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Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.
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BACKGROUND: Gallbladder cancer (GBC) is an aggressive, uncommon malignancy, with variation in operative approaches adopted across centres and few large-scale studies to guide practice. We aimed to identify the extent of heterogeneity in GBC internationally to better inform the need for future multicentre studies. METHODS: A 34-question online survey was disseminated to members of the European-African Hepatopancreatobiliary Association (EAHPBA), American Hepatopancreatobiliary Association (AHPBA) and Asia-Pacific Hepatopancreatobiliary Association (A-PHPBA) regarding practices around diagnostic workup, operative approach, utilization of neoadjuvant and adjuvant therapies and surveillance strategies. RESULTS: Two hundred and three surgeons responded from 51 countries. High liver resection volume units (>50 resections/year) organised HPB multidisciplinary team discussion of GBCs more commonly than those with low volumes (p < 0.0001). Management practices exhibited areas of heterogeneity, particularly around operative extent. Contrary to consensus guidelines, anatomical liver resections were favoured over non-anatomical resections for T3 tumours and above, lymphadenectomy extent was lower than recommended, and a minority of respondents still routinely excised the common bile duct or port sites. CONCLUSION: Our findings suggest some similarities in the management of GBC internationally, but also specific areas of practice which differed from published guidelines. Transcontinental collaborative studies on GBC are necessary to establish evidence-based practice to minimise variation and optimise outcomes.
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Neoplasias da Vesícula Biliar , Cirurgiões , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia/efeitos adversos , Inquéritos e Questionários , Ducto ColédocoRESUMO
BACKGROUND: Acute abdominal pain is a common surgical presentation. We previously found that over the last decade, more patients were admitted to hospital with non-surgical diagnoses (e.g. gastroenteritis, constipation and non-specific abdominal pain) and length of stay and use of imaging (mainly computed tomography scan) for these patients increased. This study aimed to reduce length of stay and use of imaging for patients admitted with non-surgical abdominal pain. METHODS: A prospective study was undertaken in a tertiary centre evaluating length of stay and use of additional imaging in patients with a non-surgical diagnosis after a quality improvement intervention was implemented. RESULTS: A total of 454 patients were included; 204 (44.9%) presented with non-surgical abdominal pain. During the study period, a significant reduction in computed tomography scan requests was observed (38.5-25.0%, P = 0.037) and an increasing proportion of these patients were discharged within 12 h (33.3-57.1%, P = 0.018). The number of re-presentations remained unchanged (P = 0.358). CONCLUSIONS: The study intervention increased the proportion of patients with non-surgical diagnoses that were successfully discharged within 12 h and reduced the use of additional imaging in this group. This may lead to improved use of health care resources for patients with more urgent diagnoses.
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Dor Abdominal , Constipação Intestinal , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/cirurgia , Humanos , Tempo de Internação , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Acute abdominal pain is a common surgical presentation with a wide range of causes. Differentiating urgent patients from non-urgent patients is important to optimise patient outcomes and the use of hospital resources. The aim of this study was to determine how accurately urgent and non-urgent patients presenting with abdominal pain can be identified. METHODS: A prospective study of consecutive patients admitted with abdominal pain was undertaken. Urgent patients were classified as requiring treatment (theatre, intensive care unit, endoscopy, or radiologic drainage) within 24 h. Differentiation between urgent and non-urgent was made on the basis of the initial assessment prior to the use of advanced imaging. Outcomes were compared to a final classification based on final diagnosis as adjudicated by an expert panel. RESULTS: Of the 301 patients included, 93 (30.9%) were deemed urgent based on initial assessment, compared to 83 (27.6%) on final diagnosis. Overall sensitivity for recognising urgent patients was 74.7% and specificity 89.9%, and overall accuracy was higher for senior registrars compared to junior registrars (p = 0.015). Urgent patients more often looked unwell or had peritonism on examination (39.8 vs. 17.4% and 56.6 vs. 14.7%, respectively, p < 0.001 for both). CONCLUSIONS: Registrars can accurately differentiate urgent from non-urgent patients with acute abdominal pain in the majority of cases. Accuracy was higher amongst senior registrars. The "end-of-the-bed-o-gram" and clinical examination are the most important features used for making this differentiation. This demonstrates that there is no substitute for exposure to acute presentations to improve a trainee's diagnostic skill.
