Phallus preservation and reconstruction: 5-year outcomes of national penile cancer centralisation in the Republic of Ireland.

INTRODUCTION: Penile cancer is a rare urological malignancy with an age-standardised incidence of 0.8 per 100,000 person-years [1]. Given this low incidence it has been suggested that centralised care may improve patient outcomes in relation to phallus sparing surgery and nodal assessment [2]. We aim to assess the outcomes after 5-years of national centralisation of penile cancer care. METHODS: A retrospective analysis of prospectively collected data was performed. All patients undergoing penile cancer surgery from January 2018 to December 2022 following centralisation of care were included. The primary outcome was proportion of phallus sparing procedures performed. Secondary outcomes were patient characteristics, histologic outcomes and procedures performed. RESULTS: 124 patients underwent surgery in the study period. Mean age was 64.49 (±13.87). Overall, 82.3% of patients underwent phallus sparing surgery. This remained stable over the 5-year period from 2018 to 2022 â€‹at 92%, 85%, 76%, 79% and 78% respectively (p â€‹= â€‹0.534). 62.7% had reconstruction performed, including split-thickness skin graft neoglans formation, (57.8% [n â€‹= â€‹37]), preputial flap (32.8% [n â€‹= â€‹21]), glans resurfacing (4.7% [n â€‹= â€‹3]), shaft advancement flap (1.6% [n â€‹= â€‹1]), penile shaft skin graft (1.6% [n â€‹= â€‹1]), and partial penectomy with urethral centralisation (1.6% [n â€‹= â€‹1]). Phallus preservation was not affected by positive nodal status (OR 0.75 [95% CI 0.249-2.266], p â€‹= â€‹0.564) or T-stage ≥1b (OR 0.51 [95% CI 0.153-1.711], p â€‹= â€‹0.276). There has been a significant reduction in Nx nodal status from 64% in 2017 to 15% in 2021 (p â€‹= â€‹0.009). CONCLUSION: Centralisation of treatment for rare malignancies such as penile cancer may improve oncologic outcomes and rates of phallus preservation. This study has shown centralisation to has a high rate of phallus preservation. Further long-term analysis of outcomes in Ireland is required.

Epididymo-orchitis caused by enteric organisms in men > 35 years old: beyond fluoroquinolones.

Epididymo-orchitis is a common urological condition in men of all ages, causing a unilateral or bilateral swelling of the epididymis and/or testis. It is frequently caused by sexually transmitted infections, Chlamydia trachomatis and Neisseria gonorrheae, as well as common enteric organisms implicated in urinary tract infections. Men over 35 years old may develop epididymo-orchitis associated with enteric organisms, often associated with functional bladder outlet problems such as benign prostatic hyperplasia or urethral stricture disease. Fluoroquinolones, especially ciprofloxacin, have long been the mainstay of treatment for these infections; however, rising resistance to ciprofloxacin in E. coli isolates in Europe and the USA means that there is an unprecedented necessity for alternative antimicrobials with adequate penetration into genital tissues (epididymis and testes) to allow appropriate and comprehensive treatment of epididymo-orchitis in this group of patients.

Penile cancer and phallus preservation strategies: a review of current literature.

Penile cancer is a rare malignancy in most developed nations but its management can have significant anatomical, functional and psychological effects in patients. Whilst total penectomy used to be widely practiced, it is associated with significant psychological consequences pertaining to body image and masculinity, with loss of sexual function and the ability to void upright. Recent advances in surgical techniques and technologies has allowed for many organ-sparing techniques with acceptable psychosexual and oncological outcomes. Factors to be considered in phallus preservation treatment include: local invasion, tumour stage and the ability to achieve complete oncological control. Topical chemotherapeutic agents, laser ablation, radiotherapy, Mohs micrographic surgery, glansectomy and partial penectomy have been frequently used to interfere as little as possible with functional anatomy without compromising local cancer control. The difficulty with these phallus-preserving techniques is the potential risk of disease recurrence both locally and distally. Providing that patients are suitable for penile-sparing therapy, have been informed adequately on risk of tumour recurrence and are willing to commit to rigorous close surveillance, good functional outcome as well as oncological control can be achieved.

