C. Thomas Black

Complications and reoperation after Nissen fundoplication in childhood

Over a 10 year period, 429 Nissen fundoplications were performed on children with gastroesophageal reflux. Postoperative complications occurred in 69 children (16 percent), including wrap herniation or breakdown in 29; postoperative bowel obstruction in 18; stricture in 10; intraabdominal abscess and enterocutaneous fistula in 3 patients each; and wound infection, wound dehiscence, and inadvertent splenectomy in 2 patients each. The postoperative mortality rate was 0.9 percent (4 of 429 patients) and was related to sepsis in 1 patient, a metabolic disorder in 1 patient, and underlying pulmonary disease in 2 patients. All four patients were neurologically impaired. Fundoplication successfully controlled symptoms of gastroesophageal reflux in 395 children (92 percent) over a follow-up period ranging from 6 months to 10 years. Thirty-eight patients (8.8 percent) required a second antireflux operation because of recurrent symptoms. Twenty-nine patients had severe neurologic impairment (76 percent), 5 had associated congenital malformations (13 percent), and 3 had significant pulmonary problems (8 percent). Only one child requiring reoperation was considered otherwise normal. Indications for reoperation included wrap breakdown or herniation (28 patients), stricture (6 patients), and inadequate wrap (4 patients). Twenty-four of 28 children with wrap herniation or breakdown had neurologic impairment. A second fundoplication was successful in 35 of 38 patients (92 percent). A second procedure failed in three children, who required subsequent resection and colon interposition.

A half century of experience with carcinoid tumors in children.

PURPOSE To investigate the frequency, presentation, clinical management, and prognosis of appendiceal carcinoid tumors in children. METHOD A review of our institutions experience over 50 years. RESULTS Twenty-two patients below the age of 20 presented with appendiceal carcinoid tumor. The mean age at presentation was 14.6 years. Twelve patients presented with symptoms of appendicitis. No tumor was > 2.0 cm in size. Only 2 patients underwent resection beyond appendectomy. No patient had recurrent or metastatic carcinoid tumor, and all but 1 patient (who died of ovarian choriocarcinoma) are alive without evidence of carcinoid tumors 1.5 to 30 years after diagnosis. CONCLUSIONS Appendiceal carcinoid tumors in children are rarely life-threatening and the incidence of large tumors (> 2.0 cm) is very low. The role of right hemicolectomy in large (> 2.0 cm) tumors is questionable in this age group.

Wound collagenase activity correlates directly with collagen glycosylation in diabetic rats

Extracellular glycosylation of proteins in diabetics may contribute to observed impairments in wound healing. We investigated the interactions of blood glucose concentration and wound collagen glycosylation, collagen content, and proteolytic activity during wound healing in diabetic animals. Rats were made differentially hyperglycemic with intraperitoneal injection of streptozotocin (0-65 mg/kg body weight). Animals with blood glucose concentrations greater than 240 mg glucose/dL were classified as diabetic, those with blood glucose concentrations less than 160 were grouped as nondiabetic. Polytetrafluoroethelene (PTFE) wound cylinders were surgically implanted in 32 rats and removed on postoperative day 5. Harvested cylinders were analyzed for hydroxyproline content, collagen glycosylation, and collagenase and protease activity. Collagenase activity was 14% higher in diabetics than nondiabetics (P less than .001). Glycosylation of wound collagen averaged 48.0% higher in diabetics (P less than .001). Wound hydroxyproline content was 39% lower in diabetics (P less than .05). Studies show a high degree of correlation (Pearson) of wound collagen nonenzymatic extracellular glycosylation (NEG) with mean blood glucose concentration (r = .98, P less than .001). Wound collagen glycosylation correlates strongly with both protease activity (r = .86, P less than .001) and collagenase activity (r = .83, P less than .001). This study demonstrates a significant blood glucose concentration dependent increase of glycosylation in newly synthesized collagen in hyperglycemic animals that is associated with increased collagenase activity and decreased wound collagen content.