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Dor Abdominal/diagnóstico , Sistema de Registros , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Work-related pain and discomfort experienced by surgeons is widely reported in the literature. A survey was, therefore, conducted to explore this issue among members of the European Association for Endoscopic Surgery (EAES). METHODS: The survey was emailed to 2980 EAES members in 2017 enquiring about their working practice, musculoskeletal (MSK) pain and burnout. RESULTS: A total of 569 (19%) surgeons responded, of whom 556 were practicing surgeons; 86% were consultants, 84% were male, and 94% were right-handed. Respondents operated on average 3.3 days/week with 27% of their procedures lasting longer than 3 h. The 386 endoscopists surveyed reported performing an average of 5.3 procedures/day with 83% performing endoscopy at least once per week. Over half of practicing surgeons (62%) reported their worst pain score was 3 or higher (10-point scale) in the past 7 working days, encompassing 71% of their open, 72% laparoscopic, 48% robot-assisted cases and 52% of their endoscopies. Of the 120 surgeons who had ever sought medical help for aches, pain or discomfort, 38% were currently in pain and 16% had considered leaving surgery due to their MSK pain, 26% had reported work-related pain to their employer, 26% had been on short-term disability during their career and 4% long-term disability due to MSK disorders. A significant proportion of the respondents (49%) felt their physical discomfort would influence the ability to perform or assist with surgical procedures in the future. These surgeons reported significantly lower satisfaction from their work (p = 0.024), higher burnout (p = 0.005) and significantly higher callousness toward people (p < 0.001) than those not fearing loss of career longevity. CONCLUSION: The results show that MSK pain is prevalent amongst EAES members. Nearly half the respondents had career longevity fears from pain/discomfort which, in turn, correlated with more prevalent feelings of burnout. More emphasis should be placed on the aetiology, prevention and management of musculoskeletal pain in the surgical workforce.
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Dor Musculoesquelética/epidemiologia , Doenças Profissionais/epidemiologia , Cirurgiões/estatística & dados numéricos , Adulto , Idoso , Esgotamento Profissional/epidemiologia , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/etiologia , Dor Musculoesquelética/terapia , Doenças Profissionais/etiologia , Doenças Profissionais/terapia , Duração da Cirurgia , Prevalência , Qualidade de Vida , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Superior mesenteric arteriovenous fistulae (SMAVF) are rare, usually secondary to trauma or iatrogenic injury and typically present sometime after the initial insult. REPORT: A 30 year old male underwent immediate laparotomy for abdominal gunshot injury. The small bowel mesentery contained a large haematoma and a palpable thrill. CT demonstrated a large SMAVF. At re-look laparotomy, small bowel ischaemia was noted and following this endovascular SMA stent graft insertion was performed, with excellent angiographic and clinical results. CONCLUSION: The first report of immediate traumatic SMAVF leading to acute mesenteric steal syndrome and successful management with endovascular stent insertion is presented.
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BACKGROUND: Delays to surgery for patients requiring an acute operation are associated with increased morbidity and mortality. A recent study from our institution observed long waiting times for patients booked for an acute operation. The aim of this study was to evaluate the patient's progress from presentation to arrival in the operating theatre and to identify where delays occurred. METHODS: Patients undergoing acute general surgery between July 2016 and May 2017 were studied. Data were obtained for time of presentation, imaging, theatre and booking. A time interval from presentation to booking for theatre of greater than 6 h was defined as a diagnostic delay. A time interval from booking to theatre greater than the category defined time (four-level priority system) was defined as a logistic delay. RESULTS: A total of 683 patients were included. A diagnostic delay was observed in 55.1%. This occurred more frequently in patients who required imaging prior to their operation (82.5 versus 41.1%, P < 0.001). Logistic delay occurred in 31.0% of the patients, and this was most common for patients booked as a category 3 (requiring surgery within 6 h, 41.8%, P < 0.001). Patients who had a diagnostic delay were significantly more likely to have a post-operative complication compared to patients who did not (17.2 versus 10.0%, P = 0.009). CONCLUSION: There are significant delays associated with patients presenting to the acute general surgery service and their transition to theatre. Addressing both the diagnostic and the logistic delays in our institution should result in a significant improvement in patient care.
