RESUMO
BACKGROUND: Hemorrhoids are an extremely rare condition in children, and data on its incidence and treatment in the pediatric population remains scarce. We retrospectively reviewed children who underwent sclerotherapy for internal hemorrhoids, and analyzed patients' characteristics and outcomes. METHODS: A total of 14 pediatric patients who underwent sclerotherapy were included. Patients' ages and the required amount of polidocanol, depending on the grade of hemorrhoids, and the correlation between age and volume of sclerosant, were statistically analyzed. RESULTS: Patients had a male predominance with a ratio of 2.5:1 (grade 2:6 patients, grade 3:8 patients). Four children had underlying conditions including portal hypertension and Klippel-Trenaunay syndrome. Of the 14 patients, 43% had constipation requiring medication or enema. Only one minor complication, a perianal ulceration, was found to be associated with sclerotherapy. Patients with grade 3 hemorrhoids required a significantly larger amount of polidocanol than those with grade 2 hemorrhoids. Two patients with grade 3 hemorrhoids required a second session of treatment for recurrence. The success rate of sclerotherapy with polidocanol was 86%. CONCLUSIONS: Sclerotherapy with polidocanol is a safe, effective, and less invasive treatment option for internal hemorrhoids in children. Further studies are needed to investigate this treatment approach.
Assuntos
Hemorroidas , Escleroterapia , Criança , Hemorroidas/tratamento farmacológico , Humanos , Masculino , Polidocanol , Polietilenoglicóis/efeitos adversos , Estudos Retrospectivos , Soluções Esclerosantes/uso terapêutico , Escleroterapia/efeitos adversos , Resultado do TratamentoRESUMO
Naive lymphocytes systemically recirculate for immunosurveillance inspecting foreign antigens and pathogens in the body. Trafficking behavior such as the migration pathway and transit time within the gastrointestinal tract, however, remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred to a congeneic host that had undergone mesenteric lymphadenectomy. The migration pathway was investigated using newly developed four-color immunohistochemistry and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from which they emerged in mesenteric lymph around 4 h after intravenous injection. Immunohistochemistry showed that donor TDLs predominantly transmigrated across high endothelial venules (HEVs) at the interfollicular area of the Peyer's patches (PPs), then exited into the LYVE-1+ efferent lymphatics, that were close to the venules. The rapid recirculation depended largely on the local expression of unsulfated sialyl-Lewis X on these venules where putative dendritic cells (DCs) were associated underneath. Recruited naive T cells briefly made contact with resident DCs before exiting to the lymphatics in the steady state. In some transplant settings, however, the T cells retained contact with DCs and were sensitized and differentiated into activated T cells. In conclusion, we directly demonstrated that lymphocyte recirculation within the gut is a very rapid process. The interfollicular area of PPs functions as a strategically central site for rapid immunosurveillance where HEVs, efferent lymphatics and resident DCs converge. PPs can, however, generate alloreactive T cells, leading to exacerbation of graft-versus-host disease or gut allograft rejection.
