Endovascular recanalization of the superior mesenteric artery in the context of mesenteric bypass graft infection.

Mesenteric prosthetic graft infection is a rare and challenging clinical scenario. A patient is described who developed recurrent abdominal pain after occlusion of an iliomesenteric prosthetic bypass. Endovascular recanalization of the native superior mesenteric artery, which had been occluded for more than 10 years, was accomplished using axillofemoral through-wire access and a steerable guiding catheter. The infected prosthetic was then explanted and his graft-enteric fistula repaired. Technical and strategic considerations are discussed.

Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study.

PURPOSE: To describe the response rate and survival of children and adolescents with unresected or metastatic nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) treated with vincristine, ifosfamide, and doxorubicin. PATIENTS AND METHODS: Between September 1996 and June 2000, 39 eligible patients received vincristine (1.5 mg/m(2) weekly for 13 doses), ifosfamide (3 g/m(2) daily for 3 days every 3 weeks for seven cycles), doxorubicin (30 mg/m(2) daily for 2 days for six cycles), and mesna (750 mg/m(2) for four doses after ifosfamide). Granulocyte colony-stimulating factor was administered daily (5 mug/kg) after each cycle of chemotherapy. Radiotherapy was administered from weeks 7 through 12. RESULTS: The median patient age at diagnosis was 11.7 years; the most common primary tumor site was lower extremity (36%); and synovial sarcoma was the predominant histology. More than three fourths of all tumors were 5 cm or greater at their largest diameters. The overall objective combined partial and complete response rate was 41% (95% CI, 25.7% to 56.7%). The estimated 3-year overall survival and progression-free survival rates (+/- standard deviation) for eligible patients were 59% +/- 8.2% and 43.6% +/- 7%, respectively. Patients with clinical group III disease had significantly better 3-year and progression-free survival rates compared with patients who presented with metastatic disease. CONCLUSION: The vincristine, ifosfamide, and doxorubicin regimen was moderately active against pediatric NRSTS. Patients with synovial sarcoma had higher response rates than other patients, and patients with unresected disease had improved outcomes. Patients with metastatic disease continue to fare poorly, and newer approaches are indicated for these patients.

Phase I study of combination topotecan and carboplatin in pediatric solid tumors.

PURPOSE: We conducted a phase I trial of escalating doses of topotecan (TOPO) in association with a fixed systemic exposure of carboplatin (CARBO) with or without granulocyte colony-stimulating factor (G-CSF) in children. PATIENTS AND METHODS: Two separate cohorts of patients (pts) with solid tumors were studied: (A) pts with refractory or recurrent disease and (B) pts with no prior myelosuppressive therapy or newly diagnosed tumors for which there was no standard chemotherapy. CARBO was given on day 1 at an area under the curve of 6.5, followed by TOPO as a continuous infusion for 3 days; the starting dose of TOPO was 0.50 mg/m(2)/d. Cycles were repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d starting on day 4. RESULTS: Forty-eight of 51 pts were assessable for toxicity. In group A, dose-limiting myelosuppression persisted despite de-escalation of TOPO to 0.3 mg/m(2)/d and use of G-CSF. In group B, the maximum-tolerated dose of TOPO was 0.5 mg/m(2)/d for 3 days, and 0.6 mg/m(2)/d for 3 days with G-CSF. No significant nonhematologic toxicities were observed. Among 46 pts assessable for response, one had complete response, five had partial response, and 18 had stable disease. CONCLUSION: Although this combination possesses antineoplastic activity in pediatric solid tumors, hematologic toxicity precluded any meaningful TOPO dose escalation. The addition of G-CSF did not alter this. The potential for preservation of activity and diminution of toxicity with alternative sequences and schedules of administration (topoisomerase followed by alkylating or platinating agents) should be evaluated.

Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma.

PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). PATIENTS AND METHODS: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival. RESULTS: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% +/- 9% and 56% +/- 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% +/- 10%). CONCLUSION: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.

Treatment of intraocular retinoblastoma with vincristine and carboplatin.

