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Keywords:

  • bilateral Wilms tumor;
  • nephron-sparing surgery;
  • postoperative complications;
  • renal function;
  • survival

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND.

Approximately 5% of children with Wilms tumor present with bilateral disease. The treatment challenge is to achieve a high cure rate while maintaining adequate long-term renal function. The authors of this report assessed the feasibility and outcome of nephron-sparing surgery in patients with bilateral Wilms tumor who were treated at a single institution.

METHODS.

A retrospective review was performed of all children who were treated at St. Jude Children's Research Hospital for synchronous, bilateral Wilms tumors from 1999 through 2006. Imaging studies, surgical techniques, and pathology reports were reviewed. The outcomes evaluated included surgical complications, tumor recurrence, renal function, and patient survival.

RESULTS.

Twelve patients with synchronous, bilateral Wilms tumors were identified, including 10 patients who underwent successful bilateral nephron-sparing procedures. One patient who presented with renal failure and anaplastic histology underwent bilateral nephrectomies, and 1 patient with intra-atrial tumor extension underwent an ipsilateral nephrectomy/thrombectomy and subsequent contralateral partial nephrectomy. Postoperative complications included persistent urine leak in 3 patients, macroscopic residual tumor in 2 patients, and pyelonephritis in 1 patient. Long-term complications included local tumor recurrence in 2 patients, intestinal obstruction in 2 patients, ureteropelvic junction obstruction in 1 patient, and renal failure in 1 patient. The overall survival rate was 83% (mean follow-up, 3.9 years); both patients who died had bilateral, diffuse, anaplastic histology.

CONCLUSIONS.

All patients who had bilateral Wilms tumors with favorable histology, except for 1 patient who had extensive tumor thrombus, underwent successful bilateral partial nephrectomies. Complications were minimal, and long-term renal function and survival were excellent. From this experience, the authors concluded that bilateral nephron-sparing surgery should be considered for all patients who have bilateral Wilms tumor with favorable histology, even if preoperative imaging studies suggest that the lesions are unresectable.Cancer 2008. © 2008 American Cancer Society.

Approximately 500 children are diagnosed with Wilms tumor in the U.S. each year, and from 5% to 7% of these patients will have disease in both kidneys.1 Because surgery is a critical component in the treatment of Wilms tumor, the challenge in the management of patients with bilateral disease is to achieve a high cure rate while maintaining adequate long-term renal function. With current improvements in diagnostic imaging modalities, most bilateral lesions are detected preoperatively; therefore, a thoughtful surgical approach can be planned in advance of exploration.

Several studies have demonstrated that patients with bilateral Wilms tumor are at risk for developing renal failure.2–5 A review from the National Wilms Tumor Study Group (NWTSG) indicated that, among patients who had unilateral Wilms tumor without genitourinary abnormalities, Denys-Drash syndrome, or Wilms tumor-aniridia-genitourinary abnormality-mental retardation (WAGR) syndrome, the cumulative incidence of renal failure was only 0.6%. However, in patients who had bilateral disease, the incidence of renal failure was 11.5%, and patients with Denys-Drash and WAGR syndromes had an incidence > 50%.5 The exact etiology of renal failure is not always clear and likely is multifactorial, with contributing factors including intrinsic, progressive renal disease related to a genetic predisposition, inadequate renal parenchyma after 1 or more tumor resections, the nephrotoxic effects of chemotherapy and radiation, and the potential for hyperfiltration injury to the remaining renal parenchyma.3, 5