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Diagnóstico Tardio/mortalidade , Atenção à Saúde/normas , Cirurgia Geral/estatística & dados numéricos , Salas Cirúrgicas/organização & administração , Adulto , Idoso , Diagnóstico Tardio/estatística & dados numéricos , Atenção à Saúde/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Cirurgia Geral/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Salas Cirúrgicas/estatística & dados numéricos , Organização e Administração/normas , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVES: The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS: Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS: Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.
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Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Modelos de Riscos Proporcionais , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/patologia , Projetos Piloto , Prognóstico , Estudos RetrospectivosRESUMO
Exocrine drainage following pancreas transplantation can be achieved by drainage into the bladder or bowel, the latter typically by direct duodeno-jejunostomy; the use of Roux-en-Y enteric drainage is uncommon. We report a retrospective analysis of a single-centre experience of Roux-en-Y enteric drainage following pancreas transplantation. Over a 14-year period (2001-2015), 204 consecutive adult pancreas transplants were performed (96.6% simultaneous pancreas and kidney transplants), of which 26.0% were from donors after circulatory death (DCD). During a median follow-up of 67 months (range 13-183 months), 14 (6.9%) recipients experienced complications related to their enteric drainage. Complications during follow-up included early enteric anastomotic haemorrhage (five patients), non-anastomotic enteric bleeding (one patient), small bowel obstruction (four patients) and graft duodenal perforation (two within 6 weeks, five beyond 12 months). No recipient lost their graft as a direct result of complications related to enteric drainage. Patient and pancreas graft survival at 1 year was 99.0% and 94.0% and at 5 years 91.3% and 84.9%, respectively. We conclude that Roux-en-Y enteric drainage following pancreas transplantation is a safe and effective procedure and facilitates graft salvage in the event of graft duodenal perforation.
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Anastomose em-Y de Roux/métodos , Drenagem/métodos , Transplante de Pâncreas/métodos , Adulto , Anastomose Cirúrgica , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Chronic rejection of solid organ allografts remains the major cause of transplant failure. Donor-derived tissue-resident lymphocytes are transferred to the recipient during transplantation, but their impact on alloimmunity is unknown. Using mouse cardiac transplant models, we show that graft-versus-host recognition by passenger donor CD4 T cells markedly augments recipient cellular and humoral alloimmunity, resulting in more severe allograft vasculopathy and early graft failure. This augmentation is enhanced when donors were pre-sensitized to the recipient, is dependent upon avoidance of host NK cell recognition, and is partly due to provision of cognate help for allo-specific B cells from donor CD4 T cells recognizing B cell MHC class II in a peptide-degenerate manner. Passenger donor lymphocytes may therefore influence recipient alloimmune responses and represent a therapeutic target in solid organ transplantation.
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Imunidade Adaptativa , Aloenxertos/imunologia , Linfócitos T CD4-Positivos/imunologia , Doadores de Tecidos , Animais , Autoanticorpos/imunologia , Linfócitos B/imunologia , Diferenciação Celular , Rejeição de Enxerto/imunologia , Doença Enxerto-Hospedeiro/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Imunidade Humoral/imunologia , Células Matadoras Naturais/imunologia , Camundongos Endogâmicos BALB C , Modelos Imunológicos , Peptídeos/metabolismo , Plasmócitos/patologia , Receptores de Antígenos de Linfócitos B/metabolismo , Transplante HomólogoRESUMO
Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen "indirectly," as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are "unlinked" on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the "semidirect" pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses. We show that CD8 T-cell-mediated rejection of murine heart allografts that lack hematopoietic APCs requires host secondary lymphoid tissue (SLT). SLT is necessary because within it, recipient dendritic cells can acquire MHC from graft parenchymal cells and simultaneously present it as intact protein to alloreactive CD8 T cells and as processed peptide alloantigen for recognition by indirect-pathway CD4 T cells. This enables delivery of essential help for generating cytotoxic CD8 T-cell responses that cause rapid allograft rejection. In demonstrating the functional relevance of the semidirect pathway to transplant rejection, our findings provide a solution to a long-standing conundrum as to why SLT is required for CD8 T-cell allorecognition of graft parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells provide help for generating effector cytotoxic CD8 T-cell alloresponses at late time points after transplantation.