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Endotélio/imunologia , Vigilância Imunológica/imunologia , Intestinos/imunologia , Linfócitos/imunologia , Oligossacarídeos/imunologia , Nódulos Linfáticos Agregados/imunologia , Animais , Circulação Sanguínea , Linhagem Celular Tumoral , Linfócitos/patologia , Camundongos , Ratos , Ratos Endogâmicos , Antígeno Sialil Lewis XAssuntos
Germinoma , Neoplasias do Timo , Humanos , Masculino , Germinoma/patologia , Germinoma/complicações , Criança , Neoplasias do Timo/patologia , PrognósticoRESUMO
PURPOSE: A prospective study was conducted to confirm the safety and efficacy of the selective sac extraction method (SSEM) of inguinal hernia repairs in children. METHODS: Primary endpoints of the study were the incidence of any complication related to the SSEM, or hernia recurrence. Secondary endpoints included the success rate of the SSEM, length of incision at the end of operation, and duration of operation. The incidence of contralateral manifestation of hernia was also examined. RESULTS: Between October 2009 and December 2011, a total of 317 repairs, 145 male repairs and 172 female repairs, were performed by applying the SSEM. There were three operative conversions, and the success rate of the SSEM was 99% in both male and female patients. The length of incision ranged from 4.0 to 12.5 mm (median 6.0 mm) and was ≤7.0 mm in 93% repairs. The incisional length for male repairs ranged from 4.0 to 12.5 mm (median 6.0 mm) and was ≤7.0 mm in 86% repairs, while it ranged from 4.0 to 9.0 mm (median 5.5 mm) in female repairs and was ≤6.5 mm in 96% repairs. The duration of the operation for unilateral repair ranged from 9 to 66 min (median 21 min). Eighty percent of repairs were examined 6-44 months (median 12 months) after the operation. There was one (0.4%) recurrence among 250 repairs and two (1.7%) cases of testicular dislocation among 115 male repairs. Contralateral hernia presented in 19 (9.5%) of 199 patients with unilateral hernia who underwent the follow-up. CONCLUSIONS: The feasibility of the SSEM was reconfirmed, and it was revealed that the complication and recurrence rates were low and acceptable. The SSEM is safe and effective, and should be a standard method for repairing inguinal hernia in children.
Assuntos
Hérnia Inguinal/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Seguimentos , Hérnia Inguinal/mortalidade , Humanos , Incidência , Lactente , Japão/epidemiologia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estudos Prospectivos , Recidiva , Resultado do Tratamento , CicatrizaçãoRESUMO
INTRODUCTION: Laparoscopic percutaneous extraperitoneal closure (LPEC) is an alternative to open repair for pediatric inguinal hernias; however, its application for boys remains controversial. In this study, we developed a technique to enhance the safety and feasibility of LPEC. MATERIAL AND SURGICAL TECHNIQUE: In our technique, forceps are used to pull up the peritoneum ahead on the route, creating a space between the peritoneum and structures, including gonadal vessels and vas deferens. This potentially decreases the risk of perioperative injury of these structures. This technique also allows the needle to pass on the shortest course around the inguinal ring without crossing the vas deferens, possibly lowering the likelihood of injury and preventing excessively high ligation of the vaginalis process. DISCUSSION: Our technique diversifies the LPEC methods, thereby augmenting the feasibility and safety of the procedure.
Assuntos
Hérnia Inguinal , Laparoscopia , Masculino , Criança , Humanos , Lactente , Hérnia Inguinal/cirurgia , Resultado do Tratamento , Herniorrafia/métodos , Laparoscopia/métodos , Instrumentos Cirúrgicos , Estudos RetrospectivosRESUMO
We herein report a case of cystic-type congenital biliary dilatation (CBD) in whom an extremely rare anomalous duplication of the common bile duct and pancreaticobiliary maljunction were diagnosed intraoperatively by meticulous surgical manipulations via conventional open surgery. By performing a dissection at the outer epicholedochal layer of the cyst, a thin cord-like structure shown to be the distal part of the common bile duct was identified. A further exploration revealed that the most distal (extra- and intrapancreatic) part of the common bile duct was duplicated, and each branch of the duct was connected to the main and accessory pancreatic ducts. The experience with our case and a literature review showed that extrahepatic bile duct duplication is generally associated with pancreaticobiliary maljunction and CBD. We conclude that an extremely careful exploration with delicate and meticulous surgical manipulation is essential to identify these morphological anomalies and prevent intraoperative and postoperative complications of CBD, such as pancreatic duct injury or pancreatitis.
