Influence of nitrate levels in drinking water on urological malignancies: a community-based cohort study

OBJECTIVE: To evaluate the effect of nitrate levels in the drinking water on the incidence of urological malignancies in a German community. PATIENTS AND METHODS: For 28 years (1957-86) the community of Bocholt, Germany (70,000 inhabitants) had a drinking water supply with different nitrate levels, i.e. 60 mg/L in group A (57,253 inhabitants) and 10 mg/L in group B (10,037 inhabitants). All newly diagnosed cases of urological malignancies were registered from 1986 to 1997. The incidence was calculated using an age standardization based on the German population. RESULTS: In all, there were 527 urological malignancies recorded (urothelial cancer 39.8%, renal cell carcinoma 10.8%, testicular tumours 8.0%, penile carcinoma 1.7%, prostate cancer 39.7%). The incidence per 100,000 inhabitants/year of urinary tract tumours was 33.8 in group A and only 17.1 in group B (relative risk, RR 1.98, 95% confidence interval, CI, 1.10-3.54). The RR was 0.87 (0.34-2.22) for renal tumours, 0.66 (0.14-2.88) for penile cancer and 1.06 (0.76-1.48) for prostate cancer. For testicular tumours there was an inverse association with nitrate level, with a RR of 0.43 (0.21-0.90). CONCLUSION: This study showed an association of nitrate load in drinking water and the incidence of urothelial cancer in both genders, with an inverse correlation to testicular tumours and no correlation with renal, penile and prostatic tumours.     

Referral pattern of urological malignancy in Indonesia

In the 10 years between 1976 and 1985, 202,111 patients were admitted to Hasan Sadikin Hospital, Bandung. Of these, 211 (0.1%) had a urological malignancy. Bladder tumours were commonest and constituted 39%. Testicular tumours accounted for 24%, renal tumours 18%, prostatic carcinoma 13% and penile tumours 6%. Bladder tumours were predominantly transitional cell carcinoma; only 2 patients presented with squamous cell tumours associated with bladder stones. In 50 cases of testicular tumour, 72% were seminomas and 22% were embryonal cell carcinomas. Wilms' tumours accounted for 21 of 39 cases of renal malignancy; the other 18 were renal carcinomas. No urogenital malignant disease was sufficiently common to be included in either the top 10 malignancy list or the male top 10 malignant diseases in Indonesia.     

肾移植术后并发泌尿系统恶性肿瘤22例

目的 分析肾移植受者泌尿系统恶性肿瘤的发病情况,并探讨其发病机理及治疗方法.方法 回顾性分析1978年至2010年12月间肾移植受者发生泌尿系统恶性肿瘤22例的资料.结果 22例的病理检查结果分别为膀胱移行上皮细胞癌9例(其中1例第3次手术后发现转化为腺癌),膀胱鳞状细胞癌1例,膀胱腺癌1例,肾透明细胞癌3例(其中2例为双侧肾癌),肾低分化癌1例,肾盂移行细胞癌1例,肾盂+膀胱移行细胞癌1例,输尿管移行细胞癌2例,输尿管+膀胱移行细胞癌2例,输尿管移行细胞癌+膀胱腺癌1例.肾癌及输尿管癌均发生在患者原肾及输尿管.11例膀胱癌患者中9例存活,均保有全部或部分肾功能;4例肾癌患者均在发病后半年内死亡;肾盂癌、输尿管癌除2例术后早期死亡外,其余5例存活.22例发现肿瘤后1年存活率为73.7%.结论 肾移植后泌尿系统恶性肿瘤可见少见的病理类型.治疗中应注意免疫抑制剂的使用和移植肾功能保护的问题.肾实质性恶性肿瘤预后很差.