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Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração , Isoantígenos/imunologia , Aloenxertos , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Rejeição de Enxerto/patologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos KnockoutRESUMO
Pancreatic cancer is known for its typically late presentation and poor survival rates, with overall 5-year survival of less than 5%. The role of chemotherapy alone or with radiotherapy in the management of locally advanced tumors continues to be an area of debate.We report a case of locally advanced, pancreatic adenosquamous carcinoma that was initially deemed unresectable intraoperatively. Nonetheless, the tumor was resected after radiological response to gemcitabine-capecitabine chemoradiotherapy regimen similar to the Selective Chemoradiation in Advanced LOcalised Pancreatic cancer trial. Histological examination revealed complete pathological response with extensive fibrosis (ypT0 N0). On 12-month follow-up CT, a single liver lesion in the left lateral segment was identified and confirmed to be a metastasis with cytological diagnosis via EUS and FNA. The disease remained stable and confined to the solitary hepatic metastasis after further gemcitabine chemotherapy. Therefore, a further successful resection was performed.The 2 main strategies for the management of locally advanced unresectable pancreatic cancer are chemotherapy induction followed by consolidation chemoradiotherapy or chemotherapy alone, with conflicting published evidence. Evidence for the optimal management of the rare histological type of adenosquamous carcinoma is scant. We present a case of such tumor with a complete pathological response to chemoradiotherapy. The results of future studies in the area are eagerly awaited.
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Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/cirurgia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina , Carcinoma Adenoescamoso/patologia , Quimiorradioterapia , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Terapia de Salvação , GencitabinaRESUMO
BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. METHODS: 405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.
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Amilases/análise , Fístula Pancreática/enzimologia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/cirurgia , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/epidemiologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal liver metastases staged by PET CT has not been reported. Objectives were to investigate whether PET CT staging results in actual improved long-term survival, to examine outcome in patients with 'equivocal' PET CT scans, and those excluded from hepatectomy by PET CT. METHODS: A retrospective analysis of patients undergoing hepatectomy for colorectal liver metastases between March 1998 and September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET CT staging resulted in management changes in 23% of patients. PET CT staged patients showed significantly better survival than those staged by CT alone at 3 years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of 6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT scans showed worse median survival than those with favourable PET CT (log rank P = 0.002), but may include a subpopulation whose prognosis trends towards a more favourable outcome than those excluded from liver resection by PET CT, whose median survival remains limited to 21 months. CONCLUSIONS: Staging of patients with colorectal liver metastases by PET CT is associated with significantly improved actual long-term survival, and provides valuable prognostic information which guides surgical and oncological treatments.
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Adenocarcinoma/secundário , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Feminino , Fluordesoxiglucose F18 , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Seleção de Pacientes , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
It is essential to minimize the unnecessary discard of procured deceased donor kidneys, but information on discard rates and the extent to which discard can be avoided are limited. Analysis of the UK Transplant Registry revealed that the discard rate of procured deceased donor kidneys has increased from 5% in 2002-3 to 12% in 2011-12. A national offering system for hard-to-place kidneys was introduced in the UK in 2006 (the Declined Kidney Scheme), but just 13% of kidneys that were subsequently discarded until 2012 were offered through the scheme. In order to examine the appropriateness of discard, 20 consecutive discarded kidneys from 13 deceased donors were assessed to determine if surgeons agreed with the decision that they were not implantable. Donors had a median (range) age of 67 (31-80) yr. Kidneys had been offered to a median of 3 (1-12) centers before discard. Four (20%) of the discarded kidneys were thought to be usable, and nine (45%) were possibly usable. As a result of these findings, major changes to the UK deceased donor kidney offering system have been implemented, including simultaneous offering and broader entry criteria for hard-to-place kidneys. Organizational changes are necessary to improve utilization of deceased donor kidneys.
