High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation

Patients with end-stage renal failure due to analgesic nephropathy have an increased risk of developing a urothelial carcinoma. To determine the impact of renal transplantation on the frequency of urothelial carcinomas, we analyzed 2072 patients who underwent 2371 renal transplantations between 1968 and 1993, including 78 (3.8%) with clinically proven analgesic nephropathy. Before and after transplantation a regular tumor screening was performed in patients with analgesic nephropathy by urine cytology and abdominal sonography. In 11 of the 78 patients with analgesic nephropathy (14.1%; age 51–66 years, 40–108 months after initiation of dialysis treatment, 5–77 months after transplantation), a urothelial carcinoma of the native urinary tract, especially the kidneys, was diagnosed. Therapy comprised nephroureterectomy (n=6), transurethral resection (n=6) and/or cystectomy (n=2). Seven patients died due to tumor progression 16.3 (4–33) months postoperatively and one patient died due to a perioperative complication. Despite regular tumor screening after transplantation, the diagnosis of a urothelial carcinoma was made very late, leading to a high tumor-related mortality. As a consequence, we suggest that a bilateral nephroureterectomy should be performed prophylactically in patients with proven analgesic nephropathy. In addition, a cystoscopy with lavage cytology testing of the bladder should be performed twice a year.     

Pathology of tumours of the kidney and urinary tract

The urinary tract encompasses the kidney and the urinary collecting system, ureter, bladder and urethra. Benign lesions of the kidney include angiomyolipoma and renal oncocytoma. The main subtypes of renal cell carcinoma include clear cell, papillary and chromophobe variants. Prognostic factors reported by pathologists are reviewed, including the current grading and staging systems. Urothelial tumours include urothelial carcinoma in situ, papillary urothelial carcinoma and invasive urothelial carcinoma. Aspects of their grading and staging are covered, and several less common variants and benign urothelial lesions are mentioned. General aspects of core biopsy and resection specimens for renal disease are examined, including indications for frozen section examination.     

Pathology of tumours of the kidney and urinary tract

The urinary tract encompasses the kidney and the urinary collecting system, ureter, bladder and urethra. Benign lesions of the kidney include angiomyolipoma and renal oncocytoma. The main subtypes of renal cell carcinoma include clear cell, papillary and chromophobe variants. Prognostic factors reported by pathologists are reviewed, including the current grading and staging systems. Urothelial tumours include urothelial carcinoma in situ, papillary urothelial carcinoma and invasive urothelial carcinoma. Aspects of their grading and staging are covered, and several less common variants and benign urothelial lesions are mentioned. General aspects of core biopsy and resection specimens for renal disease are examined, including indications for frozen section examination.     

Pathology of tumours of the kidney and urinary tract

The urinary tract encompasses the kidney and the urinary collecting system, ureter, bladder and urethra. Benign lesions of the kidney include angiomyolipoma and renal oncocytoma. The main subtypes of renal cell carcinoma include clear cell, papillary and chromophobe variants. Prognostic factors reported by pathologists are reviewed, including the current grading and staging systems. Urothelial tumours include urothelial carcinoma in situ, papillary urothelial carcinoma, and invasive urothelial carcinoma. Aspects of their grading and staging are covered, and several less common variants and benign urothelial lesions are mentioned. General aspects of core biopsy and resection specimens for renal disease are examined, including indications for frozen section examination.     

Nephron-sparing surgery with autotransplantation for high-grade upper urinary tract urothelial carcinoma in a patient with solitary kidney

Instead of nephroureterectomy with bladder cuff excision, nephron-sparing surgery can be considered in selected patients with non-muscle invasive upper urinary tract urothelial carcinoma. The role of kidney-sparing surgery has been established for the management of low-grade urothelial carcinoma. We report a solitary kidney patient with high-grade renal pelvis urothelial carcinoma treated with nephron-sparing surgery by ex vivo tumor excision and autotransplantation. The results of the surgery were excellent.     

