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Biomedical subjects

F J Rescorla

Publications and source records attributed to F J Rescorla.

At least 55 records · Page 3Linked to original sources

Experimental liver cancer: improved response after hepatic artery ligation and infusion of tumor necrosis factor-alpha and interferon-gamma.

BACKGROUND: The aim of this study is to investigate whether regional infusion of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) could improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer in a rat model. METHODS: Morris hepatoma 3924A was implanted intrahepatically in 50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery cannulation and ligation. The cannula was connected to an infusion port implanted subcutaneously. Animals were then divided into four groups of 10 each to receive seven daily intraarterial injections of IFN-gamma 100,000 IU/rat/day (HAL + IFN group), TNF-alpha 30 micrograms/rat/day (HAL + TNF group), IFN + TFN (HAL + IFN + TNF group), or normal saline solution (HAL group). The remaining 10 rats received a laparotomy only and served as untreated controls. Tumor volume, viable tumor area, and histopathology were assessed after 3 weeks. RESULTS: The tumor growth was significantly retarded in the HAL group compared with the controls (tumor volume 683 +/- 245 mm3 vs 2424 +/- 596 mm3, p < 0.05 ANOVA). HAL + TNF (221 +/- 93 mm3) and HAL + IFN + TNF groups (74 +/- 31 mm3), but not the HAL + IFN group (493 +/- 164 mm3), were much more effective than the HAL group in controlling tumor growth (p < 0.05). HAL + IFN + TNF achieved the best tumor control resulting in a 60% tumor-free rate (p < 0.05 vs all other groups). CONCLUSIONS: These data suggest that HAL combined with regional infusion of TNF-alpha and IFN-gamma significantly reduces tumor growth in a rat liver model. This attractive concept of combined modality therapy may have utility in the clinical setting in instances of unresectable liver cancer.

Animals↗

Surgical management of pediatric necrotizing enterocolitis.

Necrotizing enterocolitis is one of the most common gastrointestinal emergencies observed in neonatal intensive care units. Despite extensive research efforts, the etiology and pathogenesis of necrotizing enterocolitis remain unclear. Investigators have attempted to identify various laboratory and clinical factors that would serve as criteria for surgical intervention. Unfortunately, the most sensitive and specific tests detect only advanced disease and perforation. The mainstay of surgical treatment is resection with enterostomy, although resection and primary anastomosis is useful in selected cases. In addition, some neonates may benefit from peritoneal drainage, second look procedures, or proximal diversion.

Anastomosis, Surgical↗

The spectrum of biliary tract disorders in infants and children. Experience with 300 cases.

OBJECTIVES: To assess the results of surgical treatment of infants and children with biliary tract disease. DESIGN: The records of children with biliary tract disorders requiring surgical intervention were reviewed retrospectively. Diagnosis, age, sex, clinical presentation, treatment, and outcome were evaluated. SETTING: A large pediatric referral facility. PATIENTS: A total of 300 patients treated from 1972 through 1993 were evaluated, including 102 with biliary atresia, 29 with choledochal cyst, and 169 with cholelithiasis. Hepatic portoenterostomy was performed in 87 patients with biliary atresia, and biopsy alone was performed in 15. Twenty girls and nine boys, 50% of whom were younger than 3 years, had choledochal cyst. Operative management included cyst excision and hepatojejunostomy in 25 patients, cyst jejunostomy in two patients, cystduodenostomy in one patient, and choledochocele excision in one patient. Gallstones were observed in 106 girls and 63 boys; 28 were aged 0 to 5 years, 31 were aged 6 to 10 years, and 110 were aged 11 to 18 years. Open cholecystectomy was performed in 143 patients, and laparoscopic cholecystectomy was performed in 26 patients. MAIN OUTCOME MEASURES: Principal outcomes examined were surgical morbidity and mortality. RESULTS: Hepatic portoenterostomy was successful in 28 (32%) of 87 patients with biliary atresia (all younger than 3 months), and 23 showed improvement following hepatic portoenterostomy; hepatic portoenterostomy failed in 36 patients. Twenty-eight (82.3%) of 34 patients survived liver transplantation. Overall survival was 71.5%. Survival of patients with choledochal cyst was 96.4% (28/29). Cholecystectomy was successful in all 169 patients. There were eight complications and one death (0.59% mortality). CONCLUSIONS: Survival in patients with biliary atresia (71%) has improved with hepatic portoenterostomy complemented by liver transplantation. Hepatic portoenterostomy is the procedure of choice in infants younger than 3 months. An improved outlook for patients with choledochal cyst can be expected after cyst excision and hepatojejunostomy. Gallstones are relatively common in children. Both open and laparoscopic cholecystectomy are safe and effective procedures in children.

