Management of colonic complications of type IV Ehlers-Danlos syndrome: a systematic review and evidence-based management strategy.

AIM: Type IV Ehlers Danlos Syndrome (EDS) is a connective tissue disorder affecting approximately 1 per 100,000-200,000 people. Life expectancy is reduced secondary to spontaneous vascular rupture or colonic perforation. Surgery carries significant morbidity and mortality. While strategies to manage colonic perforation include primary repair with or without a defunctioning stoma, Hartmann's procedure, total abdominal colectomy with end ileostomy and ileorectal anastomosis, evidence is contradictory and has not previously been evaluated in order to form a treatment strategy. We aim to review the published literature and identify outcome data relating to operative management of colonic perforation in type IV EDS. METHODS: Pubmed, EM-BASE, Cochrane library and Google Scholar were searched with the following details: Ehlers Danlos Syndrome AND colonic surgery. The main outcome measure was re-perforation rates following colonic surgery on patients with type IV EDS. If the nature of surgery and follow up were reported, data were recorded in a SPSS database according to PRISMA guidelines. RESULTS: One hundred and nine operations have been described in 51 patients in 44 case series. There were 26 visceral re-perforations, 2 affecting the small intestine and 24 colonic. Survival analysis favoured total abdominal colectomy compared with operations where the colon was left in situ. CONCLUSIONS: Total abdominal colectomy with end ileostomy or ileorectal anastomosis are the safest strategies after colonic perforation in type IV EDS. Anastomotic leak rates are high. End colostomy is high risk for colonic re-perforation and anastomotic leak rates are extremely high. Restoration of colonic continuity should be avoided.

Recurrent intestinal fistulation after porcine acellular dermal matrix reinforcement in enteric fistula takedown and simultaneous abdominal wall reconstruction.

PURPOSE: Porcine acellular dermal matrix (PADM) has been promoted as a suitable material for the reinforcement of the abdominal wall in Ventral Hernia Working Group (VHWG) Grade 3/4 wounds by Ventral Hernia Working Group et al. (Surgery 148(3):544-548). We describe our experience of, and assess the mechanisms for the failure of PADM (PermacolTM) in intestinal and abdominal wall reconstruction (AWR) for enterocutaneous fistulation (ECF). METHODS: All patients referred to our unit who had PADM used for AWR and ECF were studied from a prospectively maintained database. Follow-up data until 31/12/2018 were analysed. PADM was explanted at further surgery and examined histologically. RESULTS: 13 patients, (median age-58.5 years) underwent AWR with PADM reinforcement. Twelve of these (92%) patients had developed abdominal wall defects (AWD) and ECF following complications of previous surgery. Six patients underwent fistula takedown and AWR with PADM, of which 5(83%) refistulated. Seven patients referred to us had already undergone similar procedures in their referring hospitals and had also refistulated. Median (range) time to fistulation after AWR with PADM was 17 (7-240) days. In all cases, PADM had been used to bridge the defect and placed in direct contact with bowel. At reconstructive surgery for refistulation, PADM was inseparable from multiple segments of small intestine, necessitating extensive bowel resection. Histological examination confirmed that the PADM almost completely integrated with the seromuscular layer of the small intestine. CONCLUSION: PADM may become inseparable from serosa of the human small intestinal serosa when it is left in the abdomen during reconstructive surgery. This technique is associated with recurrent intestinal fistulation and intestinal failure and should be avoided if at all possible.

Avoiding, diagnosing and treating well leg compartment syndrome after pelvic surgery.

