wilms tumor is the most common renal tumor in children , peaking at 23 years of age .
though uniformly fatal in previous decades , the prognosis for most patients has greatly improved due to advances in chemotherapy and surgical treatment .
most cases are unilateral and treated by resection at presentation , which allows for diagnostic pathology and bulk of disease removal .
surgery is then followed by several weeks of adjuvant chemotherapy , with radiotherapy used mainly for cases of tumor rupture or peritoneal seeding . though primary kidney resection has long been the cornerstone of effective treatment for wilms tumors , this approach has recently been reevaluated in the context of synchronous bilateral disease .
bilateral wilms tumor accounts for only 5% of cases   but is associated with higher morbidity and mortality .
frequently one kidney will have a much larger tumor burden , as in the present case , and surgery would consist of complete nephrectomy for one side and partial nephrectomy for the other .
however , as many as 15% of stage v wilms tumor patients treated in this manner eventually develop chronic renal failure by age 20 compared with 1% of unilateral wilms tumor patients , prompting efforts to surgically spare as much normal renal tissue as possible .
children 's oncology group trial aren0534calls for pre - operative neoadjuvant chemotherapy to be given in order to shrink tumors to facilitate partial nephrectomies to maximize preservation of normal renal tissue . here
, we describe a young girl with bilateral wilms tumor who had marked tumor response after 12 weeks of chemotherapy .
her case illustrates that tumor lysis precautions should be considered in children with a large amount of disease who undergo neoadjuvant treatment and that pathologic interpretation of the tumor is possible even after many cycles of chemotherapy .
a normally developed 5-year - old girl presented to the emergency department with a 1 month history of worsening abdominal pain that localized to the right upper quadrant with intermittent vomiting and fevers over the week prior to presentation . on physical examination , the child was febrile to 37.6c with abdominal distension .
a tender right - sided abdominal mass was found extending from the costal margin to the pelvis and beyond midline .
abdominal ct imaging identified a large mass arising from the right kidney with at least one smaller lesion in the left kidney ( fig . 
serum wbc and electrolytes were normal , with a serum creatinine of 0.40 mg / dl and a bun of 7 mg / dl .
figure  1:computed tomography of the patient 's abdominal disease at presentation ( a ) , after 6 weeks of chemotherapy per cog aren0534 ( b ) and post - surgically ( c ) .
( a ) axial abdominal ct image at presentation showing large right - sided renal mass ( 23  13  15.8 cm ; large triangle ) and small contralateral renal lesion ( small triangle ) , ( b ) axial abdominal ct after 6 weeks of chemotherapy showing marked response of the right - sided renal tumor ( 8.6  4.1  5.3 cm ) to therapy . left - sided renal renal tumor remained approximately stable in size ( 8 mm ) throughout neoadjuvant therapy .
( c ) post - surgical abdominal ct reflecting right radical nephrectomy and wedge resection of left kidney .
computed tomography of the patient 's abdominal disease at presentation ( a ) , after 6 weeks of chemotherapy per cog aren0534 ( b ) and post - surgically ( c ) .
( a ) axial abdominal ct image at presentation showing large right - sided renal mass ( 23  13  15.8 cm ; large triangle ) and small contralateral renal lesion ( small triangle ) , ( b ) axial abdominal ct after 6 weeks of chemotherapy showing marked response of the right - sided renal tumor ( 8.6  4.1  5.3 cm ) to therapy .
left - sided renal renal tumor remained approximately stable in size ( 8 mm ) throughout neoadjuvant therapy .
( c ) post - surgical abdominal ct reflecting right radical nephrectomy and wedge resection of left kidney .
the patient was given a presumptive diagnosis of bilateral ( stage v ) wilms tumor .
the family consented for her to participate in the children 's oncology group trial aren0534 which called for pre - operative chemotherapy in order to facilitate nephron - sparing surgery at the time of tumor resection .
a central venous catheter was placed , and neoadjuvant chemotherapy with vincristine , dactinomycin and doxorubicin was initiated . within hours of starting her therapy , we found that lactate dehydrogenase and uric acid were both elevated ( 1134 u / l and 6.3 mg / dl , respectively ; fig .  2 ) .
the patient 's hyperuricemia was felt to be consistent with tumor lysis syndrome , and allopurinol and alkalinized fluids were administered .
the hyperuricemia soon resolved , and the patient maintained normal serum creatinine , potassium and phosphorus levels throughout her hospital stay . a follow - up ct scan after 6 weeks of therapy showed a marked response to chemotherapy of the right - sided lesion ( fig . 
we decided to administer another 6 weeks of chemotherapy to improve her candidacy for right partial nephrectomy instead of whole nephrectomy . however , despite further tumor shrinkage , total nephrectomy eventually had to be performed for the right kidney because no clear surgical plane could be identified at the time of resection ( fig . 
pathologic interpretation of the right- and left - sided tumors confirmed wilms tumor in each and a focus of anaplastic disease on the right ( fig . 