Adolescent↗

Mediastinal tumors in children: experience with 196 cases.

BACKGROUND: Mediastinal masses are relatively common in infants and children. These lesions are often neoplastic in origin and have a high risk of malignancy. METHODS: This report concerns 196 infants and children with mediastinal tumors. Fifty-five cases (28%) were benign, and 141 (72%) were malignant. Diagnosis included Hodgkin's disease (47), neuroblastoma (46), non-Hodgkin's lymphoma (37), teratoma (18), ganglioneuroma (14), cystic hygroma (11), Schwannoma (five), germ-cell tumors (three), lipoma (three), thymic tumor (three), malignant histiocytosis (two), neurofibroma (two), mesenchymal sarcoma (one), rhabdomyosarcoma (one), peripheral neuroectodermal tumor (one), hamartoma (one), and hemangioma (one). Diagnoses were usually made by assessing the patient's age, radiologic evidence of tumor location, the presence of calcium in the tumor, and the presence of tumor markers (alpha-fetoprotein, vanillmandelic acid, human chorionic gonadotropin). Diagnoses were verified by histologic evaluation. Resection was the only treatment for benign tumors. Biopsy and chemotherapy (and/or radiation) were employed for lymphoid tumors, and resection and adjuvant therapy were used for other solid malignancies. RESULTS: Survival was achieved in 53 of 55 (96.3%) patients with benign tumors and 105 of 141 (74.4%) patients with malignant tumors. CONCLUSIONS: Seventy-two percent of mediastinal tumors in this study were malignant. Early diagnosis followed by biopsy and chemotherapy for lymphoid tumors or resection of nonlymphoid tumors along with aggressive adjuvant therapy result in high survival rates (74.4%). Children with benign tumors almost always survive (96.3%) after resection.

Adolescent↗

Gastrointestinal tumors in children: an analysis of 39 cases.

BACKGROUND: Gastrointestinal tumors are relatively uncommon in infants and children, and the histologic diagnoses differ from those seen in an adult practice. Furthermore, the clinical presentation of such tumors is quite variable. METHODS: We reviewed the records of 39 pediatric patients who had been treated for tumors of the alimentary tract at our hospital over the past 20 years. The symptoms, physical findings, treatments, and outcomes are tabulated and discussed. RESULTS: Non-Hodgkin's lymphoma was the predominant diagnosis. It was found in 22 children, and the survival rate was 60%. Other malignant tumors found in this pediatric series included colorectal carcinoma in four patients and gastric leiomyosarcoma in one. The outcomes of these patients were poor; four of the children have died, and one girl remains alive with extensive disease. Benign lesions included neurogenic tumors (n = 5), inflammatory pseudotumors (n = 3), hemangiomas (n = 2), teratoma and carcinoid (n = 1 each). These tumors were ultimately cured, with one exception, after surgical resection. CONCLUSIONS: Gastrointestinal tumors in children cover a broad spectrum of benign and malignant varieties and stem from conditions that differ significantly from those observed in adults. While treatment varies according to diagnosis, most patients respond best to complete resection of the primary tumor.

Adolescent↗

Lack of graft-versus-host disease after fetal intestine transplantation.

Clinical small bowel transplantation has often been complicated by lethal graft-versus-host disease (GVHD), attributed to the numerous allogeneic immunocompetent lymphocytes contained in the graft. Because the fetal immune system is relatively immature, the authors hypothesized that the risk of GVHD after small bowel transplantation might be diminished by using the fetal intestine as the donor organ. This experiment tested this hypotheses in a rat model. Jejunoileal segments harvested from Lewis (LEW) rat fetuses were transplanted subcutaneously into adult recipients of either syngeneic LEW or semiallogeneic LEW x Brown-Norway F1 (LBNF1) strains. The recipients had follow-up for 21 days after transplantation to assess the growth of the intestinal grafts ("neogut") and evaluate for GVHD. Growth of the intestinal grafts was observed in 65% (53 of 82) of the recipients, with a neogut weight of 4.5 +/- 3.7 g and length of 2.8 +/- 2.1 cm. No significant difference in graft survival rate or neogut weight and length was found between the LEW and LBNF1 recipients. Histopathologic examination of the neogut showed a mature intestinal architecture similar to that of normal adult rat intestine, with well-developed enteric lymphoid tissues including Peyer's patches. However, no clinical or histopathologic evidence of GVHD was found in any of the LBNF1 recipients. These results are consistent with the author's hypothesis and suggest that the use of fetal donor intestine for small bowel transplantation might have some immunologic advantages over the adult (immunologically mature) donor intestine.

