RESUMO
PURPOSE: Right colectomy (RC) is a frequently performed procedure. Beneath standard conventional open surgery (COS), various minimally invasive techniques had been introduced. Several advantages had recently been described for robotic approaches over COS or conventional laparoscopy. Nevertheless, novel minimally invasive techniques require continuous benchmarking against standard COS to gain maximum patient safety. Bowel dysfunction is a frequent problem after RC. Together with general complication rates postoperative bowel recovery are used as surrogate parameters for postoperative patient outcome in this study. METHODS: Retrospective, 10-year single-center analysis of consecutive patients who underwent sequentially either COS (n = 22), robotic-assisted (ECA: n = 39), or total robotic surgery (ICA: n = 56) for oncologic RC was performed. RESULTS: The conversion from robotic to open surgery rate was low (overall: 3.2%). Slightly longer duration of surgery had been observed during the early phase after introduction of the robotic program to RC (ECA versus COS, p = 0.044), but not anymore thereafter (versus ICA). No differences were observed in oncologic parameters including rates of tumor-negative margins, lymph node-positive patients, and lymph node yield during mesocolic excision. Both robotic approaches are beneficial regarding postoperative complication rates, especially wound infections, and shorter length of in-hospital stay compared with COS. The duration until first postoperative stool is the shortest after ICA (COS: 4 [2-8] days, ECA: 3 [1-6] days, ICA: 3 [1-5] days, p = 0.0004). Regression analyses reveal neither a longer duration of surgery nor the extent of mesocolic excision, but the degree of minimally invasiveness and postoperative systemic inflammation contribute to postoperative bowel dysfunction, which prolongs postoperative in-hospital stay significantly. CONCLUSION: The current study reflects the institutional learning curve of oncologic RC during implementation of robotic surgery from robotic-assisted to total robotic approach without compromises in oncologic results and patient safety. However, the total robotic approach is beneficial regarding postoperative bowel recovery and general patient outcome.
Assuntos
Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Curva de Aprendizado , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Colectomia/efeitos adversos , Colectomia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Resultado do TratamentoRESUMO
PURPOSE: To define the best possible outcomes for robotic-assisted low anterior rectum resection (RLAR) using total mesorectal excision (TME) in low-morbid patients, performed by expert robotic surgeons in German robotic centers. The benchmark values were derived from these results. METHODS: The data was retrospectively collected from five German expert centers. After patient exclusion (prior surgery, extended surgery, no prior anastomosis, hand-sewn anastomosis), the benchmark cohort was defined (n = 226). The median with interquartile range was first calculated for the individual centers. The 75th percentile of the median results was defined as the benchmark cutoff and represents the "perfect" achievable outcome. This applied to all benchmark values apart from lymph node yield, where the cutoff was defined as the 25th percentile (more lymph nodes are better). RESULTS: The benchmark values for conversion and intraoperative complication rates were ≤ 4.0% and ≤ 1.4%, respectively. For postoperative complications, the benchmark was ≤ 28% for "any" and ≤ 18.0% for major complications. The R0 and complete TME rate benchmarks were both 100%, with a lymph node yield of > 18. The benchmark for rate of anastomotic insufficiency was < 12.5% and 90-day mortality was 0%. Readmission rates should not exceed 4%. CONCLUSION: This outcome analysis of patients with low comorbidity undergoing RLAR may serve as a reference to evaluate surgical performance in robotic rectum resection.
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Laparoscopia , Protectomia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Benchmarking , Humanos , Complicações Pós-Operatórias , Neoplasias Retais/cirurgia , Reto/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do TratamentoRESUMO
Background Lung transplantation is the only treatment option for many patients with end-stage pulmonary disease. Therefore, postthoracotomy pain therapy is of vital interest. Thoracic epidural analgesia (EPI) is the "gold standard" for postthoracotomy pain, but especially in lung transplantation contraindications, and potential infectious complications limit its advantages. Under these circumstances surgically placed postthoracotomy catheter-assisted continuous paravertebral intercostal nerve block (PVB) could be of advantage. Methods We performed a retrospective cohort study of patients who underwent lung transplantation between 2005 and 2012. Groups were defined according to the type of postoperative pain therapy: PVB, EPI, and SYS (systemic analgesia). Total 44 patients were eligible. Results Postoperative opioid requirement of the PVB and EPI group was comparable and less than that of the SYS group. Patients of the PVB group were weaned earlier from mechanical ventilation after lung transplantation. Conclusion The potency of postoperative pain therapy of EPI and PVB seemed to be comparable and superior to SYS. Considering the risks and benefits, PVB could be a better choice than EPI for postthoracotomy pain therapy, especially in lung transplantation.
