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1.
Colorectal Dis ; 22(12): 1874-1884, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32445614

RESUMO

AIM: Fistula Laser Closure (FiLaC™) is a novel sphincter-preserving technique that is based on new technologies and shows promising results in repairing anal fistulas whilst maintaining external sphincter function. The aim of the present meta-analysis is to present the efficacy and the safety of FiLaC™ in the management of anal fistula disease. METHOD: The present proportional meta-analysis was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, clinicaltrials.gov, Embase, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from inception until November 2019. RESULTS: Overall, eight studies were included that recruited 476 patients. The pooled success rate of the technique was 63% (95% CI 50%-75%). The pooled complication rate was 8% (95% CI 1%-18%). Sixty-six per cent of patients had a transsphincteric fistula and 60% had undergone a previous surgical intervention, mainly the insertion of a seton (54%). The majority had a cryptoglandular fistula. Operation time and follow-up period were described for each study. CONCLUSION: FiLaC™ seems to be an efficient therapeutic option for perianal fistula disease with an adequate level of safety that preserves quality of life. Nevertheless, randomized trials need to be designed to compare FiLaC™ with other procedures for the management of anal fistulas such as ligation of intersphincteric fistula tract, anal advancement flaps, fibrin glue, collagen paste, autologous adipose tissue, fistula plug and video-assisted anal fistula treatment.


Assuntos
Qualidade de Vida , Fístula Retal , Canal Anal/cirurgia , Humanos , Ligadura , Fístula Retal/cirurgia , Resultado do Tratamento
2.
Colorectal Dis ; 22(10): 1429-1435, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-28926174

RESUMO

The following position statement forms part of a response to the current concerns regarding use of mesh to perform rectal prolapse surgery. It highlights the actions being pursued by the Pelvic Floor Society (TPFS) regarding clinical governance in relation to ventral mesh rectopexy (VMR). The following are summary recommendations. Available evidence suggests that mesh morbidity for VMR is far lower than that seen in transvaginal procedures (the main subject of current concern) and lower than that observed following other abdomino-pelvic procedures for urogenital prolapse, e.g. laparoscopic sacrocolpopexy. VMR should be performed by adequately trained surgeons who work within a multidisciplinary team (MDT) framework. Within this, it is mandatory to discuss all patients considered for surgery at an MDT meeting. Clinical outcomes of surgery and any complications resulting from surgery should be recorded in the TPFS-hosted national database (registry) available for this purpose; in addition, all patients should be considered for entry into ongoing and planned UK/European randomized studies where this is feasible. A move towards accreditation of UK units performing VMR will improve performance and outcomes in the long term. An enhanced programme of training including staged porcine, cadaveric and preceptorship sessions will ensure the competence of surgeons undertaking VMR. Enhanced consent forms and patient information booklets are being developed, and these will help both surgeons and patients. There is weak observational evidence that technical aspects of the procedure can be optimized to reduce morbidity rates. Suture material choice may contribute towards morbidity. The available evidence is insufficient to support the use of one mesh over another (biologic vs synthetic); however, the use of polyester mesh is associated with increased morbidity.


Assuntos
Laparoscopia , Prolapso de Órgão Pélvico , Prolapso Retal , Animais , Humanos , Diafragma da Pelve/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Prolapso Retal/cirurgia , Telas Cirúrgicas , Suínos , Resultado do Tratamento , Reino Unido
3.
Colorectal Dis ; 21(9): 1079-1089, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31095879

RESUMO

AIM: This was a prospective cohort study to determine the intrinsic non-modifiable factors influencing length of stay (LOS) in unselected consecutive patients undergoing elective colorectal surgery within an enhanced recovery pathway. METHODS: This study interrogated a prospective database of consecutive elective procedures from October 2006 to April 2011 at a tertiary referral academic hospital in the UK to identify independent predictors of prolonged length of stay (pLOS). pLOS was defined as longer than median length of stay (mLOS). Differences in determinants were identified in three groups of increasing operative complexity. RESULTS: In all, 872 procedures were identified and ranged from a simple ileostomy reversal to complex total pelvic exenteration. Preoperative anaemia and American Society of Anesthesiologists (ASA) Grade III+ predicted pLOS in stoma reversal surgery patients (n = 191, mLOS 4 days). In colonic and small bowel surgery (n = 444, mLOS 8 days), an open procedure, new stoma formation, planned critical care admission and ASA III+ predicted pLOS. New stoma formation and planned critical care admission predicted pLOS in patients undergoing pelvic rectal surgery (n = 237, mLOS 11 days). pLOS was associated with significantly higher morbidity across Dindo-Clavien grades and a longer time to postoperative functional recovery and discharge. CONCLUSIONS: Operative complexity is associated with longer LOS even with an established enhanced recovery pathway in place. Intrinsic non-modifiable predictors of pLOS differ with operative complexity, and this should be taken into account when planning benchmarking and research across units.