PURPOSE: To evaluate the efficacy of chemoreduction using vincristine and carboplatin in preventing or delaying external-beam radiotherapy (EBRT) or enucleation in patients with intraocular retinoblastoma. PATIENTS AND METHODS: Twenty-five patients (43 eyes) with newly diagnosed intraocular retinoblastoma received primary treatment with eight courses of vincristine and carboplatin. Focal treatments were delayed until documentation of disease progression. Outcome measures for each eye were length of time to disease progression, avoidance or delay of EBRT, and globe survival. Event-free survival was defined as the length of time to EBRT or enucleation. RESULTS: Disease in all eyes responded to chemotherapy and progressed in only two patients before completion of the eight courses of therapy. Disease in all but four eyes progressed and required focal treatments. Event-free survival estimates at 2 years were 59.2% +/- 12.0% for Reese-Ellsworth group I, II, and III eyes and 26.3% +/- 9.2% for group IV and V eyes. Nineteen eyes (44.2%) required EBRT and 13 eyes (30.2%) were enucleated. The ocular salvage rate was 83.3% for Reese-Ellsworth group I to III eyes and 52.6% for group IV and V eyes. For those patients receiving EBRT, the median time from enrollment to EBRT was 9.5 months (median age at EBRT, 21 months). CONCLUSION: In combination with appropriate early intensive focal treatments, chemoreduction with vincristine and carboplatin, without etoposide, may be an alternative treatment for patients with early-stage intraocular retinoblastoma, although additional studies are needed. Patients with advanced intraocular disease require more aggressive treatments.

Protracted intermittent schedule of topotecan in children with refractory acute leukemia: a pediatric oncology group study.

PURPOSE: To determine dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of a protracted, intermittent schedule of daily 30-minute infusions of topotecan (TPT) for up to 12 consecutive days, every 3 weeks, in children with refractory leukemia. PATIENTS AND METHODS: Forty-nine children were enrolled onto this phase I trial (24 with acute nonlymphoblastic leukemia [ANLL] and 25 with acute lymphoblastic leukemia [ALL]). TPT dosage was escalated from 2.0 to 5.2 mg/m(2)/d for 5 days and 2.4 mg/m(2)/d from 7 days to the same dose for 9 and 12 days in cohorts of three to six patients when no DLT was identified. TPT pharmacokinetics were studied in 33 children once or twice (first and last doses in patients who received TPT for > 7 days). RESULTS: Seventy assessable courses of TPT were administered to 49 children who had refractory leukemia. DLTs were typhlitis, diarrhea, and mucositis, and the MTD was 2.4 mg/m(2)/d for 9 days in this group of heavily pretreated children. In 33 patients, the median TPT lactone clearance after the first dose was 19.2 L/h/m(2) (range, 9.4 to 45.9 L/h/m(2)) and did not change during the course. There were significant responses (one complete response [CR] and four partial responses [PR] in patients with ANLL and one CR and two PRs in patients with ALL), and all but one were at dosages of TPT given for at least 9 days. CONCLUSION: The MTD was 2.4 mg/m(2)/d for 9 days. Further testing is warranted of TPT's schedule dependence in children with leukemia.

Retinoblastoma metastatic to the ovary in a patient with Waardenburg syndrome.

PURPOSE: To report a child with retinoblastoma and Waardenburg syndrome who developed ovarian metastases. DESIGN: Interventional case report. METHODS: Unilateral retinoblastoma was diagnosed in a 3-year-old girl with Waardenburg syndrome and leukocoria in the right eye. The patient had a Reese-Ellsworth Group Va tumor and underwent enucleation. Two years later, she developed metastatic disease involving the bone marrow, right humerus, both supraorbital bones, and both tibias. She was treated with chemotherapy, orbital irradiation, and bone marrow transplant but returned 7 months later with back pain and urinary retention. RESULTS: Exploratory laparotomy revealed a right ovarian mass, and the excised ovary showed metastatic retinoblastoma. The child underwent chemotherapy and remained asymptomatic for 9 months, when brain metastases were diagnosed. She died within 2 days of admission. CONCLUSION: We believe that this is the first description of a patient with retinoblastoma and Waardenburg syndrome and of an ovarian metastasis from retinoblastoma.

The emotional intelligence of surgical residents: a descriptive study.