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Analgesia Epidural , Anestésicos Locais/administração & dosagem , Cateteres de Demora , Nervos Intercostais , Transplante de Pulmão/efeitos adversos , Bloqueio Nervoso/instrumentação , Dor Pós-Operatória/prevenção & controle , Toracotomia/efeitos adversos , Analgesia Epidural/efeitos adversos , Analgésicos Opioides/administração & dosagem , Anestésicos Locais/efeitos adversos , Humanos , Transplante de Pulmão/métodos , Bloqueio Nervoso/efeitos adversos , Bloqueio Nervoso/métodos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Desmame do RespiradorRESUMO
Acute rejection and respiratory infections are major risk factors for chronic lung allograft dysfunction (CLAD) after lung transplantation. To shed light on the enigmatic etiology of CLAD, we test the following hypotheses using a new experimental model: (i) Alloimmune-independent pulmonary inflammation reactivates alloimmunity. (ii) Alloimmunity enhances the susceptibility of the graft toward pathogen-associated molecular patterns. Pulmonary Fischer 344 to Lewis rat allografts were treated with lipopolysaccharide (LPS), which consistently results in lesions typical for CLAD. Grafts, local lymph nodes, and spleens were harvested before (day 28) and after LPS application (days 29, 33, and 40) for real-time RT-PCR and immunohistochemistry. Mixed lymphocyte reactions were performed on day 33. Four weeks after transplantation, lung allografts displayed mononuclear infiltrates compatible with acute rejection and overexpressed most components of the toll-like receptor system. Allografts but not secondary lymphoid organs expressed increased levels of Th1-type transcription factors and cytokines. LPS induced macrophage infiltration as well as mRNA expression of pro-inflammatory cytokines and effector molecules of innate immunity. Unexpectedly, T-cell reactivity was not enhanced by LPS. We conclude that prevention of CLAD might be accomplished by local suppression of Th1 cells in stable grafts and by controlling innate immunity during alloimmune-independent pulmonary inflammation.
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Imunidade Inata , Transplante de Pulmão , Pulmão/fisiopatologia , Aloenxertos , Animais , Bronquiolite Obliterante/cirurgia , Proliferação de Células , Doença Crônica , Citocinas/metabolismo , Sobrevivência de Enxerto , Imuno-Histoquímica , Inflamação , Leucócitos/citologia , Lipopolissacarídeos/química , Pulmão/patologia , Pneumopatias/cirurgia , Macrófagos/citologia , Macrófagos/patologia , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Células Th1/citologiaRESUMO
PURPOSE: The treatment of transsphincteric anal fistulas is a challenge between recurrence rate and incontinence. Many surgical and conservative procedures have been described in the treatment of anal fistulas. Fistulectomy and primary sphincter reconstruction (FPSR) has not gained great popularity in this field due to the risk of sphincter damage. The aim of this study is to evaluate FPSR in the treatment of transsphincteric fistulas. METHODS: We retrospectively analyzed 50 patients with high transsphincteric fistulas of cryptoglandular origin that were treated with FPSR between 2005 and 2008. Preoperative assessment included physical and proctologic examination. Continence and pain scores were evaluated preoperatively and postoperatively. RESULTS: In our 50 patients, 22 patients (44 %) had a previous proctologic operation and 11 patients (22 %) presented with recurrent fistulas. The fistulas existed for an average of 8 months. The operation time was 28 ± 16 min. Mean follow-up was 22± months. The fistula healed in 44 patients (88 %) who developed no recurrence. In five patients (10 %), the fistula healed, but they developed a recurrence in the observation period. In one patient (2 %), the fistula did not heal. Three patients developed low-grade incontinence for flatus, and one patient with 2° incontinence improved. Preoperatively and postoperatively calculated continence and pain scores showed a slight but significant elevation in the Clinical Continence Score, the German Society of Coloproctology Score showed no significant difference, and preexisting pain was reduced significantly by surgery. CONCLUSIONS: FPSR is a safe surgical procedure for the treatment of high transsphincteric anal fistula. The primary healing rate is high with a low risk of recurrence or incontinence.
