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1.
Colorectal Dis ; 21(10): 1140-1150, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31108012

RESUMO

AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.


Assuntos
Gerenciamento Clínico , Terapia Neoadjuvante/tendências , Equipe de Assistência ao Paciente/tendências , Protectomia/tendências , Neoplasias Retais/terapia , Idoso , Feminino , Humanos , Tempo de Internação/tendências , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
2.
Tech Coloproctol ; 23(10): 981-985, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31617034

RESUMO

BACKGROUND: An anastomotic leak is the most dreaded complication after low anterior resection. Adipose tissue grafting may induce healing in a persistent anastomotic defect. The aim of the present study was to report retrospectively reviewed outcomes for a series of patients who were managed with heterotopic grafted adipose tissue to facilitate anastomotic healing. METHODS: Patients with anastomotic leakage after low anterior resection sequentially treated with grafting of adipose tissue were included in the study. All patients had pelvic radiation during treatment and had a diverting ileostomy in situ. The cohort had a persistent defect despite being treated with available modalities such as suture repair, fibrin glue, Endo-Sponge and surgical debridement. The outcomes were reviewed and reported. RESULTS: There were 11 patients (8 males and 3 females) with a median age of 54 years (range 33-72 years). Five patients experienced complete healing of the anastomotic defect with successful reversal of the diverting ileostomy. The anastomotic defect of one other patient in the series appeared to have healed and hence his diverting ileostomy was reversed. However, he presented with a recurrent leak, which ultimately necessitated an abdominoperineal resection. Another patient had a persistent defect after an attempt at adipose tissue grafting and opted to proceed with a takedown of the anastomosis. In the remaining four patients, the outcome after adipose tissue grafting remains unknown, as two patients succumbed to metastatic disease, one was lost to follow-up and the remaining patient developed a recurrence which required pelvic exenteration. Procedural associated morbidity occurred in one patient who developed fat embolism, which was treated expectantly. CONCLUSIONS: Adipose tissue grafting is safe and feasible, though its effectiveness remains uncertain. It may be useful selectively in the management of persistent anastomotic leak after radiation and low anterior resection.


Assuntos
Tecido Adiposo/transplante , Fístula Anastomótica/cirurgia , Ileostomia/efeitos adversos , Protectomia/efeitos adversos , Reto/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/etiologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
3.
Br J Surg ; 105(12): 1680-1687, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29974946

RESUMO

BACKGROUND: Surgical-site infection (SSI) is associated with significant healthcare costs. To reduce the high rate of SSI among patients undergoing colorectal surgery at a cancer centre, a comprehensive care bundle was implemented and its efficacy tested. METHODS: A pragmatic study involving three phases (baseline, implementation and sustainability) was conducted on patients treated consecutively between 2013 and 2016. The intervention included 13 components related to: bowel preparation; oral and intravenous antibiotic selection and administration; skin preparation, disinfection and hygiene; maintenance of normothermia during surgery; and use of clean instruments for closure. SSI risk was evaluated by means of a preoperative calculator, and effectiveness was assessed using interrupted time-series regression. RESULTS: In a population with a mean BMI of 30 kg/m2 , diabetes mellitus in 17·5 per cent, and smoking history in 49·3 per cent, SSI rates declined from 11·0 to 4·1 per cent following implementation of the intervention bundle (P = 0·001). The greatest reductions in SSI rates occurred in patients at intermediate or high risk of SSI: from 10·3 to 4·7 per cent (P = 0·006) and from 19 to 2 per cent (P < 0·001) respectively. Wound care modifications were very different in the implementation phase (43·2 versus 24·9 per cent baseline), including use of an overlying surface vacuum dressing (17·2 from 1·4 per cent baseline) or leaving wounds partially open (13·2 from 6·7 per cent baseline). As a result, the biggest difference was in wound-related rather than organ-space SSI. The median length of hospital stay decreased from 7 (i.q.r. 5-10) to 6 (5-9) days (P = 0·002). The greatest reduction in hospital stay was seen in patients at high risk of SSI: from 8 to 6 days (P < 0·001). SSI rates remained low (4·5 per cent) in the sustainability phase. CONCLUSION: Meaningful reductions in SSI can be achieved by implementing a multidisciplinary care bundle at a hospital-wide level.


