of MP in maintaining brush border integrity. CONCLUSIONS: In our model reproducing the conditions of deceased after cardiac arrest donors we show that MP decreases the risk of renal dysfunction and preserves kidney parenchyma. A non-invasive urinary enzyme assay can provide valuable information on graft integrity. The preservation solution used is important as the wrong solution can decrease the benefits of MP.

Efficacy and safety of prostate artery embolization for patients with lower urinary tract symptoms and indwelling urinary catheter: A retrospective multicenter study.

PURPOSE: The purpose of this multicenter study was to evaluate the clinical success at three months of prostate artery embolization (PAE), assess PAE safety in centers with various experiences and identify factors associated with PAE success. PATIENTS AND METHODS: This multicenter, retrospective study included patients who underwent PAE for lower urinary tract symptoms (LUTS) including those with indwelling urinary catheter. PAE clinical success was defined as either 25% improvement of the International Prostate Symptom Score (IPSS) or 1-point improvement of quality of life (QoL) score, or catheter removal at three months. Multivariable analyses were performed using a logistic regression adjusted on patient variables, technical parameters and center experience in PAE. RESULTS: A total of 383 men (mean age, 68.4 ± 9.7 [standard deviation] years; range: 46-94) with LUTS, including 99 (25.8%) patients with indwelling urinary catheter, were included in seven centers from January 2017 to March 2019. Five patients reported major complications (1.3%), three (0.8%) penile ulceration, three (0.8%) acute urinary retention, one (0.3%) prostatic abscess, and 56 (14.6%) minor complications. Follow up data were available for 271 patients (center 1: n = 159; other centers: n = 112). Clinical success was reported in 232 patients (85.6%). In multivariable analyses, presence of cardiovascular comorbidities (diabetes, stroke history, myocardial infarction and lower limb artery disease) was the single independent variable inversely associated with PAE clinical success (odds ratio = 0.396; 95% confidence interval: 0.17-0.91; P = 0.029). There was no center effect. CONCLUSION: Our results show that PAE is safe and effective in centers with various PAE experiences. Cardiovascular comorbidity is the single independent variable associated with PAE failure.

Immunoprotection by polyethylene glycol in organ preservation solutions is not due to an immunomasking effect.

BACKGROUND: New organ preservation solutions that contain soluble polyethylene glycol (sPEG) molecules have been associated with reduction of acute rejection episodes. METHODS: In the present manuscript we tested in vitro whether sPEG molecules were able to mask donor alloantigens and reduce graft immunogenicity. RESULTS: Immunomasking effect was only evidenced when PEG molecules were covalently bound to donor cell surface. CONCLUSION: We concluded that sPEG in preservation solution are unlikely to display 'immunocamouflage' property.

IGL-1 solution in kidney transplantation: first multi-center study.

IGL-1 solution is characterized by inversion of K+ and Na+ concentrations in the University Wisconsin (UW) solution and polyethylene glycol 35 (PEG 35) substitution for hydroxy ethyl starch. In this prospective study, 121 patients transplanted with kidneys preserved in IGL-1 solution were compared to 102 patients grafted with kidneys preserved in UW solution. Serum creatinine and creatinine clearance, delayed graft function (DGF) and rejection episodes, patient and graft survival were evaluated in the first post-transplant year. Groups were comparable regarding to donor and recipient characteristics. Median creatinine levels were significantly lower in IGL-1 group from day 6 to day 14 and it decreased more rapidly in the IGL-1 group (from day 4 to day 15: p < 0.05). Creatinine clearance values were usually higher in the IGL-1 group for the first 15 d. During the follow-up period serum creatinine concentrations were lower in IGL-1 group at one, three, six and 12 months after transplantation (p = 0.04; p = 0.06, p = 0.01 and p = 0.08, respectively) while creatinine clearance values were similar during the follow-up. No significant difference in DGF and rejection rates as well as in patient and graft survival was shown between the two groups. Kidneys preserved in IGL-1 solution showed to have the same function as kidneys preserved in UW solution.

Renal ischemic preconditioning improves recovery of kidney function and decreases alpha-smooth muscle actin expression in a rat model.