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Canal Anal/patologia , Canal Anal/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Fístula Retal/cirurgia , Adulto , Idoso , Demografia , Incontinência Fecal/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Fístula Retal/complicaçõesRESUMO
BACKGROUND: Obstructed defecation syndrome is a multifactorial disorder of the defecation process. Stapled transanal rectal resection has been used to restore function in patients suffering from obstructed defecation syndrome. OBJECTIVE: The aim of this study was to use preoperative and postoperative dynamic pelvic floor MRI combined with clinical parameters to evaluate the outcome of stapled transanal rectal resection. DESIGN AND SETTING: A prospective cohort study was conducted in a tertiary care center. PATIENTS: A group of 140 women with obstructed defecation syndrome were evaluated. INTERVENTION: All 140 patients were initially treated conservatively with laxatives, increased fluid intake, pelvic floor exercises, and biofeedback. Stapled transanal rectal resection was performed in 30 patients with rectocele who did not show improvement in symptoms after at least 6 months of conservative treatment. MAIN OUTCOME MEASURES: Preoperative diagnostic workup consisted of dynamic pelvic floor MRI, clinical examination, coloscopy, and clinical scores (Cleveland Clinic constipation score, German Working group on Coloproctology continence score, and SF-36 quality-of-life questionnaire). Postoperatively, patients were reevaluated at 3 months by means of dynamic pelvic floor MRI, clinical examination, and clinical scores; clinical scores were repeated at 6 months after the operation. RESULTS: Postoperative dynamic pelvic floor MRI performed after a median of 3.4 months showed a decrease in rectocele size from 3.3 (interquartile range, 2.8-3.8) cm to 1.5 (1.2-2) cm (P < .001). The number of patients with intussusception decreased from 21 (70%) before the operation to none after the operation (P < .001). The size of cystoceles did not change. The number of patients with incomplete evacuation was significantly reduced (P < .001). With a mean follow-up of 18 ± 4 months, patients showed a significant improvement in the quality-of-life score (P < .001) but not in the continence scores. CONCLUSIONS: Stapled transanal rectal resection is an effective treatment option for patients with obstructed defecation syndrome associated with rectocele and intussusception.
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Defecação/fisiologia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Imageamento por Ressonância Magnética/métodos , Diafragma da Pelve/cirurgia , Doenças Retais/cirurgia , Grampeamento Cirúrgico/métodos , Idoso , Colonoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Doenças Retais/fisiopatologia , Estatísticas não Paramétricas , Síndrome , Resultado do TratamentoRESUMO
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. The majority of GISTs is located in the stomach. Only 3-5% of GISTs are located in the duodenum associated with an increased risk of gastrointestinal bleeding as primary manifestation. With response rates of up to 90%, but complications like bleeding due to tumor necrosis in 3%, imatinib mesylate dramatically altered the pre- and postoperative therapy for GIST patients. CASE PRESENTATION: A 58-year-old female patient presented with acute upper gastrointestinal bleeding 2 weeks after a giant GIST of the duodenum had been diagnosed. Neoadjuvant imatinib therapy had been initiated to achieve a tumor downsizing prior to surgery. During emergency laparotomy a partial duodenopancreatectomy was performed to achieve a complete resection of the mass. Histology revealed a high-malignancy GIST infiltrating the duodenal wall. Adjuvant imatinib therapy was initiated. At follow-up (19 months) the patient is still alive and healthy. CONCLUSION: Giant GISTs of the duodenum are rare and - in contrast to other localizations - harbour a higher risk of serious bleeding as primary manifestation. Tumor necrosis and tumor bleeding are rare but typical adverse effects of imatinib therapy especially during treatment of high-malignancy GIST. In GIST patients with increased risk of tumor bleeding neoadjuvant imatinib therapy should thoroughly be performed during hospitalization. In cases of duodenal GIST primary surgery should be considered as treatment alternative.