BACKGROUND: We assessed educational needs with regard to leadership, communication, and emotional intelligence (EI) among surgical residents. METHODS: General surgery residents (n = 74) were examined using the BarOn Emotional Quotient Inventory (EQ-i) and a 20-item survey. RESULTS: Residents believed that leadership skills were important (mean 4.7, SD .5) and that they had skills in each the five EI areas (overall mean 4.1, SD .8). Both the overall group's EQ-i scores (mean 106.6, SD 11.6), as well as scores on the 20 components of the EQ-i (range of means 102-110), were higher than national norms. Individuals varied substantially on EQ-i subscale scores. CONCLUSIONS: Surgical residents believed that leadership skills are important and scored strongly on both an EI self-assessment and the EQ-i. Specific individual differences in subscale scores can potentially identify areas for direct educational intervention.

Phase I clinical trial of oxaliplatin in children and adolescents with refractory solid tumors.

PURPOSE: To evaluate the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK), and adverse effect profile of oxaliplatin in pediatric patients with refractory solid tumors and to determine whether carbamazepine reduces oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS: Three regimens of oxaliplatin (given intravenously over 2 hours) were tested: regimen A (100 mg/m2, 130 mg/m2, or 160 mg/m2 every 3 weeks to determine the MTD of oxaliplatin); regimen B (to determine whether carbamazepine starting 24 hours before and ending 48 hours after oxaliplatin reduced the dose-limiting neurotoxicity and increased the MTD of regimen A); and regimen C (to evaluate the safety of a fixed dose two-thirds the MTD of regimen A given every 2 weeks [more frequent administration but comparable dose intensity]). RESULTS: Twenty-six patients were enrolled on regimens A (n = 11), B (n = 6), and C (n = 9). The DLT was grade 3 pharyngolaryngeal dysesthesia, sensory neuropathy, and ataxia at 160 mg/m2. The MTD was 130 mg/m2 every 3 weeks. At the MTD, the median clearance rate of ultrafiltrable platinum was 9.7 L/h/m2 (range, 6.5 to 15.5 L/h/m2). Addition of carbamazepine permitted dose escalation to 160 mg/m2 without DLT. DLT was not observed with a fixed dose of 85 mg/m2 given every 2 weeks. On all regimens, hematologic toxicity was mild. No significant nephrotoxicity, ototoxicity, or cumulative neurologic toxicity was observed. CONCLUSION: The DLT, MTD, PK, and adverse effect profile of oxaliplatin in pediatric patients with refractory solid tumors are similar to those observed in adults. Carbamazepine may reduce the dose-limiting neurotoxicity of oxaliplatin.

Colorectal carcinoma in childhood and adolescence: a clinicopathologic review.

PURPOSE: Pediatric colorectal carcinoma (CRC) is rare, but the available data suggest that it is more likely than adult CRC to be advanced at presentation and to have a poor outcome. We sought to better characterize pediatric CRC. PATIENTS AND METHODS: We reviewed the clinical and pathologic features, prognostic factors, and outcome of CRC in 77 children and adolescents (ages 7 to 19 years) referred to St Jude Children's Research Hospital between 1964 and 2003. RESULTS: At presentation, 76 patients had one or more signs or symptoms of CRC (abdominal pain, altered bowel habits, weight loss, anemia). Tumors were evenly distributed between the right and left colon; 62% were mucinous adenocarcinoma. At presentation, 86% of patients had advanced-stage disease; more than half had distant metastases. Overall outcome was poor. Advanced stage and mucinous histology were significant predictors of adverse outcome. Stage-specific survival at 10 years was 67% +/- 27% (stage 1), 38% +/- 15% (stage 2), 28% +/- 11% (stage III), and 7% +/- 4% (stage 4). Although no patient had a diagnosis of polyposis syndrome before diagnosis of CRC, 17 (22%) had colon polyps and eight (including two who previously underwent pelvic radiotherapy) had multiple polyps. CONCLUSION: Initial signs and symptoms of CRC are similar in pediatric and adult patients. The strikingly higher frequency of mucinous histology suggests that the biology of CRC differs in pediatric and adult patients and may contribute to poor outcomes. Children should be included in prospective clinical trials for CRC.

Pediatric extraadrenal paraganglioma.

