Management of bilateral Wilms tumor over three decades: The perspective of a single center.

INTRODUCTION: Outcomes of Wilms tumor improved in last 50 years and excellent survival rates can be achieved especially in case of non-metastatic disease and favorable histology. Nevertheless, bilateral cases still stand as a therapeutic challenge. Prognosis of bilateral Wilms tumor (BWT) is not as good as the unilateral tumors of similar stage and histology in terms of survival and renal function. OBJECTIVE: Management of BWT is constantly evolving and still stands as a therapeutic challenge. This study is designed to review and share our experiences on this topic from a surgical standpoint. STUDY DESIGN: The records of patients treated in our clinic between 1980 and 2013 according to Turkish Pediatric Group of Oncology protocol were analyzed retrospectively and clinical data, surgical details, pathology results, long term outcomes were analyzed. RESULTS: Thirteen girls and 7 boys with a mean age of 2,5 years were treated. There were 2 patients with Wilms tumor-Aniridia-Growth Retardation complex and one with isolated hemihypertrophy. Metastasis were detected in lungs of 4 patients; liver of 2 and in the cranium of one. All patients except one with the presumptive diagnosis of unilateral Wilms tumor were given preoperative chemotherapy. To sum up; 19 nephroureterectomies, 8 partial nephrectomies and 13 enucleations were performed to 36 kidneys without any major early or late postoperative complications. Pathologic results revealed positive surgical margins in 2 lesions with enucleation and in 2 with partial nephrectomies and anaplasia in 4 patients. Two patients were not operated due to parental disapproval. Two patients had the need of dialysis; one was anephric and the others' renal functions recovered over a year. Seven patients received radiotherapy for pulmonary metastasis, positive surgical margins or local recurrences. Overall, 13 patients survived and 7 died due to metastasis, recurrences, and complication of dialysis and refusal of surgical treatment. Survival among all patients was 65% and 72.2% among operated ones. Of the 7 patients with the partial nephrectomy, 2 died and 5 survived. Among enucleation group, 8 out of 10 survived and 2 died. Survival was slightly higher among enucleation group (80% vs 71.4%). Median time of follow-up for survivors of disease is 5.8 years (min: 6 months and max: 14 years). DISCUSSION: Outcomes of BWT management have changed dramatically during the last few decades from only survival, to a long life expectancy without the need of renal replacement therapy owing to improvements in treatment options. We argue that positive surgical margins do not necessarily lead to local recurrence. For this reason it may be wiser to favor on more nephron sparing surgery than to achieve negative surgical margins. Adjuvant chemotherapy and radiotherapy may be adequate to prevent local recurrence. Also, survival did not differ significantly between different ways of nephron sparing surgeries, so it may be wiser to choose enucleation over partial nephrectomy which preserves more nephrons. Nephron-sparing surgery should have utmost importance despite the risk of positive margins. On the other hand, there is not enough data to interpret if positive surgical margins have role on distant metastases or not. Presence of metastasis and recurrence seems to be an important determinant of prognosis given the fact that none of the survivors had any metastasis or recurrence. CONCLUSION: Nephron preservation should be the aim while taking positive surgical margin risk on nephron sparing surgery side relying on postoperative chemotherapy and carefully planned radiotherapy to avoid recurrence. However, there is significant diversity on the management BWT in different centers and a certain validated guideline or protocol to provide the optimal treatment is still lacking.

Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

OBJECTIVE: Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). PATIENTS AND METHODS: We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary ß2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. RESULTS: The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine ß2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for ß2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. CONCLUSIONS: NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.

Maxillofacial osteosarcoma successfully treated with surgery and adjuvant chemotherapy in a child.

Maxillofacial osteosarcoma constitutes a minor percentage of all the head and neck tumors. We describe a 10 year-old girl presenting with swelling and pain in left maxillary region and diagnosed as low grade osteosarcoma. The patient was operated and given a chemotherapy protocol consisted of Cisplatin and Doxorubicin. After six courses of chemotherapy the patient was in complete remission and she is well with no evidence of disease for five years. Since high local recurrence rates have been reported in craniofacial osteoarcoma and we know the deleterious side effects of radiation therapy in children, we believe that best management strategy for osteosarcomas in maxillofacial region in children is radical surgical excision and postoperative chemotherapy (Fig. 3, Ref. 11).

Primitive neuroectodermal tumors of the central nervous system associated with genetic and metabolic defects.