Prevalence of diverticulosis and incidence of bowel perforation after kidney transplantation in patients with polycystic kidney disease

Sigmoid perforation due to diverticulitis is a life-threatening complication in the postoperative course of allogenic kidney transplantation. The incidence of diverticulosis is especially high among patients with autosomal dominant polycystic kidney disease (ADPKD). Thus, those who undergo allogenic kidney transplantation represent a high-risk group. The aim of this study was to evaluate the prevalence of diverticulosis in ADPKD patients awaiting renal transplantation and the incidence of bowel perforation following allogenic kidney transplantation due to ADPKD. Within the group of 1128 patients who underwent transplantation between January 1974 and January 1990, there were 46 patients (4.07 %) whose indication for transplantation was ADPKD. There was one patient who developed a sigmoid perforation under postoperative immunosuppression. Surgical treatment was a discontinuity resection of the sigmoid (Hartmann's procedure). The postoperative course was favorable, the bowel continuity has already been restored, and the graft is still functioning well. Fifteen of the 28 (53.5 %) ADPKD patients awaiting transplantation had colon diverticulosis (12 male and 3 female patients). No case of bowel perforation has thus far been observed in 15 of these patients who have undergone transplantation. A sigmoid resection was necessary in one patient due to diverticulitis without perforation. We did not find a higher prevalence of diverticulosis in patients with ADPKD, nor did we see a higher incidence of sigmoid perforation during post-transplant immunosuppression in this study. Received: 30 January 1997 Received after revision: 15 July 1997 Accepted: 19 August 1997     

Significance of atypical urinary cytology in the evaluation of patients with end‐stage renal disease for kidney transplantation – a retrospective study

To determine what percentage of renal transplant candidates have atypical urinary cytology, what proportion have urothelial carcinoma and whether cystoscopy is necessary with atypical cytology. All end‐stage renal disease (ESRD) patients (703) presenting for renal transplantation at our institution were retrospectively reviewed. Individuals producing sufficient urine were screened with urine cytology and those with atypical cytology or risk factors for bladder cancer underwent cystoscopy. Four hundred and thirty patients had available urinary cytology and, of these, 151 (35%) had atypical cytology. Of patients with atypical cytology, three were identified to have urothelial carcinoma. However, three additional patients with urothelial carcinoma did not present with atypical cytology. In total, 6 of 703 (0.85%) patients had bladder cancer. All were treated with transurethral resection and eventually underwent renal transplant. One patient has had disease progression post‐transplant to distant metastases. This is the largest study to date evaluating the incidence of urothelial carcinoma in ESRD patients presenting for transplant workup. We found the incidence of bladder cancer to be higher than in the general Canadian population, however, most lesions were low grade. We found atypical cytology in transplant candidates to be a poor predictor for these low‐grade lesions and do not recommend routine cystoscopy for atypical cytology.     

Outcomes of overseas kidney transplantation in chronic haemodialysis patients in Taiwan

Aim: Overseas kidney transplantation has often been reported to have unsatisfactory outcomes. This study aims to compare post‐transplantation outcomes between overseas and domestic kidney transplant (KT) recipients in Taiwan. Methods: The Taiwanese National Health Insurance Research Database was used to identify 310 domestic and 643 overseas KT recipients, who survived for longer than 1 month after the transplantation, in a cohort of 45 453 chronic haemodialysis patients in 1997–2002. Cox proportional hazards models were used to assess risks of mortality and graft failure. Results: The 1, 3 and 5 year survival rates for domestic KT recipients were 96.5%, 93.3% and 91.6%, respectively, while those for overseas KT recipients were 94.9%, 87.9% and 77.1%, respectively (P = 0.015). For the overseas group, those who received a KT before 2001 had significantly higher hazard ratios of mortality and graft failure (2.85 and 1.71, respectively). However, for those receiving a KT in 2001–2002, no significant outcome difference could be found between overseas and domestic recipients. Conclusion: The risk disparity between overseas and domestic KT recipients is mainly attributable to when the transplantation was performed. In attempting to dissuade potential recipients from organ trafficking, merely emphasizing the previously acknowledged poor outcomes no longer suffices as a valid reason.     

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.     

