Improved outcome for patients with middle ear rhabdomyosarcoma: a children's oncology group study.

PURPOSE: The goal of this study was to define the clinical features and optimal therapy for children and adolescents with middle ear (ME) rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We reviewed demographic data, clinical features, therapy (including chemotherapy, surgery, and radiation), and outcome for the 179 eligible patients with ME RMS who were enrolled onto Intergroup Rhabdomyosarcoma Studies (IRS) I through IV or pilot studies between November 1972 and December 1997. RESULTS: Most patients were younger than 10 years old (90%), and 63% were male. Because of the parameningeal location, most tumors were not resected before chemotherapy (group I, < 1%; group II, 4%; group III, 84%; group IV, 12%). Although most tumors were locally invasive (T2, 89%), the majority were small (< or = 5 cm, 66%), lacked nodal metastases (N0, 86%), and had embryonal histology (85%). The 5-year failure-free survival (FFS) and overall survival (OS) estimates were 67% and 72%, respectively. Both FFS and OS improved significantly over the course of IRS I through IV (3-year FFS and OS: IRS-I, 42% and 42%; IRS-II, 70% and 74%; IRS-III, 65% and 72%; IRS-IV pilot, 81% and 96%; IRS-IV, 88% and 88%, P <.001). Lower clinical group or stage and smaller tumor size were associated with better outcome. Age, sex, tumor invasiveness, and nodal metastases were not predictive of outcome. CONCLUSION: Patients with ME RMS generally present with small, unresectable, invasive tumors at a site traditionally considered prognostically unfavorable. Nevertheless, such patients have benefited markedly from improvements in multimodal, risk-based therapy during the course of IRS I through IV, and with contemporary therapy, most are cured.

Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group.

PURPOSE: To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy. PATIENTS AND METHODS: Six hundred ninety-five patients with group II tumors received chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc). RESULTS: Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506; IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%; P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy. CONCLUSION: Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy.

Hormone effects on hepatic substrate preference in sepsis.

This study addressed the effect of catecholamine stimulation on substrate utilization for gluconeogenesis, ureagenesis, and oxidation in perfused livers from septic rats. Livers were perfused with buffer containing 5 mM [14C]lactate and various concentrations of unlabeled alanine or pyruvate. Addition of alanine to lactate resulted in inhibition of gluconeogenesis and especially inhibition of gluconeogenesis from lactate. This effect was dependent upon the presence of the amino nitrogen, since the effect of pyruvate was to increase total gluconeogenesis with little effect on gluconeogenesis specifically from lactate except with phenylephrine stimulation of livers from sham-operated animals in which addition of pyruvate actually increased the rate of gluconeogenesis from lactate. Alanine itself was very poorly utilized as a gluconeogenic substrate. In contrast, the addition of alanine stimulated total oxygen consumption in both groups in the absence or presence of phenylephrine. This was the result of oxidation of added alanine in livers from sham animals, either with or without phenylephrine, and in septic animals without phenylephrine. However, in the presence of phenylephrine, the increase in total oxygen consumption was almost entirely the result of lactate oxidation. Pyruvate, on the other hand, uniformly stimulated oxygen consumption in both groups, with and without phenylephrine. Urea production was increased by alanine to a greater extent in the septic group compared to sham. However, while phenylephrine stimulated ureagenesis in the sham-operated group, it inhibited ureagenesis in the septic group. These results demonstrate that fundamental differences develop in livers from septic animals in their handling of nitrogenous and non-nitrogenous gluconeogenic substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Presence of the stress-inducible form of hsp-70 (hsp-72) in normal rat colon.

The expression of heat shock proteins (hsp) is probably one of the most primitive mechanisms of cellular protection from stress. Pathogens such as viruses and bacteria have recently been found to induce the heat shock gene expression. In the present study hsp-72, the stress-inducible form of hsp-70, was detected by Western blotting in samples from rat distal colon (DC), proximal colon (PC), and terminal ileum (TI), but was not found in proximal small bowel (PSB) or other organs (liver, kidney, spleen, heart, and brain) of unstressed animals. The signal intensity of hsp-72 in colon (DC > PC > TI > PSB) correlates qualitatively with the presence of normal gut microflora. hsp-72 was also observed in DC, to a lesser extent in PC, but not in TI or PSB of bacteria-free or antibiotic-treated rats. Inflammatory states induced by the intravenous administration of endotoxin (1 mg/kg), the subcutaneous injection of zymosan (1 g/kg) or by cecal ligation and puncture (sepsis) failed to increase the hsp-72 levels in rat colon or other organs. These results demonstrate that hsp-72 is expressed in normal rat colon. However, the induction of hsp-72 expression may not be due solely to the presence of resident bacteria in the gut, but instead, may be the result of a more complex process.