Assuntos
Doenças do Colo/cirurgia , Recuperação Pós-Cirúrgica Melhorada , Tempo de Internação/estatística & dados numéricos , Doenças Retais/cirurgia , Adulto , Idoso , Procedimentos Cirúrgicos Eletivos , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
4.
Colorectal Dis ; 20 Suppl 8: 3-117, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30508274

RESUMO

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.


Assuntos
Cirurgia Colorretal/normas , Gastroenterologia/normas , Doenças Inflamatórias Intestinais/cirurgia , Consenso , Humanos , Sociedades Médicas , Reino Unido
5.
Colorectal Dis ; 19 Suppl 3: 101-113, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28960922

RESUMO

AIM: This manuscript forms the final of seven that address the surgical management of chronic constipation (CC) in adults. The content coalesces results from the five systematic reviews that precede it and of the European Consensus process to derive graded practice recommendations (GPR). METHODS: Summary of review data, development of GPR and future research recommendations as outlined in detail in the 'introduction and methods' paper. RESULTS: The overall quality of data in the five reviews was poor with 113/156(72.4%) of included studies providing only level IV evidence and only four included level I RCTs. Coalescence of data from the five procedural classes revealed that few firm conclusions could be drawn regarding procedural choice or patient selection: no single procedure dominated in addressing dynamic structural abnormalities of the anorectum and pelvic floor with each having similar overall efficacy. Of one hundred 'prototype' GPRs developed by the clinical guideline group, 85/100 were deemed 'appropriate' based on the independent scoring of a panel of 18 European experts and use of RAND-UCLA consensus methodology. The remaining 15 were all deemed uncertain. Future research recommendations included some potential RCTs but also a strong emphasis on delivery of large multinational high-quality prospective cohort studies. CONCLUSION: While the evidence base for surgery in CC is poor, the widespread European consensus for GPRs is encouraging. Professional bodies have the opportunity to build on this work by supporting the efforts of their membership to help convert the documented recommendations into clinical guidelines.


Assuntos
Pesquisa Biomédica , Constipação Intestinal/etiologia , Constipação Intestinal/cirurgia , Medicina Baseada em Evidências , Doença Crônica , Consenso , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Seleção de Pacientes , Guias de Prática Clínica como Assunto
6.
Colorectal Dis ; 19 Suppl 3: 73-91, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28960924

RESUMO

AIM: To assess the outcomes of recto-vaginal reinforcement procedures in adults with chronic constipation. METHOD: Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. RESULTS: Forty-three articles were identified, providing data on outcomes in 3346 patients. Average length of procedures ranged between 20 and 169 min, and length of stay between 1 and 15 days. Complications typically occurred after 7-17% of procedures (range 0-61%). Post-operative bleeding was uncommon (0-4%) as well as haematoma or sepsis (0-2%). Fistulation did not occur in most studies. Two procedure-related deaths were observed for 3209 patients. Although inconsistent, 78% of patients reported a satisfactory or good outcome, with 30-50% experiencing reduced symptoms of straining, incomplete emptying or reduced vaginal digitation. About 17% of patients developed anatomical recurrence. Considering measures of harm and global satisfaction rating scales, there was insufficient evidence to prefer one type of procedure over another. There was no evidence to support better outcomes based on selection of patients with a particular size or grade of rectocoele. CONCLUSION: Evidence supporting recto-vaginal reinforcement procedures is currently derived from observational studies and comparisons, with only one high quality study. Large trials are needed to inform future clinical decision making.