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Neoplasias Duodenais/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Benzamidas , Neoplasias Duodenais/complicações , Neoplasias Duodenais/cirurgia , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib , Pessoa de Meia-Idade , Terapia Neoadjuvante , Cuidados Pré-Operatórios , Resultado do TratamentoRESUMO
PURPOSE: This study was designed to analyze the efficacy of the Surgisis Anal Fistula Plug for the closure of transsphincteric anorectal fistulas. METHODS: Patients with single transsphincteric anorectal fistulas were prospectively enrolled. Setons were used in all tracts for at least eight weeks before surgery. Continence, surgical variables, complications, and healing rates were recorded. Surgery was performed in a standardized manner. The fistula tract and external opening were debrided, the tract was irrigated, and the plug was placed. The external opening was left open. Success was defined as the absence of drainage and closure of the external opening. Follow-up examinations were performed at 2 days, 2, 4, 6, and 12 weeks, and 6 and 12 months after surgery. RESULTS: Sixty patients were enrolled. Seventeen patients were smokers, and ten had diabetes mellitus. The mean surgical time was 23 (range, 13-50) minutes; no morbidity occurred. The overall success rate after 12 months was 62%. Nineteen fistulas recurred, and four fistulas never completely healed. The success rate was significantly lower in smokers and diabetics. Two patients had a plug dislodgement, and plugs were successfully replaced. No change in continence was observed. CONCLUSION: Because there is still no standard for the treatment of high transsphincteric fistulas and because recurrence rates are high for all procedures performed, new techniques are needed for this complex disease. Our success rate of 62% is promising because this technique can be used as a first approach to close the fistula tract without destruction of the sphincter muscle.
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Implantes Absorvíveis , Curativos Biológicos , Fístula Retal/cirurgia , Tampões Cirúrgicos , Adulto , Idoso , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fístula Retal/complicações , Fístula Retal/patologia , Resultado do Tratamento , CicatrizaçãoRESUMO
PURPOSE: Widely differing surgical methods have been propagated to correct symptomatic rectocele. With transvaginal rectal repair (TVRR), we evaluate a method to reestablish the continuity of the rectal muscle wall, strengthen the weakened tunica muscularis, and restore normal rectal capacity and function. METHODS: Between 1997 and 2003, 102 female patients were treated by TVRR in cases of symptomatic rectocele. Patients without improvement following a stringent conservative treatment for a minimum of 3-6 months were selected for TVRR procedure. Patients with intussusception and slow-transit constipation were excluded from the study. To achieve optimal stabilization of the rectal wall, a transverse gathering of the rectocele was performed by a transvaginal access. RESULTS: Average patient age was 60.9 years (47-76 years), operation time was 36.5 minutes (29-67 min.), in-hospital treatment lasted 4.1 days (2-7 days), and follow-up was 18.1 months (3-48 months). We observed complications in 11% of cases. Three months after the operation, 81% of the patients were symptom-free or improved. Following an average observation time of 18.1 months (3-48 months), 70% were still symptom-free or improved. CONCLUSIONS: TVRR allows easy access for rectocele repair with a low rate of complications.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Retocele/cirurgia , Reto/cirurgia , Vagina/cirurgia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Pós-OperatóriosRESUMO
PURPOSE: Lung allografts are threatened by primary graft dysfunction, infections, and rejection. Novel therapies protecting pulmonary allografts are badly needed. Keratinocyte growth factor (KGF) protects the lung against a variety of injurious stimuli and exerts anti-inflammatory effects. The aim of the study was to test the potential of recombinant truncated KGF (DeltaN23-KGF, palifermin) to attenuate pulmonary allograft rejection. MATERIALS AND METHODS: Intratracheal instillation of 5 mg/kg DeltaN23-KGF was performed twice in donor rats on days 3 and 2 before explantation of the lung. In control animals, an equivalent volume of vehicle was instilled. Left lungs were transplanted in the fully allogeneic Dark Agouti to Lewis rat strain combination and in the less stringent Fischer 344 to Wistar Kyoto combination. Allograft recipients were additionally treated with DeltaN23-KGF post-transplantation. Graft outcome, leukocytic infiltration, and major histocompatibility complex (MHC) class II antigen expression was analyzed. RESULTS: In both rat strain combinations, DeltaN23-KGF treatment did not improve pulmonary allograft outcome. Graft infiltration by macrophages and T lymphocytes remained unchanged. In addition, we demonstrated that MHC class II antigens were more abundant in KGF-treated allografts compared to control-treated grafts, which probably results in an increased alloreactivity. CONCLUSION: In conclusion, intratracheal DeltaN23-KGF treatment is not effective to prevent acute pulmonary allograft rejection.