PURPOSE: We determined the role of ischemic preconditioning on renal function and histology in a rat model. MATERIALS AND METHODS: A total of 34 Sprague-Dawley rats (Janvier Laboratories, Le Genet-St-Isle, France) were divided into 6 groups, including sham operation, ischemic preconditioning alone (5 minutes of bilateral ischemia followed by 5 minutes of reperfusion for 3 cycles), ischemia alone (60 minutes of bilateral renal pedicle clamping), ischemic preconditioning before bilateral ischemia, ischemic preconditioning before ischemia in left nephrectomized rats and ischemic preconditioning of the left kidney alone before 60 minutes of bilateral warm ischemia to assess the effect of left kidney preconditioning on the contralateral kidney. Serum creatinine and malondialdehyde levels were recorded at days 0, 1, 3, 11 and 15. Kidneys were harvested at day 15 for histological study and alpha-smooth muscle actin typing. RESULTS: At days 1 and 3 serum creatinine and malondialdehyde levels were significantly lower in the ischemic preconditioning group compared to levels in the ischemia alone group. At days 11 and 15 creatinine and malondialdehyde levels were similar in all groups and comparable to levels at day 0. At day 15 ischemic preconditioning kidneys showed significantly decreased fibrosis and alpha-smooth muscle actin expression than ischemia alone kidneys. CONCLUSIONS: Ischemic preconditioning improves the ability of rat kidney to tolerate subsequent ischemic injury in the first 3 days after reperfusion. Moreover, fibrosis and alpha-smooth muscle actin expression are decreased in ischemic preconditioning kidneys 15 days after reperfusion, suggesting a potential interest of ischemic preconditioning in surgical situations that expose kidneys to prolonged warm ischemia.

Impact of pancreatic venous drainage site on long-term patient and graft outcome in simultaneous pancreas-kidney transplantation.

The impact of portal or systemic venous pancreas graft drainage on patient and graft outcome remains controversial. In the present study, the impact of venous drainage type on long-term patient and graft survival is assessed. From July 1996 to December 2002 80 simultaneous pancreas-kidney transplants were enrolled into a prospective study: 44 received a pancreas allograft with portal (P-SPK group) and 36 with systemic venous drainage (S-SPK group). Enteric exocrine drainage was performed in all recipients receiving the same immunosuppressive treatment. At one yr, the patient survival rates were 91.7% and 95.5% both for S-SPK and P-SPK groups, respectively; no significant difference in survival was shown at any time point of the follow-up. The one-, three-, five-, and eight-yr pancreas survival rates were 75%, 60.6%, 56.7%, and 44%, respectively in the S-SPK group compared to 88.6%, 84.1%, 78.4%, and 31.3% in the P-SPK group. The one-, three-, five-, and eight-yr kidney survival rates were 91.7%, 78.15%, 74.1%, and 57.9%, respectively in the S-SPK group compared to 93.2%, 88.6%, 78.4%, and 38.9% in the P-SPK group. Comparing the two groups, no significant difference was shown in the total number of surgical complications as well as in the number of each complication. No significant difference in long-term outcomes between the two groups was shown, even if in S-SPK group a higher incidence of pancreas graft loss has been reported and it was in part correlated to a higher number of graft thromboses.

A national study of kidney graft tumor treatments: Toward ablative therapy.

BACKGROUND: Results of the conservative treatment of renal cell carcinomas arising in functional renal transplants are unknown compared to transplant nephrectomy. Only small series or case reports have been reported. METHODS: Data were collected from 32 transplantation centers nationwide on cases of de novo tumors in functional renal transplants presumed to be malignant between January 1988 and December 2013. RESULTS: Among 116 de novo transplant tumors, 62 were treated conservatively including: 48 by partial nephrectomy (PN) and 14 by thermal ablation (TA). These patients were compared to 30 other patients who were treated by transplant nephrectomy. The median age of the transplanted kidneys at the time of diagnosis was 43.5 years old as calculated from the donor's age. Tumors treated by transplant nephrectomy presented more often with symptoms (pain, fever, impaired condition, hematuria) than tumors treated conservatively (P = .019). After PN, final histology showed 27 (47.5%) papillary carcinomas, 19 (32.2%) clear cell carcinomas, 1 mixed carcinoma, and 2 oncocytomas. The median tumor size treated by PN was 24 mm with no difference in comparison to the TA group. Nine patients treated by PN had postoperative complications (21%), including 4 requiring operative intervention (Clavien IIIb). None of the patients treated by TA had complications. Specific survival was 100% at the time of last follow-up (median time after treatment 37 months) for patients treated by PN or TA. CONCLUSION: PN proved to be efficient in the treatment of small tumors of transplanted kidneys with good long-term functional and oncologic outcomes, including avoiding return to dialysis. TA seems to be an alternative therapy with good results in selected patients.