Assuntos
Constipação Intestinal/cirurgia , Complicações Pós-Operatórias/etiologia , Retocele/cirurgia , Reto/cirurgia , Vagina/cirurgia , Doença Crônica , Constipação Intestinal/etiologia , Feminino , Humanos , Tempo de Internação , Duração da Cirurgia , Satisfação do Paciente , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Retocele/complicações , Recidiva , Resultado do Tratamento
7.
Colorectal Dis ; 19 Suppl 3: 5-16, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28960925

RESUMO

AIM: This manuscript provides the introduction and detailed methodology used in subsequent reviews to assess the outcomes of surgical interventions with the primary intent of treating chronic constipation in adults and to develop recommendations for practice. METHOD: PRISMA guidance was adhered to throughout. A literature search was performed in public databases between January 1960 and February 2016. Studies that fulfilled strictly-defined PICOS (patients, interventions, controls, outcome, and study design) criteria were included. The process involved two groups of participants: (i): 'a clinical guidance group' of 18 UK experts (including junior support) who performed the systematic reviews and produced summary evidence statements (SES) based strictly on data synthesis in each review. The same group then produced prototype graded practice recommendations (GPRs) based on coalescence of SES and expert opinion; (ii): a European Consensus group of 18 ESCP (European Society of Coloproctology) nominated experts from nine European countries evaluated the appropriateness of each prototype GPR based on published RAND/UCLA methodology. RESULTS: An overview of the search results is provided in this manuscript. A total of 156 studies from 307 full text articles (from 2551 initially screened records) were included, providing data on procedures characterized by: (i) colonic resection (n = 40); (ii) rectal suspension (n = 18); (iii) rectal wall excision (n = 44); (iv) rectovaginal septum reinforcement (n = 47); (v) sacral nerve stimulation (n = 7). The overall quality of evidence was poor with 113/156 (72.4%) studies providing only Oxford level IV evidence. The best evidence was extracted for rectal excisional procedures, where the majority of studies were Oxford level I or II. The five subsequent reviews provide a total of 99 SES (reflecting perioperative variables, efficacy, harms and prognostic variables) that contributed to 100 prototype GPRs covering patient selection, procedural considerations and patient counselling. The final manuscript details the 85/100 GPRs that were deemed appropriate by European Consensus (remaining 15 were all uncertain) and future research recommendations. CONCLUSION: This manuscript and the following 6 papers suggest that the evidence base for surgical management of chronic constipation is currently poor although some expert consensus exists on best practice. Further studies are required to inform future commissioning of treatments and of research funding.


Assuntos
Constipação Intestinal/cirurgia , Literatura de Revisão como Assunto , Viés , Doença Crônica , Medicina Baseada em Evidências , Humanos , Projetos de Pesquisa
8.
Colorectal Dis ; 19(6): 563-569, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27704667

RESUMO

AIM: Anal fistula causes pain and discharge of pus and blood. Treatment by fistulotomy has the highest success, but can risk continence; treatment needs to balance cure with continence. This study assessed the impact of fistulotomy on quality of life (QOL) and continence. METHOD: Patients selected for fistulotomy prospectively completed the St Mark's Continence Score (full incontinence = 24) and Short Form-36 questionnaires preoperatively at two institutions with an interest in anal fistula. Patients were reassessed 3 months' postoperatively. RESULTS: There were 52 patients with a median age of 44 (range 19-82) years; 10 were women. Preoperative continence scores were median 0 (range 0-23) and there was no significant difference compared with postoperative scores (median 1, range 0-24). Following fistulotomy QOL was significantly improved in four of eight domains - Bodily Pain (P < 0.001), Vitality (P < 0.01), Social Functioning (P < 0.05) and Mental Health (P < 0.001) - and returned to that of the general population. QOL for patients with intersphincteric fistula improved postfistulotomy, and for those with trans-sphincteric fistula it remained the same. Data were further examined in two groups, with and without deterioration in continence score. Where continence improved postoperatively, QOL improved in three domains; where continence deteriorated QOL improved in two domains (P < 0.05). Patients with postoperative continence scores of < 5 had worse QOL than those scoring 4 or less. CONCLUSION: QOL significantly improved at 3 months' follow-up after fistulotomy where continence was maintained or a small reduction occurred.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Incontinência Fecal/psicologia , Complicações Pós-Operatórias/psicologia , Qualidade de Vida , Fístula Retal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Incontinência Fecal/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Estudos Prospectivos , Fístula Retal/psicologia , Índice de Gravidade de Doença , Adulto Jovem
9.
Colorectal Dis ; 19(1): O54-O65, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27886434