10.8 gy of radiation to the right flank was administered because of the pathologic finding of focal anaplasia , in accordance with the aren0534 protocol .
presently the patient is well , with good renal function and in remission , now roughly 6 months after her end of therapy . 

figure  2:tumor lysis metabolic abnormalities reflecting serum uric acid and creatinine levels in the context of the therapeutic timeline . 
 figure  3:pathologic images from right - sided lesion after 12 weeks of neoadjuvant chemotherapy .
note that the architecture of the tumor is still well preserved , confirming a diagnosis of wilms tumor .
( a ) lower - power power image ( 100 ) showing the area of anaplasia ( black triangle ) immediately adjacent to an area of scarring and fibrosis ( white triangle ) , ( b ) a region of non - anaplastic glandular wilms tumor ( 400 ) , ( c ) anaplastic focus of disease ( white triangle ; 400 ) .
tumor lysis metabolic abnormalities reflecting serum uric acid and creatinine levels in the context of the therapeutic timeline .
note that the architecture of the tumor is still well preserved , confirming a diagnosis of wilms tumor .
( a ) lower - power power image ( 100 ) showing the area of anaplasia ( black triangle ) immediately adjacent to an area of scarring and fibrosis ( white triangle ) , ( b ) a region of non - anaplastic glandular wilms tumor ( 400 ) , ( c ) anaplastic focus of disease ( white triangle ; 400 ) .
wilms tumor is responsible for roughly 6% of all childhood cancers and 95% of renal tumors in the pediatric population .
survivability from this malignancy now approaches 90% with proper management , including surgery , chemotherapy and radiation .
historically , most wilms tumors have been resected at diagnosis , with adjuvant chemotherapy to manage micrometastatic disease .
even with bilateral disease , chemotherapy would typically be administered only after the large primary tumor had been removed .
however , current high - risk wilms tumor protocols , as apply to patients with bilateral disease , are designed to reduce long - term risk of renal failure by shrinking tumors with chemotherapy to enable nephron - sparing sub - total nephrectomy .
clinical trials by siop ( international society of paediatric oncology ) and other consortia have found that pre - nephrectomy chemotherapy may decrease the stage of disease and risk of tumor rupture during local control ; however , this approach brings risks of tumor lysis syndrome , veno - occlusive disease and potential interference with tumor staging and pathologic diagnosis . in the present case ,
initial chemotherapeutic management of wilms tumor was complicated by hyperuricemia , presumably caused by tumor lysis syndrome in which metabolites are released from large numbers of cancer cells dying simultaneously in response to chemotherapy .
classically , tumor lysis syndrome occurs in the setting of initial treatment of hematologic malignancies such as burkitt 's lymphoma and leukemia , presumably because of the large burden of disease and the exquisite chemosensitivity of such malignancies .
laboratory findings of tumor lysis syndrome include hyperuricemia , hyperkalemia and hyperphosphatemia with secondary hypocalcemia .
we reason that our patient developed hyperuricemia because of her large tumor burden , the chemosensitivity of her disease and perhaps because of the presence of tumors in her kidneys that may have physically interfered with normal glomerular filtration .
many cases of tumor lysis can be managed conservatively with ample hydration , alkalization and xanthine oxidase inhibition by allopurinol .
more severe or refractory cases may require administration of uric acid oxidase ( rasburicase ) , a recombinant enzyme that degrades uric acid , or hemodialysis .
our case illustrates that wilms tumor , being a chemosensitive embryonal malignancy of childhood , can also be associated with tumor lysis syndrome . in the past
, most patients with bilateral wilms tumors were treated up - front with surgery and therefore had much lower burdens of disease when adjuvant chemotherapy .
this case illustrates that if surgery is postponed , tumor lysis precautions should be considered when chemotherapy is given to patients with large wilms tumors .
this case also demonstrates that pathologic findings are preserved even after several weeks of chemotherapy .
 we describe the case of a 5-year - old girl whose abdominal pain and distension were caused by wilms tumor of the kidney . because of the bilateral nature of her disease 
 , she was spared biopsy or initial nephrectomy as part of her treatment course . 
 rather , she was treated presumptively for wilms tumor based primarily on radiologic findings . 
 neoadjuvant chemotherapy consisting of vincristine , dactinomycin and doxorubicin was given to facilitate nephron - sparing surgery for tumor resection . 
 her initial chemotherapeutic course was complicated by tumor lysis syndrome manifested by elevated serum uric acid and was treated effectively with hyperhydration and alkalization of intravenous fluids . 
 the patient 's disease responded well to chemotherapy , and she underwent successful tumor excision after 12 weeks of chemotherapy . 
 the resected tumor was identified as anaplastic wilms tumor , illustrating that pathologic identification of wilms tumor is possible even after multiple cycles of neoadjuvant chemotherapy and marked tumor shrinkage . 
INTRODUCTION
CASE REPORT
DISCUSSION