Assuntos
Pacotes de Assistência ao Paciente/normas , Equipe de Assistência ao Paciente/normas , Infecção da Ferida Cirúrgica/prevenção & controle , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Fatores de Risco , Resultado do Tratamento , Técnicas de Fechamento de Ferimentos/normas
4.
Eur Radiol ; 23(12): 3336-44, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23979104

RESUMO

OBJECTIVE: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. METHODS: A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. RESULTS: Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. CONCLUSION: K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.


Assuntos
Aumento da Imagem/métodos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Meios de Contraste , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
5.
bioRxiv ; 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37662289

RESUMO

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

6.
Br J Surg ; 99(8): 1137-43, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22696063

RESUMO

BACKGROUND: En bloc resection of adjacent pelvic organ(s) may be needed to achieve clear surgical margins in rectal cancer surgery. An institutional experience is reported with perioperative morbidity and oncological outcomes. METHODS: Patients were identified retrospectively from a prospectively collected institutional database (1992-2010). Outcomes, and clinical and pathological factors were determined from medical records. Estimated overall survival, overall recurrence and local recurrence were compared using the log rank method and Cox regression analysis. RESULTS: Among 1831 patients with rectal cancer, 124 (6·8 per cent) underwent en bloc resection of part or all of an adjacent organ (vagina/uterus/ovary 90, prostate/seminal vesicle 23, bladder/ureter 15, small bowel/appendix 7). Five-year overall survival and local recurrence rates were 53·3 and 18·8 per cent respectively. There was one postoperative death, from multiple organ failure in a patient with liver cirrhosis. Fifty-two patients underwent sphincter-preserving surgery and three (6 per cent) developed an anastomotic leak. On univariable analysis, the only factor associated with local recurrence was completeness of resection (local recurrence rate 15 per cent versus 69 per cent for R0 versus R1 resection; P < 0·001). On multivariable analysis, factors associated with overall survival were sphincter-preserving surgery, absence of metastatic disease and R0 resection. CONCLUSION: Multiple organ resection for locally advanced primary rectal cancer had good oncological outcomes when clear resection margins were achieved.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Retais/cirurgia , Vísceras/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
7.
J Exp Med ; 183(5): 2343-8, 1996 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-8642343

RESUMO

Reperfusion of ischemic tissue induces an acute inflammatory response that can result in necrosis and irreversible cell injury to both local vascular endothelium and parenchyma. To examine the pathogenesis of ischemia/reperfusion injury, we have used mice deficient in complement components C3, C4, or serum immunoglobulin in a hindlimb model of ischemia. We found that mice homozygous deficient in C3 or C4 were equally protected against reperfusion injury based on a significant reduction in leakage of radiolabeled albumin out of the vasculature. This demonstrates that classical pathway complement is an important factor in the initiation of inflammation following reperfusion. Furthermore, mice deficient in serum immunoglobulin were equally protected and this protection could be reversed by reconstitution with serum from normal mice. Thus, this report describes a novel mechanism for reperfusion injury that involves antibody deposition and activation of complement leading to inflammation permeability.


Assuntos
Proteínas do Sistema Complemento/fisiologia , Imunoglobulinas/deficiência , Isquemia/imunologia , Músculo Esquelético/irrigação sanguínea , Traumatismo por Reperfusão/imunologia , Animais , Complemento C3/deficiência , Complemento C4/deficiência , Via Clássica do Complemento , Proteínas do Sistema Complemento/deficiência , Imunoglobulina M/análise , Isquemia/patologia , Camundongos , Camundongos Mutantes , Músculo Esquelético/patologia , Traumatismo por Reperfusão/patologia
8.
J Surg Oncol ; 102(1): 3-9, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20578172