AIM: To evaluate the genetic, congenital and metabolic disorders which were detected concurrently with primitive neuroectodermal tumors (PNET) of the central nervous system in children. METHODS: Medical records of 1030 children who were admitted to our department with diagnosis of brain tumor between 1975 and 2005 were reviewed retrospectively. Medulloblastoma and supratentorial PNETs were detected in 289 patients. They were reviewed for associated metabolic conditions, genetic and congenital defects. RESULTS: One of the following conditions were detected in 10 patients with medulloblastoma and supratentorial PNETs: Neurofibromatosis type 1, Gorlin syndrome, juvenile polyposis coli, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, bilateral retinoblastoma, L-2-hydroxyglutaric aciduria, Gilbert syndrome, gray platelet syndrome, cleft lip-palate and left renal agenesis. In the patients with multiple malignant diseases, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, Gorlin syndrome and juvenile polyposis coli were diagnosed after diagnosis of the malignant tumors. Medulloblastoma was the first manifestation in the case with Gorlin syndrome. In case with retinoblastoma, pineal PNET was detected 2 months after diagnosis of retinoblastoma. Cleft lip-palate and L-2-Hydroxyglutaric aciduria were detected previously in the patients before their brain tumors whereas Gray platelet, Gilbert syndrome and left renal agenesis were diagnosed during treatment of medulloblastoma. CONCLUSION: Associated genetic, metabolic and congenital conditions were detected in 3.5% of the cases. Thus the patients with PNET should be followed for these defects.

Clinical value of cystatin c determination in children with lymphoma.

Cystatin, a proteinase inhibitor, is involved in the intracellular catabolism of proteins. We investigated the change in concentration of serum Cystatin C (CysC) in children with lymphomas and its diagnostic utility. Twenty-eight newly diagnosed patients with lymphoma were included in this study. The male/female ratio was 20/8, with a median age of 8.5 years (range 3-17 years). Thirteen patients had Hodgkin's lymphoma (HL) and 15 had non-Hodgkin's lymphoma (NHL). Cystatin C concentration was determined at the time of diagnosis and during remission. In the entire group, CysC concentrations at diagnosis and during remission were 0.87+/-0.29 mg/L and 0.86+/-0.21 mg/L, respectively (p=0.93). In the NHL group, CysC concentrations at diagnosis and remission were 0.89+/-0.32 mg/L and 0.85+/-0.23 mg/L, respectively (p=0.73). The CysC concentrations in the HL group at diagnosis and remission were 0.88+/-0.36 mg/L and 0.88+/-0.18 mg/L, respectively (p=0.73). No significant difference was observed between CysC concentrations in the HL (0.88+/-0.36 mg/L) and NHL (0.89+/-0.32 mg/L) groups. Cystatin C concentrations in all the patients with localized versus those with advanced disease were 0.91+/-0.41 mg/L and 0.88+/-0.3 mg/L, respectively (p=0.83). Cystatin C concentrations of the patients with localized and advanced HL were 0.95+/-0.45 mg/L and 0.77+/-0.14 mg/L, respectively, (p=0.41). Cystatin C level was higher in patients with localized disease, in those without B symptoms, and, at diagnosis, in those with an unfavorable response (Tab. 2, Ref. 20). Full Text in free PDF www.bmj.sk.

A newborn with infantile fibrosarcoma of foot: treatment with chemotherapy and extremity-sparing surgery.

Infantile fibrosarcoma represents less than 1% of all childhood cancers, but it is the most common soft-tissue sarcoma in those under 1 year of age. We report an infant with congenital infantile fibrosarcoma diagnosed as hemangiopericytoma. He was treated with chemotherapy and extremity-sparing surgery. Amputation was avoided.

Pineal region tumors in children: a single center experience.

Pineal region tumors are a relatively uncommon, deep-seated heterogeneous group of mass lesions of the brain. Their management is much more complicated in children with cancer, both in terms of survival and sequelae, due to primary location of the tumor and treatment modality. The goal of this retrospective study was to report the presentation, treatment, and outcome of tumors that arose from this region in 24 children treated at our institution between March 1975 and May 2006. In all, 15 (62.5%) of the 24 children were initially treated with partial or complete resection, adjuvant radiotherapy was given to 18 (75%) patients, and chemotherapy was given to 15 (62.5%) of the patients. Overall survival was 44.5%. Although statistically insignificant, the most favorable outcome were obtained in patients with grossly resected tumors (66%) and in children >10 years of age (80%). Long-term sequelae occurred at a high rate in this study due to the primary location of the tumors and treatment modalities, which warrants further investigation.

Varicella vaccination in children with lymphoma and solid tumours.