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Sobrevivência de Enxerto/fisiologia , Nefropatias/cirurgia , Transplante de Rim/estatística & dados numéricos , Seleção de Pacientes , Doadores de Tecidos/classificação , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Doadores de Tecidos/estatística & dados numéricos , Adulto JovemRESUMO
In transplantation, direct-pathway CD8 T cells that recognize alloantigen on donor cells require CD4 help for activation and cytolytic function. The ability of indirect-pathway CD4 T cells to provide this help remains unexplained, because a fundamental requirement for epitope linkage is seemingly broken. The simultaneous presentation, by host dendritic cells (DCs), of both intact MHC class I alloantigen and processed alloantigen would deliver linked help, but has not been demonstrated definitively. In this study, we report that following in vitro coculture with BALB/c DCs, small numbers (~1.5%) of C57BL/6 (B6) DCs presented acquired H-2(d) alloantigen both as processed allopeptide and as unprocessed Ag. This represented class I alloantigen provides a conformational epitope for direct-pathway allorecognition, because B6 DCs isolated from cocultures and transferred to naive B6 mice provoked cytotoxic CD8 T cell alloimmunity. Crucially, this response was dependent upon simultaneous presentation of class II-restricted allopeptide, because despite acquiring similar amounts of H-2(d) alloantigen upon coculture, MHC class II-deficient B6 DCs failed to elicit cytotoxic alloimmunity. The relevance of this pathway to solid-organ transplantation was then confirmed by the demonstration that CD8 T cell cytotoxicity was provoked in secondary recipients by transfer of DCs purified from wild-type, but not from MHC class II-deficient, C57BL/6 recipients of BALB/c heart transplants. These experiments demonstrate that representation of conformationally intact MHC alloantigen by recipient APC can induce cytotoxic alloimmunity, but simultaneous copresentation of processed allopeptide is essential, presumably because this facilitates linked recognition by indirect-pathway CD4 Th cells.
Assuntos
Apresentação de Antígeno/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Antígenos de Histocompatibilidade/imunologia , Isoantígenos/imunologia , Animais , Transplante de Coração/imunologia , Imunidade Celular , Imunidade Humoral , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , CamundongosRESUMO
Prolonged warm ischemia (WI) occurring in marginal kidney donors together with reperfusion injury determines allograft survival, in which apoptosis and inflammation play crucial roles. There is no single valid biomarker, so far, to assess the degree of kidney donor injury. To define new biomarkers for detecting initial donor ischemic injury, caspase-3, caspase-7, apoptosis, inflammation, HSP70 and renal histological changes were examined in porcine kidneys subjected to 7- 15- 25- or 40-min WI, two-hour cold storage and six-hour hemoreperfusion. Caspase-3 activity was gradually increased by prolonged reperfusion, with a decrease trend against WI time. This result was verified by raised 17 kDa active caspase-3 in postreperfusion kidneys, with elevated 12 kDa active caspase-3 and lowered precursor at seven-minute WI. Active caspase-7 was also doubled by reperfusion with decreased precursor at seven-minute WI, but declined against prolonged WI. Apoptotic cells in tubular and interstitial areas were greatly increased by reperfusion at seven-minute WI, but decreased against prolonged WI. In addition, myeloperoxidase (MPO)+ cells were dramatically increased by reperfusion and presented as a bell-shape against WI time, while HSP70 was significantly increased at 7-min WI, but decreased at 40-min WI after reperfusion. In postreperfusion kidneys, tubular dilation and cell shedding were observed at 7- and 15-min WI, while tubular vacuolation and cell debris were found in tubular lumens at longer WI times. At 40-min WI, early nuclear pyknosis, tubular epithelia detachment and peri-tubular capillary dilation were detected. Furthermore, caspase-3, caspase-7, apoptosis, but not MPO+ cells or HSP70, were correlated with renal function. In conclusion, caspase-3, caspase-7 and apoptosis appear to be better biomarkers than MPO+ cells or HSP70 for assessing warm ischemic injury in donor kidneys. Hemoreperfusion activates caspase-3 and caspase-7, promotes apoptosis of damaged cells in kidneys only with limited WI, which might be beneficial to renal structural re-modeling and functional recovery.
Assuntos
Caspase 3/metabolismo , Caspase 7/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Rim/metabolismo , Modelos Biológicos , Peroxidase/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia Quente/efeitos adversos , Animais , Apoptose , Biomarcadores/metabolismo , Rim/lesões , Rim/patologia , Perfusão , Traumatismo por Reperfusão/patologia , Suínos , Fatores de TempoRESUMO
BACKGROUND: Sirolimus is unlicensed for use in liver transplantation because of concerns over safety, particularly in regard to hepatic artery thrombosis and excess mortality. However, sirolimus offers potential advantages over calcineurin inhibitor-based immunosuppression, relating to its renal sparing and antiproliferative properties. METHODS: A review was undertaken of 148 liver transplant patients converted to sirolimus over 10 years at a single center. RESULTS: The main indications for sirolimus were renal impairment and hepatitis C virus fibrosis. One hundred eleven (75%) patients remained on sirolimus after median follow-up of 1006 days. Mean (+/-standard deviation) glomerular filtration rate improved significantly from 59+/-29 mL/min preconversion to 72+/-39 mL/min at censor point (P<0.05). Improvement in glomerular filtration rate was most marked in patients converted for renal impairment. Liver function tests remained stable or improved, particularly in patients transplanted for hepatitis C virus. Side effects attributed to sirolimus occurred in 101 (68%) patients requiring withdrawal in 20 patients (14%). Moderate increases in serum lipids were observed and controlled effectively with statins. The incidence of proteinuria increased postconversion but had no deleterious impact on renal function. No episodes of hepatic artery thrombosis were observed. CONCLUSIONS: Sirolimus was safe and may improve outcome in selected patients after liver transplantation.
Assuntos
Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Sirolimo/uso terapêutico , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hepatite C , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Lipídeos/sangue , Cirrose Hepática/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Proteinúria/induzido quimicamente , Estudos Retrospectivos , Sirolimo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The initial flush of an organ is important to remove any cellular components from the microcirculation before storage. The aim of this study was to assess graft function after an ex vivo warm flush with a novel non-phosphate buffered preservation solution AQIX RS-I (AQIX) compared with a traditional cold flush. METHODS: Porcine kidneys were either warm-flushed with AQIX RS-I at 30°C, or cold-flushed at 4°C with University of Wisconsin solution (UW) or hyperosmolar citrate (HOC) preservation solution at a pressure of 100 cmH2O (n = 6). Renal function was measured ex vivo by perfusing the organs with autologous blood at 37°C on an isolated organ perfusion system. RESULTS: The AQIX group flushed significantly quicker than the cold stored groups (22 ± 1.8 versus UW 4.9 ± 1.6 versus HOC 10 ± 1.6 mL/min/100g; P = 0.001) and gained less weight than the UW group (19 ± 2.9 versus UW 30 ± 3.4 versus HOC 21% ± 7.7%; P = 0.025). The AQIX group also had superior acid-base homeostasis. Functional results, histologic analysis, and ADP: ATP levels were comparable between the groups. CONCLUSION: Flushing kidneys with AQIX at 30°C cleared the renal microcirculation of blood more rapidly without any detrimental effects when compared to traditional cold flushing with UW or HOC at 4°C. Warm initial flushing has potential to be developed as part of normothermic renal preservation techniques.
Assuntos
Hipotermia Induzida/métodos , Transplante de Rim , Rim/fisiologia , Soluções para Preservação de Órgãos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Equilíbrio Ácido-Base/fisiologia , Adenosina/farmacologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Alopurinol/farmacologia , Animais , Citratos/farmacologia , Glutationa/farmacologia , Insulina/farmacologia , Rim/irrigação sanguínea , Microcirculação/fisiologia , Fosfatos , Rafinose/farmacologia , Cônjuges , TemperaturaRESUMO
Acute pancreatitis (AP) is an important cause of morbidity and mortality worldwide and the annual incidence appears to be increasing. It presents as a mild self-limiting illness in 80% of patients. However, one-fifth of these develop a severe complicated life-threatening disease requiring intensive and prolonged therapeutic intervention. Alcohol and gallstone disease remain the commonest causes of AP but metabolic abnormalities, obesity and genetic susceptibility are thought be increasingly important aetiological factors. The prompt diagnosis of AP and stratification of disease severity is essential in directing rapid delivery of appropriate therapeutic measures. In this review, the range of diagnostic and prognostic assays, severity scoring systems and radiological investigations used in current clinical practice are described, highlighting their strengths and weaknesses. Increased understanding of the complex pathophysiology of AP has generated an array of new potential diagnostic assays and these are discussed. The multidisciplinary approach to management of severe pancreatitis is outlined, including areas of controversy and novel treatments.