Assuntos
Fator 7 de Crescimento de Fibroblastos/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pulmão/patologia , Animais , Rejeição de Enxerto/patologia , Antígenos de Histocompatibilidade Classe II/análise , Técnicas Imunoenzimáticas , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Ratos Endogâmicos , Ratos Endogâmicos WKY , Proteínas Recombinantes/farmacologia , Traqueia/efeitos dos fármacos , Transplante HomólogoRESUMO
Alveolar macrophages (AMs) and peribronchial/perivascular macrophages are probably involved in lung allograft damage. We investigate leukocyte infiltration into graft tissue and address the question whether proliferation in situ contributes to macrophage homeostasis and accumulation. Lung transplantation was performed in the Lewis (LEW)-to-LEW and in the Dark Agouti-to-LEW rat strain combination. Graft infiltration by ED1+ and ED2+ (CD163) macrophages was analyzed by immunohistochemistry (IHC) and compared with infiltration by lymphocytes. Cells in the S-phase of the cell cycle were pulse-labeled with BrdU and detected immunohistochemically. Finally, the donor or recipient origin of AMs was determined by IHC and in situ hybridization. ED1+ AMs in allogeneic transplants increased by more than 25-fold from Days 1 to 5. In addition, large, peribronchial/perivascular infiltrates developed containing numerous ED1+ cells. Although AMs in normal rat lungs are CD163-, AMs up-regulated CD163 between Days 4 and 5, reaching maximum values on Day 6. Lymphocytes were less numerous than macrophages. About 16% of the AMs and 10% of the peribronchial/perivascular macrophages were in the S-phase of the cell cycle on Day 2 post-transplantation. No differences in the frequency of BrdU+ macrophages were obvious between isografts and allografts. AMs of donor origin increased in number considerably during allograft rejection. In conclusion, the cellular infiltrate in lung allografts is dominated by macrophages, which exhibit an unusual phenotype and a strong capacity for mitotic self-renewal.
Assuntos
Transplante de Pulmão/imunologia , Pulmão/imunologia , Macrófagos/imunologia , Transplante Homólogo/imunologia , Transplante Isogênico/imunologia , Animais , Modelos Animais de Doenças , Ectodisplasinas/metabolismo , Rejeição de Enxerto/imunologia , Pulmão/metabolismo , Transplante de Pulmão/patologia , Linfócitos/metabolismo , Linfócitos/fisiologia , Macrófagos/metabolismo , Macrófagos Alveolares/fisiologia , Ratos , Ratos Endogâmicos LewRESUMO
BACKGROUND: After transplantation, passenger leukocytes move to lymphoid organs of the recipient. These cells appear to initiate allograft rejection, but they also might be involved in tolerance induction. MATERIALS AND METHODS: Orthotopic left lung transplantation was performed in the Dark Agouti to Lewis rat strain combination with no immunosuppression. Recipient spleens were removed at intervals of 24 h until day 6 after transplantation. For comparison, spleens from renal allograft recipients were analysed. Donor-derived major histocompatibility complex (MHC) class II antigens were detected by monoclonal antibody OX76. In double-staining experiments with antibodies specific for leukocyte subpopulations, their localisation and identity was analysed. RESULTS: OX76-positive leukocytes were already detected in recipient spleens on day 1 post-transplantation. They increased in number until day 3 and decreased in number thereafter. Most of them were localised in splenic follicles and expressed the B cell variant of CD45R and IgG. Cell surface antigens typical for other leukocyte subpopulations were not detected. In the spleens of renal allograft recipients, only few donor-derived cells were seen. CONCLUSION: After lung transplantation, numerous MHC class II-positive B cells migrate to the splenic follicles of the recipient. These cells might, in part, be responsible for immunologic differences observed between renal and pulmonary allografts.