RESUMO

BACKGROUND: Examining >or=12 LN in colon cancer has been suggested as a quality metric. The purpose of this study was to determine whether the 12 LN benchmark is achieved at NCCN centers compared to a US population-based sample. METHODS: Patients with stage I-III disease resected at NCCN centers were identified from a prospective database (n = 718) and were compared to 12,845 stage I-III patients diagnosed in a SEER region. Age, gender, location, stage, number of positive nodes were compared for NCCN and SEER data in regards to number of nodes evaluated. Multivariate logistic regression models were developed to identify factors associated with evaluating 12 LNs. RESULTS: 92% of NCCN and 58% of SEER patients had >or=12 LN evaluated. For patients treated at NCCN centers, factors associated with not meeting the 12 LN target were left-sided tumors, stage I disease and BMI >30. CONCLUSIONS: >or=12 LN are almost always evaluated in NCCN patients. In contrast, this target is achieved in 58% of SEER patients. With longer follow-up of the NCCN cohort we will be able to link this quality metric to patterns of recurrence and survival and thereby better understand whether increasing the number of nodes evaluated is a priority for cancer control.


Assuntos
Neoplasias do Colo/patologia , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Benchmarking , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Programa de SEER , Adulto Jovem
9.
J Surg Oncol ; 101(7): 570-6, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20461762

RESUMO

BACKGROUND: Although primary therapy in familial adenomatous polyposis (FAP) is surgical, little is known about patients' surgical decision-making experience. The objective was to explore the decision-making process surrounding risk-reducing surgery in FAP using qualitative methodology. METHODS: In-depth, semi-structured interviews with 14 FAP patients and 11 healthcare providers with experience caring for FAP patients were conducted. Using grounded theory, line-by-line content analysis identified categories from which themes describing patients' experiences emerged; analysis continued until data saturation. RESULTS: Median age at surgery was 23 (7-37) years; at interview 41 (19-74) years. Two patients underwent surgery secondary to cancer, the remainder for risk-reduction. Content experts included colorectal surgeons (3), geneticists (2), gastroenterologists (3), nurses (3).Three themes emerged: Information: Family was the primary information source, and patients' level of information varied. The importance of up-front information was emphasized. Influences on decision-making: Influential factors included family experiences, youth, emotional state, support, and decision-making role. Although patients often sought opinions, most (12/14) wanted an active/shared role in decision-making. Life after surgery: Patients described surgery as the "easy part," emphasizing the need for long-term relationships with care providers. CONCLUSIONS: Decisions surrounding risk-reducing surgery in FAP are unique. A decision support tool may facilitate decision-making, better preparing patients for life after surgery.


Assuntos
Polipose Adenomatosa do Colo/cirurgia , Colectomia , Neoplasias Colorretais/prevenção & controle , Tomada de Decisões , Papel do Médico , Adolescente , Adulto , Idoso , Criança , Colectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Pesquisa Qualitativa , Qualidade de Vida
10.
Minerva Chir ; 65(2): 181-96, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20548274

RESUMO

Colorectal adenocarcinoma is the second leading cause of cancer deaths in Western countries. Rectal cancer comprises approximately 25% of the malignancies arising in the large bowel. However, the past two decades have seen many major advances in the diagnosis and treatment of this disease. While surgery is still the cornerstone of curative therapy, a multidisciplinary approach including neoadjuvant chemoradiotherapy has resulted in significantly improved outcomes. Information concerning the T, N, M stage and the exact location of tumor in relation to the anal verge are of crucial importance when planning a curative rectal cancer resection. Preoperative staging, utilizing a combination of diagnostic modalities, must be undertaken to determine whether or not neoadjuvant therapy is indicated. In radical resection of locally advanced low rectal cancer, several unique surgical management issues should be considered: 1) total mesorectal excision (TME); 2) longitudinal and circumferential resection margins; 3) autonomic nerve preservation (ANP); 4) sphincter preservation versus abdominoperineal resection (APR); 5) restoration of bowel continuity; and 6) laparoscopic versus open resection. The surgeon must first strive to achieve an oncologic cure, but whenever possible this should be undertaken with the goal of maintaining the patient's quality of life. The purpose of this review is to outline the critical surgical issues involved in management of locally advanced low rectal cancer.


