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Biomedical subjects

G M Haase

Publications and source records attributed to G M Haase.

At least 19 recordsLinked to original sources
PubMed1999

Current aspects of biology, risk assessment, and treatment of neuroblastoma.

Neuroblastoma is one of the most intensely studied solid malignancies that affect the pediatric age groups; its clinical presentation, treatment strategies and ultimate prognosis vary greatly. The biologic and genetic character of each tumor has an important impact on disease behavior, and clinical staging now incorporates these factors to generate an overall therapy plan. The clinical presentation of neuroblastoma is related to primary tumor location, production of metabolically active substances, and the presence of metastatic disease. There are also prognostically important associated syndromes including opsoclonus-myoclonus, Horner's syndrome, neurofibromatosis, and a variety of other neurocristopathies. The histologic features of the tumor are of prognostic significance and are utilized in treatment stratification. The International Neuroblastoma Staging System (INSS) has unified classic clinical staging. Features at diagnosis and those determined by initial operation are combined with biologic prognostic factors to achieve risk group assignment for virtually all patients. There are groups of children in which limited therapy is curative and intermediate-risk situations where standard multimodality treatment provides favorable outcomes. Unfortunately, there are many patients with high-risk disease that require intensive strategies, but success is still limited. It is in these most resistant patients that innovative approaches are being undertaken and novel strategies are being investigated.

Adolescent↗
PubMed1999

Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4.

OBJECTIVE: To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA: Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS: Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS: The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS: This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence.

Child, Preschool↗
PubMed1998

Pharmacokinetics of once-daily gentamicin dosing in pediatric patients.

BACKGROUND/PURPOSE: To achieve cost-effective health care in adults, once-daily aminoglycosides administration has been used and judged to be safe and efficacious. A similar strategy in children requires the characterization of pharmacokinetic parameters and the development of a therapeutic monitoring protocol for this antibiotic regimen. METHODS: A prospective, controlled, randomized (2:1) study was undertaken in 50 pediatric patients between June 1995 and September 1997. Children between 6 months and 18 years who required gentamicin therapy based on independent clinical assessment were eligible if they had normal renal function, no aminoglycoside allergies, were not neutropenic, or did not have cystic fibrosis. Measurements included a peak, 4-hour, 8-hour, and trough gentamicin levels to determine volume of distribution (Vd) and elimination constant (Ke). Ototoxicity and nephrotoxicity were monitored by pre- and postaudiology examinations and serial calculated creatinine clearance determinations, respectively. RESULTS: Thirty-three patients received 7.5 mg/kg every 24 hours, and 17 patients received 2.5 mg/kg every 8 hours. Most frequent indications for treatment were ruptured appendicitis (n = 19) followed by wound infections caused by trauma (n = 4), but the spectrum of treatment was broad including enteric, genitourinary, central nervous system, biliary, ophthalmologic, and orthopedic infections. Pharmacokinetic data indicated that 24-hour dosing resulted in higher peak levels compared with 8-hour dosing (20.4 +/- 45.4 v 7.2 +/- 6.2 mg/L, P < .0001) and lower trough levels (0.29 +/- .02 v 0.69 +/- 0.13, P < .0001), whereas rate of elimination constant and volume of distribution were not significantly different. No nephrotoxicity or ototoxicity has been noted in either group. CONCLUSIONS: These data confirm that once-daily dosing of gentamicin is a safe method of treatment that provides equivalent pharmacokinetics compared with traditional dosing and enhances bactericidal effect based on higher peak levels, avoids toxicity, and allows cost savings.

Adolescent↗
PubMed1998

Gastric necrosis after fundoplication: a novel approach for esophageal preservation.

An 11-year-old boy presented moribund, with massive abdominal distension. A Nissen fundoplication and gastrostomy tube had been established at age 2 years. After attempts to pass a nasogastric tube were unsuccessful, the old gastrostomy site was used to gain percutaneous access to the stomach resulting in release of gastric contents and stabilization of blood pressure and perfusion. During operation, massive gastric distention with gastric necrosis was found. Subtotal gastrectomy was performed with stapled closure of the distal intraabdominal esophagus and prepyloric region. Sump suction was placed in the proximal esophagus and the abdomen was drained widely. A distal esophageal perforation was apparent on postoperative day 19 confirmed by imaging and endoscopy. A nasoesophageal tube was passed into the abdomen, tied to a Jackson-Pratt drain, and the composite tube repositioned in the midesophagus allowing controlled proximal and distal drainage. Six months later, a Hunt-Laurence esophagojejunal pouch was created. At age 13, the child is clinically well, and enjoys 50% of his nutritional needs orally, with the remainder delivered overnight via tube feedings. This case describes gastric necrosis after gas bloat syndrome as a late complication of Nissen fundoplication. A novel approach to the management of distal esophageal perforation allowed preservation of a functional, intact native esophagus.

