A critical assessment of the prognostic value of clear cell,papillary and chromophobe histological subtypes in renal cell carcinoma: a population‐based study

OBJECTIVE

To assess the magnitude of the effect of histological subtype (HS, the three most common being clear cell, papillary and chromophobe) on cause‐specific mortality (CSM) from renal cell carcinoma (RCC).

PATIENTS AND METHODS

Univariable and multivariable Cox regression models included data from 11 618 patients treated with nephrectomy between 1988 and 2004 in nine Surveillance Epidemiology and End Results registries. We tested whether HS represents an independent predictor of CSM, and whether HS adds to the ability of other variables to predict CSM. The covariates comprised age, year of surgery, T stage, nodal status, M stage and Fuhrman grade.

RESULTS

In a multivariable model predicting CSM, HS was an independent predictor (P = 0.03), but failed to improve the accuracy of the model (+0.1% gain when HS was included in the model).

CONCLUSION

Although we confirmed that HS is an independent predictor for CSM, there was no gain in accuracy when HS was added to standard predictors of CSM. From a practical perspective, this implies that patients with clear cell, papillary and chromophobe HS share similar natural histories after nephrectomy, provided that other cancer characteristics are accounted for. From a statistical perspective, in multivariable models of CSM, the clear cell, papillary and chromophobe HS might be included as a single entity.     

Biodegradable urethral stents seeded with autologous urethral epithelial cells in the treatment of post‐traumatic urethral stricture: a feasibility study in a rabbit model

OBJECTIVE

To evaluate the adhesion and growth of rabbit urethral epithelial cells (UECs) on a biodegradable unbraided mesh urethral stent, and to assess the feasibility and effect of the cell‐seeded urethral stent for treating post‐traumatic urethral stricture (PTUS) in a rabbit model.

MATERIALS AND METHODS

Rabbit UECs were collected by biopsy from adult rabbit urethra and seeded onto the outer layer of a mesh biodegradable urethral stent. The growth of UECs in cell‐scaffolds was assessed by scanning electron microscopy, immunohistochemical and fluorescence staining. In all, 32 male New Zealand rabbits were used, with either PTUS or uninjured, as a control group. Cell‐seeded stents were implanted into the rabbits strictured urethra. The histological and immunohistochemical findings were assessed after death at 1, 2, 8, 12 and 24 weeks, respectively. The reconstruction and function were evaluated by urethroscopy and retrograde urethrography.

RESULTS

The cultured UECs adhered to the stent and grew well. Immunohistochemistry showed that the cells were stained positively for cytokeratin. At 4 weeks, vs 2 weeks, the thickness of the papillary projections of the epithelium decreased and inflammatory cell infiltration diminished. At 24 weeks the injured urethra was completely covered by integrated regeneration of three to five layers of urothelium. There was no evidence of voiding difficulty, stricture recurrence or other complications.

CONCLUSIONS

The unbraided mesh biodegradable urethral stent with autologous UECs seemed to be feasible for treating PTUS in the rabbit urethra, and provides a hopeful avenue for clinical application allowing reconstruction of PTUS.     

Pure ‘natural orifice transluminal endoscopic surgery’ for transvaginal nephrectomy in the porcine model

OBJECTIVES

To determine the technical feasibility and reproducibility of pure natural orifice transluminal endoscopic surgery (NOTES) transvaginal nephrectomy using NOTES‐specific instrumentation, with no transabdominal assistance.

MATERIALS AND METHODS

Five female farm pigs (mean weight 45 kg) had a right NOTES nephrectomy, using a single‐channel gastroscope in the first three pigs and a dual‐channel gastroscope in the remaining two. The peritoneal cavity was accessed through the posterior fornix of the vagina. Dissection was started at the lower pole of the kidney, and the ureter was retracted laterally and followed towards the hilum. An XL articulated 60 cm endo‐GIA stapler (US Surgical, Norwalk, CO, USA), inserted transvaginally via a separate vaginal incision, was used for tissue retraction and renal hilar transection. The kidney was freed, entrapped in an impermeable sac, and extracted intact transvaginally.