Assuntos
Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/normas , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Neoplasias Retais/patologia
11.
J Surg Oncol ; 100(7): 525-8, 2009 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19697351

RESUMO

BACKGROUND: Failing to meet the benchmark of 12 lymph nodes in resection specimens is an indication for adjuvant chemotherapy in stage II colon cancer. METHODS: Among consecutive eligible patients with pathologic stage II colon cancer treated at eight NCI-designated comprehensive cancer centers between September 1, 2005 and February 19, 2008, we analyzed receipt of adjuvant chemotherapy, with less than 12 versus 12+ lymph nodes removed and examined the primary explanatory variable of interest. RESULTS: Among 258 patients, 46% received adjuvant chemotherapy. An oxaliplatin-containing regimen was used 67% of the time. Younger age (<50 years, P < 0.001), presence of lymphovascular invasion (P = 0.007), and higher T stage (P = 0.007) were independently associated with adjuvant chemotherapy use. There was significant inter-institutional variability in practice with the proportion receiving treatment ranging from 17% to 64% (P < 0.05). Notably, presence of less than 12 lymph nodes in the surgical specimen was a strong predictor of treatment (P = 0.008). CONCLUSIONS: Adjuvant chemotherapy use after resection of stage II colon cancer is common, but by no means standard practice at National Comprehensive Cancer Network (NCCN) institutions. More attention to achieving the recommended benchmark for lymph node dissection has the potential to decrease exposure to the toxicity of adjuvant treatment.


Assuntos
Quimioterapia Adjuvante/estatística & dados numéricos , Neoplasias do Colo/terapia , Excisão de Linfonodo/estatística & dados numéricos , Fatores Etários , Idoso , Antineoplásicos/administração & dosagem , Neoplasias do Colo/patologia , Tomada de Decisões , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Padrões de Prática Médica
13.
Hernia ; 20(5): 723-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27469592

RESUMO

PURPOSE: Incisional hernia (IH) is a common complication after colectomy, with impacts on both health care utilization and quality of life. The true incidence of IH after minimally invasive colectomy is not well described. The purpose of this study was to examine IH incidence after minimally invasive right colectomies (RC) and to compare the IH rates after laparoscopic (L-RC) and robotic (R-RC) colectomies. METHODS: This is a retrospective review of patients undergoing minimally invasive RC at a single institution from 2009 to 2014. Only patients undergoing RC for colonic neoplasia were included. Patients with previous colectomy or intraperitoneal chemotherapy were excluded. Three L-RC patients were included for each R-RC patient. The primary outcome was IH rate based on clinical examination or computed tomography (CT). Univariate and multivariate time-to-event analyses were used to assess predictors of IH. RESULTS: 276 patients where included, of which 69 had undergone R-RC and 207 L-RC. Patient and tumor characteristics were similar between the groups, except for higher tumor stage in L-RC patients. Both the median time to diagnosis (9.2 months) and the overall IH rate were similar between the groups (17.4 % for R-RC and 22.2 % for L-RC), as were all other postoperative complications. In multivariable analyses, the only significant predictor of IH was former or current tobacco use (hazard raio 3.0, p = 0.03). CONCLUSIONS: This study suggests that the incidence of IH is high after minimally invasive colectomy and that this rate is equivalent after R-RC and L-RC. Reducing the IH rate represents an important opportunity for improving quality of life and reducing health care utilization after minimally invasive colectomy.