BACKGROUND: Patients undergoing prolonged pelvic surgery may develop compartment syndrome of one or both lower limbs in the absence of direct trauma or pre-existing vascular disease (well leg compartment syndrome). This condition may have devastating consequences for postoperative recovery, including loss of life or limb, and irreversible disability. METHODS: These guidelines represent the collaboration of a multidisciplinary group of colorectal, vascular and orthopaedic surgeons, acting on behalf of their specialty associations in the UK and Ireland. A systematic analysis of the available peer-reviewed literature was undertaken to provide an evidence base from which these guidelines were developed. RESULTS: These guidelines encompass the risk factors (both patient- and procedure-related), diagnosis and management of the condition. Key recommendations for the adoption of perioperative strategies to facilitate prevention and effective treatment of well leg compartment syndrome are presented. CONCLUSION: All surgeons who carry out abdominopelvic surgical procedures should be aware of well leg compartment syndrome, and instigate policies within their own institution to reduce the risk of this potentially life-changing complication.

Catheter-related infections in patients with acute type II intestinal failure admitted to a national centre: Incidence and outcomes.

INTRODUCTION: The management of intestinal failure (IF) requires safe and sustained delivery of parenteral nutrition (PN). The long-term maintenance of central venous catheter (CVC) access is therefore vital, with meticulous catheter care and salvage of infected CVCs being of prime importance. CVC-related infection and loss of intravenous access are important causes of morbidity and mortality in IF. Avoidance, prompt recognition and appropriate management of CVC-related infections are crucial components of IF care. However, there are few, if any, data on the occurrence of CVC-related infections in patients with acute, type 2, IF managed on a dedicated IF unit and no data on the salvage outcomes of infected CVCs in this group of patients. METHODS: This is a retrospective observational study conducted between January 2011 and July 2017. All patients with acute, type 2 IF newly admitted to a national U.K. IF unit (IFU) during these dates were included. All patients admitted to the unit with a CVC in place underwent immediate 'screening' paired central and peripheral blood cultures on arrival before the CVC was used for any infusate. A prospectively maintained database was used to record all confirmed catheter-related blood stream infections (BSI)/colonisations, demographic and clinical data. Diagnosis of catheter-related BSI/colonisation was based on quantitative and qualitative analysis of paired central and peripheral blood cultures. A standardized 10-14-day catheter salvage treatment protocol involving antibiotic and urokinase CVC locks and systemic antibiotic administration was used to salvage any infected or colonised CVCs, as appropriate. The CVC was not used for PN until successful salvage had been confirmed by negative blood cultures drawn 48 h after antibiotic completion. The development of a subsequent catheter-related BSI was recorded for all patients, both during the remaining in-patient stay on the IFU and after discharge home on PN. RESULTS: Of the 509 patients with type 2 IF admitted to the IFU during the study period, 341 (54% female; mean age 54.6 (range 16-86 years)) had an indwelling CVC that had been placed in the referring hospital. Surgical complications and mesenteric ischaemia were the most common underlying disease aetiologies. Sixty-five of 341 (19.1%) patients had an infected/colonised CVC on the initial screening set of blood cultures. A successful CVC salvage rate of 91% was achieved in this cohort after antibiotic therapy. The subsequent in-patient catheter-related BSI rate for those admitted with a CVC (n = 341) on the IFU was 0.042 per 1000 catheter days, over a total of 23,548 in-patient catheter days. Two hundred and seventy nine of 341 patients were discharged on home PN (HPN); with a subsequent catheter-related BSI rate on HPN of 0.22 per 1000 catheter days (mean duration of HPN = 778 catheter days (range:)) over a follow-up period of 216,944 out-patient catheter days. There was no increased risk of HPN-related catheter-related BSI (p = 0.09) or mortality (p = 0.4) in those admitted with an infected CVC. CONCLUSION: This is the first study to report catheter-related BSI/colonisation rates and salvage outcomes in patients with type 2 IF newly admitted to a dedicated IF Unit. We report that nearly one-fifth of all patients were referred with evidence of a catheter related BSI/colonisation; despite this, successful catheter salvage is possible and, with stringent CVC care, an extremely low subsequent catheter related BSI rates can be achieved and maintained during in-patient stay on a dedicated IF Unit and after discharge on HPN. These data provide novel evidence to support ESPEN recommendations that patients with type 2 IF are managed on a dedicated IF Unit.

Outcome of open abdominal management following military trauma.