Operative treatment of truncal vascular injuries in children and adolescents

BACKGROUND/PURPOSE Pediatric truncal vascular injuries are rare, but the reported mortality rate is high (35% to 55%), and similar to that in adults (50% to 65%). This report examines the demographics, mechanisms of injury, associated trauma, and results of treatment of pediatric patients with noniatrogenic truncal vascular injuries. METHODS A retrospective review (1986 to 1996) of a pediatric (< or = 17 years old) trauma registry database was undertaken. Truncal vascular injuries included thoracic, abdominal, and neck wounds. RESULTS Fifty-four truncal vascular injuries (28 abdominal, 15 thoracic, and 11 neck injuries) occurred in 37 patients (mean age, 14+/-3 years; range, 5 to 17 years); injury mechanism was penetrating in 65%. Concomitant injuries occurred with 100% of abdominal vascular injuries and multiple vascular injuries occurred in 47%. Except for aortic and one SMA injury requiring interposition grafts, these wounds were repaired primarily or by lateral venorrhaphy. Nonvascular complications occurred more frequently in patients with abdominal injuries who were hemodynamically unstable (systolic blood pressure [BPS] <90) on presentation (19 major complications in 11 patients versus one major complication in five patients). Thoracic injuries were primarily blunt rupture or penetrating injury to the thoracic aorta (nine patients). Thoracic aortic injuries were treated without bypass, using interposition grafts. In patients with thoracic aortic injuries, there were no instances of paraplegia related to spinal ischemia (clamp times, 24+/-4 min); paraplegia occurred in two patients with direct cord and aortic injuries. Concomitant injuries occurred with 83% of thoracic injuries and multiple vascular injuries occurred in 25%. All patients with thoracic vascular injuries presenting with BPS of less than 90 died (four patients), and all with BPS 90 or over survived (eight patients). There were 11 neck wounds in 9 patients requiring intervention, and 8 were penetrating. Overall survival was 81%; survival from abdominal vascular injuries was 94%, thoracic injuries 66%, and neck injuries 78%. CONCLUSIONS Survival and subsequent complications are related primarily to hemodynamic status at the time of presentation, and not to body cavity or vessel injured. Primary anastomosis or repair is applicable to most nonaortic wounds. The mortality rate in pediatric abdominal vascular injuries may be lower than previously reported.

Second malignant neoplasms in children after treatment of soft tissue sarcoma.

Currently, approximately 67% of children diagnosed with cancer can be expected to survive more than 5 years. Among the most significant late effects of cancer therapy is the development of second malignant neoplasm (SMN). This study was performed to identify the factors associated with the development of second malignant neoplasms after treatment for soft tissue sarcomas in childhood. Retrospectively the charts of 20 children who developed second malignant neoplasms after treatment for primary childhood soft tissue sarcoma were reviewed. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment, family histories (when available), and outcome were recorded. The mean age of the patients (10 boys, 10 girls) was 8.5 years of age (range, 1 to 20 years). Most primary tumors were rhabdomyosarcoma (14/20) and occurred in an extremity (10/20). Ninety percent of the patients (18/20) had a complete response to treatment of the primary cancer. Eleven out of 20 received combined chemotherapy and radiation therapy. The most common secondary malignancy was a bone sarcoma (6/20), followed by brain tumors (n = 3), leukemia (n = 2), and other sarcomas (n = 2). Four of the bone sarcomas developed in the field of radiation treatment. Median follow-up was 16 years (range, 1 to 26 years). The median time to development of a SMN was 11.4 years (range, 1.5 to 21 years). Survival after a second malignancy was only 30%. Two patients developed a third malignant neoplasm. The occurrence of a secondary malignancy represents a serious complication of childhood cancer. Certain tumors are related directly to treatment such as osteosarcoma within irradiated fields and secondary leukemias or lymphomas after certain chemotherapy regimens. Combined radiotherapy and chemotherapy may play an additive role in the development of second malignant neoplasms. Genetic factors may predispose affected patients to the development of both primary and secondary malignancies. Close surveillance of children previously treated for childhood cancers is warranted.

Protein glycosylation and collagen metabolism in normal and diabetic rats

The high concentration of glycosylated extracellular proteins found in diabetics may contribute adversely to wound healing. The degree of collagen glycosylation was correlated with collagenase activity and 5-hydroxyproline (5-OHP) levels in surgical wounds of normal and diabetic animals. Expanded polytetrafluoroethylene (PTFE) wound cylinders were implanted subcutaneously in 10 normal and 10 streptozotocin-induced diabetic rats. Nonenzymatic glycosylation (NEG) of protein was inhibited in half the subjects in each group by daily enteral acetylsalicylic acid (ASA). Wound cylinders were removed on the fifth day and assayed for collagenase activity and 5-OHP levels, and the degree of collagen glycosylation was measured with an assay for 5-hydroxymethylfurfural (5-HMF). Results were compared using Students two-tailed t test. When compared with controls, diabetic animals had less wound 5-OHP (1.87 +/- 0.01 vs 3.11 +/- 0.03 micrograms/cm PTFE) (P less than 0.0001), higher levels of glycosylated collagen (215 +/- 11 vs 150 +/- 9 micrograms 5-HMF/mg protein) (P less than 0.001), and increased collagenase activity (13.5 +/- 0.6 vs 11.7 +/- 0.5 microgram collagen/mg protein/hr) (P less than 0.001). When ASA was added to the diet of diabetic animals, results in each case were statistically indistinguishable from controls. The collagenase activity of nondiabetic animals receiving ASA was decreased from nondiabetic controls (7.6 +/- 0.5 vs 11.7 +/- 0.5 microgram collagen/mg protein/hr) (P less than 0.001). These data show that ASA inhibits NEG of wound collagen in vivo, and ASA may normalize some abnormalities of wound healing found in diabetic animals.