Because of an increasing appreciation of the potential for renal failure in these patients, the management of synchronous, bilateral Wilms tumors has evolved from primary kidney resection to renal-preserving surgical approaches facilitated by the use of preoperative chemotherapy. In 1979, the NWTSG formally recommended initial biopsy and chemotherapy before surgical resection of bilateral tumors.6 Since then, several studies have confirmed the beneficial effects of preoperative chemotherapy followed by conservative surgical resection in patients with amenable, favorable histology, bilateral Wilms tumors.7–17 These studies demonstrated that preoperative chemotherapy allows for tumor shrinkage, facilitating resection with preservation of unaffected parenchyma and a decreased incidence of tumor spillage. However, despite the benefits of preoperative chemotherapy, bilateral nephron-sparing surgery historically has been performed on only a minority of patients with synchronous, bilateral Wilms tumors. On NWTS-2 and -3, 20 of 145 patients (13.8%) with synchronous, bilateral Wilms tumors underwent bilateral partial nephrectomies either as the initial operation (11 patients) or after preoperative chemotherapy (9 patients).7 On NWTS-4, the increased use of preoperative chemotherapy had only a minor effect on the number of patients undergoing bilateral nephron-sparing surgery; only 36 of 186 patients (19.4%) with synchronous, bilateral Wilms tumors underwent bilateral nephron-sparing procedures.12 Other smaller series have reported performing bilateral nephron-sparing procedures in from 30% to 70% of patients with bilateral Wilms tumors.9, 10, 13–15

Since 1999, the multidisciplinary Wilms tumor treatment team at St. Jude Children's Research Hospital has attempted to perform bilateral partial nephrectomies on all patients with synchronous, bilateral Wilms tumors. In this report, we review the feasibility and safety of this approach with particular regard to surgical complications, long-term renal function, and oncologic outcome.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patients

We reviewed the records of 12 patients who underwent surgery for synchronous, bilateral Wilms tumors at St. Jude Children's Research Hospital during the 8-year period from 1999 through 2006. Patient demographics, including associated syndromes and congenital anomalies, tumor histology, surgical procedure(s) and outcomes (including surgical complications, long-term renal function, tumor recurrence, and survival), were determined from a review of each patient's medical record. This retrospective review was approved by the Institutional Review Board of St. Jude Children's Research Hospital.

All patients received preoperative chemotherapy with 3 drugs (vincristine, dactinomycin, and doxorubicin) based on a previous report from our institution suggesting that local control rates are improved with the addition of doxorubicin.18 This approach was within the scope of the recommended NWTS-5 guidelines. After initial treatment with preoperative chemotherapy, patients underwent tumor resection. Subsequent renal function was assessed by estimating the glomerular filtration rate using the Schwartz formula: creatinine clearance = (k × height in cm)/serum creatinine, in which k = 0.55 for children aged > 18 months, and k = 0.45 for children aged < 18 months. Other measures of long-term renal function included blood pressure evaluation and the need for antihypertensive medications, the presence of proteinuria, and the need for dialysis and/or kidney transplantation.

Surgical Approach

A uniform surgical approach has been taken for patients with synchronous, bilateral Wilms tumors at St. Jude since 1999, with bilateral nephron-sparing surgery being performed on all patients unless contraindicated (by anaplastic histology or by extensive intravenous tumor thrombus). We routinely perform bilateral nephron-sparing procedures during a single operation to remove all macroscopic tumor at the earliest feasible time so that the chance of developing therapy-resistant disease is minimized and to spare patients an additional operation, thereby minimizing interruption of chemotherapy.

Conduct of the operation is similar to that described by Cozzi and Zani.17 The peritoneal cavity is entered through a transverse upper abdominal incision. The kidney with the larger tumor burden is approached first, is mobilized completely, and is elevated on its vascular pedicle with a vessel loupe placed around the ureter. The lesions to be excised are identified, and the capsule of the kidney is scored with electrocautery to outline the planned extent of resection. When possible, a small rim of normal kidney (0.5–1 cm) is included around the resected lesion. At times, however, resection proceeds in the generally well defined plain between the tumor and kidney (Fig. 1). Large intraparenchymal vessels are controlled with absorbable ligatures. Hemostasis along the parenchymal surface is then completed with argon-beam coagulation. Temporary vascular occlusion is used rarely. Careful handling of the vascular pedicle is critically important, because traction injury with vascular thrombosis can occur, especially in very young patients.

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Figure 1. (A) Preoperative computed tomography scan from a patient with synchronous, bilateral Wilms tumors. (B) Postoperative magnetic resonance image from the patient 3 months after undergoing bilateral nephron-sparing resections of the tumors. A series of intraoperative photographs shows the right kidney after mobilization (C), development of the plane of resection (D), the cut surface of the kidney after tumor removal with the collecting system exposed (E), the resected specimen (F), and the reniform appearance of the kidney at the conclusion of the procedure (G).