BACKGROUND: Temporary abdominal closure (TAC) is increasingly common after military and civilian major trauma. Primary fascial closure cannot be achieved after TAC in 30 per cent of civilian patients; subsequent abdominal wall reconstruction carries significant morbidity. This retrospective review aimed to determine this morbidity in a UK military cohort. METHODS: A prospectively maintained database of all injured personnel from the Iraq and Afghanistan conflicts was searched from 1 January 2003 to 31 December 2014 for all patients who had undergone laparotomy in a deployed military medical treatment facility. This database, the patients' hospital notes and their primary care records were searched. RESULTS: Laparotomy was performed in a total of 155 patients who survived to be repatriated to the UK; records were available for 150 of these patients. Seventy-seven patients (51·3 per cent) had fascial closure at first laparotomy, and 73 (48·7 per cent) had a period of TAC. Of the 73 who had TAC, two died before closure and two had significant abdominal wall loss from blast injury and were excluded from analysis. Of the 69 remaining patients, 65 (94 per cent) were able to undergo delayed primary fascial closure. The median duration of follow-up from injury was 1257 (range 1-4677) days for the whole cohort. Nine (12 per cent) of the 73 patients who underwent TAC subsequently developed an incisional hernia, compared with ten (13 per cent) of the 77 patients whose abdomen was closed at the primary laparotomy (P = 1·000). CONCLUSION: Rates of delayed primary closure of abdominal fascia after temporary abdominal closure appear high. Subsequent rates of incisional hernia formation were similar in patients undergoing delayed primary closure and those who had closure at the primary laparotomy.

Recent developments in the surgical management of complex intra-abdominal infection.

BACKGROUND: Current guidance on the management of sepsis often applies to infection originating from abdominal or pelvic sources, which presents specific challenges and opportunities for efficient and rapid source control. Advances made in the past decade are presented in this article. METHODS: A qualitative systematic review was undertaken by searching standard literature databases for English-language studies presenting original data on the clinical management of abdominal and pelvic complex infection in adults over the past 10 years. High-quality studies relevant to five topical themes that emerged during review were included. RESULTS: Important developments and promising preliminary work are presented, relating to: imaging and other diagnostic modalities; antimicrobial therapy and the importance of antimicrobial stewardship; the particular challenges posed by fungal sepsis; novel techniques in percutaneous and endoscopic source control; and current issues relating to surgical source control and managing the abdominal wound. Logistical challenges relating to rapid access to cross-sectional imaging, interventional radiology and operating theatres need to be addressed so that international benchmarks can be met. CONCLUSION: Important advances have been made in the diagnosis, non-operative and surgical control of abdominal or pelvic sources, which may improve outcomes in the future. Important areas for continued research include the diagnosis and therapy of fungal infection and the challenges of managing the open abdomen.

Protein kinetics in human endotoxaemia and their temporal relation to metabolic, endocrine and proinflammatory cytokine responses.