Abdomen, Acute↗
PubMed1998

Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group.

OBJECTIVE: This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis. SUMMARY BACKGROUND DATA: Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome. METHODS: Variables analyzed for their impact on progression-free survival in a multi-institutional cohort of 329 patients included age, antecedent thyroid irradiation, extrathyroidal tumor extension, size, nodal involvement, distant metastases, technique of thyroid surgery and lymphatic dissection, initial treatment with 131Iodine, residual cervical disease, and histopathologic subtype. Surgical complications were correlated with the specific procedures completed on the thyroid gland or cervical lymphatics. RESULTS: The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at 10 years with 2 disease-related deaths. Regional lymph node and distant metastases were present in 74% and 25% of patients, respectively. Progression-free survival was less in younger patients (p = 0.009) and those with residual cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was more frequent after total or subtotal thyroidectomy (p = 0.001) while wound complications increased after radical neck dissections (p < 0.00001). CONCLUSIONS: The progression-free survival rate was better after a complete resection and in older patients. Progression-free survival rate was the same after lobectomy or more extensive thyroid procedures, but comparison was confounded by the increased use of total or subtotal thyroidectomy in patients with advanced disease. The risk of permanent hypocalcemia increased when total or subtotal thyroidectomy was done. Thyroid lobectomy alone may be appropriate for patients with small localized lesions while total or subtotal thyroidectomy should be considered for more extensive tumors.

Adolescent↗
PubMed1998

Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: The National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 1,687 previously untreated children less than 16 years of age with stages I to II/favorable histology (FH) or stage I/anaplastic histology WT (low-risk [LR] group) or stages III to IV/FH WT or stages I to IV/clear cell sarcoma of the kidney (high-risk [HR] group) were randomized to treatment that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either STD courses (3 days) or PI treatment with doxorubicin. RESULTS: The 2-year relapse-free survival (RFS) rates for LR patients were 91.3% for 544 randomized to treatment with PI and 91.4% for 556 randomized to treatment with STD chemotherapy (P = .988). The 2-year RFS rates for HR patients were 87.3% for 299 randomized to treatment with PI and 90.0% for 288 randomized to treatment with STD chemotherapy (P = .865). CONCLUSION: We conclude that patients treated with PI combination chemotherapy for LR or HR WT or clear cell sarcoma of the kidney have equivalent 2-year RFS to those treated with STD regimens. PI drug administration is recommended as the new standard based on demonstrated efficacy, greater administered dose-intensity, less severe hematologic toxicity, and the requirement for fewer physician and hospital encounters.

Adolescent↗
PubMed1998

Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children's Cancer Group study.

PURPOSE: To identify a biologically favorable and unfavorable subset of patients with Evans stage III neuroblastoma and to determine whether treatment stratification would improve the event-free survival (EFS) for high-risk patients and maintain excellent EFS for the lower-risk patients. PATIENTS AND METHODS: Risk stratification was performed by age, MYCN gene copy number, Shimada histopathologic classification, and serum ferritin level. Lower-risk patients were treated on the less intensive Children's Cancer Group (CCG)-3881, whereas high-risk patients were treated on CCG-3891, which included more intensive multimodality therapy and, in some cases, autologous bone marrow transplantation (ABMT). RESULTS: Of 228 Evans stage III patients entered onto the study, 92% also met the definition of International Neuroblastoma Staging System (INSS) stage 3. One hundred forty-three patients met the lower-risk criteria, which included 89 patients less than 1 year of age and 54 patients 1 year of age or greater, and favorable biology, whereas 85 patients were 1 year of age or greater and biologically unfavorable. Biologically unfavorable patients 1 year of age or greater who underwent gross surgical resection had improved survival, whereas the outcome of infants or biologically favorable older patients did not change according to resection. The EFS rate at 4 years was 100% for the patients with favorable biology of any age, 90% for those less than 1 year of age but with at least one unfavorable characteristic, and 54% for Evans stage III patients 1 year of age or greater with unfavorable biology. Age, ferritin level, MYCN copy number, Shimada histopathology, primary site, and intraspinal extension were significant univariate prognostic factors for all patients, but only MYCN copy number and age were independent factors in multivariate analyses. CONCLUSION: The excellent survival of the biologically favorable group and the historically improved EFS of the biologically unfavorable group suggest that biologic staging should be used to define the prognosis and treatment of stage III neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Intra-operative radiation therapy in pediatric neuroblastoma.