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Care is taken to determine whether the collecting system has been entered, which occurs commonly. When such a breach is identified, the cut edges of the violated calyx are closed with chromic suture, often after placing a “double-J” ureteral stent. The decision to place a ureteral stent is based on the degree of disruption of the collecting system and the complexity of its closure. A flank Penrose drain commonly is placed. Then, an attempt is made to fold the kidney over the cut surface, often encasing a piece of Surgicel, to assure additional hemostasis and so that the kidney retains a more reniform contour; the use of bolsters can facilitate this closure. This is not done, however, if excessive tension is required. If this is the case, then a tongue of omentum or Gerota fascia often is placed over the cut surface of the kidney to assist with hemostasis. At this point, attention is turned to the contralateral kidney, and a similar approach is used. Removal of regional lymph nodes can be performed at any time during the procedure. The Penrose drains generally are removed before patient discharge; internal stents are removed cystoscopically from 4 months to 6 months later.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patient Characteristics

Presentation

Twelve patients with synchronous, bilateral Wilms tumors underwent definitive surgery at St. Jude Children's Research Hospital (Table 1). Their mean age at diagnosis was 2.9 years (range, from 5 months to 9.75 years). Ten patients (83%) were boys, an unusually high percentage. However, these are highly selected patients who generally are referred because of a poor response to therapy or unfavorable anatomy. It is noteworthy that there is a greater prevalence of intralobar nephrogenic rests in boys compared with girls, and these tend to differentiate in response to treatment rather than shrinking significantly.19

Table 1. Patient Characteristics
CharacteristicNo. of patients (%)
  • WAGR indicates Wilms tumor, aniridia, genitourinary anomalies, and mental retardation.

  • *

    Some patients had more than 1 presenting symptom or associated anomaly.

Sex
 Boys10 (83)
 Girls2 (17)
Race
 Caucasian9 (75)
 African American3 (25)
Age, y
 <13 (25)
 1–23 (25)
 2–31 (8.4)
 3–42 (16.7)
 >43 (25)
Presentation*
 Increased abdominal girth10 (83.3)
 Screening ultrasound2 (16.7)
 Hypertension8 (66.7)
 Fever3 (25)
 Hematuria2 (16.7)
Metastases
 No10 (83.3)
 Yes2 (16.7)
Histology
 Favorable10 (83.3)
 Anaplastic2 (16.7)
Anomalies*
 Cryptorchidism5 (41.7)
 WAGR1 (8.3)
 Hypospadias1 (8.3)
 Duplicated ureter1 (8.3)

Bilateral renal masses were detected in 2 patients on screening ultrasonography studies, which were obtained because of a strong family history of bilateral Wilms tumors. Each of the other 10 patients presented with increasing abdominal girth, 1 of whom also had evidence of renal failure. Eight of the 12 patients had hypertension at diagnosis. Three patients also had fever at presentation, with 1 of these 3 patients having macroscopic hematuria. One additional patient had hematuria at presentation. Two patients presented with pulmonary metastases (both girls). Because no patient underwent an initial laparotomy for open biopsy and lymph node sampling, local stage at presentation could not be assessed accurately.

Associated anomalies

Six patients (50%) had an associated genitourinary anomaly. Five of these 6 patients (42%) had an undescended testis, 3 of which were bilateral; 1 of these patients also had hypospadias. This latter patient also carried the diagnosis of WAGR syndrome resulting from a germline deletion at chromosome 11p that was detected by fluorescence in situ hybridization (FISH). One of the other patients with bilateral undescended testes had a WT1 deletion detected in his tumor tissue by FISH. One patient had a unilateral duplicated ureter.

Surgery

Ten of the 12 patients underwent bilateral partial nephrectomies. In no instance did a planned partial nephrectomy have to be converted to a complete nephrectomy. Of the remaining 2 patients, 1 patient who presented with renal failure and bilateral, diffuse, anaplastic Wilms tumors underwent bilateral nephrectomies. The other patient underwent a planned nephrectomy for a tumor thrombus that extended through the renal vein and inferior vena cava (IVC) into the right atrium. The tumor thrombus remained essentially unchanged after administration of preoperative chemotherapy. Because cardiopulmonary bypass with the requisite anticoagulation was to be used, complete nephrectomy was chosen as the safest way to manage the kidney with the larger tumors (and venous thrombus). A partial nephrectomy was performed on the contralateral kidney 6 weeks later.