Assuntos
Linfócitos B/imunologia , Rejeição de Enxerto/imunologia , Transplante de Pulmão/imunologia , Baço/imunologia , Doadores de Tecidos , Animais , Linfócitos B/patologia , Ensaios de Migração de Leucócitos , Rejeição de Enxerto/patologia , Antígenos de Histocompatibilidade Classe II/análise , Transplante de Rim/imunologia , Transplante de Rim/patologia , Antígenos Comuns de Leucócito , Transplante de Pulmão/patologia , Contagem de Linfócitos , Masculino , Prognóstico , Ratos , Ratos Endogâmicos , Baço/patologia , Transplante HomólogoAssuntos
Reação a Corpo Estranho/diagnóstico por imagem , Pleura/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Implantes Absorvíveis/efeitos adversos , Diagnóstico Diferencial , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/patologia , Humanos , Masculino , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Pleura/patologia , Derrame Pleural/etiologia , Derrame Pleural/patologia , Pneumonectomia/efeitos adversos , Adesivos Teciduais/efeitos adversos , TurquiaRESUMO
Modern surgical strategies aim to reduce trauma by using functional imaging to improve surgical outcomes. This reviews considers and evaluates the importance of the fluorescent dye indocyanine green (ICG) to visualize lymph nodes, lymphatic pathways and vessels and tissue borders in an interdisciplinary setting. The work is based on a selective search of the literature in PubMed, Scopus, and Google Scholar and the authors' own clinical experience. Because of its simple, radiation-free and uncomplicated application, ICG has become an important clinical indicator in recent years. In oncologic surgery ICG is used extensively to identify sentinel lymph nodes with promising results. In some studies, the detection rates with ICG have been better than the rates obtained with established procedures. When ICG is used for visualization and the quantification of tissue perfusion, it can lead to fewer cases of anastomotic insufficiency or transplant necrosis. The use of ICG for the imaging of organ borders, flap plasty borders and postoperative vascularization has also been scientifically evaluated. Combining the easily applied ICG dye with technical options for intraoperative and interventional visualization has the potential to create new functional imaging procedures which, in future, could expand or even replace existing established surgical techniques, particularly the techniques used for sentinel lymph node and anastomosis imaging.
RESUMO
Exogenous application of keratinocyte growth factor protects the lung against a variety of injurious stimuli. KGF-treatment leads to pronounced hyperplasia of alveolar epithelial type II cells and to stabilization of surfactant homeostasis after lung injury. Epidermal fatty acid-binding protein is involved in the synthesis of surfactant phospholipids and acts as an antioxidant scavenging reactive lipids. We treated adult rats with recombinant human keratinocyte growth factor (Palifermin) via intratracheal instillation and analyzed the expression of epidermal fatty acid-binding protein mRNA and protein by quantitative RT-PCR, immunoblotting as well as immunohistochemistry. Keratinocyte growth factor-treatment in vivo leads to an increased expression of epidermal fatty acid-binding protein mRNA and protein in the total lung. Epidermal fatty acid-binding protein mRNA expression per alveolar epithelial type II cell remains constant as shown in isolated type II cells. Epidermal fatty acid-binding protein immunoreactivity is seen in most if not all hyperplastic alveolar epithelial type II cells, and is mainly localized to the cytoplasm. The increase in epidermal fatty acid-binding protein gene expression associated with type II cell hyperplasia might contribute to the molecular mechanisms mediating lung protection by keratinocyte growth factor.
Assuntos
Epiderme/efeitos dos fármacos , Proteínas do Olho/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Fator 7 de Crescimento de Fibroblastos/farmacologia , Pulmão , Proteínas do Tecido Nervoso/metabolismo , Animais , Epiderme/metabolismo , Proteínas do Olho/genética , Proteínas de Ligação a Ácido Graxo/genética , Fator 7 de Crescimento de Fibroblastos/metabolismo , Humanos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Proteínas do Tecido Nervoso/genética , Surfactantes Pulmonares/metabolismo , RatosRESUMO
KEY CLINICAL MESSAGE: A preterm infant at the age of 9 months with severe bronchopulmonary dysplasia (BPD) and large lobar emphysema, compromising ventilation into adjacent lobes with respiratory failure under maximal conservative treatment and pulmonary arterial hypertension recovered initially well after bilateral lung volume reduction surgery, but progressed 2 years later into respiratory failure. The initial imaging with Magnetic-Resonance-Imaging (MRI)-Angiography and decision-making was difficult and interdisciplinary treatment was essential.