Ultrasound of the distal pouch in infants with imperforate anus

Optimal surgical management of the newborn with imperforate anus depends on accurate determination of the level of the rectal pouch. Eighteen children with imperforate anus were evaluated with ultrasound. The distance from the end of the pouch to the perineum was measured. Ultrasound correctly predicted the level of the distal pouch in all 12 children who had confirmation of the pouch level by surgery or by distal contrast stomagrams. Six children have not yet had definitive surgery. Five children with a pouch to perineum (P-P) distance of less than or equal to 10 mm and three of six children with a P-P distance of 10 to 15 mm had successful correction by a simple perineal anoplasty. Three of six children with a P-P distance of 10 to 15 mm and all of those (seven) with a P-P distance greater than 15 mm were diverted with colostomies.

Breast cancer in adolescent females

Reports of breast cancer in adolescent females consist mostly of isolated patients. Because of this, neither the prognosis nor optimal management of the disease in this age group is clear. The authors retrospectively reviewed their 40-year single-institution experience of all patients under 20 years of age who were referred for treatment of newly diagnosed breast cancer. The charts of 16 patients, all females (age range, 13 to 19 years), were reviewed. Four patients found to have cytosarcoma phyllodes and two with tumors metastatic to the breast were excluded from further study. Ten patients had various forms of adenocarcinoma of the breast, including invasive intraductal, invasive lobular, signet ring, and secretory adenocarcinoma. Four had a family history of breast cancer. The average time from onset of symptoms to diagnosis was 3.7 months. Mammography failed to diagnose cancer in any of the four patients tested, including one with an 8-cm mass. Two patients had stage I tumors, four had stage IIA, two had stage IIIA, and two had stage IV. The patients were treated with combinations of surgery, radiation therapy, and chemotherapy. One stage I patient (with bilateral breast cancer) died of radiation-induced sarcoma after treatment; the other stage I patient is alive without disease 15 years after treatment. The 5-year survival rate for stage IIA patients was 50%; that for patients with stage IIIA or IV was 0%. Five of the 10 patients presented during the past 10 years. This study constitutes the largest single institution experience with adolescent breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Malignant solid tumors in neonates: A 40-year review

To evaluate the outcome of neonatal malignant solid tumors, we reviewed the records of 222 infants under the age of 1 year with malignant disease who were treated at the University of Texas M.D. Anderson Cancer Center over a 40-year period. Forty-five cases of neonatal (< 30 days old at the time of presentation) malignancies were found. Thirty-two infants had solid tumors and form the basis of this report. Diagnoses included soft tissue sarcoma (13), brain tumor (5), neuroblastoma (6), retinoblastoma (3), malignant melanoma (2), hemangiopericytoma (2), and nephroblastoma (1). The mean age at which initial signs and symptoms were noted was 9 days of life. Fifty-nine percent (19) presented within the first week of life, and 47% (15) presented at birth. The mean age at histological diagnosis was 54 days. The head and neck region was the most common site (18), followed by trunk (9), and extremities (5). Thirty-one patients underwent surgical resection of the primary tumor. Thirteen of those neonates received no additional chemotherapy and/or radiation therapy, whereas 18 received some combination of surgery plus perioperative chemotherapy and/or radiation therapy. Overall survival was 78% (25 of 32) with an average follow-up of 8 years (range, 2 months to 29 years). There were no survivors among those patients with distant metastatic disease at the time of diagnosis. Despite delays, prognosis is excellent in the absence of distant metastatic disease, particularly for extracranial tumors.

Melanoma as a second malignant neoplasm after childhood cancer

BACKGROUND As more children survive childhood cancers, the population at risk for second malignant tumors increases. The development of melanoma as a second malignant tumor is not well described. METHODS The M.D. Anderson Cancer Centers 50-year experience with patients who developed melanoma after treatment of a childhood cancer was retrospectively reviewed. RESULTS One hundred seventy-two patients with a second malignancy were identified; 11 patients had melanoma as a second malignancy. The most common first malignancies were Hodgkins disease, brain tumors, and retinoblastomas. Melanoma developed in an irradiated field in 4 patients. Six patients had lymphatic or distant metastasis at diagnosis. Five of 11 patients died of melanoma. CONCLUSIONS Factors contributing to melanoma as a second malignancy may include genetic factors and the effects of chemotherapy and radiation. Survivors of childhood malignancy should be considered at risk for developing melanoma, and suspicious pigmented lesions should be carefully evaluated.