Abstract：

Objective To investigate the incidence of urological malignancy in renal allograft recipients and explore the mechanism of increased incidence in China and the management. Methods A retrospective study was performed on 22 patients with urological malignancy in renal allograft recipients between 1978 and 2010. Results Twenty-two cases of urological malignancy were diagnosed by pathologic evidence, including 9 cases of transitional cell carcinoma (TCC) of bladder, 1 case of squamous cell carcinoma of bladder, 1 case of adenocarcinoma of bladder, 1 case of TCC of pelvis, 1 case of TCC of bladder and pelvis, 1 case of TCC of ureter complicated with adenocarcinoma of bladder, 2 cases of TCC of ureter, 2 cases of TCC of ureter and bladder, 3 cases of clear cell carcinoma of kidney, and 1 case of undifferentiated carcinoma of kidney. All the malignancies belonged to native organs. All the patients suffering bladder cancer had normal function of allograft. Five patients with TCC of pelvis or ureter survived and 2 cases died early after operation. All the patients suffering renal carcinoma deceased within 6 months after diagnosis. One-year survival rate was 73. 7 % after the diagnosis of urological malignancy. Conclusion Urological malignancy ranked highest in malignancy in renal allograft recipients, and rare pathological types of urological malignancy in non-renal allograft recipients are often demonstrated. The strategy of treatment should take consideration of the relationship between the usage of immunosupressive agents and the preservation of allograft function. It is critical for the therapy of malignancies to possess satisfactory allograft function. The prognosis of renal cell carcinoma is poor.     

Second primary malignancies associated with renal cell carcinoma histological subtypes

PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. CONCLUSIONS: Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.     

Measurement of in vivo urological tumour cell kinetics using multiparameter flow cytometry. Preliminary study

The in vivo labelling of urological tumour cells using the S phase marker bromodeoxyuridine (BRdU) for histochemical studies is reported. The use of multiparameter flow cytometry (FCM) with BRdU labelling to study tumour proliferation offers significant advantages. It provides simultaneous measurements of the DNA ploidy (DI), the duration of the S phase (Ts), the potential doubling time (Tpot) and the total and aneuploid tumour labelling indices (LI) from a single specimen. Heterogenous tumour cell populations can be measured with high sensitivity. We report a preliminary study to evaluate the method in the measurement of the kinetics of transitional cell carcinoma of the bladder (TCCB). Nineteen patients with TCCB, 1 with leukoplakia of the bladder, 2 with renal carcinoma, 1 with prostatic carcinoma and 1 with a squamous carcinoma of the penis were studied. Of the bladder tumours, 3 were aneuploid, DI = 1.32, 1.58 and 1.89. BRdU uptake was detected in all tumours. The median LI was 1.5% (range 0.5-10.0). In 15/19 tumours the labelling profile was satisfactory for calculation of the Ts and Tpot. The median Ts was 6.2 h and the median Tpot was 17.1 days. This study demonstrates that measurement of multiple parameters of urological tumour proliferation in vivo is possible. These parameters require further assessment as indices of biological aggressiveness and clinical prognosis.     

Urological tumours in Germany. Basic data on 56,013 cases from hospital cancer registries

Summary Since 1985 a special work group involved in the coordination of hospital cancer registries in Germany (AKKK) has been collecting, storing and analysing data on tumour patients, received from cancer centres, oncological departments and specialised practices. The documentation of tumour patients is based, among other things, on information concerning localisation, histological findings and tumour spread. The data are stored in a central database administered by the work group. At present it contains data on approximately 500,000 oncological patients. In the period from 1987 to 1992, 56,013 initial entries were made concerning patients with urological tumours. Of these cases, tumours of the kidney (n = 11,424) constituted 20.4 %. In 94.6 % of the cases, histological investigation revealed a renal cell carcinoma – pT1: 5.8 %; pT2: 53.6 %, pT3: 37.2 % and pT4: 3.4 %. Tumours of the urinary bladder (n = 16,246) constituted 29.0 % of all urological tumours. In 93.8 % of the cases a transitional cell carcinoma was detected – pTis: 1.0 %; pTa: 36.9 %; pT1: 29.6 %; pT2: 16.9 %; pT3: 11.4 %; pT4: 4.4 %. Transitional cell carcinomas of the ureter or of the collecting system (n = 1,846) constituted 3.3 % of the cases. The proportion of testicular tumours (n = 6,594) amounted to 11.8 %; 53.6 % of these germ-cell tumours (n = 6,281) were seminomas and 46.6 % were non-seminomas. In all, 66.3 % of the cases were lymph-node negative. Tumours of the prostate (n = 19,903) constituted 35.5 % of the cases. In the period from 1987 to 1992, the proportion of lymph-node-positive prostate carcinomas decreased from 39.8 % to 16.2 %. The detailed analysis of these data shows how the hospital cancer registries can support the discussion regarding diagnosis and therapy of urological tumours.      