Urological investigations of haematuria

Visible and non-visible haematuria have a wide range of possible causes including urinary tract malignancy, stone disease, infection, trauma or nephrological causes. Systematic investigation is recommended to determine the cause and management of haematuria, although up to 60% of patients will have no cause identified.This article outlines the different causes of haematuria (both visible and non-visible), investigation strategies and when to refer to urology and/or nephrology for further assessment. The evidence behind current practice in the United Kingdom (UK) is discussed and guidelines explored. Clear explanations are given of investigation and imaging modalities.     

Persistent dipstick haematuria following renal transplantation

Despite widespread testing for dipstick haematuria following renal transplantation, there are no published series describing the prevalence and possible causes of this complication in an adult population. A cross-sectional study of 640 renal transplant recipients under review at our follow-up clinic was performed. Persistent haematuria was defined as a minimum of 1+ of blood on urinalysis stick testing detected at not fewer than 75% of clinic visits since its onset, or since the start of routine testing, present over a period of at least 4 weeks. The prevalence of persistent dipstick haematuria was 13.3%. Median serum creatinine was higher in patients with persistent haematuria but age, gender and length of time since transplantation were not significantly different. Potential explanations for persistent haematuria in 21 of 85 affected patients were chronic infection, ureteric stent without chronic infection, regular or intermittent self-catheterization, persistent menstrual bleeding, anticoagulant therapy, graft calculus, and allograft renal cell carcinoma. Recurrent or de novo glomerular disease was confirmed by graft biopsy in 10 of 85 patients. Among the 41 recipients whose original cause of renal failure was IgA nephropathy (IgAN), the prevalence of persistent haematuria was 31.7% compared with 12% in the remaining patients (relative risk 2.6, 95% CI: 1.6-4.3). Persistent haematuria in IgAN patients was not associated with gender, age or time since transplantation. After 29 months of follow-up, 20% of patients with haematuria had progressed to graft failure or death compared with 11.6% of the unaffected group (p = 0.029). However, despite the association with earlier graft failure, haematuria did not predict this endpoint independently of renal function.     

72例肾移植受者术后排斥反应发生状况的调查

目的 比较不同肾源及免疫治疗方案的肾移植术后排斥反应发生状况,寻找可有效监测排斥反应的观测指标.方法 回顾分析北京大学第一临床医学院72例进行肾移植术后,发生排斥反应的状况.结果 亲属肾移植与尸体肾移植,CsA+MMF+Pred和FK506+MMF+Pred两种免疫治疗方案的肾移植受者,术后1年内排斥反应发生率都无统计学差异(P>0.05);血压和体温能有效监测排斥反应.结论 肾移植术后仍需做好监测、护理工作,减少排斥反应的发生.     

Urinary endotoxin excretion and urinary tract infection following kidney transplantation

Following kidney transplantation, urine endotoxin levels were measured among 44 patients and compared to bacterial cultures. Urine samples were collected either via transurethral catheters or – after removal of the catheter on postoperative day 4 – by midstream void. In a control group of ten healthy volunteers, urine endotoxin levels were measured daily for 10 days. Urinary endotoxin concentration was measured by means of a chromogenically modified Limulus amebocyte lysate (LAL) test. The levels among patients with positive bacteriological findings (n = 21) were always elevated ( > 0.7 EU/ml). Furthermore, there was a marked, statistically significant difference in endotoxin values between samples with bacterial growth and samples with fungal or without any growth (P < 0.001). All 21 of the 44 patients with urinary tract infection (UTI) were endotoxin-positive. Seven more patients who received antibiotics had elevated urinary endotoxin levels, but no bacterial growth in the urine culture. No bacterial infection or significant urinary endotoxin was found in the control group. In summary, the detection of urinary endotoxin in samples obtained by either suprapubic/transurethral catheters or midstream void is an early, sensitive, and specific means of diagnosis that can be carried out even during antibiotic treatment. Received: 30 June 2000 Accepted: 24 April 2001     