BACKGROUND: Varicella infection can be a severe disease, especially in immunosuppressed patients. Here, experience with live varicella vaccine to prevent varicella infection is reported in children who were undergoing treatment for lymphoma and solid tumours. METHODS: 40 children, aged between 12 months and 15 years with no clinical history of varicella, were vaccinated with live varicella vaccine. All received two doses of the vaccine subcutaneously 4 weeks apart. Serum samples were taken before the first dose and 6 weeks after the second dose of vaccine. RESULTS: Before vaccination, 32 patients were seronegative for varicella and eight were seropositive. Seroconversion was observed 6 weeks after the second dose in 24 of the 32 (75%) seronegative children. In 4 of 8 previously seropositive patients, antibody titres increased after immunisation. Zoster infection occurred 5 weeks after the second dose of vaccine in only one previously seronegative child. 7 children, who had responded to the vaccine, have been exposed to varicella in their families or in school without contracting clinical disease. CONCLUSION: Although the small number of patients in our group prevents us from drawing definitive conclusions, the varicella vaccine seems to be well tolerated and can be administered to children with lymphoma and solid tumours undergoing treatment.

Primary lacrimal sac non-Hodgkin's lymphoma in a child.

Primary lacrimal sac lymphoma is extremely rare in children. To our knowledge, only two previous cases have been reported in the literature. Here, we report the case of a 9-year-old girl with primary lacrimal sac lymphoma who has recurrent mass.

Malignant solid tumors associated with congenital immunodeficiency disorders.

This objective of this study was to evaluate patients with immunodeficiency syndromes who had developed malignant solid tumors and to examine survival rates and prognosis with respect to type of immunodeficiency disease. Twenty-two patients who were diagnosed with malignant solid tumors and immunodeficiency syndromes between January 1972 and February 2003 were analyzed retrospectively. There were 12 (55%) patients with non-Hodgkin lymphoma, 8 (37%) with Hodgkin disease, 1 (5%) with mucinous adenocarcinoma of the colon, and 1 (5%) with brain stem glioma. Fifteen (68%) patients had ataxia-telangiectasia, 3 (14%) had common variable immunodeficiency disease, 2 (9%) had Bloom syndrome, 1 (5%) had combined immunodeficiency, and 1 (5%) had selective immunoglobulin A deficiency. Out of the 15 patients with ataxia-telangiectasia 9 patients had non-Hodgkin lymphoma, 5 had Hodgkin disease, and 1 had brain stem glioma. Two patients with common variable immunodeficiency disease had non-Hodgkin lymphoma and 1 had Hodgkin disease. One of the patients with Bloom syndrome had Hodgkin disease and 1 had colon carcinoma. The overall survival for the whole group was 24%. Overall survival rates in non-Hodgkin lymphoma, Hodgkin disease, colon carcinoma, and brain stem glioma were 17, 44, 0, and 0% (p =.25), respectively. Overall survival in ataxia-telangiectasia patients was 20%. In this series, most of the patients had ataxia-telangiectasia (68%). The survival rates of the malignant diseases were very poor in immunodeficiency. Overall survival in non-Hodgkin lymphoma patients was relatively worse than Hodgkin disease patients.

Successful treatment with interferon alfa in infiltrating angiolipoma: a case presenting with Kasabach-Merritt syndrome.

We report a case of infiltrating angiolipoma who presented with a large mass on the shoulder and the signs of Kasabach-Merritt syndrome. She improved dramatically within one month and the mass completely disappeared after six months of interferon treatment.

Serum carnitine levels during the doxorubicin therapy. Its role in cardiotoxicity.

Doxorubicin is an anthracycline antibiotic with a broad spectrum of antineoplastic activity. Cardiotoxicity is a serious long-term complication of the drug. Simultaneous administration of carnitine has been proposed to prevent cardiotoxicity. We aimed to monitor the serum carnitine levels during the treatment of doxorubicin and to determine a relationship between serum carnitine levels and cardiac dysfunction. Fifteen patients were evaluated prospectively. Measurement of carnitine levels and evaluation of cardiac function were performed prior to treatment, and after cumulative doses of 180 and 300 mg/m2 of doxorubicin. A group of 20 healthy children served as control group to obtain reference values. We found subclinical abnormalities in cardiac function, while the cumulative doses of the doxorubicin was increasing. The mean end diastolic and end systolic left ventricular dimensions of the patient group after completion of the treatment were significantly increased compared with initial values. The ejection and shortening fraction of the patient group after cumulative doses of 300 mg/m2 of doxorubicin were significantly lower than those of the control group. A statistically significant augmentation was observed in mitral A, with a decrease in mitral E/A ratio. There was a trend towards lower serum carnitine levels with higher cumulative doses of doxorubicin, although it was not statistically significant. Our results invite new detailed investigations depending on the measurement of serum and urinary free and acyl carnitine and myocardial carnitine levels to evaluate possible roles of carnitine in the prevention of doxorubicin-induced cardiotoxicity.