Assuntos
Anormalidades Múltiplas , Ductos Biliares Extra-Hepáticos/anormalidades , Ductos Biliares Extra-Hepáticos/cirurgia , Sistema Biliar/patologia , Cisto do Colédoco/cirurgia , Ductos Pancreáticos/anormalidades , Ductos Pancreáticos/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Cisto do Colédoco/diagnóstico , Dilatação Patológica/congênito , Feminino , Humanos , Lactente , Complicações Intraoperatórias/prevenção & controle , Período Intraoperatório , Complicações Pós-Operatórias/prevenção & controleRESUMO
Background: Although adhesive strapping (AS) for pediatric umbilical hernia (UH), which was once obsolete, has been reconsidered as a common practice in Japan, its efficacy is still unclear. This study aimed to evaluate its efficacy by reviewing related articles. Methods: A comprehensive literature search of PubMed, Cochrane, Google Scholar, and Igaku Chuo Zasshi via Ichushi-Web was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Cohort studies reporting on the UH closure rate after AS compared with observation-only management were included. Results: A total of 10 cohort studies were included, and the overall UH closure rate was not statistically significant (p=0.31, risk ratio (RR)=0.76, 95% confidence interval (CI) 0.45 to 1.28). However, there were significant differences in the UH closure rate at the age of 6 months (p<0.01, RR=0.55, 95% CI 0.41 to 0.75) and the efficacy of preventing protruding umbilici with redundant skin (p=0.049, RR=0.16, 95% CI 0.03 to 0.99). Conclusions: Although the efficacy of AS on UH compared with observation-only management did not differ in terms of the UH closure rate, the application of AS may be effective for faster UH closure and the prevention of protruding umbilici. However, due to the high heterogeneity of the study, further large-scale studies, particularly randomized controlled trials, are warranted to reach a conclusion. PROSPERO registration number: CRD42022314417.
RESUMO
In this review article, we discussed the pathogenesis, pathophysiology, diagnosis and treatment of acute appendicitis in children. Indications for early surgery, the operative methods of laparoscopic appendectomy and the treatment outcome are also presented.
Assuntos
Apendicite/terapia , Serviços Médicos de Emergência , Doença Aguda , Adolescente , Anestesia/métodos , Apendicectomia/métodos , Apendicite/diagnóstico , Apendicite/etiologia , Apendicite/fisiopatologia , Criança , Pré-Escolar , Humanos , Laparoscopia/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia Doppler em CoresRESUMO
BACKGROUND/PURPOSE: The delayed local treatment approach (DL) in high-risk neuroblastoma (HR-NB) refers to the process in which tumor resection is performed after the completion of all the courses of chemotherapy, including myeloablative high-dose chemotherapy (HDC). Alternatively, in the conventional local treatment approach (CL), tumor resection is performed during induction chemotherapy. In this study, we compared the surgical outcomes in HR-NB patients treated by CL and DL. METHOD: Forty-seven patients with abdominal HR-NB underwent primary tumor resection from 2002 to 2018. The timing of surgery was generally determined by following the trials and guidelines available at the time. The outcomes and surgical complications between the two strategies were compared. RESULT: Operation time, blood loss, and postoperative WBC counts were lower in the DL group (nâ¯=â¯25) when compared to the CL group (nâ¯=â¯22), statistical significance notwithstanding. Major vascular structures were less frequently encased in the DL group tumors, while immediate surgical complications were significantly more frequent in the CL group (Pâ¯<â¯0.05). Furthermore, the 3-year EFSs were 50.0% and 53.9% in the DL and CL groups, respectively. CONCLUSION: DL appears to be a feasible and effective treatment option for HR-NB. Nonetheless, further verifications using larger cohorts are warranted. LEVEL OF EVIDENCE: Treatment study, Level III.
Assuntos
Neuroblastoma , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Terapia Combinada , Humanos , Quimioterapia de Indução , Neuroblastoma/tratamento farmacológico , Neuroblastoma/epidemiologia , Neuroblastoma/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
This report describes a new experimental procedure, a rat unilateral, orthotopic lung transplantation with cold storage, and evaluates its relevancy and reliability to study the early events during cold ischemia/reperfusion (I/R) injury. This model, using the cuff technique, does not require extensive training and is relatively easy to be established. The model can induce reproducible degrees of pulmonary graft injury including impaired gas exchange, proinflammatory cytokine upregulation, or inflammatory infiltrates, depending on the preservation time. The results are consistent with the previous clinical evidence, thus suggesting that this model is a valid and reliable animal model of cold I/R injury.