Animals↗

The complex nature of type A (long-gap) esophageal atresia.

BACKGROUND: The management of neonates with long-gap esophageal atresia without a fistula (type A) is complex. Options for esophageal reconstruction include use of the native esophagus or replacement with colon, stomach, or small bowel. The purpose of this study was to evaluate the long-term outcome of children variously treated with this defect. METHODS: The course of 23 infants with type A esophageal atresia were retrospectively reviewed. Diagnosis was achieved by plain radiographs and endoscopy. The mean gestational age was 33.9 weeks, and the birth weight was 1.87 kilograms. RESULTS: Two of nine infants with serious associated defects died early, and one infant with brain damage was not reconstructed. Initial treatment consisted of gastrostomy and proximal pouch suction (n = 10) or cervical esophagostomy (n = 10). Reconstructive procedures were performed in 20 infants, including colon interposition in eight infants, reversed gastric tube in two infants, and delayed primary esophageal repair (often with myotomy) in 10 infants. Secondary procedures were required for three infants with failed colons, one infant with a failed gastric tube, and one infant with a native esophageal disruption. Long-term satisfaction was 90% with esophagus, 63% with colon, and 50% with stomach. CONCLUSIONS: When possible, native esophageal reconstruction is the procedure of choice rather than esophageal replacement.

Anastomosis, Surgical↗

Familial Hirschsprung's disease: 20 cases in 12 kindreds.

This report describes 20 infants and children with a family history of Hirschsprung's disease in 12 kindreds. A total of 260 patients were treated for Hirschsprung's disease (1972 to 1991), yielding a familial incidence of 8%. There were no families with consanguineous marriage. Sixteen patients were male and four were female. The mean age at diagnosis was 18 days. Clinical presentation included delayed passage of meconium in 15, abdominal distention in 11, vomiting in 9, feeding abnormalities in 3, and complete bowel obstruction in 1. Associated congenital anomalies occurred in 25% of the patients. The extent of aganglionosis was rectal in 4, sigmoid in 4, left colon in 2, transverse or right colon in 2, and total colonic in 8. Enterocolitis occurred in 7 patients (35%); 2 at diagnosis, 2 after an ostomy, and 3 after a pull-through procedure. There were no deaths associated with enterocolitis. All patients had a proximal diverting colostomy or ileostomy, and 19 of 20 underwent a definitive pull-through procedure. Three patients were lost to follow-up and one patient died of complications of multiple congenital anomalies unassociated with Hirschsprung's disease. Of the remaining 16 patients, all of whom have undergone a pull-through procedure, 11 are fully continent, 2 have nighttime soiling, 2 are too young to evaluate bowel function, and 1 still has an ostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Distribution↗

Changes of hepatoma echo patterns with tumor growth. A study of the microanatomic basis in a rat model.

OBJECTIVES: The echo patterns of human hepatoma vary considerably as the tumors grow. This sonographic study investigates the microanatomic basis of the echo-pattern changes in an animal model. METHODS: ACI rats (n = 35) with intrahepatically implanted Morris hepatoma 3924A were imaged with 10-MHz ultrasound from days 7 to 28 after tumor implantation. The sonograms were precisely correlated with the histologic sections and microangiograms obtained from the same section plane. RESULTS: Small hepatomas (size = 6.6 +/- 1.6 mm) without necrosis demonstrated a low-echo pattern. Medium-sized tumors (size = 11.7 +/- 3.3 mm) had a low-echo periphery and a high-echo center. The low-echo periphery corresponded to viable tumor and the high-echo core corresponded to central coagulation necrosis. Large tumors (size = 20.9 +/- 7.5 mm) with extensive necrosis revealed an irregular mixed-echo pattern. CONCLUSIONS: The trend of increasing echogenicity of the hepatomas with tumor growth is due to the progression of coagulation necrosis.

Animals↗

Liver cancer ablation with extracorporeal high-intensity focused ultrasound.

Recent animal studies have demonstrated the capacity of high-intensity focused ultrasound (HIFU) to extracorporeally ablate selective tissue targets in the liver without requiring surgical exposure of the liver or insertion of instruments into the liver. The potential value of HIFU as a noninvasive local treatment for human hepatic cancers has attracted considerable interest. This report reviews the current status of HIFU research and sets forth questions for future study.

Animals↗

Neuroblastoma in the first year of life: clinical and biologic factors influencing outcome.