Penile cancer in younger men-A more aggressive disease?

INTRODUCTION: Penile cancer (PC) in men under 45 is very rare with an incidence of 0.1 to 0.8/100,000. There is little published data on disease characteristics and outcomes of PC in younger men. Herein, we evaluate the disease characteristics and outcomes of penile cancer in younger men compared to an older cohort. METHODS: This study included all men diagnosed with PC at our institution from 2016 to 2021. Primary outcomes included overall survival, cancer-specific survival, and disease-free survival. Secondary outcomes included disease characteristics and surgical management. Men aged ≤45 years (Group A) were compared with men aged >45 years (Group B) at diagnosis. RESULTS: There were 90 patients treated for invasive PC over the study period. The median age at diagnosis was 64 (26-88). The mean length of follow-up was 27 (±18) months. There were 12 (13%) in Group A, and 78 (87%) patients in Group B. Group A had a worse cancer-specific survival compared to Group B (39 months vs. not reached, HR 0.1 (95%CI 0.02-0.85, P = 0.03). There was no significant difference in overall or disease-free survival between both groups. More men in Group A had lymph node metastases at the time of diagnosis (58% vs. 19%, P < 0.001). There was no significant difference in histopathological features including tumor subtype, grade, T stage, p53 status or presence of lymphovascular or perineural invasion. CONCLUSION: In our study, younger men were more likely to have nodal involvement at time of diagnosis and had a worse cancer-specific survival.

Surgical treatment of urachal remnants in an adult population-a single-centre experience.

BACKGROUND: Urachal remnants are a rare congenital defect resulting from failure of obliteration of a fibrous tube that connects the umbilicus to the bladder dome during embryological development. Oftentimes a urachal remnant will go undiagnosed, but occasionally a patient may present with a variety of symptoms, ultimately leading to the identification of the remnant. Given its rarity, there is very limited literature available on the management of symptomatic urachal remnants, especially in adults. Surgical resection has been the first-line management of urachal remnants for years, especially given the risk of the development of urachal adenocarcinoma secondary to recurrent infection, persistent irritation, and urinary stasis associated with some urachal remnants. AIM: We present our experience in the management of symptomatic urachal remnants in adults at our institute and perform a brief literature review of the same. METHODS: A retrospective review of all cases who underwent surgical management of symptomatic urachal remnants between December 2015 and January 2022 was performed. Seven cases of urachal remnant excision in total were identified over the time period. Patient characteristics and perioperative parameters were analysed. Post-operative complications were measured in accordance with the Clavien-Dindo grading system. RESULT: In total, 7 cases of urachal remnants were treated at our institute over the study period. Four patients were treated with a TURBT and 3 patients were treated with a laparoscopic partial cystectomy. There were no intraoperative complications and one post-operative complication requiring readmission for intravenous antibiotics. There was one mortality but this was not as a direct result of the operative procedure. Mean length of stay was 1.71 days. Two of patients had histologically confirmed urachal adenocarcinoma and the remaining five patients had benign histology. Each patient was seen in the outpatients department 6 weeks post-operatively for clinical review and review of histology. No further follow-up was required for the patients with benign histology given resolution of symptoms and follow-up for the malignant histology was arranged appropriately following MDM. CONCLUSION: There is a paucity of data available on the management of urachal remnants in the adult population; however, an endoscopic or laparoscopic approach is a safe and effective method of excising symptomatic urachal remnants.

Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

Adenoid cystic carcinoma of the prostate - A rare case of genitourinary malignancy.

A 72 year old was referred to the Urology department with lower urinary tract symptoms (LUTS), an abnormal prostate on digital examination and a serum prostate specific antigen (PSA) level within normal limits. A flexible cystoscopy revealed no abnormality of the urethra and an obstructive prostate. Magnetic resonance imaging (MRI) revealed a 4.3× 4cm soft tissue mass on the posterior corpus spongiosum encasing the bulbar urethra with tumour abutting the prostate. Transperineal prostate biopsies confirmed adenoid cystic carcinoma. Cross-sectional imaging arranged for staging, revealed multiple pulmonary metastastis. The patient is currently being treated with tyrosine kinase inhibitor medication.