BACKGROUND: Sepsis is associated with profound alterations in protein metabolism. The unpredictable time course of sepsis and the multiplicity of confounding factors prevent studies of temporal relations between the onset of endocrine and proinflammatory cytokine responses and the onset of protein catabolism. This study aimed to determine the time course of whole-body protein catabolism, and relate it to the endocrine, metabolic and cytokine responses in a human endotoxaemia model of early sepsis. METHODS: Six healthy male volunteers were studied twice in random order, before and for 600 min after administration of either an intravenous bolus of Escherichia coli lipopolysaccharide (LPS) or sterile saline. Whole-body protein synthesis, breakdown and net protein breakdown were measured by amino acid tracer infusion, and related to changes in plasma levels of growth hormone, glucagon, cortisol, insulin-like growth factor (IGF) 1, tumour necrosis factor (TNF) α and interleukin (IL) 6. RESULTS: Protein synthesis, breakdown and net protein breakdown increased and peaked 120 min after LPS administration (P < 0·001), the alterations persisting for up to 480 min. These peaks coincided with peaks in plasma growth hormone, TNF-α and IL-6 concentrations (P = 0·049, P < 0·001 and P < 0·001 for LPS versus saline), whereas plasma cortisol concentration peaked later. No alterations in plasma insulin or glucagon concentrations, or in the IGF axis were observed during the period of abnormalities of protein metabolism. CONCLUSION: LPS administration induced an early protein catabolic response in young men and this coincided with changes in plasma growth hormone, TNF-α and IL-6 concentrations, rather than changes in cortisol, glucagon, insulin or the IGF axis. Surgical relevance Sepsis in surgical patients is common and remains associated with substantial mortality. Although sepsis is a heterogeneous condition and its pathophysiology therefore difficult to study, a universal and profound clinical problem is protein catabolism not responsive to nutritional support. Human experimental endotoxaemia is a promising model of clinical sepsis that can be used to elucidate underlying pathophysiology and explore novel therapeutic approaches. This study demonstrates that human experimental endotoxaemia replicates the changes in whole-body protein turnover seen in clinical sepsis. Frequent measurements allowed identification of tumour necrosis factor (TNF) α, interleukin (IL) 6 and growth hormone as putative mediators. Human experimental endotoxaemia is a valid model for further study of mechanisms and putative therapies of catabolism associated with sepsis. In particular, effects of TNF-α and IL-6 blockade should be evaluated.

Application of an LC-MS/MS method for the simultaneous quantification of human intestinal transporter proteins absolute abundance using a QconCAT technique.

Transporter proteins expressed in the gastrointestinal tract play a major role in the oral absorption of some drugs, and their involvement may lead to drug-drug interaction (DDI) susceptibility when given in combination with drugs known to inhibit gut wall transporters. Anticipating such liabilities and predicting the magnitude of the impact of transporter proteins on oral drug absorption and DDIs requires quantification of their expression in human intestine, and linking these to data obtained through in vitro experiments. A quantitative targeted absolute proteomic method employing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) together with a quantitative concatenation (QconCAT) strategy to provide proteotypic peptide standards has been applied to quantify ATP1A1 (sodium/potassium-ATPase; Na/K-ATPase), CDH17 (human peptide transporter 1; HPT1), ABCB1 (P-glycoprotein; P-gp), ABCG2 (breast cancer resistance protein; BCRP), ABCC2 (multidrug resistance-associated protein 2; MRP2) and SLC51A (Organic Solute Transporter subunit alpha; OST-α), in human distal jejunum (n=3) and distal ileum (n=1) enterocyte membranes. Previously developed selected reaction monitoring (SRM) schedules were optimised to enable quantification of the proteotypic peptides for each transporter. After harvesting enterocytes by calcium chelation elution and generating a total membrane fraction, the proteins were subjected to proteolytic digestion. To account for losses of peptides during the digestion procedure, a gravimetric method is also presented. The linearity of quantifying the QconCAT from an internal standard (correlation coefficient, R(2)=0.998) and quantification of all target peptides in a pooled intestinal quality control sample (R(2)≥ 0.980) was established. The assay was also assessed for within and between-day precision, demonstrating a <15% coefficient of variation for all peptides across 3 separate analytical runs, over 2 days. The methods were applied to obtain the absolute abundances for all targeted proteins. In all samples, Na/K-ATPase, HPT1, P-gp and BCRP were detected above the lower limit of quantitation (i.e., >0.2 fmol/µg membrane protein). MRP2 abundance could be quantified in distal jejunum but not in the distal ileum sample. OST-α was not detected in 2 out of 3 jejunum samples. This study highlights the utility of a QconCAT strategy to quantify absolute transporter abundances in human intestinal tissues.

Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks.