RESUMO

AIM: Imaging for pelvic floor defaecatory dysfunction includes defaecation proctography. Integrated total pelvic floor ultrasound (transvaginal, transperineal, endoanal) may be an alternative. This study assesses ultrasound accuracy for the detection of rectocele, intussusception, enterocele and dyssynergy compared with defaecation proctography, and determines if ultrasound can predict symptoms and findings on proctography. Treatment is examined. METHOD: Images of 323 women who underwent integrated total pelvic floor ultrasound and defaecation proctography between 2011 and 2014 were blindly reviewed. The size and grade of rectocele, enterocele, intussusception and dyssynergy were noted on both, using proctography as the gold standard. Barium trapping in a rectocele or a functionally significant enterocele was noted on proctography. Demographics and Obstructive Defaecation Symptom scores were collated. RESULTS: The positive predictive value of ultrasound was 73% for rectocele, 79% for intussusception and 91% for enterocele. The negative predictive value for dyssynergy was 99%. Agreement was moderate for rectocele and intussusception, good for enterocele and fair for dyssynergy. The majority of rectoceles that required surgery (59/61) and caused barium trapping (85/89) were detected on ultrasound. A rectocele seen on both transvaginal and transperineal scanning was more likely to require surgery than if seen with only one mode (P = 0.0001). If there was intussusception on ultrasound the patient was more likely to have surgery (P = 0.03). An enterocele visualized on ultrasound was likely to be functionally significant on proctography (P = 0.02). There was, however, no association between findings on imaging and symptoms. CONCLUSION: Integrated total pelvic floor ultrasound provides a useful screening tool for women with defaecatory dysfunction such that defaecatory imaging can avoided in some.


Assuntos
Constipação Intestinal/diagnóstico por imagem , Defecografia/métodos , Endossonografia/métodos , Distúrbios do Assoalho Pélvico/diagnóstico por imagem , Diafragma da Pelve/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ataxia/complicações , Ataxia/diagnóstico por imagem , Ataxia/fisiopatologia , Bário , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Meios de Contraste , Defecação/fisiologia , Feminino , Hérnia/complicações , Hérnia/diagnóstico por imagem , Hérnia/fisiopatologia , Humanos , Intussuscepção/complicações , Intussuscepção/diagnóstico por imagem , Intussuscepção/fisiopatologia , Pessoa de Meia-Idade , Diafragma da Pelve/fisiopatologia , Distúrbios do Assoalho Pélvico/complicações , Distúrbios do Assoalho Pélvico/fisiopatologia , Valor Preditivo dos Testes , Retocele/complicações , Retocele/diagnóstico por imagem , Retocele/fisiopatologia , Índice de Gravidade de Doença , Método Simples-Cego
10.
Ann R Coll Surg Engl ; 98(5): 334-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27087327

RESUMO

INTRODUCTION: Anal fistula affects people of working age. Symptoms include abscess, pain, discharge of pus and blood. Treatment of this benign disease can affect faecal continence, which may, in turn, impair quality of life (QOL). We assessed the QOL of patients with cryptoglandular anal fistula. METHODS: Newly referred patients with anal fistula completed the St Mark's Incontinence Score, which ranges from 0 (perfect continence) to 24 (totally incontinent), and Short form 36 (SF-36) questionnaire at two institutions with an interest in anal fistula. The data were examined to identify factors affecting QOL. RESULTS: Data were available for 146 patients (47 women), with a median age of 44 years (range 18-82 years) and a median continence score of 0 (range 0-23). Versus population norms, patients had an overall reduction in QOL. While those with recurrent disease had no difference on continence scores, QOL was worse on two of eight SF-36 domains (p<0.05). Patients with secondary extensions had reduced QOL in two domains (p<0.05), while urgency was associated with reduced QOL on five domains (p<0.05). Patients with loose seton had the same QOL as those without seton. No difference in urgency was found between patients with and without loose seton. In primary fistula patients, 19.4% of patients experienced urgency versus 36.3% of those with recurrent fistulas. CONCLUSIONS: Patients with anal fistula had a reduced QOL, which was worse in those with recurrent disease, secondary extensions and urgency. Loose seton had no impact on QOL.