Testicular tumors in children.

PURPOSE: The aim of this study was to present an updated picture of surgical management of pediatric testicular tumors based on our 30 years' experience, which consisted of one of the largest noncollected series treated in a single medical center. METHODS: Records of children who were treated for testicular tumor in our unit from 1970 to 1999, inclusive, were reviewed retrospectively. Information recorded for each patient included age, sex, past medical history, clinical characteristics, diagnostic procedures, treatment methods, histopathologic findings, and outcome. RESULTS: Fifty-one patients with a mean age of 3.8 +/- 0.5 years were treated for testicular tumors. Of these, 35 (69%) had germ cell testis tumor (GCT) and 16 (31%) had non-germ cell testis tumor (NGCT). Endodermal sinus tumor and paratesticular rhabdomyosarcoma were the dominant histologic subtypes in each group, respectively. The most common mode of presentation was painless scrotal mass. At initial presentation, retroperitoneal (n = 5), both retroperitoneal and lung (n = 2), and retroperitoneal and liver (n = 3) metastases were recorded in 10 (19%) patients. Initial operative procedures were radical inguinal orchiectomy (RIO) (n = 29), scrotal orchiectomy (SO; n = 9), bilateral RIO (n = 2), both RIO and unilateral retroperitoneal lymph node (RPLN) excision (n = 6), testis-sparing enucleation of the tumor (n = 5). SOs were performed elsewhere, and these patients underwent high ligation (n = 4) and both high ligation plus RPLN excision (n = 5) in our unit. Histopathologically, spermatic cord invasion and RPLN involvement were present in 10 patients. Scrotal recurrences were encountered in 2 patients who had scrotal orchiectomy initially. Retroperitoneal recurrences were noted in a patient presenting with stage I embryonal carcinoma and in 2 patients presenting with group IV paratesticular rhabdomyosarcoma. The mean follow-up period was 89 +/- 10 months. Four patients with stage IV embryonal carcinoma (n = 2) and group IV paratesticular rhabdomyosarcoma (n = 2) died of progression of the disease. All remaining patients were alive and disease free at their last outpatient appointment. No significant difference was noted with regard to 5-year survival rates between (1) malignant GCT and paratesticular rhabdomyosarcoma patients (91% v 80%) and (2) patients treated by RIO (88%), SO plus high ligation (87%), and RIO plus RPLN excision (80%). Five-year survival rates were 100% for stage I, II, III patients and 33.3% for stage IV and group IV patients presenting with malignant testicular tumors (P <.05). CONCLUSIONS: Childhood testicular tumors deserve special attention from the therapeutic point of the view. A solid scrotal mass should be considered malignant until proved otherwise. Any suspicion of the testicular tumor warrants an inguinal approach to prevent scrotal violation by the tumor. Current trends emphasize that testis-sparing surgery should be performed for benign lesions such as teratoma, leydig cell tumor, and epidermoid cyst based on frozen biopsy findings. Literature findings and our experience suggest that RIO is the accurate treatment for stage I malignant GCT and group I and IIa paratesticular rhabdomyosarcoma. RPLN excision is not of benefit either as a staging or therapeutic procedure in stage I and group I and IIa diseases of these tumors. RPLN excision should be reserved for (1) malignant GCT patients who have persistent elevation of alpha-fetoprotein after orchiectomy in the presence of normal total body CT scan, and for patients presenting with stage II and III disease with definitive abnormality on CT scans, and (2) group IIb, IIc, and III paratesticular rhabdomyosarcoma patients with radiologic evidence of retroperitoneal involvement on CT scans. High ligation should be done as a complementary procedure after SO to increase the survival rates. J Pediatr Surg 36:1796-1801.

Urticaria pigmentosa associated with Wilms tumor.

Urticaria pigmentosa is the most common manifestation of mastocytosis, with the majority of cases undergoing spontaneous resolution, especially in children. Several reports have documented hematologic malignancies developing in patients with urticaria pigmentosa. We present a 4.5-year-old boy with urticaria pigmentosa who developed Wilms tumor. To our knowledge, coexisting urticaria pigmentosa and Wilms tumor have not previously been described.

Monotherapy with meropenem versus combination therapy with piperacillin plus amikacin as empiric therapy for neutropenic fever in children with lymphoma and solid tumors.