BACKGROUND: Anastomotic leak (AL) represents a dreaded complication following colorectal surgery, with a prevalence of 1-19 per cent. There remains a lack of consensus regarding factors that may predispose to AL and the relative risks associated with them. The objective was to perform a systematic review of the literature, focusing on the role of preoperative, intraoperative and postoperative factors in the development of colorectal ALs. METHODS: A systematic review was performed to identify adjustable and non-adjustable preoperative, intraoperative and postoperative factors in the pathogenesis of AL. Additionally, a severity grading system was proposed to guide treatment. RESULTS: Of 1707 papers screened, 451 fulfilled the criteria for inclusion in the review. Significant preoperative risk factors were: male sex, American Society of Anesthesiologists fitness grade above II, renal disease, co-morbidity and history of radiotherapy. Tumour-related factors were: distal site, size larger than 3 cm, advanced stage, emergency surgery and metastatic disease. Adjustable risk factors were: smoking, obesity, poor nutrition, alcohol excess, immunosuppressants and bevacizumab. Intraoperative risk factors were: blood loss/transfusion and duration of surgery more than 4 h. Stomas lessen the consequences but not the prevalence of AL. In the postoperative period, CT is the most commonly used imaging tool, with or without rectal contrast, and a C-reactive protein level exceeding 150 mg/l on day 3-5 is the most sensitive biochemical marker. A five-level classification system for AL severity and appropriate management is presented. CONCLUSION: Specific risk factors and their potential correction or indications for stoma were identified. An AL severity score is proposed to aid clinical decision-making.

Anal acoustic reflectometry predicts the outcome of percutaneous nerve evaluation for faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is effective for some patients with faecal incontinence. Before insertion of a costly implant, percutaneous nerve evaluation (PNE) is undertaken to identify patients likely to report success from SNS. The aim of this study was to determine whether variables of anal sphincter function measured by anal acoustic reflectometry (AAR) could predict the outcome of PNE for faecal incontinence. METHODS: Women with faecal incontinence undergoing PNE were recruited. AAR, followed by anal manometry, was performed on the day of surgery, immediately before PNE. The outcome of PNE was determined by bowel diary results and incontinence severity score. Patients with a successful PNE outcome were compared with those with an unsuccessful outcome; logistic regression analysis was used to identify any independent predictors of success. RESULTS: Fifty-two patients were recruited, of whom 32 (62 per cent) had a successful PNE outcome and 20 (38 per cent) an unsuccessful outcome. The AAR variable opening pressure was significantly greater in patients who subsequently had a successful PNE result compared with the pressure in patients who did not (28 versus 17 cmH2 O; P = 0·008). No difference was seen in the manometric equivalent, maximum resting pressure. Opening pressure was an independent predictor of success with an odds ratio of 1·08 (95 per cent confidence interval 1·01 to 1·16; P = 0·018). CONCLUSION: AAR is a sensitive test of sphincter function and can identify differences between patients who respond to PNE and those who do not. Opening pressure is an independent predictor of success in PNE, and may be of value in the selection of patients for this expensive treatment option.

Management of large bowel obstruction with self-expanding metal stents. A multicentre retrospective study of factors determining outcome.

AIM: UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention. METHOD: A regional programme of colonic stenting for large bowel obstruction, in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success, survival, complications and reoperation. RESULTS: A SEMS was inserted in 334 patients, including 264 (79.0%) for palliation and 52 (15.6%) as a bridge to surgery. Technical success was achieved in 292 (87.4%) patients, with 46 (13.8%) experiencing a complication or technical failure. Reoperation was required in 39 (14.8%) patients stented for palliation of colorectal cancer of whom 16 (6.1%) subsequently required a colostomy. A one-stage primary anastomosis was achieved in 35 (67.3%) of the 52 patients undergoing stenting as a bridge to resection. Technical success did not vary by indication or site of obstruction (P = 0.60) but was higher for operators who had performed more than 10 procedures (OR 3.34, P = 0.001). ASA grade ≥3 predicted a worse clinical outcome (OR 0.43, P = 0.04). The through-the-scope (TTS) endoscopy technique was more successful than radiological placement alone (90.3% vs 74.8%, P < 0.001). CONCLUSION: Experienced operators using a TTS technique achieved a better outcome for the emergency management of large bowel obstruction. Older, sicker patients and those with extracolonic and benign strictures fared less well.