Assuntos
Qualidade de Vida , Fístula Retal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Incontinência Fecal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Retal/epidemiologia , Fístula Retal/fisiopatologia , Fístula Retal/psicologia , Inquéritos e Questionários , Adulto Jovem
11.
Neurogastroenterol Motil ; 28(7): 1075-82, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26968828

RESUMO

BACKGROUND: Understanding the association between structure and function is vital before considering surgery involving anal sphincter division. By correlating three-dimensional anal endosonography (AES) and three-dimensional anal canal vector volume manometry (VVM), this study details a method to produce measurements of both sphincter length and pressure leading to identification of the functionally important areas of the anal canal. The aim of this study was to provide combined detailed information on anal canal anatomy and physiology. METHODS: Twelve males and 12 nulliparous females with no bowel symptoms underwent VVM (using a water-perfused, eight-channel radially arranged catheter) and AES. KEY RESULTS: The synchronization of AES and VVM identified that the majority of rest and squeeze anal pressure is present in the portion of the anal canal covered by both anal sphincters. Nearly, 20% of overall resting anal pressure is produced distal to the caudal termination of the internal anal sphincter. Puborectalis accounts for a significantly greater percentage volume of pressure in females both at rest and when squeezing, though the total volume of pressure is not significantly greater. CONCLUSIONS AND INFERENCES: The majority of resting and squeezing pressure and the least asymmetry, in both sexes, is in the portion of the anal canal covered by external anal sphincter. In females, the external anal sphincter is shorter and a proportionately longer puborectalis accounts for a greater percentage of pressure. Sphincter targeted fistula surgery in females must be performed with special caution. A protective role for puborectalis following obstetric anal sphincter injury is suggested.


Assuntos
Canal Anal/diagnóstico por imagem , Canal Anal/fisiologia , Endossonografia/métodos , Imageamento Tridimensional/métodos , Manometria/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia
12.
Colorectal Dis ; 18(11): 1087-1093, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27027907

RESUMO

AIM: The study aimed to determine the current state of UK pelvic floor services and to discuss future strategies. METHOD: A questionnaire developed by the Pelvic Floor Society was sent in 2014 to the 175 colorectal units recognized by the Association of Coloproctology of Great Britain and Ireland. Questions included type of centre, frequency of pelvic floor clinics/interdisciplinary joint pelvic floor clinics/multidisciplinary meetings (MDMs) and workload. RESULTS: Sixty-seven (38%) centres replied including 75% of units with a consultant who was as member of the Pelvic Floor Society. Of the 67 centres 39% were tertiary centres for pelvic floor surgery (tertiary), 48% performed some pelvic floor surgery (regional) and 13% did not perform any (local). Ninety-six per cent of tertiary referral centres served a population over 500 000. The mean number of whole time equivalent consultants in tertiary centres was 1.03 and 0.77 in regional centres. Eighty per cent of tertiary centres and 56% of regional centres ran pelvic floor clinics. Eighty-four per cent of tertiary referral and 75% of regional units held or attended an MDM. Anal ultrasonography, anorectal physiology and proctography were performed in 96% of tertiary centres compared with 50% of non-tertiary units. CONCLUSION: The provision of pelvic floor services includes local, regional and tertiary centres. The overall response rate was low (38%) and biased to centres with a consultant who was a member of the Pelvic Floor Society. Not all regional or tertiary centres held an MDM or a pelvic floor clinic. Given the nature of pelvic floor pathology an integrated service should be aimed at linking different centres and specialities.


Assuntos
Cirurgia Colorretal/tendências , Previsões , Pesquisas sobre Atenção à Saúde , Distúrbios do Assoalho Pélvico , Cirurgia Colorretal/métodos , Humanos , Irlanda , Equipe de Assistência ao Paciente/tendências , Inquéritos e Questionários , Reino Unido
13.
Leukemia ; 27(1): 48-55, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22858906