Reconstruction of the male external genitalia in diverse disease processes: Our reconstructive algorithm, techniques, and experience.

Background: Male genital form and function may be rendered abnormal by a number of disease processes, with profound associated psychological and functional consequences. The aim of the study is to review our reconstructive experience with cases of genital loss or distortion due to nonmalignant diseases processes and atypical neoplasia. Materials and methods: A retrospective review of a prospectively maintained database was performed to identify reconstructive cases performed from 2018 to 2020 under the care of a single surgeon. Male patients 18 years or older with a disease diagnosis other than squamous cell carcinoma affecting genital form were included. Disease processes, patient factors, surgical techniques, and both functional and cosmetic outcomes were reviewed. Results: Fourteen cases were identified. The patients had a mean age of 52.2 years (range, 21-72 years). Acquired buried penis was present in 8 patients. Etiology of genital abnormality included balanitis xerotica obliterans (n = 6), excess skin loss at circumcision (n = 2), self-injection of petroleum jelly to penile shaft (n = 1), Fournier gangrene (n = 1), hidradenitis suppurativa (n = 1), extramammary Paget disease (n = 1), idiopathic lymphoedema (n = 1), and penoscrotal webbing (n = 1). Reconstructive techniques performed included penile debridement/shaft skin release, scrotectomy, suprapubic apronectomy, and division of penoscrotal webbing, in combination with split-thickness skin grafting where required. A penile implant was inserted in one patient. Reconstructive planning, techniques, and outcomes are described. Conclusions: A variety of reconstructive techniques in andrology can be used to improve the aesthetic and functional outcomes of multiple disease processes affecting the male external genitalia.

En bloc transurethral resection of bladder tumors: A review of current techniques.

INTRODUCTION: Growing interest surrounds the concept of en bloc transurethral resection of bladder tumors (ERBT). Theoretical advantages include improved adherence to oncological principles and potential yield of superior pathological specimens. Multiple ERBT methods exist. This review summarizes the current evidence regarding application of differing techniques and technologies to ERBT. METHODS: A systematic review of MEDLINE/EMBASE/Scopus databases was performed, using terms "en bloc," "ERBT," "bladder," and "urinary bladder neoplasm." Template-based data extraction included technique of ERBT, feasibility, tumor size, activation of obturator nerve reflex, operative complications, detrusor muscle sampling rate, and recurrence data. RESULTS: Multiple approaches to ERBT have evolved, using a variety of energy sources. The feasibility of electrocautery, laser, combined waterjet/electrocautery, and polypectomy snare techniques have been confirmed in achieving ERBT. ERBT appears safe, with a low complication rate. The use of laser energy sources reduces the risk of activating the obturator nerve reflex during lateral wall resections. Otherwise, no energy source is unequivocally superior in achieving ERBT. The rate of detrusor muscle sampling is high with use of ERBT and appears superior to that achieved with conventional TURBT (cTURBT) in multiple comparative studies. A limited number of largely non-randomized trials assess bladder tumor recurrence; current evidence suggests this is similar between ERBT and cTURBT groups. CONCLUSIONS: ERBT using a variety of technologies is feasible and safe, with a high detrusor muscle sampling rate. Further research is required to determine whether rates of residual disease or recurrence can be reduced with ERBT vs. cTURBT.

Adult testicular granulosa cell tumour: A rare case report.

Adult Granulosa cell tumours (AGT) are a rarely reported subtype of testicular cancer with an unpredictable clinical course. We report the case of a 45 year old man who was diagnosed with a 15mm testicular adult granulosa cell tumour with no metastatic disease at presentation. A radical inguinal orchidectomy was performed with histology demonstrating no invasion of the tunica vaginalis, epididymis, spermatic cord and no lymphovascular invasion. No further treatment was undertaken due to good prognostic factors. A follow up CT Thorax, Abdomen, Pelvis at 4 months demonstrated no disease progression.