RESUMO
BACKGROUND: The long-term success of human lung transplantation is limited by the development of bronchiolitis obliterans syndrome. Acute rejection episodes and infections are important risk factors and seem to play major pathogenic roles. We established a relevant experimental model that mimics important aspects of human bronchiolitis obliterans syndrome. METHODS: The Fischer 344-to-Lewis rat strain combination was used for orthotopic left lung transplantation. Isogeneic transplantations were performed in the Lewis rat. Recipients were treated with ciclosporin for 10 days. Lipopolysaccharide or vehicle was instilled into the airways 28 days after transplantation. Grafts were monitored by computed tomography, and recipients were euthanized on Days 28-90. The messenger RNA expression of selected chemokines and their receptors was measured on Days 28, 29, 33, 40 after transplantation. Graft histopathology on Day 90 was compared with lungs from patients who underwent re-transplantation due to end-stage allograft dysfunction. RESULTS: Lung allografts treated with ciclosporin and vehicle only sporadically displayed tissue remodeling. In contrast, lipopolysaccharide treatment induced severe inflammation. In the long-term, severe vascular remodeling, lung fibrosis, and fibroproliferative remodeling of airways were found that closely resemble the histopathologic changes in grafts from human patients with bronchiolitis obliterans syndrome. Chronic damage was virtually absent from pulmonary isografts and native right lungs. Chemokine (C-C motif) ligand 5 and chemokine (C-X-C motif) ligand 9-11, and their receptors, were over-expressed in allografts. CONCLUSIONS: Our experimental model mirrors key aspects of human bronchiolitis obliterans syndrome. It will be useful to elucidate its pathogenesis and to develop therapeutic approaches improving the long-term outcome of human lung transplantation.
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Bronquiolite Obliterante/metabolismo , Bronquiolite Obliterante/patologia , Modelos Animais de Doenças , Transplante de Pulmão , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/patologia , Animais , Bronquiolite Obliterante/induzido quimicamente , Quimiocinas/metabolismo , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Humanos , Terapia de Imunossupressão , Lipopolissacarídeos/efeitos adversos , Pulmão/metabolismo , Pulmão/patologia , Complicações Pós-Operatórias/epidemiologia , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Fatores de Risco , Síndrome , Receptores Toll-Like/metabolismoRESUMO
BACKGROUND: In the nonsurgical treatment of anal incontinence, the combination of amplitude-modulated medium-frequency stimulation and electromyographic biofeedback (EMG-BF), known as triple-target treatment (3T), is superior to EMG-BF alone. The aim of this trial is to compare 3T with the standard treatment, low-frequency stimulation (LFS). METHODS: 80 patients with anal incontinence of Grade I or higher who presented to physicians or centers specialized in coloproctology were enrolled in this multicenter randomized trial with blinded observer. The trial had an open parallel-group design. Randomization was performed centrally by telephone. The primary endpoint was the Cleveland Clinic Score (CCS) after self-training at home with either 3T or LFS in two 20-minute sessions per day for 6 months. The secondary endpoints included the proportion of patients regaining continence, and the patients' quality of life (QoL). On completion of the trial as planned, the results were evaluated with an intention-to-treat analysis. STUDY REGISTRATION: DRKS00000138 (http://register.germanctr.de). RESULTS: 39 patients were randomized to 3T, and 41 to LFS. After 6 months of treatment, the CCS (mean ± standard deviation) was 3.1 ± 4.2 in the 3T group and 9.6 ± 3.9 in the LFS group. The median improvement in the CCS at 6 months compared to baseline was 7 points greater in the 3T group than in the LFS group (95% CI: 5-9, p<0.001). Anal continence was regained by 54% of the 3T patients, but none of the LFS patients (95% CI for the difference: 37.18% - 69.91%, p<0.001). QoL scores were higher in all dimensions in the 3T group than in the LFS group. No major adverse effects occurred in either group. CONCLUSION: 3T is superior to LFS in the treatment of anal incontinence. The available evidence suggests that the success of 3T is based on the combined effect of biofeedback and medium-frequency stimulation. LFS of the type applied in this trial has no effect. 3T should be used in routine clinical practice instead of LFS.