RESUMO

FMS-like tyrosine kinase 3 (FLT3) normally functions in the survival/proliferation of hematopoietic stem/progenitor cells, but its constitutive activation by internal tandem duplication (ITD) mutations correlates with a poor prognosis in AML. The development of FLT3 tyrosine kinase inhibitors (TKI) is a promising strategy, but resistance that arises during the course of treatment caused by secondary mutations within the mutated gene itself poses a significant challenge. In an effort to predict FLT3 resistance mutations that might develop in patients, we used saturation mutagenesis of FLT3/ITD followed by selection of transfected cells in FLT3 TKI. We identified F621L, A627P, F691L and Y842C mutations in FLT3/ITD that confer varying levels of resistance to FLT3 TKI. Western blotting confirmed that some FLT3 TKI were ineffective at inhibiting FLT3 autophosphorylation and signaling through MAP kinase, STAT5 and AKT in some mutants. Balb/c mice transplanted with the FLT3/ITD Y842C mutation confirmed resistance to sorafenib in vivo but not to lestaurtinib. These results indicate a growing number of FLT3 mutations that are likely to be encountered in patients. Such knowledge, combined with known remaining sensitivity to other FLT3 TKI, will be important to establish as secondary drug treatments that can be substituted when these mutants are encountered.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Eritroblástica Aguda/tratamento farmacológico , Mutação/genética , Células Precursoras de Linfócitos B/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Sequências de Repetição em Tandem/efeitos dos fármacos , Tirosina Quinase 3 Semelhante a fms/genética , Animais , Benzenossulfonatos/farmacologia , Western Blotting , Células Cultivadas , Humanos , Imunoprecipitação , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patologia , Camundongos , Camundongos Endogâmicos BALB C , Niacinamida/análogos & derivados , Compostos de Fenilureia , Fosforilação/efeitos dos fármacos , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/metabolismo , Piridinas/farmacologia , Sorafenibe , Sequências de Repetição em Tandem/genética
14.
Anaesth Intensive Care ; 40(3): 479-89, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22577914

RESUMO

There is debate in Australia and New Zealand around the appropriate use of illness severity scoring systems in Australasian intensive care units. The international benchmark is the Acute Physiological and Chronic Health Evaluation (APACHE) system. In order to compare the performance of recent APACHE releases, we audited 2080 sequential patients admitted between 1 January 2006 and 31 March 2008 to the Middlemore Hospital intensive care unit, Auckland, New Zealand. We compared the predictive performance of the proprietary APACHE II, IIIh, IIIj and IV releases, and the performance of a 'localised' version of APACHE II containing re-estimated coefficients derived from a legacy dataset (7703 sequential patients admitted between 1 January 1997 and 31 December 2005). Discrimination assessed by receiver operating characteristic curves was highest with the APACHE III and IV releases, and significantly better than the APACHE II releases. Calibration assessed by the Hosmer-Lemeshow statistic was poor with all releases, although it was best with APACHE IV and 'localised' version of the APACHE II release. Overall accuracy assessed by the Brier Mean Probability score and Shapiro's R statistic was best with APACHE IV. Our study suggests the possibility of improved prediction in moving to APACHE IV from older releases, although broader multicentre study within the Australian and New Zealand critical care community is warranted. Our study also suggests localisation of the APACHE system offers further opportunity to improve prediction, although these improvements may not be major without ground-up development of a new risk prediction model within our local critical care setting.


Assuntos
APACHE , Adulto , Idoso , Calibragem , Estudos de Coortes , Interpretação Estatística de Dados , Etnicidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Valor Preditivo dos Testes , Curva ROC , Respiração Artificial , Estudos Retrospectivos , Risco , Fatores Socioeconômicos
15.
Anaesth Intensive Care ; 40(2): 260-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22417020

RESUMO

Prolonged intermittent renal replacement therapy (PIRRT) is a recently defined acute modality for critically ill patients, and in theory combines the superior detoxification and haemodynamic stability of continuous renal replacement therapy (CRRT) with the operational convenience and low cost of intermittent haemodialysis (iHD). We performed a retrospective cohort study for all critically ill adults treated with renal replacement therapy at our centre in Auckland, New Zealand from 1 January 2002 to 31 December 2008. The exposure of interest was modality (PIRRT, CRRT, iHD). Primary and secondary outcomes were patient mortality determined at hospital discharge and 90 days post renal replacement therapy inception, respectively. Co-variates included co-morbidity and baseline illness severity measured by Acute Physiology and Chronic Health Evaluation IV and Sepsis-Related Organ Failure Assessment (SOFA) and time-varying illness severity measured by daily SOFA scores. We used Marginal Structural Modelling to estimate mortality risk adjusting for both time-varying illness severity and modality exposure. A total of 146 patients with 633 treatment-days had sufficient data for modelling. With PIRRT as the reference, the adjusted hazard ratios for patient hospital mortality were 1.31 (0.60 to 2.90) for CRRT and 1.22 (0.21 to 2.29) for iHD. Corresponding estimates for mortality at 90 days were 0.96 (0.39 to 2.36) and 2.22 (0.49 to 10.11), respectively, reflecting the poorer longer-term prognosis of patients still on iHD at hospital discharge with delayed or non-recovery of acute kidney injury. Our study supports the recent increased use of PIRRT, which within limits can be regarded as safe and effective.