The relationship of human papillomavirus positivity with tumor characteristics in an Irish penile cancer population.

INTRODUCTION: Penile cancer is a rare malignancy, with a European-wide annual incidence rate of 1/100 000 males. Approximately one-third of cases are attributable to human papillomavirus (HPV) infection. p16INK4a is a recognized surrogate marker for HPV infection in penile cancer. University Hospital Waterford (UHW) is the national referral center for penile cancer in Ireland. We report the prevalence of HPV infection and histological characteristics of an Irish penile cancer cohort using p16INK4a as a surrogate marker. METHODS: Patients who attended UHW for penile cancer surgery between June 2015 and November 2020 were entered into a prospectively maintained database. Clinical, histopathological, and outcome data were collected. RESULTS: Over the study period, 70 patients with a histological diagnosis of penile squamous cell carcinoma had staining for p16INK4a, of whom 64% were positive. p16INK4a-positive patients were significantly younger at diagnosis, with a mean age of 61±15 years compared to 68±12 (p <0.05). Of note, 97% of tumors with high-risk histology were p16INK4a-positive (p<0.001). p16INK4a positivity was more prevalent among higher-grade tumors (p<0.02). Interestingly, p16INK4a status was not associated with recurrence-free or overall survival. CONCLUSIONS: Our data is representative of the Irish landscape in penile cancer over the last five years. Using p16INK4a staining, we demonstrate a high rate of HPV prevalence in penile cancer cases in our patient cohort, which is associated with prognostically worse tumor subtypes. This would suggest that HPV vaccination of adolescent boys is a useful public health intervention in preventing penile cancer in the Irish male population.

Terminology and details of the diagnostic process for testis cancer.

PURPOSE: We examined the process and causes of diagnostic delay, defined as the interval from symptom onset to diagnosis, for testis (germ cell) cancer and the change with time. Diagnostic delay influences disease burden and may be subdivided into symptomatic interval, defined as symptom onset to first presentation, and diagnostic interval, defined as first presentation to diagnosis. MATERIALS AND METHODS: We performed a single center review of 100 consecutive cases. Diagnostic delay in weeks, and symptomatic and diagnostic intervals in days were calculated, and related factors were recorded. Previous reports by the senior author (JT) in the same health care system allowed the examination of change during 2 decades. RESULTS: Mean±SD diagnostic delay was 12.5±17.4 weeks (median 6, range 1 to 104), a substantial decrease in the mean of 10 months reported by one of us (JT) in 1987. Mean symptomatic interval was 65.4±100.9 days (median 29, range 0 to 720). Mean diagnostic interval was 21.9±63.5 days (median 7, range 1 to 540). Symptomatic interval exceeded or was equal to diagnostic interval in 80 men. CONCLUSIONS: This terminology allows detailed examination of the diagnostic process for testis cancer. Aberrant diagnostic delay for testis cancer is decreasing and is now dominated by patient dependent factors. Select cases suggest that physician error remains a factor in a minority.

Urethral cancer managed with phallus preserving surgery: a case report.

BACKGROUND: Primary urethral carcinoma (PUC) is rare and accounts for < 1% of all genito-urinary cancers. There is a male predominance of 3:1 and a peak incidence in the 7th and 8th decades. The aetiology of this cancer is similar to penile cancer, and the human papilloma virus (HPV) is thought to be an essential factor in tumorigenesis. Urethral cancer should be diagnosed and staged with a combination of tumour biopsy, MRI, and CT with treatment involving a multimodal approach. Contemporary management emphasises phallus-preserving surgery where feasible. CASE PRESENTATION: Here, we describe a case of distal urethral carcinoma, which presented as a metastatic groin mass and identifying the primary lesion proved challenging. Diagnostic flexible cystoscopy identified a tiny lesion in the navicular fossa, which was biopsied and confirmed to be a squamous cell carcinoma. The patient then underwent phallus preserving surgery, including distal urethrectomy with bilateral inguinal lymph node dissections. The final stage was pT1N1M0, and adjuvant chemotherapy was started. The distal urethrectomy involved the surgical creation of a hypospadic meatus in the midshaft of the penis. Normal voiding and sexual function were preserved. CONCLUSIONS: Urethral cancer is a rare malignancy and clinicians should bear in mind that early diagnosis of this disease can be very difficult depending on the anatomical location of the tumour. Treatment currently favours penis-preserving surgery.