The average length of surgery was 255 minutes (range, 160–430 minutes, including the removal of intra-atrial tumor thrombus on cardiopulmonary bypass). In total, 51 surgical specimens were obtained from the 12 patients (average, 2.8 specimens per renal unit; range, 1–10 specimens per renal unit). The estimated blood loss ranged from 50 mL to 800 mL per procedure, and 7 patients received perioperative packed erythrocyte transfusions. Bilateral percutaneous Penrose drains were placed in 83% of patients, and ureteral stents were placed at initial surgery in 11 of 21 kidneys (52%) that underwent a nephron-sparing procedure. These rates of blood transfusion and the frequent use of internal stents most likely reflect our more aggressive attempts at resection of the tumors with preservation of uninvolved kidney. Although we have not used it, the use of warm or cold ischemia is an option that may provide help visualizing the collecting system for repair and, potentially, decrease intraoperative blood loss.

Radiation was given postoperatively to 7 of the 12 patients, and 1 of the remaining 5 patients received radiation when he suffered a local recurrence (10.5 grays [Gy], kidney). Two patients who had tumor specimens with positive margins and 1 patient who had lymph node involvement received 10.5 Gy to the involved kidney; the patient who had residual disease in the vena cava received 10.5 Gy to the entire abdomen with a boost of 9.2 Gy to the IVC. The 2 patients who had metastatic disease received 12 Gy to the lungs, and the 2 patients who had bilateral, anaplastic Wilms tumors received 19.5 Gy to the entire abdomen. Early in our series, 2 patients received 10.5 Gy to the kidneys despite having negative margins on the resected specimens, no lymph node involvement, and tumors with favorable histology.

Pathology

The histology was favorable in 20 of 24 kidneys; 2 patients had bilateral, diffuse anaplasia. Eight of 10 patients who underwent bilateral partial nephrectomies had specimens removed from both kidneys that had negative surgical margins, whereas the other 2 patients (20%) had microscopically positive surgical margins in at least 1 specimen. The specimens from the patient who underwent a unilateral nephron-sparing procedure (with a complete contralateral nephrectomy) had negative margins on all of the lesions removed from the spared kidney. However, the tumor thrombus, which was removed at the time of initial nephrectomy, was densely adherent to the wall of the IVC and could not be removed in its entirety. He received additional radiation to the residual disease in the IVC. The nephrectomy specimens from the patient who presented with end-stage renal disease and bilateral, diffuse anaplasia had negative margins.

The predominant histopathology in the resected specimens from patients with favorable histology Wilms tumors ranged from blastema-predominant Wilms tumor (2 patients), usually surrounded by a fibrous capsule, to having no viable residual tumor (2 patients). Four patients had tumors that exhibited predominantly heterologous differentiation, and 2 patients (cousins with a significant family history of Wilms tumor) had cystic Wilms tumor. Most specimens also contained nephrogenic rests. Two patients had diffuse anaplasia.

Surgical Complications

Postoperative complications

Three patients had a persistent urine leak out of a flank Penrose drain; each required an additional cystoscopic procedure: in 1 patient, a ureteral stent was placed 3 days after the initial surgery; in the other 2 patients, an existing internal stent was repositioned 5 days and 7 days after the initial surgery. In the latter patient, percutaneous drainage of a urinoma also was required. In each patient, the drainage subsided within 3 to 5 days after stent placement/manipulation, thereby permitting removal of the flank Penrose drains before hospital discharge. One patient required readmission to the hospital 2 weeks after surgery with an episode of pyelonephritis that resolved with a short course of antibiotics.

Two patients had residual Wilms tumor after their initial surgery detected on follow-up imaging studies obtained within 3 months of the initial surgery. These patients underwent immediate re-exploration and tumor resection. It is noteworthy that, in 1 patient, the tumor was completely within the collecting system (Fig. 2). It is difficult to know for certain whether these represented residual or recurrent disease. However, based on the early detection of 2 of the lesions, which were identified during continued administration of chemotherapy, we believe that these 2 lesions represent residual disease.