肾移植术后并发泌尿系统肿瘤8例报告

目的总结肾移植术后并发泌尿系统肿瘤的诊治体会。方法8例患者在肾移植术后3-16年出现间歇性血尿,通过B超、静脉尿路造影（IVU）、膀胱镜、输尿管镜、逆行肾盂造影、CT及内窥镜下取材活检等,证实1例为肾盂肿瘤,3例为输尿管肿瘤,3例为膀胱肿瘤,1例为尿道肿瘤。肾盂肿瘤和输尿管肿瘤的5例均采取肾、输尿管全程及膀胱部分切除术;3例膀胱肿瘤患者中,2例行经尿道膀胱肿瘤电切术,1例膀胱全切术,在行肿瘤切除术前后需适当调整免疫抑制治疗方案。术后通过膀胱灌注给予丝裂霉素、吡柔比星、表阿霉素等进行化疗。结果1例患者因肿瘤复发或新发而接受了二次肿瘤切除术,1例发生肺转移;8例患者10次手术均顺利,治疗效果满意。结论对肾移植术后并发泌尿系统肿瘤的患者,关键在于早期诊断、积极治疗,应慎重对待肾移植术后出现血尿的患者,以免漏诊。     

High incidence of and risk factors for metachronous bilateral upper tract urothelial carcinoma in Taiwan

AIM: Urothelial carcinoma (UC) can occur multifocally in the whole urothelium. A higher rate of bilateral metachronous upper tract (UT) UC was noted in Taiwan. The incidence and risk factors were largely unknown and hence were explored in the study. METHODS: From January 1977 through June 2003, 462 patients with unilateral UT-UC were studied retrospectively. The cumulative incidence of contralateral recurrence was analysed with the Kaplan-Meier analysis. Potential risk factors for contralateral recurrence including age, smoking, bladder cancer, renal function, diagnostic year etc. were evaluated with the log-rank test. Independent risk factors were identified by using the Cox regression analysis. RESULTS: The median follow-up time was 34 months (6-337). Among the 462 patients, 52 (11.3%) developed metachronous contralateral UC. The 2, 5, and 10-year contralateral disease-free survivals were 93.5%, 84.0%, and 75.7%, respectively. The median time to contralateral recurrence was 31.0 months. With the univariate analysis, only poor renal function (serum creatinine < or > OR =2.0 mg/dL, P < 0.001) and late diagnostic year (before or after 1990, P < 0.001) were risk factors for contralateral recurrence. In the multivariate analysis, poor renal function (hazard ratio: 2.98; 95% confidence interval: 1.67-5.33; P < 0.001) and late diagnostic year (hazard ratio: 4.27; 95% confidence interval: 1.71-10.65; P = 0.002) remained independent risk factors. CONCLUSIONS: The incidence of metachronous UT-UC is high in Taiwan. Patients who had either chronic renal insufficiency or a disease diagnosed after 1990 had a higher risk of contralateral recurrence.     

Influence of late-stage chronic kidney disease on overall survival in patients with upper tract urothelial carcinoma following radical nephroureterectomy

ObjectivesThe prevalence of both chronic kidney disease (CKD) and upper tract urothelial carcinoma (UTUC) in Taiwan is unusually high, and we aimed to investigate the impact of preoperative renal function on UTUC after radical nephroureterectomy.Materials and methodsBetween 2000 and 2013, 248 UTUC patients were enrolled in this retrospective study after excluding patients who had concomitant muscle-invasive bladder cancer, whose tumor metastasized at initial presentation, and who received perioperative chemotherapy or radiotherapy. The significance of CKD on overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS) was evaluated by Cox proportional hazard model.ResultsThe median follow-up time was 45.41 months. Overall 5-year OS, CSS, and BRFS rates were 78.27%, 87.81%, and 70.42%, respectively. Aging, late-stage CKD, and nonorgan-confined primary tumor stage were independent predictors for OS after adjustment. Nonorgan-confined primary tumor stage and lymph node involvement were two independent predictors for CSS after adjustment. Concomitant bladder tumor was the only significant predictor for BRFS after adjustment.ConclusionPatients with late-stage CKD had a higher risk of having poor OS. Patients with concomitant bladder tumor had a greater risk of having bladder cancer recurrence despite primary tumor stage. Concomitant bladder tumor, however, had no effect on OS and CSS in this study.