Long-Term Surveillance and Laparoscopic Management of Zinner Syndrome.

Zinner syndrome was first described in 1914 and represents the triad of unilateral renal agenesis and ipsilateral seminal vesicle cyst and ipsilateral ejaculatory duct obstruction. Seminal vesicle cysts are often asymptomatic but can also present with pain, haematospermia, or other lower urinary tract symptoms. Treatment strategies include observation and surgical excision. We present the laparoscopic management of an enlarged seminal vesicle cyst, consistent with Zinner syndrome, 14 years after the initial diagnosis. A 58-year-old male patient was diagnosed with a left-sided seminal vesicle cyst while undergoing assessment for renal transplant due to progressively worsening renal function in his solitary right kidney. The otherwise asymptomatic cyst enlarged from the time of initial diagnosis in 2004 (11.3 cm × 9.7 cm × 13.1 cm) to nearly double the size in 2018 (12.8 cm × 11.9 cm × 14.2 cm). This cyst size ultimately precluded renal transplant, and the patient was referred for excision. Laparoscopic excision of the cyst was performed, histopathology confirmed seminal vesicle cyst tissue, and there has been no recurrence of the cyst to date. The patient remains active on the renal transplant waitlist. Zinner syndrome is a rare syndrome, with the seminal vesicle cysts being managed by observation or surgical excision. We report the longest documented observation of a seminal vesicle cyst, culminating in a safe and successful laparoscopic excision.

The Pull-through Anastomosis of Ureter to Enteric Conduit (PAUTEC): A Novel Technique for Urinary Diversion.

OBJECTIVE: To describe and illustrate a novel technique of uretero-ileal anastomosis for use in urinary diversion - the Pull-through Anastomosis of Ureter To Enteric Conduit (PAUTEC). A second objective was to evaluate the surgical outcomes of the PAUTEC anastomosis. MATERIALS AND METHODS: Our novel anastomotic technique was described step-by-step and visually depicted with illustrations and the accompanying narrated video. Additionally, to evaluate safety and efficacy, a retrospective review of a prospectively maintained database was performed. Patients who underwent radical cystectomy alone or during pelvic exenteration, with ileal conduit diversion incorporating PAUTEC, 2016-2020 with ≥6 months follow-up were included. Surgical outcomes and renal function were analysed. RESULTS: PAUTEC anastomosis was performed on 43 ureters in 23 patients. Mean age was 66 years [50-80] and 21 of 23 patients were male. One patient had a conservatively-managed small urine leak. No ureteric strictures have been identified to date. Mean serum creatinine was 1.15 mg/dL [0.69-2.08] (102umol/L, range 61-184 umol/L) preoperatively, and 1.09 mg/dL [0.61-2.59] (96.3 umol/L, range 54-229 umol/L) at follow-up, demonstrating no significant change (P= .26, paired t-test). Mean follow-up was 15 months [6-44]. CONCLUSION: A PAUTEC technique of uretero-ileal anastomosis is feasible and technically straightforward, with satisfactory outcomes observed to date.

Evaluation of Microdissection Testicular Sperm Extraction (mTESE), Outcomes and Predictive Factors in Ireland: The Gold Standard for Men with Non-Obstructive Azoospermia.