Genetic component in the inflammatory response induced by bacterial lipopolysaccharide.

Multiple organ dysfunction syndrome (MODS) appears to be the result of a complex program influenced by multiple factors, including environmental, physiological, and immunological conditions. Thus, an uncontrolled inflammatory response following a stochastic event, the initial injury, is believed to be the cause for the development of this syndrome. Several lines of evidence suggest that a genetic component could contribute to the regulation of the inflammatory response, as well, but no direct evidence demonstrates a heritable predisposition to MODS. In the present study, a genetic contribution was demonstrated for the inflammatory response induced by the administration of bacterial lipopolysaccharide (LPS) in different, genetically distinct strains of inbred mice. A survey of five inbred strains showed that mortality following administration of Escherichia coli LPS (20 mg/kg) was highest in C57BL/6J (B6) mice, while A/J mice were the most resistant. Accordingly, B6 and A/J mice were examined further for differences in the inflammatory response elicited by LPS. B6 mice showed higher levels of circulating interleukin-1beta and interleukin-6, as well as higher mRNA levels of hepatic beta-fibrinogen (an acute-phase gene) and metallothionein. Surprisingly, the circulating levels of tumor necrosis factor-alpha were significantly higher in A/J than in B6 mice after LPS administration. Since B6 and A/J mice were bred and raised in identical environments and received the same LPS challenge, the contrasting inflammatory response that was observed is largely attributable to genetic differences between these two strains. These data illustrate that the response to injury could be modulated by the genetic background of the individual. This information may be pertinent for the care of critically ill patients.

Frequent detection of tumor cells in hematopoietic grafts in neuroblastoma and Ewing's sarcoma.

Many poor-risk neuroblastomas and tumours of the Ewing's sarcoma family (ET) recur despite autologous transplants. Recurrence may be due to tumor cells contained in the BM harvests or PBSC harvests. The objectives of this prospective study were to: (1) determine the incidence and degree of tumor cell contamination in paired BM and PBSC harvests; and (2) determine the efficacy of tumor cell purging by immunomagnetic CD34+ cell selection. 198 samples from 11 consecutive patients with neuroblastoma or Ewing's sarcoma were analyzed. We assayed tumor contamination by RT-PCR assay for PGP 9.5, plus immunohistochemistry for neuroblastoma-specific antigens (the latter in neuroblastoma only). None of these patients had tumor cells detected in their BM by clinical histology immediately before BM or PBSC harvests. However, 82% of PBSC and 89% of backup BM harvests were contaminated with tumor by RT-PCR and/or immunocytochemistry assays. Unselected PBSC and BM harvests contained similar quantities of tumor cells (median, approximately 200000 cells). Cyclophosphamide plus G-CSF mobilization did not affect the incidence or level of contamination in PBSC harvests, as compared to blood obtained before mobilization. Immunomagnetic CD34+ cell selection depleted tumor cells by a median of 3.0 logs for PBSC, and 2.6 logs for BM harvests.

Impaired metabolic response to endotoxin in obstructive jaundice.

Surgical management of extrahepatic cholestasis is frequently complicated by sepsis, which can be explained in part by diminished function of the reticuloendothelial system. We have explored the possibility that the metabolic response to infection may also be abnormal. Fischer 344 rats underwent either bile duct ligation (BDL) or sham operation and were studied 3 days after operation. Hepatic amino acid uptake measured in vivo by the accumulation of 14C-alpha-aminoisobutyric acid or in vitro by the rate of transport of 14C-alanine by isolated hepatocytes was unaltered in the BDL animals, while gluconeogenesis from alanine by viable hepatocytes from BDL rats was actually enhanced. However, the expected increase in hepatic amino acid uptake in response to endotoxin was diminished in the BDL animals. In addition, we observed impaired responses of the jaundiced animals to glucagon and interleukin-1, two mediators of the hepatic acute phase response to endotoxin. These data suggest that while hepatic amino acid transport is normal in the basal state, the rat with extrahepatic biliary obstruction does not respond appropriately to stress and that this defect cannot be explained solely on the basis of altered handling of endotoxin by the reticuloendothelial system.