Assuntos
Criopreservação , Lesão Pulmonar/etiologia , Transplante de Pulmão/efeitos adversos , Preservação de Órgãos , Traumatismo por Reperfusão/etiologia , Animais , Modelos Animais de Doenças , Transplante de Pulmão/métodos , Masculino , Ratos , Ratos Endogâmicos LewRESUMO
BACKGROUND: Multicenter study was undertaken to analyze the results of laparoscopic and open Kasai portoenterostomy. METHODS: Subjects were infants with type III biliary atresia who underwent open operation (n = 106) or laparoscopic operation (n = 21) between January 2012 and December 2015. Clinical data were compared between open and laparoscopic operations (2016-0534). Propensity score matching was performed to reduce the effect of treatment selection bias. Multivariate analyses were used to estimate the effect of the surgical approach on the jaundice clearance rate and the native liver survival rate. RESULTS: The postoperative jaundice clearance rate and the 1-year native liver survival rate were not significantly different between open and laparoscopic operations. Rates of cholangitis and major complications of laparoscopic operation were comparable to those of open operation. Blood loss, time to resume oral intake, time to drain removal, and duration of analgesic usage of laparoscopic operation were significantly superior to those of open operation. Similar results were observed when analysis was adjusted based on propensity score. Multivariate analyses demonstrated that only age at operation was a poor prognostic factor. CONCLUSION: Laparoscopic Kasai portoenterostomy was associated with several favorable perioperative outcomes compared with open Kasai portoenterostomy. The difference of surgical approach was not a significant independent predictor.
Assuntos
Atresia Biliar/cirurgia , Portoenterostomia Hepática/métodos , Atresia Biliar/epidemiologia , Feminino , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Laparoscopia , Masculino , Portoenterostomia Hepática/estatística & dados numéricos , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Ischemia/reperfusion evokes a functionally relevant inflammatory response within the muscularis propria of small bowel grafts by activation of resident macrophages and leukocyte recruitment. We hypothesized that immunomodulatory perioperative treatment with glycine attenuates the proinflammatory cascade and improves smooth muscle dysfunction of small bowel grafts. METHODS: Orthotopic SBTx was performed in Lewis rats. Glycine (1 mg/g body weight) was infused (0.1 mL/g/hr) for 2 hr before harvest as preconditioning in the donor, and for 2 hr from the onset of reperfusion in the recipient. Transplanted vehicle (isotonic saline)-treated animals and naive animals served as controls. Rats were sacrificed after 3 hr and 24 hr. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by real-time-PCR. Jejunal circular smooth muscle contractility was assessed in a standard organ bath. RESULTS: Compared with vehicle controls, glycine-treated graft muscularis expressed a significant alleviation in mRNA peak expression for IL-6, IL-1beta, ICAM-1, MCP-1, TNFalpha, COX-2, and iNOS. Also glycine-treated grafts exhibited significantly less infiltration with ED-1-positive macrophages and MPO-positive neutrophils as well as reduced apoptosis. Concurrent to these results, vehicle controls showed an 80% decrease in smooth muscle contractility, whereas glycine-treated animals exhibited only a 40% decrease in contractile activity compared with controls. CONCLUSIONS: The data indicate that perioperative glycine treatment reduces the molecular and cellular inflammatory response within the grafts and improves smooth muscle dysfunction after transplantation. Therefore, the glycine-activated chloride channel on resident and infiltrating leukocytes could be a promising pharmacologic target to attenuate ischemia/reperfusion injury after ITx.