External beam irradiation (EBRT) has been shown to improve response rates and event-free survival in children with neuroblastoma and regional lymph node metastases. Irradiation during surgical exposure (intra-operative radiotherapy, IORT) with displacement of adjacent radiosensitive organs out of the treatment field allows for more precise delineation of the target volume and significantly reduces the amount of normal tissue exposed to irradiation. We have incorporated IORT into the treatment regimen of 24 children with neuroblastoma between the years of 1983-1991. IORT was directed to any residual tumor or the tumor bed; the median dose of radiation was 1,000 cGY, equivalent to 3,000 cGY of conventional EBRT. There were 11 males and 13 females. Two patients had stage II, 12 patients had stage III, and 10 patients had stage IV disease. Ten children received IORT for suspected recurrent or persistent neuroblastoma. Twelve patients were disease-free survivors following IORT with a median follow-up of 54 months. For those patients with stage III disease, seven children were disease-free survivors, while only three of 10 patients with stage IV disease survived (median follow-up 30 months). Disease-free Survival (DFS) correlated with the achievement of local tumor control in children with both stage III and IV neuroblastoma. There was limited morbidity and no episodes of obstructive uropathy were encountered. We conclude that IORT appears to be well tolerated and may have therapeutic benefit for a select group of patients with neuroblastoma. IORT merits future exploration by prospective study.

Child↗
PubMed1997

Prospective, randomized evaluation of the efficacy of fibrin sealant as a topical hemostatic agent at the cannulation site in neonates undergoing extracorporeal membrane oxygenation.

BACKGROUND: The topical hemostatic effect of fibrin sealant that has been solvent/detergent treated and plasminogen depleted was evaluated in a multicenter prospective, randomized controlled study at the cannulation site wound of infants undergoing extracorporeal membrane oxygenation (ECMO). METHODS: The test group received standard cauterization and Fibrin sealant, while the control group was given cauterization alone to control hemostasis at this site. Efficacy data were available on 173 randomized study subjects of whom 149 met study entry criteria. All were managed according to standard ECMO practice. RESULTS: Fibrin sealant reduced the risk of bleeding, was associated with less shed blood, and was associated with shorter duration of hemorrhage. Further, control infants showed an increased bleeding risk with less depressed fibrinogen levels and prothrombin time elevations >18 seconds prior to ECMO. CONCLUSION: Fibrin sealant is useful as a topical hemostatic agent in patients with coagulopathy not responding to standard surgical techniques.

Blood Loss, Surgical↗
PubMed1997

Nephroblastoma.

Effective diagnosis, staging, and multimodality therapies dramatically decreased the morbidity and mortality of children with Wilms Tumor. Increasing awareness of the disease, biology, genetics, and epidemiology improved assessment of clinical syndromes and led to more risk-based treatment. The role of tumor imaging is being defined, and primary exploration with nephrectomy remains of value to confirm histological diagnosis and disease stage. Primary chemotherapy with delayed resection is evolving into the preferred approach for large inoperable tumors, bilateral disease, and those tumors with extensive intravascular involvement. Current therapeutic trials will be nonrandomized and emphasize biological tumor features for future patient stratification. A selected group of young patients with small localized favorable histology tumors will be treated with surgery alone.

Child↗
PubMed1997

Acute abdomen. Special considerations for the neurologically and immunologically impaired child.

The neurologically or immunologically impaired child suspected of having an acute abdomen presents a formidable challenge. However, a thorough understanding of the underlying pathophysiology of the disease on the normal host response to an intraabdominal disease permits early recognition and initiation of treatment. Classic findings of the acute abdomen are the exception rather than the rule. These children require constant vigilance and repeated examination. Radiographic studies should be used early and often. The advent of minimally invasive surgical techniques offers the opportunity to intervene early both diagnostically and therapeutically. Ultimately, however, the best outcomes will be achieved by those who employ sound surgical judgment and avoid unnecessary therapeutic delay owing to inexperience, inattention, or indecision.