Assuntos
Biorretroalimentação Psicológica/instrumentação , Terapia por Estimulação Elétrica/instrumentação , Eletromiografia/instrumentação , Incontinência Fecal/terapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-CegoRESUMO
In the lung, epidermal fatty acid-binding protein (E-FABP) is expressed by alveolar macrophages (AM) and alveolar epithelial cells type II (AEII). E-FABP may regulate macrophage activation and is involved in the metabolism of surfactant phospholipids. As macrophage activation and surfactant dysfunction are associated with rejection, we hypothesize that E-FABP expression is changed during acute rejection of pulmonary grafts. Orthotopic left lung transplantations were performed in the Dark Agouti to Lewis and in the isogeneic Lewis to Lewis rat strain combinations. E-FABP expression was analyzed in the lung by immunohistochemistry, immunoblotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Alveolar leukocytes obtained by bronchoalveolar lavage were analyzed by RT-PCR. Immunohistochemistry of isografts revealed strong E-FABP immunoreactivity in AEII and a moderate immunoreactivity in AM. In allografts undergoing acute rejection, AM exhibiting increased E-FABP immunoreactivity accumulated. Immunoblots revealed a single band at 15 kDa, which corresponds to the expected molecular mass of E-FABP. The levels of E-FABP mRNA were higher in allografts than in isografts and control lungs. Furthermore, alveolar leukocytes isolated by bronchoalveolar lavage from allografts displayed higher E-FABP mRNA expression levels than leukocytes from isografts and controls. In conclusion, we demonstrate for the first time upregulation of E-FABP expression in AM during severe inflammation.
Assuntos
Proteínas do Olho/biossíntese , Proteínas de Ligação a Ácido Graxo/biossíntese , Rejeição de Enxerto/imunologia , Transplante de Pulmão/imunologia , Ativação de Macrófagos/imunologia , Macrófagos Alveolares/imunologia , Proteínas do Tecido Nervoso/biossíntese , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Proteínas do Olho/genética , Proteínas do Olho/imunologia , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/imunologia , Imunidade Inata/imunologia , Immunoblotting , Imuno-Histoquímica , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/imunologia , Surfactantes Pulmonares/imunologia , RNA/química , RNA/genética , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não ParamétricasRESUMO
BACKGROUND: Monocytes and macrophages play an important role in acute pulmonary allograft rejection. Acetylcholine has been shown to exert anti-inflammatory effects on these cells via nicotinic acetylcholine receptors. The aim of this study was to test for the hypothesis that a global nicotinic stimulation of pulmonary allograft recipients attenuates acute rejection. METHODS: Orthotopic left lung transplantation was performed in the Fischer 344-Wistar Kyoto rat strain combination. Graft recipients treated with nicotine added to the drinking water were compared with untreated allograft recipients. Graft histopathology, leukocytic infiltration, expression of inducible nitric oxide (NO) synthase and cytokine expression were analyzed during the process of acute rejection on Day 7 post-transplantation using quantitative reverse transcript-polymerase chain reaction (RT-PCR), enzyme-linked immunoassay (ELISA) and immunohistochemistry. The right native lung of the experimental animals was included as an internal control. RESULTS: Nicotine treatment resulted in a marked reduction in lung allograft infiltration by CD68-like antigen(+) alveolar and tissue macrophages, whereas resident mature macrophages (CD163(+)) and T cells remained unchanged. Concomitantly, inducible NO synthase expression, which was predominantly localized in alveolar macrophages of control allografts, decreased in response to nicotine. In contrast, cytokine mRNA and peptide levels were only marginally affected by nicotine. CONCLUSIONS: Stimulation of nicotinic acetylcholine receptors results in a marked attenuation of important hallmarks of pulmonary allograft rejection, indicating that cholinergic therapies may be beneficial for lung allograft recipients.