Decreased Radiation Exposure and Increased Efficacy in Extracorporeal Lithotripsy Using a New Ultrasound Stone Locking System.

PURPOSE: To compare fluoroscopy duration, radiation dose, and efficacy of two ultrasound stone localization systems during extracorporeal shockwave lithotripsy (SWL) treatment. PATIENTS AND METHODS: Monocentric prospective data were obtained from patients consecutively treated for renal stones using the Sonolith(®) i-sys (EDAP TMS) lithotripter, with fluoroscopy combined with ultrasound localization using an "outline" Automatic Ultrasound Positioning Support (AUPS) (group A), or the "free-line" Visio-Track (VT) (EDAP-TMS) hand-held three-dimensional ultrasound stone locking system (group B). Efficacy rate was defined as the within-groups proportion stone free or with partial stone fragmentation not needing additional procedures. Statistical analysis used Pearson chi-square tests for categoric variables, nonparametric Mann-Whitney tests for continuous variables, and linear regression for operator learning curve with VT. Continuous variables were reported as median (range) values. RESULTS: Patients in group A (n=73) and group B (n=81) were comparable in baseline characteristics (age, kidney stone size, others) and in SWL application (duration, number of shocks, energy [Joules]). During SWL, the median (range) duration (seconds) of radiation exposure was 159.5 (0-690) in group A and 3.5 (0-478) in group B (P<0.001) and irradiation dose (mGy.cm(2)), 10598 (0-54843) in group A and 163 (0-13926) in group B (P<0.001). Fluoroscopy time significantly decreased with operator experience using VT. The efficacy rate was 54.5% in group A and 79.5% in group B (P=0.001). CONCLUSION: VT significantly reduced fluoroscopy use during SWL and the duration and dose of patient exposure to ionizing radiation. Stone treatment efficacy was significantly greater with VT mainly because of a better real-time monitoring of the stone.

LESS living donor nephrectomy: Surgical technique and results.

PURPOSE: We present the findings of 50 patients undergoing pure trans-umbilical laparo-endoscopic single-site surgery (LESS) living donor nephrectomy (LDN), between February 2010 and May 2014. MATERIALS AND METHODS: Laparo-endoscopic single-site surgery LDN was performed through an umbilical incision. Different trocars were used, namely Gelpoint (Applied Mιdical, Rancho Santa Margarita, CA) SILS port (Covidien, Hamilton, Bermuda), R-port (Olympus Surgical, Orangeburg, NY) and standard trocars, inserted through the same skin incision but using separate fascial punctures. The standard laparoscopic technique was employed. The kidney was pre-entrapped in a retrieval bag and extracted trans-umbilically. Data were collected prospectively including questionnaires containing patient reported oral pain medication duration and time to recovery. RESULTS: LESS LDN was successful in all patients. Mean warm ischemia time was 6.2 min (3-15), mean procedure time was 233.2 min (172-300), and hospitalization stay was 3.94 days (3-7) with a visual analogue pain score at discharge of 1.32 (0-3). No intraoperative complications occurred. The mean time of oral pain medication was 8.72 days (1-20) and final scar length was 4.06 cm (3-5). Each allograft was functional. CONCLUSION: Although challenging, trans-umbilical LESS LDN seems to be feasible and safe. Hence, LESS has the potential to improve cosmetic results and decrease morbidity.

Positive resection margins in partial penectomies: sites of involvement and proposal of local routes of spread of penile squamous cell carcinoma.