Cell-mediated immune response is better preserved by laparoscopy than laparotomy.

BACKGROUND: This study compares the effects of carbon dioxide pneumoperitoneum versus laparotomy on cellular-mediated immune response in a murine model. METHODS: Sixty-eight female C3H/He mice were sensitized to keyhole limpet hemocyanin (KLH) and to a mouse mammary carcinoma cell line (MC2) before surgery. Animals were randomized into 4 groups: group I, anesthesia (control); group II, pneumoperitoneum with carbon dioxide; group III, extraperitoneal wound; group IV, laparotomy. All animals were challenged subsequently with KLH and MC2 tumor cells. Delayed-type hypersensitivity skin reaction (DTH) to KLH was measured on postoperative days (PODs) 1, 2, 4, and 5. Tumor growth was assessed weekly as an indicator of postoperative cellular immune response. RESULTS: Compared with preoperative values, postoperative DTH skin reactions were significantly less for all PODs in groups III and IV (P < .05), on POD 1 and 4 in group II (P < .05) and POD 4 for group I (P < .05). Group IV showed significantly fewer DTH skin reactions for all PODs compared with groups I and II (P < .05) and all PODs except on day 2 compared with group III (P < .05). Tumor growth was significantly increased at postoperative week 2 (n = 3/17 mice) and 3 (n = 4/17 mice) in group IV, when compared with groups I and II (P < .05). CONCLUSIONS: Cellular immunity is preserved after carbon dioxide pneumoperitoneum compared with extraperitoneal incisions and laparotomy as measured by DTH and the ability to reject an immunogenictumor.

Childhood trauma. Now and in the new millennium.

Given the magnitude of childhood injuries that occur yearly in the United States, physicians need integrated echelons of care that include regional pediatric trauma centers, trauma centers with pediatric commitment, and EDs appropriate for children. Head injury is the most significant cause of morbidity and mortality among children, but physicians are far from effectively evaluating the dynamics of cerebral metabolism and oxygen delivery in the acute resuscitation of injured children. Critically injured children must be kept normothermic, and attention to the signs of hypovolemic shock must be monitored. Secondary brain ischemia frequently occurs because the details of resuscitation are not carefully monitored. A "leader" must be designated, and this should be someone experienced in childhood trauma. The younger the child and the more severe the injury, the more important is the notion of "experience." The ultimate goal, now and in the new millennium, should not be who, where, or when to administer care to critically ill or injured children but rather the quality of the treatment of these children.

Fecal incontinence in children with anorectal malformations.

Children with anorectal malformations suffer from postoperative fecal incontinence as well as other forms of defecation disorders such as constipation, soiling, and incontinence associated with episodes of diarrhea. Indiscriminate use of laxatives, enemas, and pharmacotherapy is not recommended. Rather, it is possible to systematically diagnose and manage fecal incontinence after reconstruction for anorectal malformations. Three groups of children have been identified: candidates for reoperation, candidates for a bowel management program, and pseudoincontinent children. Postoperative evaluation for fecal incontinence should include accurate identification of the type of anorectal anomaly and knowledge of the original reconstructive procedure. In addition, history, physical examination, and review of radiological studies are mandatory, with detailed attention paid to the status of the striated external sphincter musculature and sacrum. Children then can be managed based on the type of fecal incontinence from which they suffer. Bowel management is successful only when performed in an organized manner, and it is recommended as an outpatient procedure.

The night after surgery. Postoperative management of the pediatric outpatient--surgical and anesthetic aspects.

Outpatient or "ambulatory" anesthesia and surgery has revolutionized the way surgery is practiced in the United States. Safe, reliable, inexpensive, and convenient outpatient surgery is an attractive option for parents, children, health care providers, and insurers.

Susceptibility of hepatic microcirculation to reperfusion injury: a comparison of adult and suckling rats.

