[Colovesical fistulas : An interdisciplinary challenge]. / Die kolovesikale Fistel : Eine interdisziplinäre Herausforderung.

BACKGROUND: The aim of treatment of patients with colovesical fistulas should be prompt elimination of the infection and the social burden. We focused on the question whether a minimally invasive surgical approach as a cooperation between surgeons and urologists is possible. This requires effective diagnostics prior to the operation. METHODS: Since 2007 a total of 32 patients with the clinical suspicion of colovesical fistula have undergone extensive preoperative diagnostics. Operative treatment aimed primarily for a minimally invasive approach. In particular, the validity of preoperative diagnostics was analyzed and surgical results were characterized by clinical success, complications and long-term effects. RESULTS: The medical history significant for colovesical fistula and detected urinary infection provided the best evidence for the specific diagnosis. Cystoscopy, computed tomography (CT) scan and colonoscopy were only partially effective for predicting a fistula as subsequently diagnosed by histopathological investigations. Fistulas due to diverticulitis of the sigmoid colon occurred in 28 cases, while in 3 subjects there was a gynecological and inflammatory cause (malignant tumor growth, n = 1). A laparoscopic approach achieving repair and healing of the fistula was possible in 29 cases including conversion in 3 subjects because of intraoperative complications. The remaining patients underwent conventional treatment. The disease-related complication rate as revealed during follow-up was 10%. DISCUSSION: Laparoscopic repair and healing of a colovesical fistula is possible in the majority of cases by the recommended preoperative ureteral stenting. As part of diagnostic measures, the medical history significant for a fistula and detection of urinary infections are the most reliable aspects. In the case of this combination together with a further diagnostic measure, a laparoscopic approach is always recommended. The recurrency rate is 0%.

[Current value of laparoscopy for renal transplantation]. / Aktueller Stellenwert der Laparoskopie für die Nierentransplantation.

Laparoscopic techniques have not only become increasingly more important for patients on dialysis or after kidney transplantation, they also represent the operative standard procedures as almost all patients additionally suffer from concomitant diseases and do carry a higher operative risk. Therefore, these patients will derive special benefits from minimally invasive procedures offering lower morbidity and quick recovery. In centers with expertise in minimally invasive procedures, laparoscopic donor nephrectomy has already replaced open live donor nephrectomy as the standard procedure.

[Preparation for clinical introduction of advanced laparoscopic procedures: laparoscopic renal autotransplantation]. / Vorbereitung zur klinischen Etablierung fortgeschrittener urologischer Operationstechniken: Laparoskopische Autotransplantation am Tiermodell.

BACKGROUND: After long term clinical training at teaching hospitals, individuals or complete teams have reported on the establishment of laparoscopic nephrectomy and prostatectomy. This, however, is difficult to realize at many clinics due to the current staffing situation. In the following an alternative approach will be presented. METHODS: After 50 hours of practice on a pelvic trainer during which the laparoscopic handling and especially various suturing techniques were learnt (A) a total of 15 pigs (approx. 40 kg, in general aesthesia, right sided positioned, with 7 ports) have been operated from February to August 2006: 1. laparoscopic nephrectomy, 2. laparoscopic in-situ cold perfusion, 3. laparoscopic renal autotransplantation (B). Directly after this a two month clinical training at a recognized laparoscopic center took place (C). RESULTS: After completion of phase A, an extended experimental operation phase B followed, marked by complications such as: bleeding (n=5), skin emphysemas (n=3), technical failures (n=2), non-optimal placement of ports (n=6), problems with placement the cold perfusion catheters (n=7), and unsuitable surgical instruments (n=2). Eleven laparoscopic nephrectomies were successful; only during the last three operations a sufficient end-to side anastomosis has been achieved (anastomosis time range 80110 min of which was 50% in cold ischemia). During the external clinical training (C) (through 2. and 1. assistance) five endoscopic extraperitoneal prostatectomies (surgery time range 145-235 min) and two radical nephrectomies have been independently carried out (180-230 min). CONCLUSIONS: Using the pig model laparoscopic renal autotransplantation ideally combines ablative and reconstructive operation techniques. For this reason it is especially suitable for young urologists learning to perform nephrectomies and prostatectomies. For beginners in laparoscopy this entails long but mentor independent learning phases A, B thereby shortening the subsequent clinical training at the teaching hospital (C).