BACKGROUND: Pediatric paraganglioma is rare and extraadrenal paraganglioma has not been characterized in children. METHODS: The authors reviewed the medical records and pathology samples of children with extraadrenal paraganglioma treated at our institution between December 1978 and September 2000. Clinical presentation, treatment, and outcome were evaluated. RESULTS: Eight patients (median age, 11.4 years) were identified, 4 were boys and none had a family history of paraganglioma or associated syndromes. Primary tumors arose in the retroperitoneum (n = 3), carotid body (n = 2), jugulotympanic ganglion (n = 1), cervical-paraspinal region (n = 1), and lung (n = 1). Extraadrenal paraganglioma had not been suspected at presentation in any patient. Of 5 patients who underwent gross total resection at the time of diagnosis, 4 remain disease free, 1 had microscopic residual tumor and died of disease. Three patients had initially unresectable disease, 2 are disease free after neoadjuvant therapy and delayed surgery, and 1 has persistent disease after tumor embolization and radiotherapy. CONCLUSIONS: Pediatric extraadrenal paraganglioma occurs most commonly in the retroperitoneum and head and neck, and the diagnosis usually is not suspected at the time of presentation. Surgery is the mainstay of treatment, and outcome is good after gross total resection. Neoadjuvant therapy can facilitate complete resection of initially unresectable tumors.

Patterns of abdominal relapse and role of sonography in Wilms tumor.

This study characterizes the patterns of abdominal recurrence of Wilms tumor and describes the role of sonography in its detection. Twelve patients who had initial tumor recurrence in the abdomen were evaluated. Five patients had recurrence in the kidney; all had nephrogenic rests detected by computed tomography (CT) or magnetic resonance (MR) imaging but not by sonography. The remaining 7 patients had recurrence in the peritoneum (4), the nephrectomy site (2), or the regional lymph nodes (1); tumor spillage had occurred in five of these patients. Four recurrences were detected during therapy, and eight within 3 years after completion of therapy. Seven of the 12 recurrences were first detected by sonography. All 11 sonograms obtained at the time of relapse showed tumor recurrence. Nine patients died a median of 10 months after relapse. The results suggest that regular sonographic surveillance for 3 years after therapy is likely to reveal most abdominal recurrences. Supplementation with CT or MR imaging is indicated for detection of nephrogenic rests.

High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma.

BACKGROUND: High-dose methotrexate (HDMTX)-induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX-induced nephrotoxicity has been managed with high-dose leucovorin, dialysis-based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase-G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX-induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis-based methods of MTX removal with treatment using CPDG2. METHODS: The literature was reviewed for osteosarcoma trials, use of dialysis-based methods for MTX removal, and reports of MTX-induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG2 and renal recovery after CPDG2 rescue was obtained from the database of a compassionate-release trial. RESULTS: Approximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade >/= 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis-based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG2. CPDG2 did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis-based methods. CONCLUSIONS: HDMTX-induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG2 should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently.

Ocular preservation after 36 Gy external beam radiation therapy for retinoblastoma.

PURPOSE: The purpose of this study was to document the ocular preservation rate after 36 Gy external beam radiation therapy (EBRT) for retinoblastoma. PATIENTS AND METHODS: Forty-nine eyes of 38 patients were treated with a median dose of 36 Gy EBRT. The patient population included 7 unilateral and 31 bilateral presentations, with a median age at diagnosis of 4 months. Eyes enucleated at the time of diagnosis or treated with other measures were not included in the analysis of ocular preservation. The median age at EBRT was 8 months. Patients were monitored for progression of disease after EBRT and second malignant neoplasms. RESULTS: The median follow-up was 88.6 months, with an estimated ocular preservation rate of 82.0% +/- 5% at 10 years. There was a difference in the ocular preservation rates for patients with advanced disease (Reese-Ellsworth group III-V) compared with early disease. Metastatic disease developed in two patients, and a second malignant neoplasm developed in three. Patients treated with en face electrons experienced a lower 5-year estimate of ocular preservation than those treated with photons, although patients treated with electrons were more likely to have advanced disease. CONCLUSIONS: The use of low-dose EBRT (36 Gy) results in ocular preservation rates that are comparable to those of high-dose EBRT. The use of electrons requires careful treatment planning and computerized dosimetry.

Treatment of refractory osteosarcoma with fractionated cyclophosphamide and etoposide.