Primary graft failure and vascular thromboses are frequent complications of liver transplantation, yet the mechanisms responsible remain unclear. Previous work from our laboratory has shown that hepatic reperfusion injury results in damage at the microvessel level. The present study was performed to determine whether an increased susceptibility of immature animals to microvascular injury during reperfusion might be a contributing factor in these complications. Suckling (35 to 50 g) or adult (250 to 400 g) rats were subjected to 30 or 60 minutes of hepatic ischemia to the left and median lobes followed by 90 minutes of reperfusion. Control animals were sham-operated, time-matched rats. At the end of reperfusion, fluorescein-labeled albumin was injected systemically to mark perfused sinusoids. Frozen sections of liver biopsies were viewed under fluorescence microscopy. The perfused sinusoid density was determined by point count analysis and expressed as the number of intersections of perfused sinusoids with 25 randomly oriented points superimposed on the sinusoid field. In sham-operated rats, at both 30 and 60 minutes, there were no differences between sucklings and adults. After 30 minutes of ischemia and 90 minutes of reperfusion, adults showed a significantly decreased density of perfused sinusoids (4.5 +/- 0.1 intersections per field) when compared with suckling rats (6.0 +/- 0.3 intersections per field, P less than .001). However, in rats subjected to 60 minutes of ischemia followed by 90 minutes of reperfusion, the microvascular injury was more severe in suckling rats (2.7 +/- 0.2 intersections per field) than in adults (4.7 +/- 0.2 intersections per field, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine triphosphate: a potential therapy for hypoxic pulmonary hypertension.

In this study we investigated whether a low-dose infusion of ATP-MgCl2 could ameliorate the pulmonary hypertension resulting from hypoxic pulmonary vasoconstriction. Three-week-old piglets were anesthetized, intubated, ventilated with room air, and cannulated for the measurement of pulmonary and systemic arterial pressure and pulmonary artery flow (cardiac output). The ventilator inflow was then changed to a mixture containing 10% oxygen, 4% CO2, and balance nitrogen. Serial infusions of ATP-MgCl2 at 0.1, 0.5 and 1.0 mg/kg/min were compared to preinfusion hypoxia baselines. Hypoxia alone produced a significant elevation in pulmonary artery pressure. Although all dose rates of ATP-MgCl2 produced a significant decrease (30%) in mean pulmonary artery pressure, we observed a maximum decrease in MPAP at the lowest rate of ATP infusion. Pulmonary artery flow rose slightly during ATP infusion; therefore, it was the change in pulmonary vascular resistance that accounted for the decrease in pulmonary artery pressure. In contrast, the systemic pressure was significantly decreased only during the 1.0 mg/kg/min infusion. The predominant pulmonary effects are a result of the virtual clearance of ATP-MgCl2 in a single pass through the circulation. Adenosine in the presence or absence of MgCl2 produced only a 10% reduction in mean pulmonary artery pressure, and MgCl2 had no effect when infused alone. From these results, we conclude that a low-dose infusion of ATP-MgCl2 could ameliorate the vasoconstriction associated with hypoxic pulmonary hypertension without significant deleterious systemic side effects.

The effect of adenosine triphosphate on the functional status of the ductus arteriosus.

We investigated whether a low-dose infusion of ATP-MgCl2 could affect the functional status of the ductus arteriosus during hypoxia-induced pulmonary vasoconstriction. Three-day-old piglets were made hypoxic by ventilation with a mixture containing 10% oxygen, 4% CO2, and balance nitrogen. Serial infusions of ATP-MgCl2 at 0.1, 0.5, and 1.0 mg/kg/min were compared with preinfusion hypoxia baselines. The functional status of the ductus arteriosus was determined by change in transit time of a bolus of iced saline between thermistor probes in the pulmonary artery and aorta. The method was validated using a Blalock-Taussing shunt (subclavian to pulmonary artery) in 3-week-old piglets instrumented in a similar manner. In these three-day-old piglets, hypoxia alone produced a significant elevation in pulmonary artery pressure and reduction in PO2. All dose rates of ATP-MgCl2 produced a significant decrease in mean pulmonary artery pressure. Systemic pressure was significantly decreased only during the 1.0-mg/kg/min infusion. Transit times of a bolus of iced saline during the validation were definitive for characterizing a situation of "shunt open" or "shunt closed." Infusion of ATP-MgCl2 produced no change in the status of the ductus arteriosus in 45 (94%) of the determinations. In only three cases was the effect of ATP-MgCl2 sufficient to result in a functional change in the status of the ductus arteriosus. Pre- and postductal pulmonary artery PO2 were not altered during ATP-MgCl2 infusion, thus corroborating the transit time determinations. From these results, we conclude that an infusion of ATP-MgCl2 does not alter the functional status of the ductus arteriosus.