BACKGROUND: Microdissection testicular sperm extraction (mTESE) is the gold standard approach in sperm retrieval in men with non-obstructive azoospermia (NOA). The purpose of the study was to assess the outcomes for Irish men who have undergone mTESE with a single surgeon. METHODS: This is a retrospective, single cohort study. Thirty-four patients underwent mTESE between September 2015 and June 2019. A p<0.05 was considered statistically significant. RESULTS: In this study, sperm retrieval rate (SRR) was 47.06%. (16/34). The mean age in those who had retrieved sperm at mTESE was 37.9±2.6 years. Johnson Score (JS) and FSH were statistically different between successful and unsuccessful mTESE groups (p=0.017*10-5 and p=0.004, respectively). Optimal cutoff values for FSH, T and JS were 15 IU/L, 13 nmol/L and 5, respectively. The pregnancy rate was 63.64% (7/11) among men who went on to use mTESE sperm in an ICSI cycle. CONCLUSION: The combination of mTESE/Intracytoplasmic sperm injection (ICSI) is the best option available for men with NOA who prefer to achieve paternity using their own DNA. Given the overall SRRs in mTESE, it is imperative to continue research for a predictive model to better counsel azoospermic men regarding the use of mTESE. For this purpose, large, multicenter, randomized controlled trials are needed.

Phallus Preservation in Penile Cancer Surgery: Patient-reported Aesthetic & Functional Outcomes.

OBJECTIVE: To assess patient-reported outcomes of oncoplastic penile reconstruction using standardized questionnaires. Whilst organ-preserving penile cancer surgery has evolved, aiming to preserve genital function, reduce psychological morbidity of radical penectomy, and maximise patient quality of life, few studies have evaluated patients' final perceptions. METHODS: Following ethical approval, patients post partial/radical glansectomy with reconstruction 2016-2019, under a single surgeon, were identified. Patients were posted a modified Index of Male Genital Image, the IIEF-5, a customised questionnaire exploring outcomes of urinary and sensory function and the EORTC QLQ-C30 to complete and return. Questionnaires were nonidentifiable, however study ID linked responses to the procedure performed. RESULTS: A total of 130 questionnaires were received from 35 patients post penile reconstruction, giving a response rate of 71.4% (35/49). Mean time from surgery was 22 months (4-51), and mean age 61 years (31-79). The majority (82.4%, n = 28) were satisfied or felt neutral about the appearance of their genitalia. High satisfaction with postprocedure urinary function was reported; 85.3% (29/34) could void from a standing position and 79.4% (27/34) reported little or no spraying of urine. Nineteen patients (55.89%) were sexually active, with mean IIEF-5 scores of 14.9 (5-25) (partial glansectomy) and 15.8 (5-25) (radical glansectomy). Mean QoL over past week on 7-point EORTC QLQ-C30 scale was 5.88 (3-7). CONCLUSION: We report good aesthetic and functional outcomes in a unique study exploring penile cancer surgery patient-reported outcome measures. These results strongly support phallus-preserving phallic-preserving strategies as the standard of care in eligible patients undergoing penile cancer surgery.

A gender comparison of postobstructive injury in the rat kidney.

BACKGROUND/AIMS: Unilateral ureteral obstruction (UUO) results in renal injury. Studies report increased injury indices in male rats following UUO. Our study examined whether this gender-based renal response to UUO was reflected in sustained differences following relief of obstruction. METHODS: Adult male/female rats (200-400 g) were subjected to either sham surgery (S/RN) or UUO (UUO/RN). At 24 h, obstruction was relieved and all animals underwent contralateral nephrectomy. Five days after initial surgery, animals were placed in metabolic cages and given water ad libitum for 24 h followed by a 24-hour period of complete water restriction. On day 7, animals were euthanized and samples harvested. Tubular injury, urinary volume/osmolality, creatinine clearance, plasma arginine vasopressin, renal medullary V2 receptor and aquaporin 2 (AQP2) expression were measured. RESULTS: Male UUO/RN rats showed increased renal apoptotic injury and reduced creatinine clearance rates (glomerular filtration rate) vs. females. No gender-dependent differences were observed in urinary osmolality or concentrating ability. AQP2 expression increased post-obstruction. CONCLUSION: Increased injury in males following UUO remains manifest during early recovery after release of obstruction. Despite this, the grade of postobstructive diuresis is not significantly altered between sexes. This may reflect reduced glomerular filtration rate and elevated AQP2 in male rats.

