Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

Upper urothelial tumors in emigrants from Balkan endemic nephropathy areas in Serbia

AIM: The aim of the study was to investigate upper urothelial tumors (UUT) in emigrants from Balkan endemic nephropathy (BEN) areas in Serbia and compare them with UUT from both endemic and nonendemic areas. MATERIALS AND METHODS: A total of 1,121 patients from the state cancer database, between 1960 and 1998, were investigated. Sixty of them were emigrants from BEN areas. RESULTS: UUT in emigrants from BEN areas occurred after 21.7+/-9.9 years (median 20) spent in a rural environment. The time spent outside of the BEN regions was 33.2+/-12.8 years (median 31, range 10-72). Age at surgery was 55 years (range 31-89). In emigrants from BEN areas, there was a significant association of other diseases with UUT: renal failure in 63%, bladder tumors in 23.3% and bilateralism in 6.7% of the patients. Bilateralism was statistically more frequent in emigrants from BEN areas (p=0.04), as were low-grade tumors (p=0.03). There was no statistical difference in tumor stage between patients from BEN areas and from outside of them. Relatives of the emigrants from BEN areas were also affected by BEN, UUT and both of them (33%). CONCLUSIONS: It is concluded that hereditary as well as environmental factors are important for the expression and evolution of the disease. An early period of life spent in the endemic region seems important for the later development of UUT in emigrants from BEN regions. Different time spans spent in the endemic region have no effect on the age of appearance of UUT.     

Prognostic value of Balkan endemic nephropathy and gender on upper tract urothelial carcinoma outcomes after radical nephroureterectomy: A cohort study

BackgroundTo identify the prognostic impact of residence in a BEN-endemic area and gender on upper tract urothelial carcinoma (UTUC) outcomes in Serbian patients treated with radical nephroureterectomy (RNU).MethodsThe study included 334 consecutive patients with UTUC. Patients with permanent residence in Balkan endemic nephropathy (BEN) or non-endemic areas from their birth to the end of follow-up were included in the analysis. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates.ResultsFemale patients were more likely to have preoperative pyuria (P = 0.01), tumor multifocality was significantly associated with the female gender (P = 0.003). Gender was not associated with pathologic stage and grade, lymph node metastasis, lymphovascular invasion, adjuvant chemotherapy, bladder cancer history, tumor size, distribution of tumor location, preoperative anemia and demographic characteristics. A total of 107 cases recurred, with a median time to bladder recurrence of 24.5 months. History of bladder tumor (HR, 1.98; P = 0.005), tumor multifocality (HR, 3.80; P < 0.001) and residence in a BEN-endemic area (HR, 1.81; P = 0.01) were independently associated with bladder cancer recurrence. The 5-year bladder cancer RFS for the patients from areas of BEN was 77.8 % and for the patients from non-BEN areas was 64.7 %. The 5-year CSS for the men was 66.2% when compared to 66.6% for the women (P = 0.55).ConclusionsResidence in a BEN-endemic area represents an independent predictor of bladder cancer recurrence in patients who underwent RNU. Gender cannot be used to predict outcomes in a single-centre series of consecutive patients who were treated with RNU for UTUC.     

Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract

OBJECTIVE

To identify the prognostic factors predictive of metachronous bladder transitional cell carcinoma (TCC) in a multi‐institutional dataset of patients who had undergone nephroureterectomy (NU) for nonmetastatic upper urinary tract (UUT) TCC.

PATIENTS AND METHODS

The clinical and pathological data of 231 patients who had had NU for UUT‐TCC from 1989 to 2005 in three European centres were collected retrospectively, and analysed for clinical and pathological variables.

RESULTS

The median follow‐up was 38 months; during the follow‐up, bladder TCC was detected in 109 patients (47.2%), and was significantly more common in patients who had UUT‐TCC after previous bladder TCC (P < 0.001), in those with ureteric cancer (P = 0.022), and in those with pT2 UUT‐TCC (P = 0.017). On multivariate analysis, a previous history of bladder TCC was the only independent predictor of metachronous bladder TCC (hazard ratio 2.825; P < 0.001). The 5‐year probability of being free from metachronous bladder TCC was 45.5%. A history of bladder TCC (P < 0.001) and UUT tumour site (P = 0.01) were significantly associated with the probability of bladder recurrence‐free survival. On multivariate analyses, a previous history of bladder TCC (hazard ratio 2.226; P < 0.001) and the presence of ureteric TCC (1.562; P = 0.036) were independent predictors of the probabilities of being free from metachronous bladder TCC.