Assuntos
Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Hérnia Incisional/epidemiologia , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Colectomia/métodos , Feminino , Humanos , Incidência , Hérnia Incisional/etiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos
14.
Shock ; 5(6): 402-7, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8799951

RESUMO

Restoration of blood flow to ischemic skeletal muscle results in a reperfusion injury characterized by permeability edema in part mediated by neutrophils that adhere via the selectin family of adhesion molecules. Rats underwent 4 h of hindlimb tourniquet ischemia followed by 4 h reperfusion. The role of neutrophils was determined by rendering one group of animals neutropenic before ischemia. In additional experimental groups, selectins were blocked with either a soluble form of the selectin counter-receptor, sialyl-Lewis X (SLX) or a monoclonal antibody directed against P-selectin (PB1.3). Neutrophil depletion resulted in a 36.1% reduction in hindlimb permeability (p < .05). SLX reduced hindlimb permeability index (PI) 23.9% at 1 mg/kg and 36.1% at 10 mg/kg compared to a nonfucosylated oligosaccharide, sialyl-N-acetylactosamine (p < .05). SLX also reduced neutrophil sequestration by 48.6% (p < .05). PB1.3 reduced hindlimb injury by 26.5% (p < .05) but did not reduce leukosequestration. We interpret these data to indicate that ischemia and reperfusion lead to selectin-mediated neutrophil sequestration. The oligosaccharide SLX, while moderately effective in limiting neutrophil sequestration was as effective as neutrophil depletion in reducing hindlimb permeability. The lack of concordance between the ability of SLX and PB1.3 in limiting neutrophil sequestration and permeability indicate mechanisms of action of these two agents that are in addition to the blocking of adhesion.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD15/uso terapêutico , Músculo Esquelético/irrigação sanguínea , Oligossacarídeos/uso terapêutico , Selectina-P/imunologia , Traumatismo por Reperfusão/terapia , Animais , Permeabilidade Capilar , Adesão Celular , Masculino , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia , Antígeno Sialil Lewis X
15.
Surgery ; 119(6): 652-6, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8650605

RESUMO

BACKGROUND: Ischemia and reperfusion injury of rodent intestine is complement mediated. P-selectin antagonism reduces local injury, yet neutrophil depletion does not. This study tests the thesis that the protective mechanism of P-selectin antagonists involves complement inhibition. METHODS: We subjected rats (n = 86) to 50 minutes of complete mesenteric ischemia and 4 hours of reperfusion. Treatment with a monoclonal antibody (PB1.3) against P-selectin reduced intestinal injury as judged by 125I-albumin permeability index (7.33 +/- 0.40) compared with saline solution treatment (11.4 +/- 0.49) (p < 0.05). RESULTS: However, intestinal neutrophil sequestration assessed by myeloperoxidase assay was unchanged. Immunohistochemistry revealed that mucosal C5b-9 was deposited in animals treated with saline solution and was absent in the sham group. PB1.3 treatment reduced C5b-9 deposition in the intestinal mucosa compared with that in animals treated with saline solution (p < 0.05). Neutrophil-dependent remote lung injury assessed by 125I-albumin permeability and pulmonary myeloperoxidase assay were not significantly reduced by PB1.3. Treatment with a soluble form of P-selectin ligand, sialyl Lewisx (sLex), reduced intestinal myeloperoxidase (0.065 +/- 0.006) compared with saline solution treatment (0.136 +/- 0.02) (p < 0.05), but it did not reduce permeability. Remote lung permeability was reduced (4.52 +/- 0.65 x 10(-3)) by sLex compared with saline solution treatment (6.11 +/- 0.41 x 10(-3)) (p < 0.05). CONCLUSIONS: Antagonizing the lectin domain of P-selectin and thereby neutrophil adhesion was without local benefit in this model. In contrast, PB1.3 exerted a novel antagonism of P-selectin and reduced complement deposition.