Management of a floating sternum after repair of pectus excavatum.

PURPOSE: The aim of this study was to examine the authors' experience with patients who have floating sternum after correction of pectus excavatum via the classical Ravitch procedure. A floating sternum is defined as a sternum in which the only attachment to the chest wall is its superior (cranial) border, and in which the body is secured only by the manubrium and whatever lateral and inferior fibrous bands are present. Typically, a floating sternum is caused by either extensive resection of the costal cartilages and perichondrium during correction of pectus excavatum or failure of proper regrowth of these cartilages. METHODS: The authors retrospectively assessed the charts of all patients diagnosed with a floating sternum noting age at original correction of pectus excavatum, time from original correction of pectus excavatum to diagnosis of floating sternum, age at correction of floating sternum, complaints before stabilization of the sternum, methods of repair, and postoperative complications. RESULTS: Between July 1993 and June 1999, floating sternum was diagnosed in 7 patients. The mean age of patients who underwent operative correction of a floating sternum was 28.9 years (range, 16 to 42 years). The mean time interval between original correction of pectus excavatum, or "redo," and diagnosis of a floating sternum was 9.9 years (range, 2 to 20 years). Complaints before correction of the floating sternum included sternal pain and instability, exercise intolerance, and difficulty breathing. Operative repair consisted of mobilizing the lateral and inferior edges of the sternum, detaching the fibrous perichondrium, performing anterior sternal osteotomies, and finally supporting the sternum with substernal Adkins struts. All 7 patients had successful stabilization of the sternum. Two of 7 patients underwent 2 procedures to successfully stabilize the sternum. One patient has Adkins struts still in place because of hematopoetic malignancy. Six of 7 patients are now without symptoms. CONCLUSIONS: A floating sternum is a morbid phenomenon that may manifest many years after the original procedure. It can cause significant sternal pain, chest wall instability, and respiratory dysfunction, which are the hallmark indications for correction. Repair of a floating sternum can be accomplished successfully.

Septation and differentiation of the embryonic human cloaca.

BACKGROUND/PURPOSE: Limitations in methodologies have fostered controversy regarding the septation of the human embryonic cloaca. The aim of this study was to evaluate the septation of the human embryonic cloaca. METHODS: Using the Carnegie Embryological Collection and specimens at Johns Hopkins, Baltimore, MD, the authors studied 12 embryos and five fetuses. Embryo photomicrographs were reconstructed using three-dimensional modeling. RESULTS: In Carnegie stage 13 the authors observed a cloaca, distinct primitive urogenital sinus, and anorectum separated by the urorectal septum. The primitive urogenital sinus and anorectum enter the cloaca separated from the amniotic space by the cloacal membrane. As the embryo becomes a fetus it lengthens, grows, expands and rotates through a process called transformation. Transformation gives rise to a loss of caudal curvature and a decrease in distance between the septum and membrane, but these structures do not fuse. Disintegration of the cloacal membrane produces openings for the urogenital sinus and anorectum. CONCLUSIONS: The observations suggest that the urogenital sinus and anorectum form early and are separated by the urorectal septum as a passive structure. There does not appear to be septation or differentiation of the cloaca itself.

Criteria for safe cost-effective pediatric trauma triage: prehospital evaluation and distribution of injured children.

In an effort to maximize staff utilization, all pediatric trauma patients were triaged by emergency room personnel to one of two tiers, based on information reported by prehospital providers over radiotelephones. A total of 952 patients less than 15 years of age were evaluated during a 1-year period. The triage criteria had a sensitivity of 86% in predicting which trauma patients would require operating room and/or pediatric intensive care, while maintaining a specificity of 90%. Fifteen patients died; however, by TRISS methodology there were no unexpected deaths and four unexpected survivors. All eventual deaths were initially captured from field data by the severely injured triage criteria. The study data suggest that physician-controlled two-tiered field triage criteria can safely serve to maximize staff utilization in the emergency room.

Laparoscopic Nissen fundoplication with carbon dioxide pneumoperitoneum preserves cell-mediated immunity in an immature animal model.