Assuntos
Glicina/uso terapêutico , Intestinos/transplante , Período Intraoperatório , Músculo Liso/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Ciclo-Oxigenase 2/genética , Primers do DNA , Regulação da Expressão Gênica , Molécula 1 de Adesão Intercelular/genética , Interleucinas/genética , Intestinos/patologia , Masculino , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiopatologia , Óxido Nítrico Sintase Tipo II/genética , Ratos , Ratos Endogâmicos Lew , Traumatismo por Reperfusão/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Isogênico/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: It has been shown that in transplantation the intestinal muscularis may act as an immunologically active layer via the activation of resident macrophages and the recruitment of leukocytes. Thus we hypothesized that inflammation within the intestinal muscularis is involved in the promotion of acute rejection in intestinal allografts and that this causes smooth muscle dysfunction. METHODS: Orthotopic allogenic and small bowel transplantation (Brown-Norway rats-Lewis rats) was performed without immunosuppression. Animals were sacrificed 1, 4, and 7 days after small bowel transplantation. Isogenic transplanted grafts (Brown-Norway rats-Brown-Norway rats) as well as nontransplanted bowel served as controls. Mediator mRNA expression was determined by real-time reverse-transcriptase polymerase chain reaction. Leukocyte infiltration was evaluated in muscularis whole mounts by immunohistochemistry. Apoptosis was evaluated by TdT-mediated dUTP-X nick end labeling assay. Contractility was assessed in a standard organ bath under bethanechol stimulation. Statistical analysis was performed using a Student's t test and one-way analysis of variance. RESULTS: Transplanted animals showed a significant early inflammatory response within the graft muscularis because of reperfusion injury. Only allogenic transplanted animals exhibited a significant second molecular inflammatory peak in the muscularis during rejection (mRNA induction for interleukin (IL)-6, intercellular adhesion molecule-1, monocyte chemoattractant protein (MCP)-1, interferon-gamma, IL-2, tumor necrosis factor-alpha, IL-10, inducible nitric oxide synthase). These findings were associated with significant leukocyte infiltration within the muscularis, increasing apoptotic cells and massive impairment of smooth muscle contractile activity by 78%. CONCLUSIONS: The data shows that transplantation results in an early and temporary inflammatory response within the intestinal graft muscularis, that is reactivated and intensified during acute allograft rejection. The immunoreaction within the intestinal muscularis leads to intestinal allograft smooth muscle dysfunction.
Assuntos
Rejeição de Enxerto/patologia , Intestinos/transplante , Transplante Homólogo/patologia , Doença Aguda , Animais , Betanecol/farmacologia , Inflamação/etiologia , Intestinos/patologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/patologia , Músculo Liso/fisiopatologia , Músculo Liso/transplante , Peroxidase/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante Isogênico/patologiaRESUMO
BACKGROUND: Acute rejection in small bowel transplantation is associated with dysmotility. Therefore, host and organ not only face the threat of destructive immunological processes but also the risk of bacterial translocation, endotoxemia, and systemic inflammatory response syndrome. We hypothesized that dysmotility during acute rejection is based on an alloreactive leukocyte infiltrate and coexpression of the kinetically active mediator inducible nitric oxide synthase (iNOS) in the muscularis propria. MATERIALS AND METHODS: Allogenic and isogenic rat small bowel transplantation (SBTx; Brown Norway [BN] to Lewis and BN to BN) was performed without immunosuppression. Animals were sacrificed 4 and 7 d after SBTx. Leukocyte infiltration and iNOS protein was investigated by immunohistochemistry and immunohistology. Real-time reverse transcription polymer chain reaction was used to detect iNOS expression. Griess reaction was used to evaluate NO production. Spontaneous, bethanechol-stimulated, and L-N(6)-(1-iminoethyl)-L-Lysin-blocked jejunal circular muscle contractions were measured in a standard organ bath in vitro. RESULTS: On d 7 after SBTx, allogenic transplanted animals showed significant infiltration with ED-1- and ED-2-positive monocytes and macrophages within the muscularis parallel to the manifestation of acute rejection. Additionally, immunohistochemistry localized iNOS protein in leukocytes within the muscularis. Reverse transcription polymer chain reaction showed a significant increase in iNOS mRNA expression (460-fold) in allogenic transplanted muscularis compared to isogenic transplanted muscularis (2.5-fold). Compared to controls, allogenic grafts showed a 73% decrease in smooth muscle contractility, while isogenic grafts showed only an 8% decrease of contractility on d 7. L-N(6)-(1-iminoethyl)-L-Lysin application in vitro significantly improved muscle contractility and decreased NO production. CONCLUSION: The data show that inflammation associated iNOS expression in the intestinal graft muscularis is involved in motoric graft dysfunction during acute rejection.
