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Biomedical subjects

J L Grosfeld

Publications and source records attributed to J L Grosfeld.

At least 73 records · Page 4Linked to original sources
PubMed1995

The efficacy of early ERCP in pediatric pancreatic trauma.

Recognition of pancreatic injuries is frequently delayed, and optimal treatment is often controversial. The use of endoscopic retrograde cholangiopancreatography (ERCP) has allowed accurate delineation of pancreatic ductal injuries; however, the small size of children and the concern with inducing pancreatitis and/or lesser sac contamination have limited its use in children. In 1988, the authors began using ERCP for selected pancreatic injuries. This report describes their experience with this technique and examines the role of ERCP in pediatric pancreatic injuries. Six children with pancreatic transections resulting from blunt trauma were treated between 1988 and 1993. The age range was 2 1/2 to 8 years, and the weight range was 13.6 to 27.9 kg. The average period from injury to referral to the hospital was 14 days (range, 2 to 30 days). All six children presented with chemical evidence of pancreatitis and had an initial computed tomography (CT) scan; five scans were interpreted as being normal. Five of the six patients had subsequent CT scans, which showed lesser-sac fluid collection. Three patients were treated with drainage (2 percutaneous, 1 open [outside hospital]), and when this failed, ERCP was performed, at 13.6 days (average) after presentation. These three patients underwent ERCP relatively early in the course (an average of 3 days after presentation). All six children had major ductal transections documented through ERCP. After ERCP, the serum amylase level remained elevated in three, increased in one, and normal in one. (It was not measured in one of the recent cases taken for immediate operation.)(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Does preoperative chemotherapy for hepatic tumors have an adverse effect on hepatic proliferation after delayed liver resection?

The authors evaluate the effect of preoperative cisplatin and Adriamycin on hepatic proliferation after delayed partial hepatectomy. Sprague-Dawley rats were placed into five experimental groups. Group I received 0.9% saline intraperitoneally (IP). Group II received 2 mg/kg of cisplatin IP. Group III received 4 mg/kg of cisplatin IP. Group IV received 6 mg/kg of Adriamycin intravenously. Group V received 0.9% saline IP. Groups I through IV underwent 70% partial hepatectomy 2 and 10 days after chemotherapy. They were killed 24 hours later, and analyses were performed. Group V animals underwent celiotomy and were killed. Hepatic proliferation was evaluated by tritiated thymidine (3H-TdR) incorporation into DNA, quantitative image analysis (QIA), and proliferating cell nuclear antigen immunostained hepatic nuclei (PCNA). 3H-TdR incorporation values in animals treated 2 days before partial hepatectomy in treatment groups II through IV were similar to those of the hepatectomized controls. Although among the animals treated 10 days before partial hepatectomy there was inhibition of 3H-TdR DNA incorporation in the Adriamycin group, no significant differences were noted between all treatment groups. QIA of the S-phase nuclei (an indicator of proliferation) indicated that the animals treated with 2 mg/kg of cisplatin had significantly more nuclei than those treated with Adriamycin. PCNA labeling showed a decrease in proliferating nuclei in all treatment groups compared with the control hepatectomized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction.

One feature of enteric mucosal immunity is oral tolerance (OT), a state of diminished systemic immune responsiveness to an antigen induced by previous oral feeding of that antigen. Because OT induction requires an interaction between the intestinal and systemic immune systems, the authors plan to use it as a method in experimental small bowel transplantation (SBT) to evaluate the ability of the intestinal allograft to cooperate immunologically with the host. Two different methods have been used in experimental SBT to establish graft venous drainage: anastomosis of the graft mesenteric vein to the recipient portal vein or to the inferior vena cava. This experiment was designed to examine the role of the intestinal venous drainage routes in OT induction. Rats with a surgically created mesenterico-caval shunt (MCS) and their sham controls received an immunization protocol to induce OT to ovalbumin. The results showed that OT was readily induced in the sham animals, but not in the animals with MCS. These results indicate that intestinal venous drainage through the liver plays a central role in OT induction. Therefore, future analyses of OT in allogeneic SBT will require an animal model with portal venous drainage of the intestinal graft.

Administration, Oral↗
PubMed1994

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↗
PubMed1994

Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

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↗
PubMed1993

Ovarian neoplasms in children.

OBJECTIVE: To review the clinical presentation, treatment, and outcome in a series of children with ovarian neoplasms. DESIGN: A retrospective review of the medical records in a case series of 29 girls with ovarian neoplasms. The length of follow-up ranged from 6 months to 7 1/2 years and averaged 3.0 years in the girls with malignant tumors. SETTING: The patients were treated at a large referral children's hospital. PATIENTS: Twenty-nine girls with ovarian neoplasms were treated from 1976 to 1992. The average age of the patients was 10 years and ranged from 2 to 16 years. MAIN OUTCOME MEASURES: The principal outcomes examined were mortality and surgical morbidity. RESULTS: The most common presenting symptoms for these ovarian tumors in pediatric patients included chronic abdominal pain, an abdominal mass, or distention. Three girls presented with precocious puberty or hirsutism. In 27 cases, the tumor was a primary ovarian lesion. In two patients, the ovarian mass was the presenting finding for a stage IV non-Hodgkin's lymphoma. Seventeen tumors were benign and 12 were malignant. Tumors originating from the germ-cell line predominated (n = 17). Seven of the 10 ovarian malignant neoplasms were stage I at the time of diagnosis. All but one of the girls with malignant tumors received either adjunctive radiation therapy or multiple-agent chemotherapy. Two girls with sex cord/stromal cell tumors who presented with stage I disease ultimately developed widespread metastases. Both girls with large epithelial tumors survived. All of the girls with benign tumors and seven (70%) of 10 with malignant lesions survived. CONCLUSION: Ovarian tumors are unusual lesions in the pediatric population. Unlike in adults, such neoplasms generally originate from the germ-cell line. Whereas most ovarian tumors in girls are benign, some children have malignant tumors that are very aggressive and do not respond well to adjuvant therapy. In particular, malignant sex cord/stromal cell tumors, even when they present at an early stage, may behave unpredictably.