Recurrence in patients with penile carcinoma occurs in about one third of cases, usually due to insufficient surgery or positive resection margins. An evaluation of surgical resection margins in penectomy specimens was performed to determine precise anatomic sites of tumor involvement, hoping to advance knowledge concerning the local routes of spread of penile carcinomas. A pathologic study of 80 partial penectomies revealed 14 positive margins. Margins were examined after their separation from the main specimen as follows: 1) proximal urethra and surrounding tissues consisting of urethral epithelium with Litree glands, lamina propria, corpus spongiosum, and penile fascia (periurethral cylinder); 2) proximal shaft with corresponding corpora cavernosa separated and surrounded by the tunica albuginea and penile fascia; and 3) skin of shaft with underlying corporal dartos. In 9 patients, only one site was involved by carcinoma, and in 5 there were multiple contiguous sites (for a total of 20 anatomic sites). The distribution of the various sites involved by carcinoma was as follows: urethral epithelium, 4 cases (2 in situ and 2 invasive carcinomas including intraluminal spread); lamina propria, 5 cases; corpus spongiosum, 3 cases; penile fascia, 6 cases; and corpora cavernosa and skin, 1 case each. One of the in situ lesions was discontinuous with the main glans tumor, and the other one was continuous with it. The penile fascia was the most commonly involved site followed by the urethral lamina propria and epithelium. Dissemination to outer skin, corpora cavernosa, and corpus spongiosum was less frequent. The highly vascularized and innervated loose connective tissue of the penile fascia appears to facilitate tumor spread. The urethra is either a pathway for in situ tumor progression from glans to urethra or part of a field prone to malignant transformation. The infrequent involvement of corpora cavernosa is probably due to the tunica albuginea acting as a barrier preventing tumor spread. Based on these observations and the examination of hundreds of penectomy specimens, we are proposing five probable routes of local spread for penile cancer: 1) horizontal and superficially spreading from one epithelial mucosal compartment (glans, coronal sulcus, and foreskin) to the other; 2) following the penile fascia; 3) through spaces created by feeding vessels in the tunica albuginea; 4) vertical spreading involving step-by-step different penile anatomic compartments; and 5) along the urethral epithelium.

Preputial variability and preferential association of long phimotic foreskins with penile cancer: an anatomic comparative study of types of foreskin in a general population and cancer patients.

Difficulty in foreskin retraction and phimosis are risk factors for penile carcinoma that may be related to the anatomically variable length of the foreskin. This observation has stimulated us to postulate the hypothesis that foreskin length is related to penile cancer. To compare the foreskin in the general population and patients with penile cancer, an anatomic classification of foreskin was designed. We examined the foreskin of 215 uncircumcised males without cancer (age range 15-93 years) and the foreskin of 23 patients with cancer (age range 31-90 years). Foreskin types were classified as long (with the preputial orifice located beyond glans meatus and entirely covering the glans), medium (with the preputial orifice located between meatus and glans corona), and short (with the preputial orifice located between corona and coronal sulcus). Phimosis was defined as a nonretractable prepuce of the long type. We found that 77% of noncancer population cases had long foreskin and that only 7% of these cases were phimotic. Cancer patients showed long foreskin in 78% of the cases, and phimosis was significantly frequent in this group (52%) as compared with the other (p <0.001). Coexistence of a long foreskin and phimosis may explain the high incidence of penile cancer in some geographic regions. To better document these findings, a comparison of foreskin types in countries with high and low incidence of penile cancer will be interesting. However, because phimosis appears to be a major factor, the presence of long foreskin may be a necessary but not a sufficient condition for cancer development. For these reasons we support preventive circumcision in patients with long and phimotic foreskins living in high-risk areas. Cancers not related to long foreskins and phimosis may be causally different.

Autopsy findings in 14 patients with penile squamous cell carcinoma.

The aim of this study was to describe pathologic features found at autopsy of 14 patients with penile cancer. Nine patients died from disseminated disease; 5 of them presented local/regional recurrences. Five patients died from other causes, 2 of them postoperatively. Local recurrence sites were corpus cavernosum, Buck's fascia and urethra, regional skin, and prostate. Metastatic sites were lymph nodes (9 cases), liver (7 cases), lungs (6 cases), heart (5 cases), adrenals, bone and skin (3 cases each), thyroid and brain (2 cases each), and pancreas, spleen, and pleura (1 case each). Patients with heart metastasis had arrhythmias. Patients who died and who did not die from penile cancer had different profiles: low-grade superficial tumors with usual and warty subtypes versus high-grade deeply invasive basaloid or hybrid verrucous/sarcomatoid carcinomas. A natural history model for penile cancer routes of spread is proposed: local intrapeneal, regional and systemic nodes, regional skin, liver, lungs, heart, and other multiple sites.