Radiation enteritis leading to intestinal failure: 1994 patient-years of experience in a national referral centre.

BACKGROUND/OBJECTIVES: Chronic radiation enteritis (RE) has been reported in up to 20% of patients receiving pelvic radiotherapy and can lead to intestinal failure (IF), accounting for 3.9% of new registrants for home parenteral nutrition (HPN) in the UK annually. Our aim is to report nutritional and survival outcomes for patients with RE referred to a national IF unit. SUBJECTS/METHODS: A retrospective study of all new admissions over a 13-year period at the Intestinal Failure Centre, Manchester, UK. Data are presented as median (range). RESULTS: Twenty-three (3.8%) of 611 patients were admitted with IF secondary to RE. The primary site of malignancy was genitourinary in 17 (74%) patients. Radiotherapy was administered 9.5 (1-42) years previously. Patients underwent 2 (1-5) laparotomies prior to intestinal failure unit (IFU) admission. Twelve (52%) patients were admitted with intestinal obstruction and 11 (48%) with intractable weight loss and/or high output fistulae/stomas. Additional conditions contributing to IF were noted in 11 (48%) patients. Twenty-two (96%) patients had 2 (1-5) laparotomies prior to IFU referral. At discharge, 5 (22%) patients resumed oral diet without the need for artificial nutrition support, 3 (13%) required enteral feeding and 13 (56%) commenced HPN. The 10-year survival of the patient cohort was 48.2%. CONCLUSIONS: Surgical intervention is infrequently required, whereas the majority of patients with IF secondary to RE require long-term HPN. The judicious use of surgery in selected patients, coupled with an aggressive medical strategy to detect and treat contributing factors, and optimal enteral feeding may allow a modest proportion of patients with IF secondary to RE to achieve independence from PN.

Absolute abundance and function of intestinal drug transporters: a prerequisite for fully mechanistic in vitro-in vivo extrapolation of oral drug absorption.

The use of whole body physiological-based pharmacokinetic (PBPK) models linked with in vitro-in vivo extrapolation (IVIVE) of kinetic parameters from laboratory experiments, has become embedded within many of the pharmaceutical industry and is used even as part of regulatory submissions. These include the influence of transporter proteins on drug disposition, a subject for which we have witnessed an increasing awareness. A combination of the development of high-powered analytical techniques and antibody-based technology, together with a realization that an understanding of absolute transporter protein abundances together with activity can potentially enhance the modelling of transporter kinetics by PBPK-IVIVE link models. This review summarizes the mechanistic approaches to integrate suitable non-biased in vitro transporter kinetic data relevant to the intestine (i.e. 'intrinsic' K(i) , 'intrinsic' K(m) ), by in vitro system modelling for these kinetic inputs with the advantages of, and challenges for, generating these data for input into PBPK models. This step is considered as a prerequisite for mechanistic modelling of the oral absorption for drugs that are substrates for transporters. Various approaches are provided to integrate intestinal transporter expression into PBPK models with a perspective on the incorporation of the absolute abundance/activity of transporters to enhance the predictive power of the models. We define the key intestinal tissue and functional expression-based scaling factors required. The objective is to use these for facilitating the extrapolation from in vitro intestinal transporter assays to the in vivo system, using absolute quantification methodologies. The models could be used to elucidate the complex relationship and relative importance of metabolizing enzymes and transporters in drug disposition and toxicity.

Comparative study of anal acoustic reflectometry and anal manometry in the assessment of faecal incontinence.