Assuntos
Rejeição de Enxerto/enzimologia , Intestino Delgado/transplante , Leucócitos/fisiologia , Músculo Liso/fisiopatologia , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Motilidade Gastrointestinal , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Imuno-Histoquímica , Técnicas In Vitro , Inflamação/fisiopatologia , Intestino Delgado/enzimologia , Intestino Delgado/patologia , Intestino Delgado/fisiopatologia , Leucócitos/patologia , Masculino , Músculo Liso/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Transplante IsogênicoRESUMO
BACKGROUND/PURPOSE: Differences in clinical features between congenital pulmonary airway malformation (CPAM) and bronchial atresia (BA) have not yet been clearly described. METHODS: We retrospectively reviewed 112 patients with a pathological diagnosis of CPAM or BA. The clinical parameters were statistically analyzed between these diseases. RESULTS: Seventy-one patients received prenatal diagnosis and 41 received postnatal diagnosis. The percentage of prenatal diagnosis was significantly higher in CPAM patients (84% vs 50%, pâ¯<â¯0.001). Among patients with prenatal diagnosis, the backgrounds were not different between the two diseases except for the number of Caesarean sections (81% vs 9%, pâ¯<â¯0.0001). The numbers of patients that underwent fetal interventions and emergent neonatal surgery were higher in CPAM (51% vs 15%, pâ¯<â¯0.01 and 76% vs 12%, pâ¯<â¯0.0001), although there was no statistical difference in survival rate (86% vs 97%, pâ¯=â¯0.2). In patients receiving postnatal diagnosis, pneumonia was the primary symptom in most BA patients, whereas respiratory distress was the major symptom in patients with CPAM. Age at presentation of the primary symptom was significantly older in BA patients (4.2â¯years vs 1.2â¯years, pâ¯<â¯0.005). CONCLUSION: CPAM and BA have distinct clinical features in terms of therapeutic and natural history. Careful imaging evaluation and pathological analysis can lead to an accurate diagnosis of BA. TYPE OF STUDY: Prognostic study. LEVEL OF EVIDENCE: Level II. This study is categorized as a "Prognostic Study" with LEVEL III of Evidence.
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Broncopatias/diagnóstico , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico , Broncopatias/congênito , Broncopatias/terapia , Malformação Adenomatoide Cística Congênita do Pulmão/terapia , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVES: Granulocyte apheresis (GCAP), involving the removal of granulocytes from the blood, may improve clinical symptoms and facilitate a reduction in the dose of steroids in adult patients with ulcerative colitis. As a preliminary trial, GCAP was used to taper the dose of steroids in 4 pediatric patients with ulcerative colitis. METHODS: Three males and 1 female ranging from 11 to 17 years old were treated with GCAP once per week for 5 consecutive weeks/course. The ages of patients at clinical onset ranged from 8 to 12 years and the length of time from the clinical onset to GCAP treatment ranged from 28 to 58 months (median, 38.5 months). RESULTS: In 2 patients, symptoms and signs indicating disease activity improved after 2 courses of GCAP. Laboratory data and endoscopic findings also improved after treatment and the clinical efficacy was judged to be excellent in these patients. In 1 patient, GCAP improved laboratory and endoscopic hallmarks, but bloody stools persisted. Finally, the treatment was ineffective in the fourth patient who eventually underwent surgery. CONCLUSIONS: GCAP is effective in improving clinical symptoms and may play an important role in converting steroid therapy to other treatments in children with steroid-refractory or steroid-dependent ulcerative colitis.
