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Biomedical subjects

K Newman

Publications and source records attributed to K Newman.

At least 19 recordsLinked to original sources

Complete surgical resection combined with aggressive adjuvant chemotherapy and bone marrow transplantation prolongs survival in children with advanced neuroblastoma.

BACKGROUND: A multi-modality approach combining surgery with aggressive chemotherapy and radiation is used to treat advanced neuroblastoma. Despite this treatment, children with advanced disease have a 20% 2-year survival rate. Controversy has developed regarding the efficacy of combining aggressive chemotherapy with repeated surgical intervention aimed at providing a complete surgical resection (CSR) of the primary tumor and metastatic sites. Several prospective and retrospective studies have provided conflicting reports regarding the benefit of this approach on overall survival. Therefore, we evaluated the efficacy of CSR versus partial surgical resection (PSR) using a strategy combining surgery with aggressive chemotherapy, radiation, and bone marrow transplantation (BMT) for stage IV neuroblastoma. METHODS: A retrospective study was performed with review of the medical records of 52 consecutive children with neuroblastoma treated between 1985 and 1993. Twenty-eight of these 52 children presented with advanced disease, 24 of which had sufficient data to allow for analysis. All children were managed with protocols designed by the Children's Cancer Group (CCG). Statistical analysis was performed using Student's t test, chi 2 test, and Kaplan-Meier survival curves. RESULTS: Mean survival (35.1 months) and progression-free survival (29.1 months) for the CSR children was statistically superior to that of the PSR children (20.36 and 16.5 months, p = 0.04 and 0.04, respectively). Similar significance was demonstrated using life table analysis of mean and progression-free survival of these two groups (p = 0.05 and < 0.01, respectively). One-, 2-, and 3-year survival rates for the CSR versus the PSR group were 100%, 80%, and 40% versus 77%, 38%, and 15%, respectively. An analysis of the BMT group compared with those children treated with aggressive conventional therapy showed improvement in mean and progression-free survival. CONCLUSIONS: Aggressive surgical resection aimed at removing all gross disease is warranted for stage IV neuroblastoma. CSR is associated with prolonged mean and progression-free survival. BMT prolongs mean and progression-free survival in children with stage IV disease. These results suggest that CSR and BMT offer increased potential for long-term remission in children with advanced neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols

Aortic mural thrombus presenting as pseudovasculitis.

Three months after splenic infarct, a 50-year-old woman underwent arteriography for persistent low-grade fever and abdominal complaints. After 5 months of corticosteroid therapy for "polyarteritis nodosa," another arteriogram confirmed embolic disease; transesophageal echocardiography (TEE) showed a pedunculated mobile thrombus in the aortic arch. We suggest this represents "pseudovasculitis" from an aortic thrombus.

Aorta, Thoracic

Pancreatoduodenectomy with preservation of the stomach and pylorus: a safe and effective alternative in children.

The time-honored surgical approach to resectable tumors of the head of the pancreas or distal common bile duct has been a Whipple operation for adults and children. In recent years, pylorus-preserving pancreatoduodenectomy has been used for adults. The postoperative physiological advantages may be enhanced in children, and for this reason the pylorus-sparing approach was used in a 15-year-old girl with a tumor of the distal common duct. The pylorus-preserving pancreatoduodenectomy was safe and effective in this patient and should be considered for children with resectable tumors of the distal common bile duct and pancreatic head.

Adolescent

Functional results in young women having clitoral reconstruction as infants.

Nine young women who had clitoral recession for clitoromegaly as infants have been evaluated for anatomical appearance, psychosocial adjustment, and sexual function. Highly satisfactory anatomic results were obtained, although two patients required subsequent revision. The tested psychological parameters were essentially normal. Virtually all patients were sexually active and all but one have achieved regular painless orgasm. Surgical reconstruction has been accomplished by recessing the entire disfigured clitoris, thereby conserving all erectile tissue and preserving sensation. In addition to assessment of anatomical appearance, long-term follow-up of children with ambiguous genitalia requires regular evaluation of social, psychological, and sexual parameters.

Adolescent

A strategy for resection of Wilms' tumor with vena cava or atrial extension.

Resection of a Wilms' tumor that extends into the vena cava or right atrium results in excellent survival when combined with adjuvant therapy. Preoperative identification of the presence of intravascular tumor thrombus and the level of vascular involvement is essential. It facilitates safe surgical resection, with cardiopulmonary bypass immediately available for retrohepatic and atrial tumors. Six patients with intracaval or intracardiac tumor thrombus were treated over a 5-year period with no perioperative deaths. Preoperative chemotherapy was useful in two patients with extensive tumors and pulmonary metastases. Our results using an integrated management plan suggest that an aggressive surgical approach is justified for this extensive variant of Wilms' tumor.

Algorithms

The surgical management of infants and children with ambiguous genitalia. Lessons learned from 25 years.

Over a 25-year period, 91 children with ambiguous genitalia have received surgical management. Female sex assignment was made for 79. Of these, 60 patients underwent extensive clitoral reconstruction consonant with the female assignment. Forty-two patients had vaginal reconstruction. Factors relating to success include: (1) prompt and appropriate sex assignment; (2) early and accurate diagnosis; (3) conservative reconstruction of the clitoris at an early age (less than 1 year); and (4) choice of vaginal reconstruction based on the severity of the malformation. Long-term follow-up demonstrates satisfactory anatomic and functional results when clitoral surgery alone was required. Functional results for patients with extensive vaginal reconstruction have been compromised. Physicians caring for children with congenital intersexual anomalies can expect to encounter a wide spectrum of anatomic and physiologic derangements. Cosmetic appearance alone is an inadequate measure of success because endocrinologic, social, psychological, and sexual factors must be blended into comprehensive evaluation of these patients. The management plan must be flexible and individualized, incorporating long-term follow-up to adulthood.