The survival for infants less than 1 year of age with neuroblastoma is twice that of older children. This report describes 70 babies with neuroblastoma who experienced an 84% survival. Survival was 100% for stages I, II, and III, 81% for stage IV-S, and 50% for stage IV. Most survivors had favorable biologic characteristics including spontaneous regression, favorable Shimada histology, normal first chromosome, aneuploid tumors, absent or low N-myc oncogene expression, and normal serum ferritin levels.

Biomarkers, Tumor↗

Sonographic and computed tomography characteristics of liver ablation lesions induced by high-intensity focussed ultrasound.

RATIONALE AND OBJECTIVES: The authors have previously demonstrated the ability of high-intensity focused ultrasound (HIFU) to extracorporeally induce selective tissue destruction in the liver without causing damage to the intervening abdominal wall. The potential usefulness of HIFU as a noninvasive therapy for liver cancer has been suggested. This study observes sonographic and computed tomography (CT) characteristics of HIFU-ablated liver tissue in an attempt to assess the possibility of using these imaging methods to monitor the therapeutic results. METHODS: A sonoablated lesion was induced in the liver in each of 20 rabbits with a HIFU therapeutic system. Sequential imaging of the hepatic sonolesions with sonography and CT was performed up to 8 days after treatment, and the imaging patterns were correlated with the histopathology. RESULTS: Hepatic sonoablated tissue could be clearly visualized by sonography as a hypoechoic lesion. On contrast-enhanced CT, the sonolesions were depicted as nonenhanced low-density regions. There was good correlation among the sizes of sonography- and CT-depicted lesions and pathologic specimens. CONCLUSION: In this model, sonography and contrast-enhanced CT were useful imaging modalities for monitoring sonolesion evolution after HIFU treatment.

Animals↗

Hirschsprung's disease. Evaluation of mortality and long-term function in 260 cases.

This report describes 260 patients treated for Hirschsprung's disease. There were 213 boys (82%) and 47 girls (18%). Age at diagnosis was younger than 30 days in 106 patients (41%), 1 month to 1 year in 90 patients (35%), and older than 1 year in 64 patients (25%). Diagnosis was achieved with barium enema and rectal biopsy. Aganglionosis involved the rectum or rectosigmoid in 174 patients (67%), the left colon in 38 patients (15%), and the proximal colon in 23 patients (9%); 25 patients (9%) had total colonic aganglionosis. Enterocolitis occurred in 47 cases (18%). Following an initial colostomy or ileostomy, a definitive pull-through procedure was performed in 247 patients (95%) (modified Duhamel in 185, Soave in 25, Swenson procedure in 15, and anomyectomy/sphincterotomy in 22); the overall survival rate was 93.8% (244 of 260 patients). An increased mortality was associated with Down syndrome, total colonic aganglionosis, and enterocolitis. Long-term follow-up (mean, 6 years 10 months) was available in 103 patients who underwent a Duhamel procedure. Sixty-seven (65%) had normal bowel function, 28 (27%) occasionally used enemas or stool softeners, and eight (8%) had severe constipation or soiling. Bowel habits improved with time and were considered normal in 58% of patients at less than 5 years of follow-up and in 88% of patients at more than 15 years of follow-up. The Duhamel operation is a very effective definitive procedure for Hirschsprung's disease. Long-term follow-up is an important component of patient care.

Anastomosis, Surgical↗

Air reduction of an intussusception caused by a pathologic lead point in an infant.

Lead points that are the cause of an ileocolic intussusception are rare in infants [1], as is successful reduction using barium [2]. Air reduction of an intussusception with a pathologic lead point has not been previously reported. We report a case of an infant with an ileocolic intussusception secondary to a duplication cyst that was successfully reduced with air. The pathologic lead point was recognized at the time of reduction and confirmed with water-soluble contrast. Air is both a diagnostic and therapeutic contrast agent.

Air↗

Effects of high-intensity focused ultrasound in the treatment of experimental neuroblastoma.

This report evaluates the effect of high-intensity focused ultrasound (HIFU) on subcutaneous murine neuroblastoma C1300. HIFU treatment was administered with a focused 4-MHz quartz transducer with a peak intensity of 550 W/cm2. In experiment 1, 60 animals with tumor were divided into four groups. Group I (n = 15) were controls; group II (n = 15) received adriamycin, 5 mg/kg intraperitoneally; group III (n = 15) received HIFU; and group IV (n = 15) received both adriamycin and HIFU. All the animals in groups I and II died of tumor by 35 days. Fifty-three percent (8/15) of mice in group III and 80% (12/15) in group IV were cured with no evidence of tumor (NET) at 200 days. Log-rank statistics showed significant prolongation of survival in the groups III and IV as compared with groups I or II (P less than .05). In experiment 2, 45 animals with tumor were divided into three groups. Group I (n = 15) were controls; group II (n = 15) received HIFU; and group III (n = 15) received repeated HIFU. The results showed 47% (7/15) of mice in group II and 67% (10/15) in group III were NET at 200 days. Significant survival prolongation was achieved in groups II and III in comparison with group I (P less than .05). In experiment 3, 90 mice received either tumor (n = 60) or saline (n = 30) inoculation in the left flank. On day 5, 45 mice with tumor were treated with HIFU (group I), while the other 15 mice with tumor (group II) had a sham procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A reproducible rat liver cancer model for experimental therapy: introducing a technique of intrahepatic tumor implantation.

To investigate therapeutic strategies for hepatoma, it is necessary to have a reproducible animal model with a tumor growth pattern allowing accurate assessment of results. Many techniques of intrahepatic tumor implantation (IHTI) have been devised for intrahepatic tumor models. Most of them, however, have the disadvantage of high rates of artificial tumor dissemination during tumor implantation, which interferes with the evaluation of therapy. To overcome this problem, we have developed a technique of IHTI in which a piece of Gelfoam is placed into a small incision in the liver for the purpose of both hemostasis and formation of a tension-free pocket to accept the tumor implant. In 583 ACI rats receiving IHTI with Morris hepatoma 3924A, the tumor take rate was 100%. Resembling the natural course of human hepatoma, the implanted tumor grows locally early in the course of disease and eventually invades the surrounding organs causing ascites and also metastasizes to the lung. Liver microangiography demonstrated that the tumor received blood supply mainly from the hepatic artery. This IHTI technique was also compared to two other methods of IHTI: insertion of fragments without using Gelfoam and implantation with a tumor cell suspension. A significantly lower rate of early lung metastases was achieved with our technique (0%) in comparison with other two techniques (41 and 80%). We conclude that this rat liver cancer model is reproducible and allows efficient evaluation of treatment modalities for liver cancer without interference from tumor at undesirable sites.

Animals↗

Delayed surgical repair and ECMO improves survival in congenital diaphragmatic hernia.

One hundred ten infants with congenital diaphragmatic hernia (CDH) developed life-threatening respiratory distress in the first 6 hours of life. Associated anomalies were present in 33%. Twenty-eight of 65 infants (43%) treated before 1987 (pre-extracorporeal membrane oxygenation [ECMO] era) survived after immediate CDH repair, and mechanical ventilation with or without pharmacologic support. Only two of 16 (12.5%) infants requiring a prosthetic diaphragmatic patch survived. Since 1987, 31 of 46 (67.4%) infants with birth weight, gestational age, and severity of illness similar to the pre-1987 group survived. All patients were immediately intubated and ventilated. Seven (four with lethal chromosomal anomalies) infants died before treatment, and 30 stabilized (partial pressure of carbon dioxide [PCO2] < 50; partial pressure of oxygen [PO2] > 100; pH > 7.3) and underwent delayed CDH repair at 5 to 72 hours. Fifteen did well on conventional support and survived. Fifteen infants deteriorated after operation: 11 were placed on ECMO with eight survivors, and four infants were not considered ECMO candidates. Nine babies failed to stabilize initially and were placed on ECMO before CDH repair (alveolar-arterial gradient > 600 and oxygenation index > 40), and seven survived. The overall survival rate was 80% at 3 months in this ECMO-treated group. Early mortality was due to inability to wean from ECMO (one), intracranial hemorrhage (one), liver injury (one), and pulmonary hypoplasia (one). Nine of 11 babies requiring a prosthetic patch in the post-1987 ECMO group survived (81.8%). There were three late post-ECMO deaths (3 to 18 months) of right heart failure (two) and sepsis (one). Symptomatic gastroesophageal reflux occurred in nine cases, six requiring a fundoplication in the bypass babies. Recurrent diaphragmatic hernia occurred in nine cases (five ECMO). The overall survival rate was significantly improved in the delayed repair/ECMO group (67% versus 43%; p < 0.05) and was most noticeable in infants requiring a prosthetic diaphragm (81.2% versus 12.5%; p < 0.005). These data indicate that early stabilization, delayed repair, and ECMO improve survival in high-risk CDH. Early deaths are related to pulmonary hypertension and can be reversed by ECMO.

Extracorporeal Membrane Oxygenation↗