CONCLUSION

In this multi‐institutional study of patients who had had NU for UUT‐TCC, a history of bladder TCC was the only independent predictor of metachronous bladder TCC, while both a history of bladder TCC and the presence of ureteric tumours were predictive of the probabilities of being free from metachronous bladder TCC.     

Prognostic value of lymph node dissection in patients with muscle-invasive transitional cell carcinoma of the upper urinary tract

OBJECTIVES: To analyze the prognostic role of lymphadenectomy (LND) in patients with muscle-invasive transitional cell carcinoma (TCC) of the upper urinary tract (UUT) managed with radical surgery. METHODS: From 1986 to 2003, 132 consecutive patients with muscle-invasive TCC of the UUT underwent radical surgery. LND was performed in 95 cases. Patients were stratified according to the presence of LND and lymph node (LN) status. Univariable and multivariable Cox regression models determined the effect of age, pT, grade, nodal status (pN), number of LNs removed, year of surgery, and postoperative chemotherapy on disease-free survival (DFS) and cancer-specific survival (CSS) in the overall population and in patients who underwent LND. RESULTS: The actuarial 5-yr CSS in pNx patients was significantly worse than in pN0 patients (48% vs. 73%, p=0.001) and comparable to pN+ outcome (48% vs. 39%, p=0.476). In the entire population, multivariable Cox regression analyses indicated that pT and pN status were independent predictors of DFS (p=0.04, hazard ratio [HR]=1.82 and p<0.01, HR=1.34, respectively) and CSS (p<0.01, HR=2.42 and p=0.04, HR=1.32, respectively). In patients who underwent LND, the number of LNs removed was an independent predictor of DFS (p=0.03, HR=0.928) and of CSS (p=0.007, HR=0.903). The extent of LND again resulted in an independent predictor either of DFS or CSS (p=0.04, HR=0.904 and p=0.01, HR=0.867, respectively) in the subgroup of pN0 patients. CONCLUSIONS: LND emerged as a strong independent predictor of DFS and CSS in patients surgically managed for a muscle-invasive TCC of the UUT.     

Clinical and epidemiological features of patients with genitourinary tract tumour in a blackfoot disease endemic area of Taiwan

OBJECTIVES

To evaluate the clinical and epidemiological characteristics of patients with genitourinary (GU) tract transitional cell carcinoma (TCC) in an endemic area of blackfoot disease (BFD), the arsenic‐exposed group, to compare them with characteristics among other non‐BFD endemic areas (unexposed group).

PATIENTS AND METHODS

In all, 474 patients with pathologically diagnosed GU‐TCC were enrolled in the study. All follow‐up data were prospectively collected and entered into a database throughout the study period. Statistical analysis was used to determine the association between clinical variables and prognosis, and multivariate regression models were used to assess the association between arseniasis and mortality from GU‐TCC.

RESULTS

There were no significant differences between the groups in age, sex, tumour stage and grade. However, the exposed group had a significantly higher proportion of females. The overall 5‐year survival rate of patients with upper urinary tract (UUT) TCC was 49%, and the two groups had similar 5‐year survival rates. The overall 5‐year survival rate of patients with urinary bladder (UB) TCC was 68.3%, and there was a statistically significant difference in survival between the groups, with a 5‐year survival rate of 58.7% for the exposed and 72.4% for the unexposed group. For patients with early‐stage (pTa and pT1) UB cancers, the death rate was five times higher in exposed patients with tumour progression and recurrence after transurethral resection of bladder tumour than in the unexposed group.

CONCLUSIONS

There was a significantly higher mortality rate for UB‐TCC among exposed patients in the area endemic for arseniasis than in those from other non‐endemic areas. The arsenic content of artesian‐well water might contribute to the increased ratio of female patients with GU‐TCC and the unusually high incidence of UUT‐TCC in the BFD endemic area in Taiwan.     

Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology

OBJECTIVE: To evaluate patients with a history of transitional cell carcinoma (TCC) of the upper urinary tract (UUT) to determine the incidence, pathological distribution, and risk factors for developing subsequent bladder tumours. PATIENTS AND METHODS: Between 1993 and 2003, 103 patients were treated at our institution for UUT-TCC. We reviewed demographic, clinical, surgical, and pathological data from these patients at a median follow-up of 38.7 months, and used univariate and multivariate analyses with logistic regression modelling to determine prognostic variables for bladder recurrences. RESULTS: In all, 51 (49.5%) patients developed bladder tumours after treatment for UUT-TCC, at a mean interval of 13.2 months. Patient age (P = 0.01), UUT tumour size (P = 0.03), UUT tumour multifocality (P = 0.05), a history of bladder tumours (P = 0.03), and the number of previous bladder tumours (P = 0.05) predicted the development of bladder recurrences on univariate analysis. On multivariate analysis, only a previous history of bladder tumours (odds ratio 2.6, P = 0.05) remained significant. Over 90% of the recurrent bladder tumours were superficial, with two-thirds of these being low to moderate grade. Six patients had muscle-invasive disease, and five had a cystectomy. CONCLUSION: Bladder tumours occurred in half the patients after treatment for UUT-TCC; > 60% of these subsequent bladder tumours were superficial, low- to moderate-grade lesions. Neither the pathology of the UUT tumours nor the method of treatment for the UUT disease was associated with recurrent bladder tumours. Only a history of bladder cancer predicted the development of subsequent bladder tumours.     

Independent predictors of contralateral metachronous upper urinary tract transitional cell carcinoma after nephroureterectomy: Multi-institutional dataset from three European centers

Objectives:   To identify the variables predictive of contralateral metachronous upper urinary tract transitional cell carcinoma (UUT-TCC) after nephroureterectomy (NFU) for non-metastatic UUT-TCC.
Methods:   Clinical and pathological data of 234 patients who had undergone NFU for UUT-TCC from 1989 to 2005 in three European urological centers were retrospectively collected and analyzed.
Results:   The median follow-up duration for the whole cohort was 34 months. Contralateral metachronous UUT-TCC was detected in 14 patients (6%). Three patients were treated by NFU, while seven patients underwent ureterectomy and reimplantation and four patients were treated by endoscopic resection plus bacillus Calmette–Guérin instillations within the UUT through a nephrostomic tube. On univariate analysis, a prior history of bladder TCC before NFU was the only factor predictive of the occurrence of contralateral UUT-TCC. Specifically, the 5-year probabilities of being free from contralateral UUT-TCC were 96.6% for the patients with de novo UUT-TCC, and 91.1% and 55.3% for those having non-muscle-invasive and muscle invasive bladder TCC before the UUT cancer, respectively. All survival differences were statistically significant (no history of bladder TCC vs history of non-muscle-invasive bladder TCC, log rank P value 0.015; history of non-muscle-invasive bladder TCC vs history of muscle-invasive bladder TCC, log rank P value 0.035).
Conclusions:   In our multicenter dataset of patients who had undergone NFU for UUT-TCC, contralateral metachronous UUT-TCC occurred in 6% of the patients. A prior history of bladder TCC before NFU was the only variable predictive of UUT recurrence at univariate analysis.     

Rural-urban differences in the presentation, management and survival of breast cancer in Western Australia

From all women diagnosed with invasive breast cancer in 1999 in Western Australia, rural and urban women were compared with regard to mode of detection, tumour characteristics at presentation, diagnostic investigations, treatment and survival. Women from rural areas with breast cancer (n=206, 23%) were less likely to have open biopsy with frozen section (P<0.001), breast-conserving surgery (P<0.001), adjuvant radiotherapy (P=0.004) and hormonal therapy (P=0.03), and were less likely to be treated by a high caseload breast cancer surgeon (P<0.001). Adjusting for age and tumour characteristics, rural women had an increased likelihood of death within 5 years of breast cancer diagnosis (HR 1.62, 95% CI 1.10-2.38). This difference was not significant after adjustment for treatment factors (HR 1.36, 95% CI 0.90-2.04).     

Survival analysis in patients with upper urinary tract transitional cell carcinoma: a comparison between open and hand-assisted laparoscopic nephroureterectomy

OBJECTIVE: To evaluate the stage- and grade-specific survival rate in patients with upper urinary tract (UUT) transitional cell carcinoma (TCC) after open (ONU) or hand-assisted laparoscopic nephroureterectomy (LNU) with bladder-cuff excision. PATIENTS AND METHODS: From January 1998 to April 2005, 143 patients with UUT-TCC were treated with either ONU or LNU and enrolled in the study. The peri-operative data were collected by retrospective chart review. The recurrence, metastasis and survival rate were calculated. RESULTS: The 5-year disease-specific survival of patients with pT1 disease was 88.1% after ONU and 92.0% after LNU (P = 0.745); the respective values for patients with pT2 were 11/17 and 12/15 (P = 0.874), and for pT3 were six/11 and 12/15 (P = 0.476). The incidence of bladder recurrence within 2 years after surgery was 24.7% for ONU and 19.7% for LNU (P = 0.475). CONCLUSION: The results were similar after ONU or LNU with bladder-cuff excision; bladder-cuff excision using a hand-assisted device is effective and serves as a treatment option for patients with UUT-TCC.     

机器人辅助腹腔镜根治性膀胱切除术的预后风险因素

目的:探讨机器人辅助腹腔镜根治性膀胱切除术(RARC)后的预后风险因素。方法:回顾性分析南京鼓楼医院2014年12月至2018年12月收治的224例行RARC患者的临床和随访资料,男193例,女31例。平均年龄68(36~92)岁。7例(3.1%)接受新辅助化疗。125例(55.8%)美国麻醉医师协会(ASA)评分>2...     

91例家族性胃癌的临床特点及预后分析

目的：探讨家族性胃癌的临床病理特征及预后,为制定合理的治疗方案提供临床依据。方法回顾性分析天津医科大学肿瘤医院胃部肿瘤科2003年3月至2007年10月收治的91例家族性胃癌患者的临床资料,选取同期293例散发性胃癌患者的临床资料进行对比分析。结果家族性胃癌患者肿瘤直径小于或等于5 cm者所占比例明显高于散发性胃癌患者[65．9％（60/91）比52．6％（154/293）,P＝0．025],低分化者所占比例高于散发性胃癌患者[68．1％（62/91）比55．6％（163/293）, P＝0．034]。家族性胃癌患者术后5年总体生存率明显低于散发性胃癌患者（25．6％比38．9％,P＝0．001）;进一步分层分析,T4期家族性胃癌与散发性胃癌患者5年生存率分别为14．5％和30．5％;N3期患者分别为10．4％和17．3％,差异均有统计学意义（P＜0．05）;两组间其他T分期和N分期5年生存率的差异均无统计学意义（P＞0．05）。单因素分析显示,肿瘤大小、肿瘤部位、病理类型、手术方式、浸润深度和淋巴结转移与家族性胃癌患者预后有关;多因素分析显示,肿瘤大小（HR＝2．271）、病理类型（HR＝1．449）、浸润深度（HR＝1．748）及淋巴结转移（HR＝1．487）是影响家族性胃癌患者预后的独立危险因素。结论与散发性胃癌比较,家族性胃癌患者具有肿瘤分化差和预后不佳的特点。     

5-aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer

OBJECTIVE: To assess the influence of 5-aminolaevulinic acid-induced fluorescence cystoscopy (FC) during transurethral resection (TUR) on the recurrence rate and the length of tumour-free interval in stage Ta/T1 transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: In all, 122 patients with primary or recurrent stage Ta/T1 bladder TCC treated with TUR were enrolled in a prospective randomized study. In group A the TUR was performed with standard white-light endoscopy, and in group B with FC. The patients were followed using standard cystoscopy and urinary cytology. The recurrence-free interval was evaluated in whole groups, for single and multiple, and for primary and recurrent tumours separately. RESULTS: At the time of the first cystoscopy (10-15 weeks after TUR) tumour recurrence was detected in 23 of 62 patients (37%) in group A, but only in five of 60 patients (8%) in group B. The recurrence-free survival rates in group A were 39% and 28% after 12 and 24 months, compared to 66% and 40% respectively in group B (P = 0.008, log-rank test). In separate analyses, the recurrence-free survival rates were significantly higher using FC in multiple (P = 0.001) and in recurrent (P = 0.02) tumours. In solitary and primary tumours the median time to recurrence was also longer in group B, but the difference was not statistically significant. CONCLUSION: 5-aminolaevulinic acid-induced FC during TUR reduces the recurrence rate in stage Ta/T1 bladder TCC. The most significant benefit is in patients with multiple and recurrent tumours.     

The percutaneous treatment of upper urinary tract urothelial tumours

Summary This paper reports the management of eight upper urinary tract (UUT) transitional cell tumours (TCC) treated by percutaneous endoscopic resection (n=7) or laser coagulation. Two patients with small, solitary-low-grade TCC and negative urine cytology are free of recurrence after 2 years. Of the remainder, two died of TCC, two proceeded to nephroureterectomy for highgrade or recurrent invasive tumors, one underwent a second percutaneous resection of a recurrent superficial TCC and one was lost to follow-up. The patient who died from high-grade invasive TCC had tumour protruding from the nephrostomy track. We feel that percutaneous surgery has a very limited place in the management of UUT TCC and should be reserved for palliation of proven solitary, low-grade superficial tumours with negative cytology in patients requiring conservative treatment.     

Elective endoscopic management of transitional cell carcinoma first diagnosed in the upper urinary tract

OBJECTIVE

To report our experience using ureteroscopic or percutaneous management of upper urinary tract (UUT) transitional cell carcinoma (TCC) in patients with no history of bladder TCC.

PATIENTS AND METHODS

Between 1983 and 2004 we identified 22 patients who underwent endoscopic management of TCC first diagnosed in the UUT and in the setting of a normal contralateral kidney. We performed a retrospective chart review and conducted outcome analyses.

RESULTS

The median (range) age at diagnosis was 64 (37–86) years and the median tumour size was 0.8 (0.3–2.6) cm. The tumour grade was 1, 2, or diagnosed as visual low grade in two (9%), seven (32%), and 13 (59%) patients, respectively; no patient had grade 3 TCC at diagnosis. Tumour stage was Ta or visual Ta in all patients. The median follow‐up was 4.9 (0.4–17) years during which 11 (50%) patients developed 21 UUT recurrences and 10 (45%) patients developed bladder TCC. At last follow‐up, seven (32%) patients required a nephroureterectomy for recurrent TCC and two (9%) patients died from TCC. Among 13 patients with a diagnosis based on visual inspection only, three recurred with grade 3 invasive TCC during follow‐up. No patient with pathological confirmation of low‐grade/stage TCC recurred with high‐grade or invasive TCC.

CONCLUSIONS

Recurrence is common after endoscopic management of UUT‐TCC, underscoring the need for strict surveillance. Patients diagnosed visually, without adequate tissue for pathological examination, can recur with high‐grade invasive TCC. No patient with pathological confirmation of low‐grade TCC developed progressive disease during follow‐up.     

Clinical significance of lymphovascular invasion in upper urinary tract urothelial cancer

OBJECTIVES

To clarify the significance of lymphovascular invasion (LVI) in patients with pT3N0M0 upper urinary tract (UUT) urothelial carcinoma (UC) relative to prognosis in terms of disease‐specific survival, as LVI, which implies both blood vessel and lymph vessel involvement, is reportedly a poor prognostic factor in patients with UUT‐UC.

PATIENTS AND METHODS

The clinical records of 90 patients who had surgery for UUT‐UC were reviewed retrospectively. The median patient age was 71 years and the median follow‐up was 42 months. The prognostic significances of LVI (with vs without), T stage (<1 vs 2–4), grade (1–2 vs 3), N stage (0 vs 1–2), age (≤70 vs >70 years), gender and tumour location (renal pelvis vs ureter) for survival time were evaluated.

RESULTS

LVI of UUT‐UC was found in 34 patients (37.8%). There were significantly higher frequencies of LVI with advancing stage and lymph node metastasis. Kaplan‐Meier analysis showed that LVI was strongly associated with disease‐specific survival in all patients (P < 0.001) and in patients with pT3N0M0 disease (P < 0.001). Univariate analyses showed that LVI, T stage, N stage and tumour grade were significantly related to disease‐specific survival in all patients (P < 0.001, <0.001, 0.003 and 0.007, respectively). Multivariate analysis using Cox proportional hazards model showed that LVI was the only prognostic factor with independent significance for disease‐specific survival (P < 0.001).

CONCLUSIONS

LVI appears to be an important and independent prognostic factor for UUT‐UC in patients treated by nephroureterectomy. Our data suggest that the LVI status might be a predictive marker for disease‐specific survival in patients with T3N0M0 UTT‐UC.     

Hemodialysis treatment in patients with Balkan endemic nephropathy: an epidemiological study

AIM: To analyze hemodialysis (HD) treatment of patients with Balkan endemic nephropathy (BEN) from five endemic villages in the South Morava Region of Serbia. Analyses of patterns of incidence may generate hypotheses about the underlying causes of BEN, and prevalence data provide information on the current and likely future burden on health services for managing BEN. METHODS: A total of 143 end-stage kidney disease patients (ESKD) with BEN were admitted to the renal replacement program from 1974 to 2004: 121 to HD, 15 peritoneal dialysis, and 7 kidney transplantation. As a control group, 117 patients with other kidney disease (chronic pyelonephritis, glomerulonephritis, and ischemic nephropathy) admitted to HD at the time of BEN patients and matched by age and gender were studied. RESULTS: Most of the BEN patients (93.4%) treated by HD were born from 1917 to 1941. The majority of patients (79.3%) started HD from 1977 to 1991 (period of 15 years). The mean age of BEN patients starting HD treatment was 49.1 years in the period from 1974 to 1978, and increased steadily in the following years, being 72.5 years in the last period of study (2004-2006) The mean survival time of BEN males was 4.70 (95% CI 3.66-5.75) and for females was 5.02 (95% CI 1.47-4.53). Difference between males and females was not statistically significant (log rank 0.14, p = 0.7, P > 0.5). Mean survival times of 4.84 (95% CI 3.97-5.70) in BEN patients and 3.1 (95% CI 2.78-3.84) in other kidney disease patients were found. Difference between BEN patients and controls was statistically significant (log rank 8.38, p = 0.0038, P < 0.01). CONCLUSION: The population of endemic villages around the South Morava River admitted to HD treatment after 1974 was exposed to environmental toxicant(s) from 1917 to 1941. The most intense effect of environmental exposure was in that period, with ESKD in patients in their forties. The exposure to environmental toxicants has diminished, so ESKD of BEN has become less frequent and manifested in the older age, mean 72.5 in the period from 2004 to 2006. Different type of exposure was registered in some other endemic regions in Serbia and abroad.     

Contemporary results of radical radiotherapy for bladder transitional cell carcinoma in a district general hospital with cancer-centre status

OBJECTIVE: To assess the current efficacy and safety of definitive external beam radiotherapy (EBRT) in the treatment of invasive bladder transitional cell carcinoma (TCC) in a district general hospital with cancer-centre status. PATIENTS AND METHODS: The case notes of all patients with bladder TCC undergoing EBRT with curative intent over an 8-year period (1988-95) were reviewed. Additional missing outcome data were collected. RESULTS: In all, 120 patients (109 men; median age 70 years, range 34-90) underwent radical EBRT (40-65 Gy; fraction median=20) over the 8-year period. Staging, as assessed by examination under anaesthesia and computed tomography, was T1 in 16%, T2 in 43%, T3 in 38% and T4 in 3%. In 96 patients (80%) the tumour was poorly differentiated (G3). The overall morbidity at 12 months was 12%; proctitis occurred in nine patients (8%) and cystitis in five (4%). Sixty-seven patients (59%) developed a local recurrence and in 36 (30%) this was invasive. The overall median survival was 60 months. Thirty-three patients underwent salvage cystectomy with a subsequent median survival of 12.5 months. CONCLUSION: Modern radical multifraction EBRT in invasive bladder TCC has a low morbidity, with an overall median survival of 5 years.     

Effect of acute kidney injury on short-and long-term mortality of patients with acute myocardial infarction

Objective To evaluate the role of acute kidney injury (AKI) in predicting the early (30-day) and late (30-day to 5-year) mortality of acute myocardial infarction (AMI) patients during hospitalization. Methods A total of 1371 adult patients diagnosed with AMI in the First People's Hospital of Changzhou from January 2008 to December 2012 were analyzed retrospectively with collecting their relevant clinical data from the hospital's database. AKI was categorized according to the 2012 KDIGO AKI criteria. To compare between death group and non-death group in AMI patients during 30-day and 30-day to 5-year. Different AKI stages of patients were compared, and their all-cause mortality were analyzed by Kaplan-Meier. Using multivariate COX regression analysis with two models to assess the factors for AMI patients in 30-day to 5-year. Results The prevalence of AKI after AMI in death group was higher than that in non-death group (the 30-day prevalence was 72.7% vs 27.4%, P＜0.001; the 5-year prevalence was 36.3% vs 26.2%, P=0.013). In both early (30-day) and late (30-day to 5-year) follow up, the KDIGO grading distribution of AKI was different between death group and non-death group (P＜0.001 in 30-day follow up and P=0.002 in 30-day to 5-year follow up). Among the 1371 AMI patients,410 (29.9%) developed AKI during the hospital stay. The 30-day and 30-day to 5-year mortality rates were 5.6% (77/1371) and 11.3% (146/1294) respectively. All-cause mortality and cardiovascular mortality were significantly higher in patients with AKI-Ⅰstage, AKI-Ⅱ stage and AKI-Ⅲ stage than those with non-AKI (all P＜0.001), especially in patients with AKI-Ⅲ stage. Further stroke history (HR=3.122, P=0.012), AKI severity (AKI-Ⅰstage HR=3.034, P=0.028; AKI-Ⅱ stage HR=7.832, P＜0.001; AKI -Ⅲ stage HR=9.919, P＜0.001), and β-blocker therapy (HR=0.591, P=0.040) were independent predictors of 30-day mortality, while aging (HR=1.061, P＜0.001), albumin (HR=0.943, P=0.023), AKI -Ⅲ stage (HR=3.944, P=0.007), β-blocker therapy (HR=0.660, P=0.041) and percutaneous coronary intervention (HR=0.256, P＜0.001) were independent predictors of 30-day to 5-year mortality. Both at early (30-day) and late (30-day to 5-year) follow-up, AKI with or without baseline renal dysfunction were independent predictors of death in patients with AMI (all P＜0.05). Conclusions AKI strongly correlated with short- and long-term all-cause mortality of AMI patients, regardless of the baseline renal impairment. Specifically, the more severe AKI, the higher short-term mortality AMI patients have.     

Global and specific histone acetylation pattern in patients with Balkan endemic nephropathy,a worldwide disease

Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy present in the Danube river regions in several Balkan countries. There appears to be a polygenic susceptibility to the disease in interaction with multiple environmental factors (aristolochic acid, ochratoxin A). In a previous study SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs of BEN patients from Serbia and Bulgaria. Emerging connections between DNA methylation and histone acetylation prompted the present study on histone acetylation in patients with BEN. Methods: The study involved 39 patients with BEN, and 39 controls collected from non-endemic regions in Serbia. The EpiSeeker Histone H3 and H4 Total Acetylation Detection colorimetric Kits and specific acetylated at lysine 18 H3K18 and H3K36 acetylated at lysine 36 detection kits were used. Results: It was documented that total H4 histone acetylation level was increased significantly, while total H3 histone acetylation did not differ significantly. Specific histone structure and functional properties may be affected by the observed derangement of H3 histone acetylation pattern, since H3K36 site was significantly more acetylated, while H3K18 tended to be less acetylated than in control subjects. Multiple regression analysis revealed a statistically significant relationship between H4, H3T and H3K36 in BEN patients. Conclusion: This preliminary study suggests that the acetylation of histone lysine residues was detectable and found increased at specific sites of H3 and total H4 histones isolated from urothelial cells of patients with BEN. Having in mind a possible mechanism and biological role of epigenetic chromatin modification in urothelial tumor development they obtained results may open opportunity for selective therapeutic interventions in patients with BEN.