RESULTS

All five procedures were successful with no addition of a transabdominal laparoscopic port or open conversion. The total operative duration decreased from 200 min in the first pig to 60 min in the last (mean 113 min); the mean blood loss was <50 mL, the mean kidney length was 13.9 cm and the weight was 142 g. There were no intraoperative complications; at autopsy, there was no pelvic or bowel injury.

CONCLUSIONS

Pure NOTES transvaginal nephrectomy is feasible in the porcine model. It has the potential of a less morbid approach, providing truly scar‐less surgery. Further development of instrumentation is necessary.     

The aggressiveness of urinary tract urothelial carcinoma increases with the severity of chronic kidney disease

OBJECTIVE

To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT‐UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end‐stage renal disease (ESRD) have a higher incidence of UT‐UC, but the relationship between early stages of CKD and characteristics of UT‐UC are less well known.

PATIENTS AND METHODS

The study included 267 patients with pathologically confirmed UT‐UC from January 1994 to December 2006; all had a physical examination (blood pressure), and measurements of laboratory data (serum creatinine, serum haemoglobin) and pathological data. The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Patients were divided into three groups by individual GFR (mL/min), i.e. >60 (no/mild CKD), 30–60 (CKD stage 3) and <30 (CKD stage 4/5).

RESULTS

The CKD stages included 81 (30.3%) patients with none/mild CKD, 121 (45.3%) with CKD stage 3 and 65 (24.3%) with CKD stage 4/5. There was a significant and parallel increase in the frequency of UT‐UC as CKD severity increased from none/mild CKD to stage 3 (11% vs 55%), and from CKD stage 3 to 4/5 (55% vs 71%; P < 0.05). Pathologically, the frequency of high‐grade and high T stage UT‐UC in patients with CKD stage 3 (90% and 35%, respectively) and CKD stage 4/5 (91% and 29%, respectively) were significantly greater than in the group with none/mild CKD (P < 0.001). Advanced age and more distant metastasis were independent risk factors for patient survival.

CONCLUSION

The aggressiveness of UT‐UC increased with the severity of CKD, and this might have important clinical consequences.     

Sexual satisfaction of women partners of circumcised men in a randomized trial of male circumcision in Rakai,Uganda

OBJECTIVE

To investigate the effect of adult medical male circumcision on female sexual satisfaction.

SUBJECTS AND METHODS

We investigated self‐reported sexual satisfaction among 455 women partners of men circumcised in a randomized trial of male circumcision for the prevention of human immunodeficiency virus in Rakai, Uganda. Women aged 15–49 years were interviewed about their sexual satisfaction before and after their partners were circumcised. We analysed female‐reported changes in sexual satisfaction using chi‐square or Fisher’s exact tests.

RESULTS

Only 2.9% (13/455) of women reported less sexual satisfaction after their partners were circumcised; 57.3% (255/455) reported no change in sexual satisfaction and 39.8% (177/455) reported an improvement in sexual satisfaction after their partner’s circumcision. There were no statistically significant differences in sexual satisfaction before and after partner’s circumcision by age, religion and education status.

CONCLUSION

The overwhelming majority of women (97.1%) report either no change or improved sexual satisfaction after their male partner was circumcised. These findings suggest that male circumcision has no deleterious effect on female sexual satisfaction.     

Factors for conversion in laparoscopic cholecystectomy for acute cholecystitis: Is timing important?

Aim: Laparoscopic cholecystectomy is regarded as the gold standard treatment for gallstones. Conversion to open cholecystectomy is still common, and preoperative factors to predict conversion are useful in clinical practice. The aim of this study was to evaluate preoperative factors that could predict conversion in acute cholecystitis. Methods: This is a retrospective review of 83 patients with a diagnosis of acute cholecystitis who had laparoscopic cholecystectomy carried out as an emergency operation. Clinical, biochemical, and operative factors were analyzed for association with conversion. Results: A total of 83 patients were recruited to this study. The overall conversion rate was 33.7% (28/83). A longer duration of symptoms before presentation (P = 0.005) and surgery that was carried out over 48 h after admission (P = 0.022) were associated with a higher conversion rate. Emergency operations that began between 20.00 hours and 08.00 hours were also associated with a higher rate of conversion (P = 0.003). Other factors that were associated with conversion included male sex (P = 0.004), low albumin level upon admission (P = 0.024), prolonged prothrombin time (P = 0.040), and a raised serum total bilirubin level (P = 0.024). ASA scores were found to be similar in both groups (P = 0.509). Multivariate analysis by logistic regression showed that the independent risk factors for conversion in emergency laparoscopic cholecystectomy were surgery >48 h after admission (P = 0.028), emergency operation started between 20.00 hours and 08.00 hours (P = 0.026), and longer duration of symptoms before presentation (P = 0.034). Conclusions: Laparoscopic cholecystectomy should be carried out within 48 h of the patient being admitted for acute cholecystitis. The operation should be carried out during the daytime.     