Assuntos
Complexo de Ataque à Membrana do Sistema Complemento/fisiologia , Intestinos/irrigação sanguínea , Isquemia/metabolismo , Selectina-P/fisiologia , Animais , Anticorpos Monoclonais/imunologia , Masculino , Neutrófilos/fisiologia , Permeabilidade , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley
16.
J Appl Physiol (1985) ; 86(3): 938-42, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10066708

RESUMO

Intestinal ischemia-reperfusion injury is dependent on complement. This study examines the role of the alternative and classic pathways of complement and IgM in a murine model of intestinal ischemia-reperfusion. Wild-type animals, mice deficient in complement factor 4 (C4), C3, or Ig, or wild-type mice treated with soluble complement receptor 1 were subjected to 40 min of jejunal ischemia and 3 h of reperfusion. Compared with wild types, knockout and treated mice had significantly reduced intestinal injury, indicated by lowered permeability to radiolabeled albumin. When animals deficient in Ig were reconstituted with IgM, the degree of injury was restored to wild-type levels. Immunohistological staining of intestine for C3 and IgM showed colocalization in the mucosa of wild-type controls and minimal staining for both in the intestine of Ig-deficient and C4-deficient mice. We conclude that intestinal ischemia-reperfusion injury is dependent on the classic complement pathway and IgM.


Assuntos
Proteínas do Sistema Complemento/fisiologia , Imunoglobulina M/fisiologia , Enteropatias/imunologia , Traumatismo por Reperfusão/imunologia , Animais , Complemento C3/deficiência , Complemento C3/genética , Complemento C3/fisiologia , Complemento C4/deficiência , Complemento C4/genética , Complemento C4/fisiologia , Proteínas do Sistema Complemento/deficiência , Proteínas do Sistema Complemento/genética , Edema/patologia , Genes RAG-1/genética , Técnicas Imunoenzimáticas , Enteropatias/patologia , Camundongos , Camundongos Knockout , Traumatismo por Reperfusão/patologia
17.
J Appl Physiol (1985) ; 83(4): 1090-5, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9338415

RESUMO

Acid aspiration may result in the development of the acute respiratory distress syndrome, an event associated with significant morbidity and mortality. Although once attributed to direct distal airway injury, the pulmonary failure after acid aspiration is more complex and involves an inflammatory injury mediated by complement (C) and polymorphonuclear leukocytes. This study examines the injurious inflammatory cascades that are activated after acid aspiration. The role of neutrophils was defined by immunodepletion before aspiration, which reduced injury by 59%. The injury was not modified in either P- or E-selectin-knockout mice, indicating that these adhesion molecules were not operative. C activation after aspiration was documented with immunochemistry by C3 deposition on injured alveolar pneumocytes. Animals in which C activation was inhibited with soluble C receptor type 1 (sCR1) had a 54% reduction in injury, similar to the level of protection seen in C3-knockout mice (58%). However C4-knockout mice were not protected from injury, indicating that C activation is mediated by the alternative pathway. Finally, an additive effect of neutrophils and C was demonstrated whereby neutropenic animals that were treated with sCR1 showed an 85% reduction in injury. Thus acid aspiration injury is mediated by neutrophils and the alternative C pathway.


Assuntos
Via Alternativa do Complemento/fisiologia , Neutrófilos/fisiologia , Pneumonia Aspirativa/fisiopatologia , Animais , Complemento C3/metabolismo , Proteínas Inativadoras do Complemento/farmacologia , Via Alternativa do Complemento/efeitos dos fármacos , Via Clássica do Complemento/efeitos dos fármacos , Via Clássica do Complemento/fisiologia , Selectina E/fisiologia , Técnicas Imunoenzimáticas , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Selectina-P/fisiologia , Pneumonia Aspirativa/patologia , Alvéolos Pulmonares/patologia
18.
J Am Coll Surg ; 191(2): 184-90; discussion 190-1, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10945362