The single insult of hypoxic preconditioning induces an antiapoptotic response in human proximal tubular cells, in vitro, across cold storage.

OBJECTIVE: To examine whether hypoxia (one of the many components of ischaemic preconditioning) can induce a protective response in culture renal tubular cells, and thus determine if non-lethal periods of hypoxia could confer protection against apoptotic injury to human proximal tubular cells during cold storage and subsequent cytotoxic insult, and establish the cellular mechanisms by which this protection is induced. MATERIALS AND METHODS: Human proximal tubular cells (HK-2) were pre-incubated for 24 h in normoxic or hypoxic conditions and then incubated at 4 degrees C for 6 h to mimic cold storage, before being returned to normal conditions and exposed to varying concentrations of cyclosporine A (CSA). Cell viability and apoptosis were measured using propidium iodide staining and flow cytometry. The expression of heat-shock protein (HSP)-70 was determined by Western blotting. RESULTS: Hypoxia had no effect on cell viability or apoptosis. Pre-exposure of cells to hypoxia significantly protected against CSA-induced damage even after a period of cold storage. Western blotting analysis showed that hypoxia up-regulated the anti-apoptotic protein HSP-70. HK-2 cells over-expressing HSP-70 mimicked hypoxia preconditioning, in that they were protected during cold storage and CSA-induced apoptosis. CONCLUSION: Exposure of renal tubular cells to a sequential model of cold storage, reperfusion and incubation with CSA resulted in apoptotic cell death. Preconditioning these cells with hypoxia induced a protective response and up-regulation of the anti-apoptotic protein HSP-70. There was a similar response in non-preconditioned cells over-expressing HSP-70. Further understanding of the cellular changes occurring during this period of preconditioning will allow the development of more targeted, clinically relevant methods of preconditioning in renal transplantation.

The impact of pancreas and kidney transplant on cardiovascular risk factors (analyzed by mode of immunosuppression and exocrine drainage).

INTRODUCTION: The aim of this study was to determine the cardiovascular (CV) risk factor response in Irish patients with type 1 diabetes following simultaneous pancreas and kidney transplantation (SPK), analyzing response based on mode of immunosuppression and surgical drainage in a uniquely homogenous population. METHODS: A retrospective review of SPKs carried out between 1993 and 2005 in the National Renal and Pancreatic Centre of Ireland was performed. Weight, glycated hemoglobin (HBA1c), lipid profile, and blood pressure (BP) were measured pre- and post-operatively. RESULTS: Fifty-eight SPK patients with functioning grafts were analyzed. Thirty-two were male. Following transplantation, mean HbA1c fell from 8.1 (+/-1.5) to 5.2 (+/-0.5)% (p < 0.0001), total cholesterol from 5.2 (+/-1.2) to 4.5 (+/-1.0) mmol/L (p = 0.0004), serum triglycerides from 1.5 (+/-0.6) to 1.1 (+/-0.6) mmol/L (p < 0.0001), and serum creatinine from 699.3 (+/-273.4) to 162.5 (+/-135.8) mmol/L (p < 0.0001). Systolic and diastolic BP fell from 148.5 (+/-23.3) to 136.9 (+/-22.4) mmHg (p = 0.02), and 84.8 (+/-11.7) to 77.8 (+/-10.4) mmHg (p = 0.003), respectively. Cholesterol reduction was significantly greater in the group that received cyclosporine (n = 29) compared with a tacrolimus and mycophenolic acid mofetil (MMF) combination (1.3 +/- 0.3 vs. 0.2 +/- 0.2 mmol/L, p = 0.003). Choice of exocrine vs. endocrine graft drainage did not affect risk factor response. CONCLUSION: SPK resulted in significant improvements both in glucose control and other measured CV risk factors.