Clitoris

The surgical management of children with incompletely resected hepatic cancer is facilitated by intensive chemotherapy.

This prospective study was undertaken to evaluate the efficacy of continuous-infusion doxorubicin and cisplatin (CI-DOX/CPPD) for the treatment of children with incompletely resected hepatic cancer. Of the 46 evaluable patients, 32 had hepatoblastoma (70%) and 14 had hepatocellular carcinoma. Ten children had stage II tumors (microscopic residual), 25 were defined as stage III (gross residual), and 11 had distant metastasis (stage IV). Twelve patients underwent initial incomplete resection of their hepatic lesions and in the 34 others tumor biopsy specimens were obtained. Chemotherapy was administered and the majority of the children (70%) had an excellent clinical response with a decrease in both alpha-fetoprotein levels and measured tumor dimensions. The combination of CI-DOX/CPDD clearly facilitated surgical management, allowing for delayed hepatic resections in 20 of the 34 patients (59%) whose tumors were initially biopsied and considered to be unresectable. Overall survival in this study demonstrates a significant improvement in comparison to the historical controls. Twenty-one patients (46%) remain in complete clinical remission an average of 30 months following diagnosis (range, 17 to 40 months). The outcome of the children with hepatoblastoma was much better than those with hepatocellular carcinoma (63% v 17% survival). Survival of the 20 children who underwent delayed hepatic resections was not statistically different from the 12 patients whose hepatic tumors were removed at the initial laparotomy (41% v 58% survival). Although no obvious survival advantage was observed in those patients who underwent initial hepatic resections, there did appear to be an increased risk of postoperative complications in children whose tumors were resected following chemotherapy (8% v 25%).

Adolescent

Successful closure of intestinal fistulae in an infant using the somatostatin analogue SMS 201-995.

Enterocutaneous and other gastrointestinal fistulae create tough challenges with respect to wound care, nutrition, and strategy for closure. SMS 201-995 is a long-acting somatostatin analogue that has been effective in the treatment of adult enteric fistulae. The use of SMS 201-995 as an adjunct in the successful closure of intestinal fistulae in an infant is reported. This newborn infant developed a high-output enterocutaneous fistula and multiple enteroenteric fistulae after an intestinal resection for necrotizing enterocolitis. Copious fistulae output led to extensive wound breakdown, dehydration, and failure to thrive. Despite traditional management with bowel rest, total parenteral nutrition, antibiotics, and wound care, the high-output fistulae persisted unabated. On postoperative day 12, SMS 201-995 was started at 0.7 microgram/kg subcutaneously twice daily and gradually increased to 2.5 micrograms/kg. Within 2 days of SMS 201-995 therapy, the fistulae drainage had decreased from 62 mL/kg/d to 36 mL/kg/d, a 42% decrease from pretreatment levels. By day 8 of treatment, all fistulae had closed. After 14 days of treatment, the wound had healed and the infant was gaining weight. An upper gastrointestinal examination showed a patent ileostomy and no fistulae. Feeding was initiated, SMS 201-995 was discontinued without significant ileostomy output increase, and successful ileostomy closure took place 4 weeks posttreatment. Furthermore, the infant had no demonstrable side effects from the drug. Use of this drug should be considered in the treatment of other infants with complex, recalcitrant gastrointestinal fistulae.

Enterocolitis, Pseudomembranous

Special studies of the Hickman catheter of a patient with recurrent bacteremia and candidemia.

A patient with acute non-lymphocytic leukemia developed Staphylococcus epidermidis bacteremia and candidemia after maintenance chemotherapy and was treated satisfactorily. He returned 3 months later with abdominal pain due to an abdominal aortic aneurysm. At laparotomy, the aneurysm was found to be infected with Candida albicans. Following surgery, repeated positive blood cultures for C. albicans led to removal of his Hickman catheter. Culture of the catheter tip yielded C. albicans and S. epidermidis. Study of the catheter by scanning and transmission electron microscopy demonstrated yeast-like cells and gram-positive cocci in a biofilm. These studies suggest that the Hickman catheter was the source of the persistent candidemia and that it may have been the origin of the infection of the aneurysm.

Antineoplastic Agents

Excretion of chloroquine, dapsone and pyrimethamine in human milk.

The concentration of chloroquine (CQ), dapsone (DDS) and pyrimethamine (PYR) in plasma and milk were measured following the coadministration of a single dose of chloroquine and Maloprim to lactating women. The milk to plasma area under the concentration-time curve (AUC) ratio ranged from 1.96 to 4.26 for CQ, 0.22 to 0.45 for DDS and 0.46 to 0.66 for PYR. Assuming a daily milk ingestion of 1 l by the infant, the maximum percentage of the maternal dose for CQ, DDS and PYR in milk was 4.2%, 14.3% and 45.6%, respectively, over a 9 day period.

Adult

A high-precision automatic closed-circuit respirometer for small animals.

An automatic apparatus for the continuous measurement of O2 consumption of small laboratory animals is described. By use of a high-sensitivity pressure transducer with associated circuitry together with a peristaltic O2 delivery system, the closed respirometer chamber is maintained at atmospheric pressure +/- 0.5 mmH2O. O2 delivery is measured to within 0.25 ml by recording rotations of the peristaltic pump, following calibration by the withdrawal of a preset volume of air from the chamber. Static trials (with the chamber empty) indicate a high degree of reproducibility of data with the chamber pressure remaining at atmospheric pressure +/- 0.5 mmH2O as a result of the proportional, as opposed to fixed-volume, delivery of O2. Trials with mice and rats have likewise produced data with a high degree of reproducibility.

Animals