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Figure 2. (A) This magnetic resonance image was obtained 6 weeks after initial bilateral nephron-sparing surgery and demonstrates residual tumor within the collecting system (arrow). (B) This intraoperative photograph of the right kidney, with the collecting system open, demonstrates the pedunculated, intracalyceal lesion (arrow).

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Long-term complications

Two patients developed an adhesive partial small bowel obstruction 5 weeks and 2 years, respectively, after their initial surgery for Wilms tumor and required re-exploration for lysis of adhesions. Seven months after surgery, it was noted that 1 patient had developed unilateral hydronephrosis from a uteropelvic junction obstruction secondary to extrinsic scar tissue. This was relieved successfully with a pyeloplasty. Finally, 1 patient developed end-stage renal disease and began dialysis nearly 5 years after his initial surgery for Wilms tumor. He recently underwent a successful cadaveric kidney transplantation.

Oncologic Outcomes

The incidence of local recurrence after renal salvage procedures in patients enrolled on NWTS-4 was 8.2%, an incidence that was higher than that observed after complete nephrectomy (approximately 2%).12 In our series, 1 patient had a local recurrence in 1 of his kidneys 1 year after undergoing bilateral partial nephrectomies. The margins of the resection specimens at initial surgery had been negative. The recurrence, which occurred in the patient who had residual tumor within the collecting system described above, was noted in the parenchyma of the same kidney approximately 8 months later. This was resected with another nephron-sparing procedure after the patient was pretreated with chemotherapy comprised of ifosfamide, carboplatin and etoposide (ICE).

A second patient who had blastema-predominant histology and specimens with positive margins at initial resection, for which he received 10.5 Gy of radiation, developed synchronous recurrences in both kidneys detected 2 years after surgery. He received ICE-based chemotherapy followed, again, by bilateral nephron-sparing procedures; However, he recently developed a second relapse in the right kidney. Currently, he is receiving targeted topotecan-based therapy according to our recently published institutional protocol.20

The overall survival rate was 83%, and 9 of 10 patients had no evidence of disease at a median follow-up of 3.9 years (range, 1–8 years). The 2 deaths occurred in patients who had bilateral, diffuse anaplasia, 1 of whom had metastatic disease at presentation. It is interesting to note that the patient who had nonmetastatic, bilateral anaplastic Wilms tumors died 3 years after the completion of therapy because of multiorgan failure but without evidence of residual disease.

One of the patients in this series developed a second neoplasm 18 months after the completion of therapy for Wilms tumor. Although we believed initially that the second neoplasm was recurrent Wilms tumor, after re-exploration it proved to be mesenteric fibromatosis and was resected completely. After re-exploration and resection of a recurrence of this lesion 9 months later, the patient currently is disease-free from both tumors 3 years after this surgery without having received adjuvant therapy for the fibromatosis.

Long-term Renal Function

Before the initiation of therapy, all patients but 1 had normal baseline renal function estimated using the Schwartz formula; the remaining patient, who was believed to have polycystic kidney disease (as assessed by imaging studies), developed renal failure by the time the correct diagnosis of Wilms tumor (bilateral, anaplastic) was made and underwent bilateral nephrectomies, necessitating dialysis. Another patient developed end-stage renal disease that required dialysis nearly 5 years after the completion of therapy. He recently underwent a cadaveric renal transplantation. This patient had intrinsic renal disease, hypertension on presentation (and after surgery), bilateral undescended testes, and an 11p13 deletion of the tumor on karyotype analysis. The other patient with bilateral, anaplastic Wilms tumors had normal renal function at the time of death. Each of the remaining 9 patients had normal renal function according to the Schwartz formula at their most recent follow-up (mean, 137.7 mL per minute per 1.73 m2; range, 111–209 mL per minute per 1.73 m2), and none had clinically significant proteinuria. At their most recent follow-up, 7 of 10 patients (70%) had hypertension that required antihypertensive medication.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