RESUMO

BACKGROUND: Even after an apparent complete resection of sarcomatous pulmonary metastases, 40% to 80% of patients will re-recur in the lung. The benefit of subsequent re-resection is poorly defined. This study examines patient survival after repeat pulmonary exploration for re-recurrent metastatic sarcoma at a single institution. STUDY DESIGN: Between July 1982 and December 1997, data on 3,149 adult in-patients with soft tissue sarcoma were prospectively gathered. Of these, pulmonary metastases were present or developed in 719 patients and 248 underwent at least one resection. Of the patients relapsing in the lung after an apparently complete resection, 86 underwent reexploration. Disease-specific survival (DSS) after re-resection was the end point of the study. Time to death was modeled using the method of Kaplan and Meier. The association of factors to time-to-event end points was analyzed using the log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. Clinicopathologic factors were analyzed with the Pearson chi-square or Fisher's exact test when appropriate. RESULTS: The median DSS after re-resection for all patients undergoing at least two pulmonary resections was 42.8 months with an estimated 5-year survival of 36%. The median DSS in patients with complete reresection was 51 months (n = 68) compared with 6 months in patients with an incomplete re-resection (n = 16, p<0.0001). Patients with one or two nodules at re-resection (n = 39) had a median DSS of 51 months compared with 20 months in patients with three or more nodules (n = 40, p = 0.003). Patients in whom the largest metastasis re-resected was less than or equal to 2 cm (n = 33) had a median DSS of 44 months compared with 20 months in patients with metastasis greater than 2 cm (n = 43, p = 0.033). Patients with primary tumor high-grade histology (n = 75) had a median DSS of 32 months and patients with low-grade histology (n = 11) had a median DSS that was not reached (p = 0.041). Three independent prognostic factors associated with poor outcomes may be determined preoperatively: > or =3 nodules, largest metastases > 2 cm, and high-grade primary tumor histology. Patients with either zero or one poor prognostic factor had a median DSS > 65 months and patients with three poor prognostic factors had a median DSS of 10 months. CONCLUSIONS: Reexploration for recurrent sarcomatous pulmonary metastases appears beneficial for patients who can be completely re-resected. Outcomes are described by factors that may be determined preoperatively, including metastasis size, metastasis number, and primary tumor histologic grade. Patients who cannot be completely re-resected or those with numerous, large metastasis and high-grade primary tumor pathology have poor outcomes and should be considered for investigational therapy.


Assuntos
Neoplasias Pulmonares/secundário , Recidiva Local de Neoplasia/cirurgia , Sarcoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Modelos Lineares , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasia Residual , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reoperação , Sarcoma/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
19.
Eur J Radiol ; 82(1): 85-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23088880

RESUMO

PURPOSE: To describe the clinical and CT imaging features of goblet cell carcinoid (GCC) neoplasm of the appendix. METHODS AND MATERIALS: A computer search of pathology and radiology records over a 19-year period at our two institutions was performed using the search string "goblet". In the patients with appendiceal GCC neoplasms who had abdominopelvic CT, imaging findings were categorized, blinded to gross and surgical description, as: "Appendicitis", "Prominent appendix without peri-appendiceal infiltration", "Mass" or "Normal appendix". The CT appearance was correlated with an accepted pathological classification of: low grade GCC, signet ring cell adenocarcinoma ex, and poorly differentiated adenocarcinoma ex GCC group. RESULTS: Twenty-seven patients (age range, 28-80 years; mean age, 52 years; 15 female, 12 male) with pathology-proven appendiceal GCC neoplasm had CT scans that were reviewed. Patients presented with acute appendicitis (n=12), abdominal pain not typical for appendicitis (n=14) and incidental finding (n=1). CT imaging showed 9 Appendicitis, 9 Prominent appendices without peri-appendiceal infiltration, 7 Masses and 2 Normal appendices. Appendicitis (8/9) usually correlated with typical low grade GCC on pathology. In contrast, the majority of Masses and Prominent Appendices without peri-appendiceal infiltration were pathologically confirmed to be signet ring cell adenocarcinoma ex GCC. Poorly differentiated adenocarcinoma ex GCC was seen in only a small minority of patients. Hyperattenuation of the appendiceal neoplasm was seen in a majority of cases. CONCLUSIONS: GCC neoplasm of the appendix should be considered in the differential diagnosis in patients with primary appendiceal malignancy. Our cases demonstrated close correlation between our predefined CT pattern and the pathological classification.


Assuntos
Neoplasias do Apêndice/diagnóstico por imagem , Tumor Carcinoide/diagnóstico por imagem , Radiografia Abdominal/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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