Assuntos
Injúria Renal Aguda/terapia , Estado Terminal/terapia , Terapia de Substituição Renal , Injúria Renal Aguda/mortalidade , Estudos de Coortes , Estado Terminal/mortalidade , Interpretação Estatística de Dados , Determinação de Ponto Final , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Nova Zelândia , Modelos de Riscos Proporcionais , Risco , Resultado do Tratamento
16.
Anaesth Intensive Care ; 39(6): 1103-10, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22165366

RESUMO

In this study, we evaluated the performance of a humidified nasal high-flow system (Optiflow, Fisher and Paykel Healthcare) by measuring delivered FiO, and airway pressures. Oxygraphy, capnography and measurement of airway pressures were performed through a hypopharyngeal catheter in healthy volunteers receiving Optiflow humidified nasal high flow therapy at rest and with exercise. The study was conducted in a non-clinical experimental setting. Ten healthy volunteers completed the study after giving informed written consent. Participants received a delivered oxygen fraction of 0.60 with gas flow rates of 10, 20, 30, 40 and 50 l/minute in random order FiO2, F(E)O2, F(E)CO2 and airway pressures were measured. Calculation of FiO2 from F(E)O2 and F(E)CO2 was later performed. Calculated FiO2 approached 0.60 as gas flow rates increased above 30 l/minute during nose breathing at rest. High peak inspiratory flow rates with exercise were associated with increased air entrainment. Hypopharyngeal pressure increased with increasing delivered gas flow rate. At 50 l/minute the system delivered a mean airway pressure of up to 7.1 cm H20. We believe that the high gas flow rates delivered by this system enable an accurate inspired oxygen fraction to be delivered. The positive mean airway pressure created by the high flow increases the efficacy of this system and may serve as a bridge to formal positive pressure systems.


Assuntos
Manuseio das Vias Aéreas/instrumentação , Capnografia , Oximetria , Oxigenoterapia/instrumentação , Pressão do Ar , Algoritmos , Catéteres , Pressão Positiva Contínua nas Vias Aéreas , Exercício Físico/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Fluxo Expiratório Máximo , Cavidade Nasal/fisiologia , Oxigênio/sangue , Faringe/fisiologia , Respiração com Pressão Positiva , Taxa Respiratória/fisiologia , Adulto Jovem
17.
Neurogastroenterol Motil ; 23(9): 886-e393, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21722268

RESUMO

BACKGROUND: Vector volume manometry (VVM) can be used to assess patients with fecal incontinence. The VVM may be performed using a station pull through, or an automated technique. Currently no standard technique or equipment exists to assess anal canal VVM. This study aimed to assess the different techniques to produce repeatable results, and generate normal values for the vector volume profile. METHODS: Anal canal VVM was performed using a water-perfused system on 12 male and 12 nulliparous female volunteers. Manometry was performed with an automated puller withdrawn at 3 and 25mms(-1) using a station technique. The VVM profiles were calculated using 4, 8, and 16 channels. KEY RESULTS: The greatest repeatability of vector volume profile was seen with faster puller speed (25mms(-1) ) and with an 8-channel catheter. Men had higher squeeze volumes, maximal squeeze pressure, average squeeze pressure, and squeeze high pressure zone length. Women had a significantly greater anal canal asymmetry on both station and automated pull through at rest and when squeezing. Squeeze vector volume of pressure, mean maximum squeeze pressure, and the average squeeze pressure were significantly higher when calculated using the station technique. CONCLUSIONS & INFERENCES: The faster puller speed has improved agreement between vector profiles, which is most marked during active contraction. The 8-channel catheters have the greatest agreement between profiles. There is variation in values between automated manometry and the stationary pull through technique. The improved repeatability in automated VVM for healthy controls should improve its diagnostic utility in patients with incontinence.