Abdomen, Acute↗
PubMed1996

Laparoscopic thal fundoplication with gastrostomy in children.

A technique was developed to adapt the Thal fundoplication to the laparoscopic approach. Modifications include tying an umbilical tape (as a loop) around the esophagus for retraction, interrupted fundoplication sutures, and extracorporeal gastrostomy through a trocar site. This technique was completed successfully in 10 pediatric patients.

Adolescent↗
PubMed1996

Recurrent appendicitis after initial conservative management of appendiceal abscess.

Therapy for children with appendiceal abscess remains controversial. The authors present two such cases initially treated conservatively, without interval appendectomy, that later had recurrent appendicitis. An 8-year-old boy presented with fever, abdominal pain, and a right-lower-quadrant abscess (noted by ultrasonography). During laparotomy, the abscess was drained and the appendix was not found. He was lost to follow-up but returned 2 1/2 years later with perforated appendicitis. An appendectomy was performed, and image-guided drainage of a postoperative abscess was required. A 10-year-old girl presented with fever and right-lower-quadrant pain. Computed tomography showed a multiloculated mass. During laparotomy, the cecum was found to be densely adherent to the pelvic organs and bowel, so the surrounding abscess was drained. Interval appendectomy was refused. The patient returned 8 months later with recurrent acute appendicitis and an appendiceal abscess requiring appendectomy and drainage. Although initial drainage alone of appendiceal abscess is efficacious, the authors strongly advocate interval appendectomy as a critical component of the complete management of this entity.

Abscess↗
PubMed1996

Current surgical management of Wilms' tumor.

Wilms' tumor is an ideal model to demonstrate how multimodality treatment strategies have reduced disease mortality over the past three decades. More than 80% of all patients are currently long-term survivors. Greater understanding of biology and awareness of clinical syndromes have led to more risk-based therapies. Although routine imaging provides adequate information for staging, advanced radiographic techniques, including spiral CT scanning and enhanced magnetic resonance imaging, can delineate improved anatomic detail. Recently, parenchymal sparing operations have been undertaken as long-term renal insufficiency after nephrectomy for Wilms' tumor has been more frequently recognized. Primary chemotherapy with delayed tumor resection is increasingly advocated for patients with bilateral disease, tumors with intravascular extension, or for those whose tumors are considered "inoperable." Technical advances, including intraoperative ultrasonography, regional hypothermia, laser technology, and minimally invasive surgery, will influence future tumor resections. Nevertheless, primary nephrectomy with appropriate operative guidelines and systemic therapy remain important standards for management of sporadic unilateral Wilms' tumor.

Antineoplastic Agents↗
PubMed1996

Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children's Cancer Group studies.

PURPOSE: To compare event-free survival (EFS) for patients with stage IV neuroblastoma who were treated with induction chemotherapy followed by additional courses of the same chemotherapy or by intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT). METHODS: Two hundred seven children who were diagnosed with stage IV neuroblastoma after 1 year of age were given five to seven courses of induction chemotherapy consisting of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CCC-321-P2). This chemotherapy was continued for 13 total courses for some patients, whereas intensive chemoradiotherapy with ABMT was given to others (CCG-321-P3). The decision to continue chemotherapy versus to consolidate with chemoradiotherapy was not randomized but was made by parents and physicians. Marrow used for ABMT was purged ex vivo and was free of immunocytologically detectable neuroblastoma cells. RESULTS: One hundred fifty-nine of 207 patients (77%) remained event-free during induction therapy. Of these, 67 received chemoradiotherapy/ABMT (CCG-321-P3) and 74 continued chemotherapy (CCG-321-P2). Using Cox regression analysis, the relative risk (RR) of an event after chemoradiotherapy/ABMT was estimated to be 58% of that for patients who continued chemotherapy (P = .01). Similarly, Kaplan-Meier analysis estimated EFS at four years for the chemoradiotherapy/ABMT and chemotherapy groups to be 40% and 19% respectively (P = .019). Subgroups appearing to benefit from chemoradiotherapy/ABMT were those with only a partial tumor response to induction chemotherapy (RR = 0.43; P = .008; EFS, 29% v 6%) and those whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%). CONCLUSION: Consolidation with intensive, myeloablative chemoradiotherapy followed by purged ABMT may be more effective than continuing chemotherapy for patients with stage IV neuroblastoma.

Adolescent↗