New cut-off point between T1 and T2 renal cell carcinoma - necessary for a better discriminatory power of the TNM classification.

PURPOSE: We evaluated the pathological features of tumor size, lymph node and distant metastases, cell type, growth pattern, infiltration pattern, histological grade, local invasion and venous involvement of organ-confined renal carcinomas. The aim of this study was the re-evaluation of the TNM classification and the tumor cut-off point between T1 and T2 for renal cell carcinomas from the 1987 to the 1997 versions. MATERIALS AND METHODS: (1) Patients with renal cell carcinoma who had been operated between October 1992 and August 2001 were evaluated. 437 of 691 patients showed T1 and T2 tumors. These organ-confined tumors have been divided into five groups: group 1: tumor-size of 20 mm or less (n = 16), group 2: 21-30 mm (n = 79); group 3: 31-40 mm (n = 83; group 4: 41-70 mm (n = 184), and group 5: more than 70 mm in diameter (only T2, n = 75). Follow-up ranged from 0 to 100 months (average 28.63 months). (2) Of 15,347 autopsies performed in Jena between 1985 and 1996, 272 renal cell carcinomas were revealed. In 145 of these 272 cases renal cell carcinomas were limited to the kidney. These 145 tumors were divided accordingly into 5 groups: group 1: 20 mm or less (n = 33), group 2: 21- 30 mm (n = 31); group 3: 31-40 mm (n = 29); group 4: 41-70 mm (n = 42), and group 5: T2 (n = 10). Clinicopathological criteria examined were lymph node and distant metastases, cell type, growth pattern, infiltration pattern, histological grade, local invasion and venous involvement. To identify the optimal cut-off point between T1 and T2 disease the chi2 test was used. RESULTS: (1) In the clinical series only 1.8% (n = 8) of all cases showed lymph node metastases. Distant metastases were shown in 57 cases (13.04%); within group 1: 0%, group 2: 7.59%, group 3: 1.20%, group 4: 15.76%, group 5: 28%. The tumor grading was statistically correlated with tumor size. (2) In the pathological series 94 of the evaluated 145 patients were downstaged from T2(1987) to T1(1997). Lymph node and distant metastases were well correlated with tumor size. Lymph node metastases were seen in 0, 12.9, 31, 29.3 and 40% (group 1 to group 5) and distant metastases in 12.1, 25.8, 41.4, 47.7 and 60%. There were no statistically significant differences between T2(1997) and T1(3-7 cm). The tumor grading was statistically correlated with tumor size (grade 1: in 66.7, 25.8, 17.2, 9.5 and 0%). CONCLUSION: Our data suggest that the current cut-off diameter between T1 and T2 renal cell carcinomas (7 cm) is too high. Lowering the cut-off level will result in better discriminatory power of the TNM classification. From our data, we conclude that the cut-off diameter should be lowered to 3.5 cm (p < 0.001).

Endocrine alteration in the adrenal gland in kidney transplant patients.

INTRODUCTION: Endocrine alterations associated with chronic renal failure have been reviewed recently. Some of these alterations are of clinical relevance. The aim of this study was to investigate the effect of renal transplantation on the endocrine system of the adrenal gland of the transplant recipients. METHODS: The serum angiotensin-converting enzyme (SACE), plasma renin (PR) and plasma aldosterone (PA) were examined in 30 patients before and after renal allotransplantation. Additionally measured parameters were blood pressure, serum creatinine, potassium, sodium, the duration of dialysis and immunosuppressive medication. RESULTS: Six weeks after renal transplantation, serum creatinine decreased from 820.07 +/- 172.01 to 138.12 +/- 67.54 micromol/l. In the same period, serum potassium decreased from 5.42 +/- 0.89 to 4.17 +/- 0.42 mmol/l. PA and PR decreased from 1,150.84 +/- 976.06 to 233.52 +/- 217.07 micromol/l, and from 121.07 +/- 100.12 to 26.16 +/- 10.86 microU/ml, respectively. SACE decreased from 0.21 +/- 0.21 to 0.13 +/- 0.11 micromol/l. No significant correlation was seen with blood pressure, serum sodium, the duration of dialysis and immunosuppressive drugs. Additionally, 2 patients with acute renal graft dysfunction showed significant increases in PR and PA. After successful treatment both levels declined very quickly to prerejection levels. Patients after binephrectomy show no elevation in PR (5-47 microU/ml) or PA (21-416 micromol/l) neither before nor after renal transplantation. CONCLUSIONS: We conclude that renal transplantation has profound effects on the recipient's renin-angiotensin-aldosterone system. Because of the rapid depression after renal transplantation, it does not appear to be involved in the pathogenesis of post transplantation hypertension but may reflect a role for repair processes after renal allotransplantation.