PURPOSE: The aim of this study is to elucidate the effects of laparoscopic Nissen fundoplication (LNF) with carbon dioxide (CO(2)) or helium (He) on the cell-mediated immune response in a pediatric animal model compared with open Nissen fundoplication (ONF). METHODS: Cell immune response was evaluated in 45 1-week-old Sprague Dawley rats using the delayed type hypersensitivity (DTH) skin test. Animals were sensitized against keyhole limpet hemocyanin (KLH) by subcutaneous injection (0.5 mg) in complete Freund's adjuvant. Animals were challenged 2 weeks later by an intradermal injection of KLH (0.3 mg) in sterile saline (challenge 1, baseline). Rats with positive DTH skin reaction at 24 and 48 hours after challenge 1 were put randomly into 4 groups (n = 10 each): I, only anesthesia (control); II, LNF with CO(2), III, LNF with He; IV, ONF. Animals were injected intradermally with KLH (0.3 mg) immediately before the procedures (challenge 2) and 3 and 6 days postoperatively (challenges 3 and 4). RESULTS: DTH skin reactions were measured 24 and 48 hours after each challenge. There were no significant changes in cell-mediated immunosuppression after LNF with CO(2). However, a transient cell-mediated immunosuppression was observed after LNF with He and ONF. All fundoplications were intact at the time of necropsy. CONCLUSIONS: These data suggest a transient suppression of cell-mediated immunity in open procedures when compared with laparoscopic interventions using CO(2) in a pediatric animal model. In addition, the type of gas used during laparoscopy also may modulate this transient immunosuppression.

Immune response: effects of operative stress in a pediatric model.

PURPOSE: The purpose of this study is to delineate the effect of different operative procedures on the cell-mediated immune response in a pediatric animal model using the delayed type hypersensitivity (DTH) skin test. METHODS: Sprague Dawley rats (1 week old) were sensitized against keyhole limpet hemocyanin (KLH). Animals were challenged 2 weeks later by an intradermal injection of KLH (0.3 mg) in sterile saline. Rats with positive DTH skin reactions at 24 and 48 hours after challenge (baseline) were divided randomly into five groups (n = 10 each): group I, unmanipulated control; group II, anesthesia; group III, anesthesia and midline extraperitoneal incision; Group IV, anesthesia and laparoscopy (pneumoperitoneum with carbon dioxide); Group V, anesthesia and midline laparotomy. Before each procedure (day 0) and on postoperative days 3 and 6, animals were again challenged intradermally with KLH (0.3 mg). DTH skin reaction was evaluated 24 and 48 hours later. RESULTS: A statistically significant difference (P < .05) in DTH skin reaction at 24 and 48 hours was observed between postoperative days 1 to 5 in the extraperitoneal and laparotomy groups with respect to baseline and the control group. Statistically significant differences were found in postoperative days 1, 4, and 5 between laparoscopy and laparotomy. The laparoscopy group showed a statistically significant decrease in DTH skin induration on postoperative day 2 when compared with the control group. At postoperative day 7 and 8 there was no statistical difference in DTH skin response comparing baseline values or between groups. CONCLUSIONS: These results suggest that in a pediatric animal model, abdominal surgical procedures accompanied by extensive tissue dissection produce a cellular immunosuppression, lasting up to 7 days, which is not observed in less invasive procedures. Observations concerning lesser immunosuppressive effects of laparoscopy when compared with laparotomy in adult models, as previously described by our laboratory, were also found in this pediatric model.

Phlegmasia cerulea dolens: the role of non-operative therapy.

Thrombectomy and thrombolysis are often advocated in the treatment of phlegmasia cerulea dolens, but frequently result in incomplete clot removal, recurrence of thrombosis, local and systemic hemorrhagic complications and chronic venous stasis; this state is associated with a rate of major amputation and death of up to 50%. Non-operative therapy includes elevation, hydration and heparinization and excludes all methods aimed at surgical removal or chemical lysis of the thrombus. In 1982 it was decided to use non-operative therapy as the first line of treatment for phlegmasia cerulea dolens. In the last 9 years seven extremities in six patients with this condition have been treated. One patient had advanced gangrene on presentation and one underwent emergency thrombectomy. Five extremities (in five patients) were treated with non-operative therapy. Ischemia was rapidly corrected in all five patients. Edema resolved completely after 3-4 days in four patients. There were no complications attributable to the therapy. Two of six (33%) patients died from terminal disease. Non-operative therapy appears to be effective in preventing limb loss and avoiding the risks of thrombectomy and thrombolysis in critically ill patients.