The purpose of this study was to compare meropenem monotherapy with combination therapy for empirical treatment of neutropenic fever in children with lymphoma and solid tumors. Ninety episodes of neutropenic fever in children (0.7-16.0; mean age 7.7 years) with solid tumors in a single center were randomized to receive either meropenem (50 mg/kg/dose-maximum 1 g, every 8 hours) or piperacillin (200 mg/kg/dose, every 6 hours) plus amikacin (15 mg/kg daily). Failure was defined as treatment modification. Non-Hodgkin's lymphoma (NHL) accounted for 62.2 percent of all episodes, and solid tumors (37.8%) for the rest. Blood cultures were positive in 23 percent of all episodes. Sixty-seven percent of all isolated microorganisms stained Gram-positive. Overall success was 70.0 percent (63/90). The success with meropenem was comparable to that seen with piperacillin plus amikacin: 76.6 versus 64.6 percent (p = 0.25). The failure rate was 33 percent with Gram-positive culture and 78 percent with Gram-negative or mixed cultures. The solid tumor group had significantly less bacteremia (4/34 versus 17/56; p < 0.05) and treatment failure (3/34 versus 24/56; p < 0.001) than the NHL group. No serious drug-related adverse event was noticed. Meropenem monotherapy was as effective as piperacillin plus amikacin combination in the empirical treatment of neutropenic fever in children with lymphoma and solid tumors.

Fibrolamellar hepatocellular carcinoma with skeletal metastases.

Skeletal metastases is relatively rare in hepatocellular carcinoma and accounts for 4-16% of extrahepatic metastases. The authors report a 13-year-old girl with fibrolamellar hepatocellular carcinoma, who rejected further systemic chemotherapy following hepatic lobectomy and experienced sternal and vertebral painful metastases nearly 5 years after the operation. The sternal metastatic lesion was removed surgically, whereas external irradiation was delivered to the lumbar vertebral lesion. The patient received no systemic treatment following metastases and died with widespread disease. Despite metastatic disease, the patient survived 6.5 years following the initial diagnosis.

Scleroderma in a child after chemotherapy for cancer.

The association of malignancy with scleroderma is very rare in childhood. A 13-year-old girl was diagnosed as having thymic carcinoma and received systemic chemotherapy. She presented with symptoms of Raynaud's phenomenon 9 months after the cessation of chemotherapy. She also had difficulty in swallowing. Based on the presence of Raynaud's phenomenon, characteristic skin changes over the face and hands, oesophageal involvement and pulmonary restrictive defect demonstrated by pulmonary function tests, the diagnosis of generalised scleroderma was established. There was no evidence of tumor recurrence. Although she was treated with penicillamine and prednisolone, no significant improvement was achieved in her condition during the 14-month follow up.

Expression of adhesion molecules LFA-1, ICAM-1, CD44, and L-selectin in childhood non-Hodgkin lymphomas.

BACKGROUND: The aim of the present study was to analyse the expression of adhesion molecules in childhood non-Hodgkin lymphomas and to correlate the findings with clinical features and prognosis. PROCEDURE: Samples were obtained from pleural and peritoneal fluids, bone marrow aspirates, and tissue biopsies from 21 patients (median age: 8 years). There were 9 T-cell and 12 B-cell lymphomas. The expression of CD18, CD44s, CD54, CD62L were investigated with flow cytometry by using monoclonal antibodies. RESULTS: Absence of CD18, which was independent from immunophenotype, was found in 67% of patients. Positive CD44s and CD62L expression were observed in 48 and 63% of the cases, respectively. In all of the cases with T-cell lymphoma, CD54 was negative, whereas 8 of 12 cases with B-cell lymphoma expressed this molecule (P = 0.005). There was no correlation between location of disease and the expression of adhesion molecules, except CD54 that was negative in all mediasten lymphoma (P = 0.004). CD62L (+) patients had more frequently stage IV disease than CD62L (-) ones (P = 0.01). Two-year overall survival was 83 and 29% in CD18 (+) and CD18 (-) cases; 55 and 36% in CD44s (+) and CD44s (-) cases; 46 and 42% in CD54 (+) and CD54 (-) cases; 42 and 50% in CD62L (+) and CD62L (-) cases. CONCLUSIONS: The expression of LFA-1 on lymphoblasts is lost in the majority of childhood non-Hodgkin lymphomas. ICAM-1 is not detected on neoplastic cells of patients with T-cell lymphoblastic lymphoma. L-selectin positivity correlates with disseminated disease. There is no significant relationship between the expression of adhesion molecules and the survival rates, although CD18(+) cases had better overall survival rate than CD18(-) cases.