泌尿系肿瘤患者血清中肿瘤坏死因子的水平及意义

为探讨泌尿系肿瘤患者血清中肿瘤坏死因子（ＴＮＦ）的水平及意义，采用生物活性法对５０例泌尿系肿瘤患者血清中ＴＮＦ水平进行了测定。结果：肾癌、输尿管癌、前列腺肉瘤、睾丸精原细胞瘤和胚胎癌患者血清ＴＮＦ水平高于正常人，而膀胱癌、肾盂癌与正常人无明显差异，同时发现肾癌患者血清ＴＮＦ水平与肿瘤直径及分期相关。结果提示ＴＮＦ可能参与了肾癌的发生发展，并可成为判定肾癌发展状况及预后的临床指标，而ＴＮＦ与膀胱癌关系不密切。     

Molecular positron emission tomography and PET/CT imaging in urological malignancies

OBJECTIVES: Positron emission tomography (PET) provides unique insights into molecular pathways of diseases. PET using [F-18]-fluorodeoxyglucose (FDG) has gained increasing acceptance for the diagnosis, staging, and treatment monitoring of various tumour types. The aim of this review is to provide an update on the current status of molecular PET and PET/CT imaging in urological malignancies. METHODS: The current literature on PET and PET/CT imaging was reviewed and summarized for prostate cancer, bladder cancer, renal cell carcinoma, and germ cell tumours. RESULTS: Depending on the radiotracer used, PET offers diagnostic information based on glucose, choline or amino acid metabolism and has also been applied to imaging tumour cell proliferation and tissue hypoxia in urological malignancies. The diagnostic performance of FDG-PET is hampered by the renal excretion of FDG and by the low metabolic activity often seen in tumours such as prostate cancer. However, new PET tracers including radiolabelled choline and acetate may offer an alternative approach. There is consistent evidence that FDG-PET provides important diagnostic information in detecting metastatic and recurrent germ cell tumours and it might offer additional information in the staging and restaging of bladder and renal cancer. CONCLUSIONS: Although PET imaging has been shown to be a clinically useful tool, its application in urological malignancies still needs to be fully determined by larger prospective trials. The introduction of novel PET radiopharmaceuticals along with the new technology of PET/CT will likely change the future role of molecular imaging in urological malignancies.     

Transplant recipients with a history of a malignancy: risk of recurrent and de novo cancers

A review is presented of outcomes of kidney and heart transplant recipients who had a history of a preexisting malignancy. Reasons for differences in recurrent malignancy rates reported by the Cincinnati Transplant Tumor Registry and the Australia/New Zealand Registry are discussed. Data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database indicated that 2.1% of 65 999 kidney and 3.0% of 18 954 heart recipients had a preexisting malignancy with 31 recurrences (2.3%) in kidney and 16 recurrences (2.8%) in heart recipients. De novo malignancies in kidney and heart recipients with a past malignancy were significantly greater (P < .0001) than that of recipients with no past history. The low incidence of recurrence in the United Network for Organ Sharing data made it difficult to evaluate the relative risk of developing a recurrence. Therefore, a review of the literature for the incidences of late recurrences (>5 years) of treated malignancies in nontransplant patients was made to provide a perspective on the risks of recurrence of these tumors. The specific malignancies reviewed included renal carcinoma, malignant melanoma, carcinoma of the lung, breast, colon, thyroid, seminoma and other testicular tumors, prostate cancer, Hodgkin's, and non–Hodgkin's lymphoma. Finally, a discussion of prevention and treatment of recurrent malignancies in transplant patients is made.     

Concurrent Renal Cell Carcinoma and Transitional Cell Carcinoma in a Chronic Hemodialysis Patient

A 60-year-old female patient had been on maintenance hemodialysis for 12 years was suffering from gross hematuria. Subsequent image studies revealed left renal and ureteral tumors. She then received left radical nephroureterectomy. Histological examination revealed the renal tumor was renal cell carcinoma and ureteral tumor was transitional cell carcinoma respectively. To our knowledge, this is the first reported case of simultaneous occurrence of these two urological cancers in a chronic hemodialysis patient. Our case may imply the increased susceptibility of urological malignancy in dialysis patients. Physicians should always raise the possibility of urological malignancy when a dialysis patient with gross hematuria is encountered. A thorough and careful screening for the malignancy should be performed on a regular basis in these patients with high risk.     

Concurrent renal cell carcinoma and transitional cell carcinoma in a chronic hemodialysis patient

A 60-year-old female patient had been on maintenance hemodialysis for 12 years was suffering from gross hematuria. Subsequent image studies revealed left renal and ureteral tumors. She then received left radical nephroureterectomy. Histological examination revealed the renal tumor was renal cell carcinoma and ureteral tumor was transitional cell carcinoma respectively. To our knowledge, this is the first reported case of simultaneous occurrence of these two urological cancers in a chronic hemodialysis patient. Our case may imply the increased susceptibility of urological malignancy in dialysis patients. Physicians should always raise the possibility of urological malignancy when a dialysis patient with gross hematuria is encountered. A thorough and careful screening for the malignancy should be performed on a regular basis in these patients with high risk.     

Integrating metastasectomy in the management of advanced urological malignancies-where are we in 2005?

PURPOSE: In the past patients with metastatic cancer were considered incurable and they were not candidates for surgical management of metastases. However, experience with testicular cancer has shown that metastasectomy can often be the final, critical step in achieving disease-free status. We summarized the most current data on metastasectomy for advanced urological malignancies. MATERIALS AND METHODS: We performed an extensive review of the literature from 1990 to the present using MEDLINE. Only original reports were included with an emphasis on specific malignancies and specific sites of metastasis. RESULTS: There is increasing evidence that patients with metastatic renal cell carcinoma and bladder carcinoma can be cured by surgical resection of metastases, usually combined with systemic therapy. The ideal patient has responded to systemic therapy and has few metastatic sites. CONCLUSIONS: Metastasectomy should frequently be done in patients with advanced testicular cancer and it should increasingly be considered in patients with metastatic renal cell carcinoma or bladder carcinoma. This technique may be used for cure and palliation. Specific patient factors determine the likelihood and degree of potential benefit.     

Stellenwert der Positronenemissionstomographie bei urologischen Tumoren

Positron emission tomography/computed tomography (PET/CT) is widely used for imaging urological neoplasms. This overview should help the urologist actively involved in oncology to assess the value of PET or PET/CT in each tumor entity. Besides prostate, testicular, renal, and bladder cancer less common urological malignancies like penile carcinoma and retroperitoneal masses are discussed. Differences in using PET/CT for primary diagnosis, staging, or restaging are outlined separately. Appropriate indications for the use in clinical practice are cited.     

Prevalence of cancer history prior to renal transplantation

Recurrent and de novo cancers contribute to morbidity and mortality post-transplantation. However, data on cancer prevalence in waiting list patients are lacking. The purpose of this study was to determine the prevalence of malignancy in patients considered for renal transplantation. Records of 382 potential renal transplant recipients were reviewed for the presence of malignant tumours. In 38 patients 45 tumours were detected. Forty-two malignancies were histologically confirmed, in three patients the evaluation was ongoing. Fourteen tumours were diagnosed before and 31 after initiation of dialysis. Overall cancer prevalence was 9.9%. For patients in the waiting list, the mean time from diagnosis of the malignancy was 2.2 years. Twenty of 45 (44%) tumours were located in the urinary system. The majority of malignancies was treated with a curative intention. Thus, 68% of patients with malignancies were listed as 'transplantable' or 'temporarily not transplantable'. From the waiting list, 13% were removed , 8% died and 11% had their evaluation halted because of their malignancy. Four patients received a transplant while eight patients died or were removed permanently from the list prior to transplantation. Death or removal from the list was as frequently related to tumour progression as to other causes (four patients each). A substantial number of waiting list patients had a history of malignancy. Future strategies have to identify patients at risk to assure intensive monitoring for recurrence, selection of patients who do not benefit from deferred transplantation and consideration of specific immunosuppressive protocols.     

The Role of Microscopic Hematuria in the Evaluation of Urologic Malignancy in Renal Transplant Recipients

Urologic malignancy is a relatively uncommon but serious complication following kidney transplantation. The reported prevalence of renal cell carcinoma (RCC) of the native kidneys is 4.4% and of bladder malignancy is 2.6%. However, presently there are no universal guidelines for prospective screening of urologic malignancies after kidney transplantation. We routinely monitored all renal transplant recipients for microscopic hematuria and persistent hematuria (>3 separate occasions) results in imaging studies (ultrasound or computed tomography scan) of both native kidneys and the allograft. Cystoscopy is performed if imaging studies are negative. This retrospective study identified a total of 18 urologic malignancies among the study cohort, which consisted of 539 patients with an incidence of 3.3% (12 cases of RCC of native kidneys [10/12 had hematuria], and six cases of bladder and ureteral malignancies [6/6 had hematuria]). There were no significant differences between cyclosporine- and tacrolimus-based immunosuppression (IS). Among RCC recipients, two lost the allograft from chronic allograft nephropathy and one patient died unrelated to malignancy. Among patients with bladder and ureteral malignancies, two lost the graft possibly from IS reduction and one had BK virus nephropathy prior to diagnosis of bladder carcinoma. In conclusion, screening transplant recipients routinely for persistent microscopic hematuria may identify urologic malignancies in renal transplant recipients.     

Chemosensitivity studies of urological malignancies

Chemosensitivity tests to anticancer agents using human tumor clonogenic assay (HTCA), novel dye exclusion method (NDE assay), sub-renal capsule assay (SRCA), and chick embryo method (CE method) were utilized to measure the sensitivity of urological malignancies. Surgical tumor specimens from 67 patients with urological malignancies were subjected to HTCA developed by Hamburger and Salmon. An appreciable growth of colonies was obtained in 20 out of 33 renal cancers, 20 out of 30 urothelial cancers and 1 out of 4 testicular tumors examined and colonial growth adequate for chemosensitivity was obtained in 30 of the 67 patients. More than 70% decrease in the plating efficiency after anticancer drug exposure according to Von Hoff's definition, or more than 1.0 value of the "in vivo -in vitro therapeutic index" in terms of the ratio of IC90 to the peak plasma concentration of the drug tested was defined as susceptible. According to Von Hoff's definition, susceptibility to vinblastine (VBL) and cis-dichlorodiammine platinum (CDDP), was seen in 4 out of 11 patients with renal cancer, in 4 out of 15 patients with urothelial cancer and 1 out of 4 patients with renal cancer, respectively. With adriamycin (ADM) it was seen in 3 out of the 15 patients with urothelial cancer, 2 out of 10 patients with renal cancer and 1 patient with testicular tumor. According to TI, susceptibility to VBL was seen in 3 out of 7 patients with renal cancer, and with CDDP it was seen in 2 out of 12 patients with urothelial cancer, and 1 out of 2 patients with renal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)     

Malignant disease in renal transplant recipients--our experience

Kidney transplantation is a treatment of choice for patient with end stage renal disease. Chronic renal failure is characterized with weak cellular and humoral immunity. In our paper we present our experience with presence of malignancy in renal transplant patients. Urology clinic in Belgrade transplanted 411 patients over the period of 16 years. Living donor transplantation was performed for 272 and cadaveric kidney transplant for 139 patients. In the postoperative follow up, malignancies were diagnosed in 7 of the transplanted patients. Three patients developed basal cell skin carcinoma, one was diagnosed with adenocarcinoma of the transplanted kidney, one developed transitional cell carcinoma of the bladder and testicular tumors were diagnosed in two patients. Postoperative immunosuppressive therapy usually double or triple when patients are in the immunological high risk group. Incidence of malignancy according to big health centers is around 1 in every 1000 transplanted patients. It is also noted the rise of incidence of malignancies in transplanted patient in over 50%.     

Retroperitoneal anomalies in men with testicular germ cell tumours

OBJECTIVES: To assess whether vascular and other retroperitoneal anomalies are more frequent during retroperitoneal lymph node dissection (RPLND) for metastatic testicular tumours (when retroperitoneal masses persist after chemotherapy) than would be expected, based on the initial observations from one centre with a large experience of RPLND in the UK. PATIENTS AND METHODS: A prospective series of 278 consecutive patients treated with RPLND for testicular tumours comprised the sample population. For each patient the presence or absence of four factors from the history was recorded. Each patient then underwent RPLND. During surgery, a template was constructed of the anatomy of the retroperitoneum and the information stored. Eight different retroperitoneal anatomical anomalies were identified in the sample population; the incidence of each was then compared with the largest available study of a normal population, and differences analysed statistically. RESULTS: Of the 278 patients who had RPLND, 55 had 59 anomalies (21%), found by history and as retroperitoneal vascular and urological anomalies; cryptorchidism was present in 7.6%, 9.5 times the incidence in the control population (P < 0.01). A left-sided inferior vena cava was present in 3.6% of patients, 21 times the incidence in the control population (P < 0.001); a retro-aortic left renal vein in 3.2%, four times that in the control population (P < 0.05); and ipsilateral renal agenesis had an incidence of 1% in the test population, 11 times greater than in the control population (P < 0.01). CONCLUSIONS: This prospective study of 278 RPLNDs provides evidence that some retroperitoneal anatomical anomalies are associated with testicular germ cell tumours. The link between maldescent and testicular tumours, rather than an isolated association, should be considered as part of a spectrum of retroperitoneal anomalies that occur in these men.     

Low incidence of malignancies following renal transplantation in India

Summary: Renal transplant recipients have an increased incidence of certain malignancies. the nature of these malignancies varies with the geographic location and the nature of immunosuppressive therapy. There are no reports on the incidence and spectrum of cancers in renal transplant recipients from India. In a retrospective analysis of 294 patients followed up for more than 6 months after transplantation at our centre, we noted six malignancies in four patients, giving an incidence of 2%. Among 157 of those who were followed up for more than 2 years, the incidence was 3.8%. the mean duration of follow up was 5.8 years (range 6 months to 18.5 years). Cyclosporine was given for the first year after transplantation in 168 patients and 126 patients received only azathioprine and steroids. the interval between transplantation and development of malignancies varied from 24 to 169 months. the tumours included extranodal non-Hodgkin's lymphoma (NHL) involving the central nervous system and small bowel and carcinoma of the tongue in one case each. the fourth patient, who survived for 14 years after transplantation, developed three squamous cell malignancies during this period: carcinoma of the cervix, perianal region and nasopharynx. Both patients with NHL died despite surgical excision of the tumour. None of the patients developed a cutaneous malignancy. In conclusion, renal transplant recipients living in a tropical environment have alow incidence of malignancies compared to those in temperate zones. This discrepancy can be explained by an absence of malignant tumours of the exposed skin in our patients. the absence of any tumours within the first 2 years is also unusual.