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Colite Ulcerativa/terapia , Granulócitos , Leucaférese , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Criança , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Mesalamina/uso terapêutico , Projetos Piloto , Prednisolona/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The effect of graft length on rejection reaction in small bowel transplantation (SBT), which is poorly understood, is tested using rat allogenic SBT models with a short course of tacrolimus. MATERIALS AND METHODS: Inbred Brown Norway rats (major histocompatibility complex: RT1) and Lewis rats (RT1) were used as donors and recipients, respectively. The intestinal tract of the recipient was partially or totally replaced by segmental (15 cm) or whole (70 cm) donor intestine, using two different SBT models. With tacrolimus treatment (0.64 mg/kg per day, 0-13 postoperative days, intramuscularly), recipients' body weights and their survival were evaluated. To compare the extent of peripheral chimerism, donor passenger leukocytes were followed using flow cytometry with a donor-specific monoclonal antibody, OX-27. For the periodical histologic analysis, heterotopic SBT and protocol biopsies of the graft were also performed with short or long intestinal grafts. RESULTS: In a classical Monchik and Russell orthotopic SBT model, whole SBT recipients survived more than 60 days. However, all of the allogenic segmental SBT recipients died within 14 days without histologic sign of graft rejection. In the modified orthotopic SBT model using a cuff technique without systemic clamping, all recipients with segmental allograft survived longer than 29 days. However, recipients with whole graft tended to survive longer than those with segmental graft. The suffering period, lasting from the onset of rejection to death, was significantly shorter in the segmental group than in the whole group. Flow cytometric analysis showed that recipients with whole intestinal grafts had significantly higher ratio of donor passenger leukocytes in peripheral blood. Histologic studies of the protocol biopsies showed that the shorter graft tended to be more severely rejected than the longer graft. CONCLUSIONS: We have demonstrated experimentally that long intestinal grafts have immunologic advantage over short grafts.
Assuntos
Sobrevivência de Enxerto/imunologia , Intestino Delgado/transplante , Transplante Homólogo/imunologia , Animais , Imunossupressores/uso terapêutico , Intestino Delgado/imunologia , Complexo Principal de Histocompatibilidade , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Tacrolimo/uso terapêutico , Transplante Heterotópico/imunologiaRESUMO
BACKGROUND: Donor passenger leukocytes (DPLs) that migrate after organ transplantation stimulate the recipient immune system and normally cause rejection and graft vs. host reaction. However, DPLs also contribute to the unresponsiveness to the donor organ. The quantity and quality of these migrating cells are considered dependent on individual transplanted organs. We compared the DPLs of the liver, which might contain somatic stem cells, with those of intestinal grafts that have highly immunogenetic cells. To study DPLs over a long period, we used green fluorescent protein (GFP) transgenic (Tg) rats developed by us as donors. METHODS: We performed orthotopic liver transplantation (OLT) and small bowel transplantation (SBT) from GFP Tg rats to wild recipients. A short course of tacrolimus (0.64 mg/kg, intramuscularly) was used to prevent antigenicity of the GFP. The fate of the DPLs in the peripheral blood and the recipient bone marrow was monitored by flow cytometry. Using long-surviving recipients, the GFP(+) cells in the graft and various host immunologic organs were measured and characterized by immunohistochemical staining. RESULTS: In both groups, the numbers of the GFP(+) cells in the peripheral blood increased transiently and then gradually decreased to undetectable levels. While no GFP(+) cells were identified in the long-surviving-recipient bone marrow, there were a few GFP(+) cells in the graft liver, graft mesenteric lymph nodes and the recipient spleen. These cells showed major histocompatibility complex (MHC) class II antigen. There was no significant difference in the migration patterns of the GFP(+) cells in the OLT and SBT rats. CONCLUSIONS: In both the OLT and SBT groups, the DPLs migrated transiently in the recipient peripheral blood. A small numbers of MHC class II-positive DPLs were present at the graft site and in the host spleen, but not in the bone marrow. There were no significant differences in the migration patterns of the DPLs between the OLT and SBT rats over the long term.