Assuntos
Canal Anal/fisiologia , Manometria/métodos , Manometria/normas , Incontinência Fecal/diagnóstico , Feminino , Humanos , Masculino , Manometria/instrumentação , Contração Muscular , Pressão , Valores de Referência
18.
Colorectal Dis ; 13(2): e20-32, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21040361

RESUMO

AIM: This study reports the short- and long-term outcomes of laparostomy for intra-abdominal sepsis. METHOD: Twenty-nine sequential patients with intra-abdominal sepsis treated with a laparostomy over 6 years were included. RESULTS: The median age of the patients was 51 years, postoperative intensive care unit stay was 8 days, postoperative length of hospital stay was 87 days and follow up was 2 years. The expected mortality of 25% was insignificantly different from the observed mortality of 33% (P = 0.35). Seven per cent of patients required percutaneous drainage of intra-abdominal collections. An enterocutaneous fistula developed in 31% of all patients and in 15% of those treated with vacuum dressings. Component-separation fascial reconstruction was successful and uncomplicated in 83% of recipients compared with 25% of mesh repairs. CONCLUSION: Laparostomy does not significantly reduce mortality from the expected rate and commits the patient to a prolonged recovery with a high risk of enterocutaneous fistulation. Component-separation fascial reconstruction has a better outcome than mesh repair.


Assuntos
Abdome , Enterostomia , Sepse/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fístula Intestinal/etiologia , Laparotomia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento
19.
Colorectal Dis ; 12(6): 555-60, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19341404

RESUMO

INTRODUCTION: Abdominoperineal excision (APE) following radiotherapy is associated with a high rate of perineal wound complications. The use of myocutaneous flaps may improve wound healing. We present our experience using myocutaneous flaps for immediate reconstruction. METHOD: Prospective data were collected on patients undergoing APE from October 2003 to December 2008. Patient demographics, operating time, wound complications and length of stay were recorded. RESULTS: Fifty-one patients underwent APE for rectal adenocarcinoma, 21 had primary closure and 30 had myocutaneous flap closure (24 VRAM, 6 gracilis). The proportion of patients undergoing preoperative radiotherapy in each group were 62% and 93% respectively (P = 0.011). There were no major complications following primary closure of the unirradiated perineum. Major perineal wound complications requiring reoperation or debridement were seen in three (14%) patients following primary closure and five (17%) patients with flap closure. After radiotherapy, closure with a flap reduced the length of stay from 20 to 15 days, but this difference was not statistically significant (P = 0.36). CONCLUSION: The use of flap closure in irradiated patients is associated with fewer perineal complications and a shorter hospital stay.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Retais/cirurgia , Retalhos Cirúrgicos , Abdome/cirurgia , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Períneo/cirurgia , Complicações Pós-Operatórias , Procedimentos de Cirurgia Plástica , Neoplasias Retais/radioterapia , Reto do Abdome/cirurgia , Cicatrização
20.
Dis Colon Rectum ; 51(6): 961-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18288538

RESUMO

PURPOSE: Patients on renal replacement therapy are reported to have a high complication rate after abdominal surgery, the result of uremia and immunosuppression. A review of this group of patients undergoing colorectal surgery was undertaken. METHODS: Seventy-three separate colorectal operations were performed for 44 patients. Thirty-eight patients were on dialysis and 35 had a renal transplant. Data (coexisting disease, preoperative blood results, operative details, complications, and colorectal POSSUM score) were completed for each surgical event. RESULTS: Forty-two elective and 31 emergency procedures were performed. Infective complications were common (overall 60 percent). There were two anastomotic leaks in the elective group, but five leaks from seven emergency anastomoses. Stomas were frequently raised. Ninety percent of patients who survived and had a defunctioning stoma underwent a successful reversal. The overall major complication rate after elective and emergency surgery was 19 and 81 percent, respectively, and mortality was 5 and 26 percent, respectively. CONCLUSIONS: Renal patients have a high rate of complications after colorectal surgery, and emergency surgery has a significant risk of anastomotic leak. Primary anastomosis should be avoided in all patients undergoing emergency intestinal resections. Subsequent surgery to restore intestinal continuity is possible in 90 percent of patients with far fewer complications.


Assuntos
Cirurgia Colorretal , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Terapia de Substituição Renal , Adulto , Idoso , Feminino , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
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