Adolescent↗
PubMed1993

Multifocal primary neuroblastoma.

UNLABELLED: The purpose of this study is to present three patients with multifocal primary neuroblastoma, to review the literature, and describe the radiographic findings. SUBJECTS AND METHODS: Three children with multifocal neuroblastoma have been identified. The case histories and imaging findings in these patients are reviewed. RESULTS: Two children had synchronous and one child had metachronous multifocal primary neuroblastoma. The primary tumors were both in the abdomen in one patient, both in the chest in another patient, and in the chest and abdomen in the third patient. Evidence for multifocal origin of these tumors, rather than metastatic spread, is presented. CONCLUSION: Multifocal primary neuroblastomas can occur. The tumors maybe synchronous or metachronous. Awareness of this disorder may prevent errors in diagnosis and staging. Although not identified in our patients there is a strong familial incidence of neuroblastomas in those patients with multifocal tumors.

Adrenal Gland Neoplasms↗
PubMed1993

Blood clearance and organ localization of Candida albicans and E coli following dual infection in rats.

Immunosuppressed prematures, cancer patients, and transplant recipients are susceptible to bacterial or fungal sepsis or both. This report evaluates whether the ability of the reticuloendothelial system (RES) to remove blood-borne viable radiolabeled 35S Escherichia coli and 3H-Leucine Candida albicans is adversely affected by a dual intravenous challenge of these organisms. Male Sprague Dawley rats (n = 150) weighing 175 to 180 g were placed in 5 experimental groups (n = 30). Group I received intravenous (IV) C albicans (10(7)/mL), group II received E coli (10(9)/mL), group III received a dual injection of C albicans and E coli, group IV received Candida 1 hour prior to E coli, and group V received E coli 1 hour prior to fungi. At 1, 4, and 24 hours, tissue samples (50 to 100 mg) of liver, spleen, kidneys, and lungs were processed for liquid scintillation counting. Organ distribution of bacteria and fungi was calculated and expressed as mean percent +/- SD of labeled organisms. The liver trapped 72% +/- 10% and the lungs 1.1% +/- 0.3% of E coli (group II) (P < .001). The organ distribution of Candida (group I), however, was similar in liver and lungs (42.5% +/- 10% and 41.4% +/- 6.4%, respectively). Liver localization of E coli was unaffected by simultaneous or staggered fungal injection (groups III, 4, and V). Lung distribution of E coli following dual injection (group III) was significantly higher than controls (group II) (3.6% +/- 0.7% v 1.1% +/- 0.3%; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Early use of cisplatin is safe after partial hepatectomy.

Although cisplatin is widely used in the treatment of liver tumors, little information is available concerning its effect on liver regeneration. This report evaluates the effect of cisplatin on liver regeneration after hepatectomy (HPx). One hundred sixty male Sprague-Dawley rats were placed into five experimental groups following 70% hepatectomy. Group I (untreated controls, n = 32) received 0.9% saline intraperitoneally (IP); group II (n = 31), cisplatin 4 mg/kg IP; group III (n = 36), cisplatin 10 mg/kg IP; group IV (n = 34), cisplatin 20 mg/kg IP; and group V (n = 27), doxorubicin 6 mg/kg intravenously (IV). Five additional sham groups underwent celiotomy without hepatectomy (n = 106) followed by the above treatment protocols. Liver regeneration was evaluated by liver weight, DNA incorporation measured by tritiated thymidine (3H-TdR), and quantitative image analysis (QIA) of hepatic nuclei at 18, 24, 36, 48, and 72 hours, and 5 days postoperatively. 3H-TdR incorporation peaked at 36 hours and was similar in hepatectomized controls group I (404 +/- 110 counts per minute [CPM]/mg liver weight) and cisplatin-treated rats (groups II to IV) (P > .05, ANOVA). All sham groups were similar to controls. QIA of feulgen-stained touch preps identified polyploid, stem line, and proliferating nuclei in both controls and treated groups. At 36 hours, QIA showed differences in mitotic status of sham, control, and adriamycin-treated HPx rats, consistent with 3H-TdR incorporation. In contrast, although cisplatin-treated rats receiving 4 mg/kg showed proliferating nuclei, QIA demonstrated decreasing hepatocyte proliferation with higher doses of cisplatin (10 mg/kg, and 20 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