PURPOSE: Standard multiagent chemotherapy for osteosarcoma may include platinum compounds, doxorubicin, and high-dose methotrexate. By identifying new chemotherapeutic strategies, the outcome of these patients can be improved and the toxicity of treatment regimens decreased. PATIENTS AND METHODS: The authors evaluated the activity of the combination of cyclophosphamide (500 mg/m2 per day for 5 days) and etoposide (100 mg/m2 per day for 5 days) given with granulocyte colony-stimulating factor (G-CSF) to children with osteosarcoma unresponsive to conventional treatment. RESULTS: Fourteen patients with refractory osteosarcoma were treated with this combination. Twelve patients had been previously treated with a multiagent regimen that included carboplatin, ifosfamide, methotrexate, and doxorubicin. Seven of 11 evaluable patients had a poor histologic response in their primary tumor at the time of definitive surgery (Huvos grade 1 or 2). Sites of relapse included lung, bone, and brain. A total of 47 courses were given. An overall response rate of 28.5% was achieved. A complete response was obtained in one patient (7.1%), a partial response was obtained in three patients (21.4%), and stable disease for 1 to 4 months was achieved in five patients (35.7%). Five patients (35.7%) had progressive disease. Grade 4 neutropenia was the primary form of toxicity observed; the median duration of absolute neurophil count less than 500/microL was 4 days. CONCLUSIONS: The combination of cyclophosphamide and etoposide resulted in a response rate of 28.5% in patients with refractory or relapsed osteosarcoma, and its incorporation into front-line therapies deserves further evaluation.

Treatment of metastatic retinoblastoma.

PURPOSE: The risk for death in patients with retinoblastoma is increased in those who present with metastatic disease, and the role of intensive chemotherapy and autologous hematopoietic stem cell rescue in these patients remains unclear. DESIGN: Nonrandomized interventional case series. PARTICIPANTS: Four consecutive patients with metastatic retinoblastoma. METHODS: We treated four patients with retinoblastoma metastatic to the bone and bone marrow with intensive chemotherapy, consolidation with megatherapy, and autologous hematopoietic stem cell rescue. Chemotherapy included courses of carboplatin and etoposide alternating with cyclophosphamide, etoposide, and either carboplatin or cisplatin. Radiation therapy was delivered to areas of bone metastases. MAIN OUTCOME MEASURES: Patient survival. RESULTS: All patients completed and responded to the scheduled therapy; complete response of the bone marrow disease was documented after two courses of chemotherapy in all cases. Two patients are long-term survivors. CONCLUSIONS: The treatment described has been successful in obtaining disease-free survival in patients with metastatic retinoblastoma.

Survival after recurrence of Ewing tumors: the St Jude Children's Research Hospital experience, 1979-1999.

BACKGROUND: Despite improved therapies, 30-40% of patients with Ewing tumors (ET) experience recurrence and have a poor prognosis. The authors analyzed factors prognostic of survival in patients with recurrent ET. METHODS: The authors assessed the relation between postrecurrence survival (PRS) and demographic, disease, and treatment factors in 71 patients who experienced recurrent ET after treatment on one of three consecutive institutional protocols. RESULTS: Thirty-four patients (47.9%) had distant recurrence, 25 patients (35.2%) had local recurrence, and 12 patients (16.9%) had both distant and local recurrence at a median of 1.7 years after diagnosis. The probability of 5-year PRS (+/- 1 standard error) was 17.7%+/-4.5%. Recurrence > or = 2 years after diagnosis predicted a significantly better outcome (5-year PRS, 34.9%+/-8.5%) compared with earlier recurrence (5.0%+/-2.8%; P < 0.001). Patients who had both local and distant recurrence fared worse (5-year PRS, 12.5%+/-8.3%) compared with patients who had local recurrence alone (21.7%+/-7.8%) or distant recurrence alone (17.6+/-6.1%). Among patients with local recurrence alone, those who underwent salvage with radical surgery had significantly higher 5-year PRS estimates (31.4%+/-11.6%) compared with the other patients (9.1%+/-6.1%; P = 0.023). Pulmonary irradiation significantly improved the outcomes of patients with isolated pulmonary recurrence (5-year PRS estimate, 30.3%+/-12.5% vs. 16.7%+/-10.8%, respectively; P = 0.018). CONCLUSIONS: Although outcomes are generally poor after patients experience recurrence of ET, certain patient groups differ appreciably in their likelihood of survival. Patients who experience recurrence > or = 2 years after diagnosis and patients who have local recurrence that can be treated with radical surgery and intensive chemotherapy have the most favorable outcomes.