Assuntos
Intestino Delgado/citologia , Intestino Delgado/transplante , Leucócitos/citologia , Transplante de Fígado , Doadores de Tecidos , Animais , Animais Geneticamente Modificados , Peso Corporal , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Sobrevivência Celular , Citometria de Fluxo , Genes Reporter/genética , Proteínas de Fluorescência Verde , Imuno-Histoquímica , Intestino Delgado/imunologia , Intestino Delgado/cirurgia , Leucócitos/imunologia , Leucócitos/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/cirurgia , Transplante de Fígado/imunologia , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Linfonodos/citologia , Linfonodos/imunologia , Masculino , Ratos , Ratos Wistar , Baço/citologia , Baço/imunologia , Taxa de Sobrevida , Tacrolimo/farmacologiaRESUMO
BACKGROUND: Intestinal grafts greatly affect nutrition and immunology in the host. The growth of the recipient and incidence of graft-versus-host disease depend on graft length. A larger graft may affect the host immune system, but little is known about how the length of the intestinal graft severely affects surgical intervention. We developed a cervical small bowel transplantation (SBT) rat model that minimized technical variations using a cuff method and studied the effects of graft length on surgical damage in SBT. MATERIALS AND METHODS: We transplanted a whole (70 cm) or partial (15 cm) intestine into a syngeneic rat combination of LEW (MHC haplotype: RT1(l)) to LEW and evaluated changes in perioperative hemodynamics and the endogenous endotoxin level. Natural killer (NK) cell activity in the peripheral blood and the immunologic response of the recipient spleen were also studied. RESULTS: In the whole SBT model, body weight loss was more severe than in the segmental SBT model; the rats in the former model often died, while all in the latter survived indefinitely. The systemic blood pressure markedly decreased in the whole SBT group immediately after reperfusion. The proliferative activity of splenic lymphocytes stimulated by concanavalin A was also more severely inhibited in the former model than in the latter postoperatively. NK cell activity in the whole SBT rats declined more severely than the segmental SBT rats 3 days postoperatively. CONCLUSION: The longer graft severely induced surgical intervention; and influenced host immunosuppression, resulting in the higher mortality in rats undergoing whole SBT.
Assuntos
Intestino Delgado/transplante , Imunologia de Transplantes , Transplante/efeitos adversos , Transplante/métodos , Animais , Pressão Sanguínea/fisiologia , Peso Corporal , Endotoxinas/metabolismo , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Ratos , Imunologia de Transplantes/fisiologiaRESUMO
Two kinds of surgical models of small intestinal transplantation (SITx) in rats, namely heterotopic (HIT) and orthotopic transplantion (OIT), have been reviewed. In OIT, the small intestine of the recipient is removed and the transplanted intestine replaces it in continuity. On the other hand, in the HIT model, the small intestinal grafts are rendered dysfunctional without alimentary tract continuity. Histological evidence showed that acute rejection appeared earlier in HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa produced in the chronic rejection process were more pronounced in HIT allografts. The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal trophic factors, because oral feedings can stimulate tropic hormones for mucosal growth, and provide nutrients for enterocytes. Intestinal permeability was consistently higher after HIT than after OIT. The HIT grafts demonstrated less contractility and less response to chemical stimulation than did OIT grafts. The OIT models are advantageous in studies of intraluminal nutrients, and intestinal secretions in these models might modulate the intestinal immune status and possibly delay rejection. The superior intestinal barrier function and the delayed onset of rejection in OIT rats suggest that nutrients and other factors in the succus entericus are important for the maintenance of intestinal graft function.