Renal cell carcinoma in renal graft recipients and donors: incidence and consequence.

INTRODUCTION AND OBJECTIVES: Numerous studies have reported an increasing incidence of small renal cell carcinoma (RCC). De novo RCC in a renal allograft is a rare event and has special implications in renal transplant recipients. The objective of this study was to retrospectively evaluate the incidence of RCC in renal graft recipients and donors and to determine a procedure in cases with newly detected small renal tumors at the time of kidney preparation before transplantation. MATERIAL AND METHODS: We mailed a questionnaire to 38 German transplant clinics and received answers from 27 centers. A total of 10,997 renal graft recipients were included in the period of 1990-1998. RESULTS: In 30 kidneys (0.273%) RCC was detected at the time of preparation before transplantation. There were 23 male and 3 female donors. No bilateral RCC was described. The mean age of the donors with RCC was 50.9 years (range 37-72 years). The tumors had a mean size of 2.2 cm (range 0.4-6 cm). 67% of the patients had a renal tumor smaller than 20 mm. In 26/27 centers the decision to transplant relies on the result of the immediate section for microscopic examination. 16 patients (0.145%) developed RCC 3-12 years after renal transplantation (mean 7.4 years). The mean tumor size was 2.5 cm (range 2-2.8 cm). In 50% a grade 1 and in the other 50% a grade 2 carcinoma was found. CONCLUSIONS: Because of the RCC incidence in donor candidates we recommend an ultrasound screening of the native kidneys before renal explantation and an immediate preparation of the kidney surface especially in donors older than 45 years. In cases with small renal lesions we recommend an immediate section for microscopic examination before transplantation to prevent tumor implantation into an otherwise healthy patient. The frequency of RCCs after renal transplantation necessitates careful clinical and instrumental examinations in organ-transplanted recipients both before and at regular intervals after transplantation, including the patient's kidneys.

Computerized contrast angiosonography: a new diagnostic tool for the urologist?

OBJECTIVES: To evaluate the diagnostic potential of echo-enhanced ultrasonography (US) for depicting the vascularization pattern of renal cell carcinoma (RCC), and calculating the first-pass effect using harmonic imaging, against that obtained by triphasic helical computed tomography (CT). PATIENTS AND METHODS: Sixty patients with surgically confirmed RCC underwent US using B-mode and power Doppler methods with or without an intravenous microbubble echo-enhancing agent. After depicting and defining the tumour extent by B-mode US, the first-pass effect/enhancement by the echo-enhancing agent within the lesion, and that of a reference area of unaffected renal cortex, were recorded on-line by calculating the mean pixel intensity. Time-intensity curves, i.e. the rise time and gradient of both the suspected tumour and reference areas, were constructed. RESULTS: Using B-mode US, the extent of all tumours was delineated (mean tumour size 3.8 cm, SD 0.6). After applying the microbubble agent all tumours were enhanced, whereas the perfusion was decreased (in 48%), increased (in 16%) or similar (in 36%) compared with the cortical reference area. Using the Hounsfield classification, these results correlated well with the hypo/hypervascularity shown on CT. CONCLUSION: Ultrasonography has considerable potential in diagnosing RCC, if combined with echo-enhancing methods, harmonic imaging and computer-based calculation of tumour vascularization. Dynamic US studies should provide a diagnostic yield similar to that of CT.

Fetal fibronectin: a new screening-marker for bladder cancer?

Early detection of transitional cell carcinoma (TCC) of the urinary bladder is essential for effective treatment. While several serum markers have been evaluated, none have been widely accepted for practical clinical use. Thus, urinary markers have been introduced and investigated to detect the evidence of bladder cancer. But sensitivity and specificity range around 80% respectively. In a prospective study we evaluated fetal fibronectin in the urine of patients with TCC of the urinary bladder. The positivity of oncofetal fibronectin was measured in morning urine samples by membrane immunoassay. This FFN membrane immunoassay is a qualitative test, a solid-phase immunogold assay. A positive sample will result in a single spot after binding of the oncofetal fibronectin-immunogold complex to the membrane containing a monoclonal antibody specific to oncofetal fibronectin (FDC-6, which specifically recognizes III-CS region). The morning urine samples were collected from patients with TCC before they underwent transurethral resection (n=40, 34 non-invasive and 6 invasive carcinomas) and healthy controls (n=20). Oncofetal fibronectin was investigated in the surgical samples by immunohistochemistry (antibody FDC-6, APAAP technique). We found a positive result for oncofetal fibronectin in 38/40 patients with transitional cell carcinoma of the urinary bladder. Two patients with a small pTaG1-TCC showed negative results. In the urine of healthy controls no positive results were detected. Thus, there is a sensitivity of 95% and a specificity of 100%. The TCC was demonstrated as a source of oncfn. To our knowledge this is the first study showing that patients with an evident TCC have a demonstrable amount of oncofetal fibronectin in the urine. We conclude that a positive result is common in TCC-patients. The sensitivity and specificity of this test seems to be extraordinarily high. Because of the small number of cases further studies are required.

[Post-traumatic and postoperative asymptomatic urinoma. 2 case reports]. / Das posttraumatische und postoperativ asymptomatische Urinom. Zwei Fallberichte.

A urinoma is a collection of extravasated urine developing after injury to the urinary tract, almost always asymptomatic, but requiring urgent surgical treatment. A Medline search for the term urinoma in publications appearing between 1996 and 1998, turned up only two reports describing an asymptomatic course. We now describe two cases of urinomas that remained asymptomatic over a period of four months. Although initially misinterpreted, a subsequent revisionary operation nevertheless resulted in a cure. In case 1, the urinoma appeared after an operation to treat recurrent rectal cancer; in case 2, the causal mechanism was an avulsed ureter. Treatment is orientated to the location (intra- or retroperitoneal) and extent of the injury, and comprises temporary stenting, drainage and, where necessary, plastic reconstruction. Even in the absence of a clinical correlate, any urinary retention newly discovered on ultrasonography must be investigated by uroradiography.

Preoperative simulation of partial nephrectomy with three-dimensional computed tomography.

OBJECTIVE: To evaluate prospectively the accuracy of computer-aided three-dimensional (3D) volume-rendered computed tomography (CT) in determining the appropriate anatomical limits (tumour size, tumour location, multifocality and vascular supply) and as a potential tool in the preoperative simulation of nephron-sparing surgery (NSS) in patients with small-volume renal cell carcinoma (RCC). PATIENTS AND METHODS: The study included 36 patients who underwent transperitoneal radical nephrectomy for RCC of < 4 cm diameter. Helical CT was undertaken before surgery and the extent of the tumour, the course of major renal arteries and veins, and the relationship of the tumour to the collecting system were shown by 3D volume-rendered CT. The CT findings were compared with the pathological results of all kidney specimens, obtained using 3-mm step-sections. RESULTS: Before nephrectomy, 39 renal tumours were identified in the 36 patients; three renal lesions of < 4 mm were not detected. All main venous branches and 42 of 43 arteries were identified by 3D volume-rendered CT. Knowing these features, a partial nephrectomy was simulated; a surgical lesion to the pelvicalyceal or vascular system which would have been produced by the simulated surgery was displayed in colour on the simulated surface of the section. CONCLUSION: Computer simulation provided an excellent 3D reconstruction of all kidneys, including the tumour, vasculature and renal hilum, allowing a significantly better preoperative evaluation of the renal mass. Visualizing possible resection margins and predicting the operative risks seem to be major advantages of this new method, especially when preparing for complex surgery. Reconstructed 3D CT appears to be a useful tool for defining the indications for and limitations of NSS.

Sacral nerve stimulation for pain relief in interstitial cystitis.

A 60-year-old woman was treated for severe interstitial cystitis pain using sacral nerve stimulation. Pain and accompanying bladder dysfunction were improved by temporary and permanent sacral nerve stimulation. Six months after implantation of a sacral neuromodulator the patient is pain free and significantly improved on bladder dysfunction. Interstitial cystitis may be an indication for functional electrostimulation.

Bronchogenic cyst. A rare differential diagnosis of retroperitoneal tumors.

Subdiaphragmatic bronchogenic cysts are rare, and those located retroperitoneally are exceptional. A review of the English-language literature revealed only 16 reported cases. We describe an additional case of a retroperitoneal cyst presenting as an asymptomatic adrenal mass and discuss clinical, radiographic, surgical and pathological findings as well as its embryological background.

The correlation of p53 protein overexpression and p53 antibodies in serum of patients with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Mutations of p53 gene were demonstrated in many solid tumors with varying frequency. We analyzed the relationship between p53 protein expression in bladder cancer tissue, p53 autoantibodies in serum and the clinical course of 32 patients with and 10 patients without transitional cell carcinoma of the urinary bladder. MATERIALS AND METHODS: In the 32 patients studied, bladder cancer was diagnosed as pTaG1-2 in 8 cases, pT1G2 in 6, pT1G3 in 7, pT2G2-3 in 7, pT3G2-3 in 3 and pT4 in 1 patient. Anti-p53 antibodies were detected by an enzyme-linked immunosorbent assay. Immunohistochemical staining was performed using a standardized alkaline phosphatase monoclonal anti-alkaline phosphatase method. To prove the statistical significance of tumor grading and staging, the Kruskal-Wallis test was applied (p < 0.01). The mean follow-up was 26 months. RESULTS: We found 12.5% p53 autoantibody-positive sera without a statistically significant correlation with tumor grade (p = 0.0569) and category (p = 0.612). Three of 4 patients who had p53 autoantibody-positive sera died within 9 months. All of these sera-positive patients had p53 protein-positive tumor tissue. Control sera were all negative for p53 autoantibodies. CONCLUSION: This study shows a strong relationship between p53 protein overexpression and the occurrence of p53 autoantibody in bladder cancer. The expression of p53 autoantibodies seems to be an event in cases of bladder cancer with an unfavorable tumor-specific outcome. Because of the small number of cases and the short follow-up time, further quantitative studies will hopefully demonstrate whether this might be of prognostic importance.

A study of pelvic floor function pre- and postradical prostatectomy using clinical neurourological investigations, urodynamics and electromyography.

OBJECTIVES: Incontinence after radical prostatectomy is addressed to sphincter damage and/or bladder dysfunction. Taking into account a high cure rate of incontinence by pelvic floor biofeedback treatment, the search for further mechanisms of a complex physiological concept seems feasible. METHODS: To characterize pelvic floor function, 18 patients were prospectively evaluated before and after radical prostatectomy by clinical neurourological tests, urodynamics and needle/surface electromyography (EMG). RESULTS: In all patients (mean age 62 years) investigations were completed successfully. The outcomes of neurourological investigations (sacral reflexes, voluntary pelvic floor contraction and relaxation) and needle EMG showed no significant changes in the pre-/postoperative comparison. Only by using surface EMG polygraphy change of activation patterns during pelvic floor contraction (decreased mean and medium frequency) could be found. CONCLUSION: In patients without preexisting bladder dysfunction and with a basically normal operative and postoperative course, fine motoric changes of pelvic floor function are the main finding. This cannot be explained by a pure anatomical approach. Neurophysiological events, like a barrage of nociceptive information, caused by surgical dissection and an inflammatory reaction due to the healing process, contribute to altered processing within the central nervous system. The appreciation of these mechanisms, well studied in neuroscience and pain research, offers a better understanding of surgery-related short- and longterm morbidity after pelvic surgery, i.e., urinary incontinence and erectile dysfunction.

Effective analgesia for extracorporeal shock wave lithotripsy: transcutaneous electrical nerve stimulation.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) has revolutionized the treatment of urinary stone disease. However, the most appropriate analgesia offering pain-free treatment, minimal side effects, and adequate cost effectiveness remains to be established. This prospective study was performed to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) during ESWL using third-generation lithotripters. METHODS: Two pairs of stimulator electrodes were placed paravertebrally at L1 and near the lithotripter shock tube before ESWL. Treatment was carried out as follows: (a) shock wave administration was begun (no current = sham TENS); (b) in the case of severe pain, TENS was begun; and (c) if patients experienced no pain relief, analgesic drugs were given intravenously. RESULTS: Of 149 patients, 92 (62%) did not need any analgesia (neither TENS nor medication). In 42 (72%) of the remaining 57 patients, a TENS-related, pain-relieving response was observed. ESWL-induced pain could be reduced by 39.2%. The degree of fragmentation assessed by two urologists was found to be 90% for patients receiving TENS compared with a retrospectively analyzed control group (94%, n = 100). CONCLUSIONS: Two different theories explaining TENS-related analgesia are known: segmental (spinal) and supraspinal (central) inhibition. Since we did not observe any analgesic effect in patients having both pairs of electrodes attached around the shock tube (n = 30), supraspinal inhibition obviously accounts for the abovementioned pain relief. We conclude that TENS is a noninvasive, cost-effective method to achieve side-effect-free analgesia in ESWL using third-generation lithotripters.

Real indications for adrenalectomy in renal cell carcinoma.

OBJECTIVES: Adrenalectomy is a part of radical nephrectomy because of the surgical oncology principle of a 'wide margin beyond the malignancy' and due to concern over possible metastases to the ipsilateral adrenal gland, especially in upper pole tumors. But, neither the frequency, predisposing factors of the renal cell carcinoma nor mechanisms of involvement of the adrenal gland are well defined. We assessed the ipsilateral adrenal involvement in renal cell carcinoma to determine whether ipsilateral adrenalectomy during radical nephrectomy is essential. MATERIAL AND METHOD: In a series of 15,347 autopsies in Jena from 1985 through 1996, 272 renal cell carcinoma with 24 adrenal metastases were found. In the same period 9 adrenal metastases were found in 639 radical nephrectomies. Contralateral and bilateral metastases were seen in 15 cases of the autopsy series and in 2 cases of the operative series. RESULTS: The risk of adrenal metastases correlated with multifocal tumors, pleomorphic cell type, anaplastic growth pattern and tumors that were larger than 2.5 cm. Of the 24 renal cell carcinomas with adrenal metastases in the autopsy series, 23 had evidence of widespread disease and 22 had lymph node metastases. A preoperative abdominal computerized tomography was performed in all 9 patients of the operative series with renal cell carcinoma and adrenal involvement. The adrenal gland was considered abnormal in 8 of the 9 cases (88.9%). Only in 1 patient was the computerized tomography incorrectly interpreted as negative. CONCLUSION: We think adrenalectomy should only be performed if there is radiographic evidence of metastases in the adrenal gland or adrenal infiltration by a large upper-pole tumor is possible. Macroscopically normal adrenal glands should not be removed during tumor nephrectomy because the need and benefit of routine adrenalectomy are extremely limited.

Multifocality in renal cell carcinoma: A bilateral event?

OBJECTIVES: The major disadvantage of nephron-sparing surgery for renal cell carcinoma is the risk of local recurrence. This is most likely a manifestation of undetected small additional tumors in the renal remnant. To define more clearly the incidence and nature of unilateral and bilateral multifocal tumors, an autopsy study was undertaken. MATERIALS AND METHODS: In a series of 14,793 autopsies from 1985 to 1995, 260 renal cell carcinomas were found. In all cases of renal cell carcinoma a search for small renal lesions was performed in the apparently normal-appearing portion of the kidneys. Every kidney was serially and systematically cut (5 mm) to probe for intraparenchymal lesions. RESULTS: Of the 260 renal cell carcinomas 36 cases (13.85%) had multifocal malignant and/or benign nodules. The number of the additional nodules ranged from 2 to 18. 12% of the malignant multifocal carcinomas were limited to the ipsilateral kidney and 88% were bilateral. The average size of the multifocal renal lesions was 8.7 x 9.0 x 9.5 (range 3-23) mm. Renal cell carcinomas with low stage and good grading have a higher incidence of multifocal nodules. No significant difference was found with regard to metastasized and nonmetastasized renal cell carcinomas. In 38.1% of all chromophilic renal cell carcinomas additional nodules were found. CONCLUSIONS: Multifocality in renal cell carcinomas cannot be predicted reliably, although the papillary histological pattern, good grading and low staging seems to be associated with a higher incidence of multifocality. Nearly 90% of the multifocal nodules were bilateral.