BACKGROUND: Anal acoustic reflectometry (AAR) is a reproducible technique providing a novel physiological assessment of anal sphincter function. It may have advantages over conventional anal manometry. The aims of this study were to determine the ability of AAR and anal manometry to identify changes in anal sphincter function in patients with faecal incontinence (FI) and to relate these changes to the severity of FI. METHODS: Women with FI underwent assessment with AAR and anal manometry. All patients completed the Vaizey FI questionnaire and were classified according to symptom type (urge, passive or mixed) and integrity of the anal sphincters. The ability of AAR and anal manometry to correlate with symptom severity was evaluated. AAR was compared with anal manometry in detecting differences in anal sphincter function between symptomatic subgroups, and patients with and without a sphincter defect. RESULTS: One hundred women with FI were included in the study. The AAR variables opening pressure, opening elastance, closing elastance and squeeze opening pressure correlated with symptom severity, whereas the manometric measurements maximum resting pressure and maximum squeeze pressure did not. Unlike anal manometry, AAR was able to detect differences in anal sphincter function between different symptomatic subgroups. [corrected]. An anal sphincter defect was not associated with a significant change in anal sphincter function determined by either AAR or anal manometry. CONCLUSION: In the assessment of women with FI, AAR variables correlated with symptom severity and could distinguish between different symptomatic subgroups. AAR may help to guide management in these patients.

Autologous reconstruction of massive enteroatmospheric fistulation with a pedicled subtotal lateral thigh flap.

BACKGROUND: Reconstruction of massive contaminated abdominal wall defects associated with enteroatmospheric fistulation represents a technical challenge. An effective technique that allows closure of intestinal fistulas and reconstruction of the abdominal wall, with a good functional and cosmetic result, has yet to be described. The present study is a retrospective review of simultaneous reconstruction of extensive gastrointestinal tract fistulation and large full-thickness abdominal wall defects, using a novel pedicled subtotal thigh flap. METHODS: The flap, based on branches of the lateral circumflex femoral artery, was used to reconstruct the abdominal wall in six patients who were dependent on artificial nutritional support, with a median (range) of 4·5 (3-23) separate intestinal fistulas, within open abdominal wounds with a surface area of 564·5 (204-792) cm2. Intestinal reconstruction was staged, with delayed closure of a loop jejunostomy. Median follow-up was 93·5 (10-174) weeks. RESULTS: Successful healing occurred in all patients, with no flap loss or gastrointestinal complications. One patient died from complications of sepsis unrelated to the surgical treatment. All surviving patients gained complete nutritional autonomy following closure of the loop jejunostomy. CONCLUSION: Replacement of almost the entire native abdominal wall in patients with massive contaminated abdominal wall defects is possible, without the need for prosthetic material or microvascular free flaps. The subtotal pedicled thigh flap is a safe and effective method of providing definitive treatment for patients with massive enteroatmospheric fistulation.

Skeletal muscle contractile properties and proinflammatory cytokine gene expression in human endotoxaemia.

BACKGROUND: Muscle dysfunction associated with sepsis contributes to morbidity and mortality but the underlying mechanisms are unclear. This study examined whether muscle weakness relates to an intrinsic defect in contraction, or to central mechanisms associated with acute illness, and whether systemic endotoxaemia induces changes in gene expression for proinflammatory cytokines within human muscle in vivo. METHODS: In this experimental study, 12 healthy men received intravenous Escherichia coli lipopolysaccharide (LPS, 4 ng/kg) or saline (control). Voluntary and electrically stimulated quadriceps contraction, and tumour necrosis factor (TNF) alpha mRNA expression in quadriceps muscle biopsies were studied before and after the infusion. RESULTS: Endotoxaemia induced transient weakness of voluntary quadriceps contraction, equivalent to a 7.8 (95 per cent confidence interval 2.1 to 13.5) per cent reduction in contractile force at 180 min (P = 0.027) and a 9.0 (5.2 to 12.8) per cent reduction at 300 min (P = 0.008). Electrically stimulated contraction was unaffected. LPS administration resulted in an apparent fibre-specific induction of TNF-alpha mRNA. CONCLUSION: Endotoxaemia results in a reduction in voluntary muscle contractile force without an apparent defect in stimulated muscle contraction. Loss of volition may be a more important factor than intrinsic dysfunction in acute sepsis-associated human muscle weakness.

Is TNP in the open abdomen safe and effective?

Much of the evidence for the use of TNP in the open abdomen comes from data on trauma patients. In view of the potentially severe complications, much greater evidence is needed for its application on patients with abdominal sepsis.