Intralesional administration of epidermal growth factor‐based formulation (Heberprot‐P) in chronic diabetic foot ulcer: treatment up to complete wound closure

Previous studies have shown that an epidermal growth factor‐based formulation (Heberprot‐P) can enhance granulation of high‐grade diabetic foot ulcers (DFU). The aim of this study was to explore the clinical effects of this administration up to complete wound closure. A pilot study in 20 diabetic patients with full‐thickness lower extremity ulcers of more than 4 weeks of evolution was performed. Mean ulcer size was 16·3 ± 21·3 cm². Intralesional injections of 75 μg of Heberprot‐P three times per week were given up to complete wound healing. Full granulation response was achieved in all 20 patients in 23·6 ± 3·8 days. Complete wound closure was obtained in 17 (85%) cases in 44·3 ± 8·9 days. Amputation was not necessary in any case and only one relapse was notified. The most frequent adverse events were tremors, chills, pain and ardour at site of administration and local infection. The therapeutic scheme of intralesional Heberprot‐P administration up to complete closure can be safe and suitable to improve the therapeutic goal in terms of healing of chronic DFU.     

Epidermal growth factor in clinical practice – a review of its biological actions,clinical indications and safety implications

Chemotaxis, mitogenesis, motogenesis and cytoprotection are common cellular events involved in both tumourigenesis and tissue repair, which appear amplified upon growth factors exposure. Epidermal growth factor (EGF) promotes these events in epithelial and mesenchymal cells through the binding to a specific tyrosine kinase receptor. In experimental oncology settings, EGF does not initiate malignant transformation but exhibits ‘tumour promotion’. These observations have raised doubts on the clinical use of EGF despite solid demonstrations of efficacy in experimental conditions and clinical trials. The results of a Pubmed and Bioline investigation on EGF clinical uses and preclinical safety data are presented here. EGF topical administration has been used since 1989 to enhance the healing process of a variety of peripheral tissues wounds (16 clinical reports), as well as its intravenous, oral and rectal administration for gastrointestinal damages (11 clinical reports). EGF therapeutic efficacy and excellent tolerability seem demonstrated. Lack of long‐term adverse effects is highlighted in those studies with 6, 12 and 24 months of patients follow‐up. Although post‐treatment follow‐up may fall short for malignant growth, there are no reports on evidences linking EGF clinical use with cancer. A multicentre, nationwide survey in Cuba, 15 years after randomly using silver sulphadiazine with EGF or not in burn victims yielded that cancer incidence was comparable between EGF‐treated and control subjects and that such incidence rate does not differ from the age‐matched national incidence for those 15‐year period. All the animal species subjected to long‐term EGF systemic administration exhibit dose‐dependent and reversible epithelial organs hyperplasia with no changes in cells phenotypic differentiation. Histotypic pre‐malignant markers were not identified. The results emerged from co‐carcinogenesis studies and from transgenic mice over‐expressing EGF are conflicting and indicate that EGF overexposure, either innate or postnatal, may not be sufficient to transform cells. The ability of EGF to heal injured tissues in life‐threatening scenarios or to assist in preventing physical and social disability advocates for its clinical use under a rational medical risk/benefit balance.     

Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti‐CD20 Monoclonal Antibodies

Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti‐CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2–21] months vs. 83[6–149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64–4898) at diagnosis to 4489 (898–13 855) (p = 0.038). Twelve months post‐Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial.