The Treatment of Chyluria Secondary to Advanced Carcinoma of the Prostate

The treatment of chyluria secondary to advanced carcinoma of the prostate

SA Cluskey, A Myatt and MA Ferro Department of Urology, Huddersfield Royal Infirmary, Huddersfield, UK

Chyluria has not been previously reported as being associated with carcinoma of the prostate. The most common cause is lymphatic filariasis, a parasitic disease. Non-parasitic chyluria is rare. We describe a case of chyluria associated with carcinoma of the prostate. We describe our successful management in this case and highlight how urologists may overcome problematic chyluria in patients with advanced carcinoma of the prostate. Prostate Cancer and Prostatic Diseases (2008) 11, 102–105; doi:10.1038/sj.pcan.4500994; published online 31 July 2007

Keywords: chyluria; androgen blockade; TURP

Introduction 3-week history of back pain. He had not opened his bowels for 3 days but reported passage of flatus. He Chyluria occurs as a result of abnormal communication was referred to the acute surgical team for further in- between lymphatics and the urinary tract. It may be vestigation. associated with flank pain, fever, dysuria, haematuria At the time of admission, his symptoms included and chylous clot retention.1–3 Worldwide, the most general malaise, back pain and poor mobility. He was common cause is lymphatic filariasis, a mosquito-borne indeed bed bound. He reported no difficulty in passing parasitic disease endemic to tropical and subtropical urine, although he had been treated for a suspected areas. Wuchereria bancrofti is implicated in most cases. urinary tract infection 3 weeks earlier. Clinical examina- The adult worms inhabit peripheral lymphatics, ulti- tion found his general condition to be very poor but mately leading to lymphangiectasia. Chyluria is thought revealed no specific signs to indicate a cause. He was to result from the rupture of small lymphatics of the afebrile and his cardiovascular and respiratory systems collecting duct.4 Non-parasitic causes of chyluria are were normal. His abdomen was soft and non-tender, but rare. Cases associated with structural lymphatic abnorm- distended. A fullness of the right lower quadrant, but no alities,5 lymphatic tumours6 and tuberculosis7 have been expansile aortic pulsation, was detected. He had audible described. Chyluria has also been observed after trauma, bowel sounds. Digital rectal examination revealed hard including intravascular catheterization8 and open faeces and a malignant feeling prostate. Clinically, his surgery.9,10 prostate was adenocarcinoma stage T3. Anal tone and We describe a case of chyluria as the presenting feature perianal sensation were normal as was neurological of advanced prostate adenocarcinoma. This association examination of the lower limbs. Abdominal radiograph has not been previously reported in the literature. The showed moderate gaseous distension of the large bowel management of problematic chylous material causing but no abnormal small bowel dilatation. retention of urine and catheter blockage, and resolution A contrast CT of the abdomen and pelvis (Figure 1) of chyluria after androgen blockade is described. confirmed marked faecal loading of the caecum but no inflammatory process or obstructing large bowel lesion. Extensive retroperitoneal lymphadenopathy was identified, commencing just above the level of the right renal Case report vein. A nodal mass measuring 6 cm in maximum A 75-year-old Guyanese man, residing in the United diameter, intimately related to the inferior vena cava Kingdom, with type II diabetes mellitus and ischaemic and right common iliac vein, extended into the right heart disease presented to his general practitioner with a external iliac nodal group. A large prostate was noted. Prostate-specific antigen (PSA) measured 2962 mg/l, his alkaline phosphatase was mildly raised to 204 IU/l. Correspondence: SA Cluskey, Department of Urology, Huddersfield There were no other relevant abnormal blood results. Royal Infirmary, Acre Street, Lindley, Huddersfield, West Yorkshire The patient was referred to urology with a working HD3 3EA, UK. E-mail: [email protected] diagnosis of metastatic prostate cancer. Received 3 December 2006; revised 28 March 2007; accepted 6 April On the day of admission, a 12Ch urethral catheter 2007; published online 31 July 2007 was inserted to monitor his urine output. There was no Chyluria and advanced carcinoma of the prostate SA Cluskey et al

chyluria after relief of his bladder outflow obstruction 103 with a channel transurethral resection of his prostate (TURP). This was undertaken 10 weeks after treatment initiation. A normal bladder was observed on cysto- scopic examination and no chylous material was evident at the ureteric orifices. Thirty-three grams of tissue was resected to create a good channel. His recovery was unremarkable, postoperatively. Following the removal of his catheter, the patient established normal micturition and was able to void the chylous urine with only 38 ml of residual urine. Histological examination of TURP chippings failed to identify neoplasia. To confirm our clinical diagnosis of prostatic adenocarcinoma, we elected to collect further tissue for histological examination. Transrectal biopsies of the peripheral prostatic tissue had the histological features of poorly differentiated prostate adenocarcinoma, Gleason grade 4 þ 5 in 50% of one core out of five from the right side of the prostate and grade 4 þ 5inup to 70% of all five cores from the left side of the prostate. When reviewed 17 weeks after commencing anti- androgen therapy, the patient reported a good urinary flow. Most importantly, he reported that his urine was Figure 1 Contrast CT abdomen and pelvis. Axial image demon- clear, with no apparent chylous material. Repeat mid- strating the right paracaval nodal mass (arrow). stream urine specimen was negative for triglyceride. Serum PSA was 234 mg/l and alkaline phosphatase was 187 IU/l. The patient continues to improve steadily and is under regular outpatient review at the time of writing comment regarding the appearance of the 500 ml this report. residual volume of urine. However, within 24 h, the catheter had blocked and was subsequently changed to a 22Ch three-way catheter with irrigation. Blood-stained, thick, ‘creamy’ urine was observed. Initial therapy was Discussion bicalutamide 150 mg o.d., followed by subcutaneous goserelin 10.8 mg after 3 weeks and at 12-week intervals. A number of existing reports described cases of inter- The patient remained clinically stable and afebrile. Oral mittent chyluria, which was not associated with bio- ciprofloxacin 500 mg b.d. was started empirically and chemical disturbance and had little impact on the continued for 7 days; however, urine cultures did not patient’s well-being.3,5,8 Conversely, the persistent loss grow significant colonies of bacteria. Further analysis of of lipid and protein in the urine can lead to hypoprotei- the urine identified a triglyceride concentration of naemia, weight loss and malnutrition, warranting 2.01 mmol/l but no cholesterol. Following centrifugation, definitive treatment.11 Optimum management of this a layer of chylomicrons formed on the top of the urine condition is likely to depend on symptom severity, consistent with the presence of lymphatic material.11 biochemical derangement and the underlying cause of A radionuclide bone scan showed widespread abnor- chyluria. mal areas of tracer uptake throughout the ribs, pelvis and The urinary lipids have been shown to originate from thoracic spine. No definite renal uptake was demon- dietary fat. Absolute lipid content therefore varies strated and the appearance was that of a superscan.12 between fasting and postprandial samples; indeed, this Further diagnostic tests ruled out myeloma. The patient’s is often evident clinically.11,13 One conservative manage- back pain was managed effectively with oral analgesics. ment strategy is to restrict dietary fat or consume only Isotope lymphoscintigraphy performed 8 weeks after the medium-chain triglycerides, as these are transported onset of symptoms did not positively identify a connec- directly to the liver by the portal venous system.14 tion between the lymphatic and genitourinary systems. However, dietary restriction of a patient with advanced His PSA fell to 567 mg/l within 4 weeks of starting malignancy would have been undesirable in this case. androgen blockade therapy, although problematic chy- Anti-filarial agents such as diethylcarbamazine and luria persisted. By this time, his constipation had been ivermectin kill circulating microfilariae, although adult treated successfully with conservative measures. A trial worms may be resistant. The major role of drug therapy without catheter was unsuccessful and smaller calibre is to interrupt disease transmission through the mosquito urethral catheters rapidly blocked leaving this patient vector.15 Treatment can result in lasting symptomatic resident in hospital with continuous bladder irrigation relief, although recurrence of chyluria after medical through a 22Ch three-way catheter. The patient’s general therapy has been reported.2 Reliable diagnosis of condition improved with the continued androgen block- lymphatic filariasis can be problematic. Chyluria and ade therapy. His back pain subsided and his mobility other chronic manifestations of filariasis, including improved. He was no longer confined to his bed. He was lymphoedema and hydrocele, may occur many years deemed ready for surgical intervention for his persistent after the death of the adult worm.4,16 Furthermore, chyluria. We thought that he might void this thick reliable detection of microfilariae in a thick blood film

Prostate Cancer and Prostatic Diseases Chyluria and advanced carcinoma of the prostate SA Cluskey et al

104 from an infected individual may depend on the time of freedom from the catheter, although chyluria persisted. day that the specimen was obtained.16 Ultrasound The complete resolution of chyluria, in response to scanning is utilised in some endemic regions to identify androgen blockade, paralleled the fall in serum PSA and adult worms in the lymphatic vessels around the supports the suggestion that his prostate malignancy spermatic cord.17 Detection of antibodies against the was the causative factor of his chyluria, particularly adult worm is considered to be a reliable test for because no other medical treatments or interventions infection,18 although this was not available to us. We were adopted. It is probable that a reduction in the could not definitely exclude lymphatic filariasis in our tumour bulk and retroperitoneal lymph node mass patient who had emigrated from a geographic area with alleviated lymphatic obstruction, which had led to a high prevalence of filarial infection. However, in the chyluria. absence of other stigmata of infection and in the context of the confirmed diagnosis of metastatic prostate cancer, together with his response to androgen blockade therapy, specific diagnostic tests to confirm filarial infection were Conclusion not undertaken. TURP has not been described previously as part of the Demonstration of the anatomical site of lymphaticour- management of chyluria. In this case, it was a useful inary communication can direct the management of non- treatment modality in managing the problematic chylous parasitic or intractable chyluria. Lymphoscintigraphy material causing retention of urine and catheter block- has gained popularity as a safe, rapid and reproducible age. The resolution of chyluria, in response to androgen method to assess structural and functional lymphatic blockade, suggests that prostatic adenocarcinoma was transport pathways. This involves peripheral subcuta- the causative factor of chyluria in this case. This is an neous injection of a technetium 99m-labelled macromo- important observation for urologists who might encoun- lecule, which enters the lymphatic vessels and is ter similar cases. transported towards the thoracic duct. A high-resolution scintiscan camera produces an anatomical image of lymphatic transport, identifying abnormal nodes and delayed transport suggestive of lymphatic obstruction.19 References Lymphoscintigraphy has been used to demonstrate lymphaticourinary fistulae in previously reported cases 1 Franco-Paredes C, Hidron A, Steinberg J. A woman from British of chyluria. 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