With improved survival for patients with Wilms tumor, because of the use of more effective, multimodality therapy, has come the desire to decrease the intensity of therapy in order to avoid therapy-related complications. This objective of diminishing therapy intensity while maintaining excellent survival includes reducing the extent of surgical resection. Since 1999, we have adopted a surgical approach to these patients in which, after preoperative chemotherapy, nephron-sparing procedures are attempted on both kidneys as the initial, definitive surgical procedure for all patients, regardless of the radiographic appearance of the tumors and kidneys. In all 10 patients for whom this procedure was planned, it was accomplished successfully, often despite preoperative imaging studies suggesting that kidney preservation may not be possible (Fig. 3). Overall, despite this aggressive surgical approach, our results with regard to complications and to functional and oncologic outcomes compare favorably with those obtained through the larger cooperative groups (Children's Oncology Group, International Society of Pediatric Oncology).21 All patients in our series who had Wilms tumors with favorable histology remained alive at a mean of nearly 4 years after initial surgery, although 1 patient recently suffered a second intrarenal recurrence. Neither of the patients who had bilateral anaplastic histology remained alive, highlighting the critical prognostic value of tumor histology. It is noteworthy, however, that 1 of those 2 patients died of therapy-related complications, without evidence of disease at the time of death, 4 years after initial diagnosis.

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Figure 3. (A) Images from the preoperative computed tomography scan in a boy aged 1.5 years with synchronous, bilateral Wilms tumors. The patient was being considered for bilateral nephrectomies at the time of his referral to St. Jude Children's Research Hospital. The white arrows in the middle image highlight compressed, normal renal parenchyma around the tumor. (B) Postoperative magnetic resonance images after successful bilateral partial nephrectomies.

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Approximately 12% of patients with synchronous, bilateral Wilms tumors who were treated on Children's Oncology Group protocols developed renal failure, usually because of the need for bilateral nephrectomy for persistent or recurrent tumor in the remaining kidney.3, 5 For this reason, we perform bilateral nephron-sparing procedures on all patients unless they were contraindicated. Although partial nephrectomy is more complex technically than complete nephrectomy and has greater potential for postoperative complications, including bleeding and urinary leak, complications in our series were minor and infrequent. No significant postoperative bleeding occurred, and urine leaks were managed easily with routine placement of percutaneous perinephric drains and/or internal ureteral stents.

An additional complication was failure to identify and resect all macroscopic disease, which occurred in 2 patients. In both of those patients, this most likely was residual disease that was missed at the initial surgery rather than early tumor recurrence. Because of these episodes, currently, we are performing routine intraoperative ultrasound to assist in the identification of residual masses. One of these 2 patients sustained a local recurrence, 1 of the 2 local recurrences in our series of 12 patients. Thus, the local recurrence rate in our series was 16.7%, although 1 of these patients recently suffered a second local recurrence, for which he is currently receiving topotecan-based relapse therapy. The other patient was free of disease 3 years after resection of his recurrent disease. To date, none of the 10 patients has had a distant recurrence.

Only 1 patient in our series developed renal failure after bilateral nephron-sparing surgery. He began dialysis nearly 5 years after surgery and recently, at the age of 8 years, underwent kidney transplantation. It is doubtful that his renal failure developed because of inadequate residual renal parenchyma; rather, it most likely was caused by intrinsic renal disease. Despite maintaining a brisk daily urinary output, he ultimately required dialysis for electrolyte management. We believe that the time the patient remained off dialysis, from age 1 year to age 6 years, was of significant benefit, because patient survival on dialysis while awaiting renal transplantation is much better in patients ages 6 to 12 years compared with patients aged < 5 years.22 In addition, the availability of appropriately sized deceased donor organs and long-term results for deceased donor organ recipients suggest a significantly improved outcome in recipients aged > 2 years.23 Although nearly all of the remaining 9 patients currently are taking antihypertensive medication, each has a normal estimated creatinine clearance with no clinical evidence of renal insufficiency. However, the follow-up still is relatively short.

From a technical standpoint, when assessing preoperative radiographic images, the size of the renal lesions does not appear to influence resectability; we have not determined an upper limit to the size of tumor that can be resected successfully and actually have observed that discrete, large lesions are the easiest to identify and remove. Often, large lesions compress adjacent normal kidney parenchyma such that, at the time of exploration, more useful, viable renal parenchyma exists than may have been anticipated by the preoperative imaging studies. Because of this, we believe strongly that nephron-sparing surgery should be attempted on both kidneys in patients with bilateral Wilms tumors despite preoperative imaging studies suggesting that the lesions are inoperable, because the resectability of large lesions cannot always be determined accurately by current imaging modalities.

Many of the resected specimens in our series contained nephrogenic rests. Distinguishing nephrogenic rests from Wilms tumor on preoperative imaging studies often is quite difficult. Both active nephrogenic rests and Wilms tumor are bright on T2-weighted magnetic resonance (MR) images (Fig. 4A). Nephrogenic rests often homogeneously enhance less than normal kidney on contrast-enhanced MR images or computed tomography scans, and they are often lenticular. Wilms tumors often are inhomogeneously enhancing, especially when they are larger, and they usually are round. Sclerotic nephrogenic rests or treated, inactive Wilms tumor may be dark on T2-weighted MR imaging (Fig. 4B).24 Distinguishing nephrogenic rests from Wilms tumor by macroscopic inspection of the kidney at the time of surgical exploration is nearly impossible. Therefore, lesions of uncertain histology should be removed at the time of surgical exploration, if feasible, or at least biopsied.

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Figure 4. These axial T2-weighted magnetic resonance images were obtained after patients received chemotherapy. (A) The bright lesion (arrow) most likely represents an active nephrogenic rest or Wilms tumor. (B) The dark lesion (arrow) most likely represents a sclerotic nephrogenic rest or a treated, inactive Wilms tumor.

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At the time of resection, we make every attempt to remove a rim of uninvolved kidney with each lesion that is resected. However, this is not always possible, because many tumors abut the vascular pedicle or the collecting system, or they are just too numerous. In those patients, a marginal resection is performed in which the tumor is enucleated from the surrounding parenchyma. Despite this approach, tumor was identified at the resection edge (positive margins) in only 7 of 51 resected specimens (14%), and those 7 specimens were obtained from 2 patients. One of the reasons for this relatively low incidence most likely relates to the presence of a fibrous rim or capsule that usually surrounds Wilms tumors and is, in fact, a characteristic used to distinguish Wilms tumor from nephroblastomatosis histologically (Fig. 5).25 It is possible that the pseudocapsule is a result of the compression of surrounding tissue (normal renal parenchyma) by a highly proliferative, rapidly expanding Wilms tumor that does not occur with slower growing rests. Nevertheless, tumor enucleation does carry a higher risk of having a positive margin, which will mandate the use of radiation. It also is worth noting, however, that there have been several reports suggesting that overall survival for patients with positive margins in the resection specimens is not affected adversely; the critical prognostic factors remain tumor histology and the presence of metastatic disease.7, 12, 16, 18, 26 Although we did not encounter this circumstance in the current series, because of the resistance of anaplastic Wilms tumor to adjuvant therapy, if we did detect anaplasia at the margin of a surgical specimen, then we would perform a repeat resection, most likely a completion nephrectomy.

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Figure 5. Histologic findings in resection specimens from patients who were treated for bilateral Wilms tumor that distinguish Wilms tumor from nephrogenic rests. (A) The fibrous capsule (c) at the edge of a Wilms tumor (WT) (original magnification, × 4). (B) Nephrogenic rests (NR) (intralobar) without a surrounding pseudocapsule (original magnification, × 10).

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Thus, we believe that surgeons should not approach cases of bilateral Wilms tumors with preconceived notions regarding resectability. In our experience, nephron-sparing surgery for children with bilateral Wilms tumors is nearly always technically feasible, with few complications. This approach, when combined with adjuvant therapy, provides an opportunity to preserve renal function while maintaining a high probability of cure and should be considered strongly for all patients who have synchronous, bilateral Wilms tumors, despite the radiographic appearance of the kidneys and associated tumors. In addition, we believe that this operative intervention should be done early, by 12 weeks after the initiation of chemotherapy, because little significant further change in tumor size is likely,27 and it is important to determine the exact tumor histology.26, 28 In patients who have numerous small lesions in the kidneys that appear to be nephrogenic rests or cysts on imaging studies, representative biopsies can be obtained. Careful radiographic follow-up of these lesions will be required looking for changes in character, consistency, and/or size that may suggest the emergence of another focus of Wilms tumor. In addition to long-term oncologic surveillance, these patients require long-term nephrologic follow-up, because some will have progressive renal dysfunction, likely because of intrinsic renal disease.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES