Alec Engledow

The Management of Enterocutaneous Fistula in a Regional Unit in the United Kingdom: A Prospective Study

BACKGROUND: Enterocutaneous fistula associated with type 2 intestinal failure is a challenging condition that involves a multidisciplinary approach to management. It is suggested that complex cases should only be managed in select national centers in the United Kingdom. METHODS: Over an 18-month period, we prospectively studied all patients referred to us with established enterocutaneous fistulas. Patients followed standardized protocols. Eradication of sepsis, appropriate wound management, establishment of nutritional support, and restoration of normal physiology were attempted. Definitive surgical management was deferred for at least 6 months after the last abdominal surgical intervention. Follow-up was for a minimum of 6 months. RESULTS: Of 55 patients, 10 were internal referrals and 45 were from institutions elsewhere. The mean age was 50 years. Nine patients had colonic fistulas. Forty-six had small bowel fistulas; 19 of these (35%) were associated with inflammatory bowel disease. Patients had undergone a median of 3 previous operations. Four fistulas (7%) healed spontaneously. Thirty-five patients (63%) underwent definitive surgery. Recurrent fistula occurred in 4 patients (13%); 1 required further surgery, and 3 healed spontaneously. The overall mortality rate was 7% (4/55 patients), with 3 patients dying before definitive surgery and 1 patient dying postoperatively. CONCLUSIONS: Our results compare favorably with data from designated national centers (overall mortality, 9.5%–10.8%; operative mortality, 3%–3.5%), suggesting that these patients can be effectively managed in regional units that have sufficient expertise, interest, and volume of patients. Rationalization of funding and referral of patients with type 2 intestinal failure to regional centers may allow national centers to conserve their scarce resources.

Laparoscopic resection of diverticular fistulae: a 10-year experience.

Objective  Until recently the laparoscopic approach was reserved for uncomplicated diverticular disease. We show that fistulating diverticular disease can be resected safely, with good clinical outcome via a laparoscopic approach.

Incisional hernia rates following laparoscopic colorectal resection

INTRODUCTION In published series with satisfactory follow-up incisional hernia rates following laparotomy vary between 4 and 18%, with up to 75% developing within two years of operation. This therefore represents the commonest complication following open abdominal surgery and a substantial added workload for the colorectal/general surgeon. AIM To prospectively review incisional hernia rates in patients undergoing laparoscopic colorectal resection in a single centre. METHODS All laparoscopic wounds were closed in identical fashion to open closure technique, utilising 0-monofilament, polyglyconate and a mass closure technique, followed by a subcuticular, polyglactin-910 suture for skin closure. All patients were subsequently examined in an outpatient setting by a senior surgeon independent to the original procedure. RESULTS 167 consecutive patients undergoing laparoscopic colorectal resections (94M:73F; median age 68 years) were included. Median incision length for specimen extraction was 6 cm (range 3-11 cm) and patients were followed-up for a median of 36 months (range 24-77 months). Twelve (7%) patients developed an incisional hernia (ten in specimen extraction wounds and two in port-site wounds), ten of whom underwent successful laparoscopic repairs. Of the remaining patients, one remains symptomatic and awaits repair, and one is asymptomatic and unfit for surgery. CONCLUSIONS The well-documented advantages of laparoscopic surgery include reduced hospital stay, early return to activity, decreased analgesic requirements and improved cosmesis. However, the results of this study suggest that incisional hernia rates are not decreased by laparoscopic surgery, although the hernias may be smaller and more amenable to repair by laparoscopic approaches.

Multifunctional Imaging Signature for V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations in Colorectal Cancer

This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. Methods: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: 18F-FDG uptake (18F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. Results: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%–93.9%), 0% (0%–10.4%), and 90.1% (79.2%–96.0%), respectively. KRAS mutants with high 18F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low 18F-FDG SUVmax, high MPP, and high blood flow expressed mcm2 (P = 0.036). Conclusion: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor 18F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Commercial software upgrades may significantly alter Perfusion CT parameter values in colorectal cancer

ObjectiveTo determine how commercial software platform upgrades impact on derived parameters for colorectal cancer.Materials and methodsFollowing ethical approval, 30 patients with suspected colorectal cancer underwent Perfusion CT using integrated 64 detector PET/CT before surgery. Analysis was performed using software based on modified distributed parameter analysis (Perfusion software version 4; Perfusion 4.0), then repeated using the previous version (Perfusion software version 3; Perfusion 3.0). Tumour blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were determined for identical regions-of-interest. Slice-by-slice and ‘whole tumour’ variance was assessed by Bland-Altman analysis.ResultsMean BF, BV and PS was 20.4%, 59.5%, and 106% higher, and MTT 14.3% shorter for Perfusion 4.0 than Perfusion 3.0. The mean difference (95% limits of agreement) were +13.5 (−44.9 to 72.0), +2.61 (−0.06 to 5.28), −1.23 (−6.83 to 4.36), and +14.2 (−4.43 to 32.8) for BF, BV, MTT and PS respectively. Within subject coefficient of variation was 36.6%, 38.0%, 27.4% and 60.6% for BF, BV, MTT and PS respectively indicating moderate to poor agreement.ConclusionSoftware version upgrades of the same software platform may result in significantly different parameter values, requiring adjustments for cross-version comparison.

The Flow–Metabolic Phenotype of Primary Colorectal Cancer: Assessment by Integrated 18F-FDG PET/Perfusion CT with Histopathologic Correlation

The aim of this study was to assess the in vivo flow–metabolic phenotype in primary colorectal cancer with integrated 18F-FDG PET/perfusion CT and its relationship to gold standard histopathologic assessment of angiogenesis and hypoxia. Methods: 45 patients (26 male and 19 female; mean age, 67.6 y) with primary colorectal cancer underwent integrated 18F-FDG PET/perfusion CT, deriving tumor glucose metabolism (maximum standardized uptake value) and regional blood flow. From this cohort, 35 underwent surgery subsequently, without intervening neoadjuvant treatment, allowing histopathologic correlation with tumor stage, CD105 microvessel density, vascular endothelial growth factor (VEGF), glucose transporter protein 1 (Glut-1), and hypoxia-inducible factor 1 expression. Results: The flow–metabolic ratio was significantly lower for tumors with higher VEGF (3.65 vs. 5.98; P = 0.01) or hypoxia-inducible factor 1 expression (3.63 vs. 5.48; P = 0.04) versus tumors with lower expression. There were significant negative correlations between the tumor flow–metabolic ratio and VEGF expression (r = −0.55, P = 0.0008), indicating that tumors with low blood flow but higher metabolism were associated with higher VEGF expression. Flow and metabolism were coupled in higher-stage (stage III/IV) tumors but not lower-stage tumors (stage I/II) (r = 0.47, P = 0.03, vs. r = 0.09, P = 0.65, respectively. Conclusion: Tumors with a low-flow–high-metabolism phenotype demonstrated higher VEGF expression and may reflect a more angiogenic phenotype.

Marathon-induced ischemic colitis: why running is not always good for you

We present the case of a 31 year-old man who presented to the emergency department of University College Hospital London after collapsing upon finishing the London marathon. Contrast-enhanced multidetector computed tomography scanning revealed ischemic colitis of the cecum and ascending colon, which progressed to the development of clinical peritonism after 48 hours. This patient subsequently underwent a laparotomy and right hemicolectomy, with ileostomy formation, on the third day after admission. Operative and histologic findings confirmed ischemic colitis of the cecum and proximal colon. The postoperative recovery was uneventful, and he was discharged home well. Possible mechanisms of ischemia in marathon runners and those undergoing intense exercise include a combination of splanchnic vasoconstriction, dehydration, and hyperthermia, combined with mechanical forces. Most patients presenting with marathon-running-induced ischemic colitis respond to conservative treatment and the need for operative intervention is extremely rare.

Temporary sacral nerve stimulation alters rectal sensory function: a physiological study.

BACKGROUND: The indications for sacral nerve stimulation are increasing, but the mechanism remains poorly understood. OBJECTIVE: This study aimed to examine the effect of sacral nerve stimulation on rectal compliance and rectal sensory function. DESIGN: This was a prospective study. SETTINGS: This study took place at a university teaching hospital. PATIENTS: Twenty-three consecutive consenting patients (22 female; median age, 49 y) undergoing temporary sacral nerve stimulation for fecal incontinence were prospectively studied. Clinical response was assessed by the use of bowel diaries and Wexner scores. MAIN OUTCOME MEASURES: Anal manometry, rectal compliance, volume and pressure thresholds to rectal distension (barostat), and rectal Doppler mucosal blood flow were measured before and at the end of stimulation. RESULTS: Sixteen patients (70%) had a favorable clinical response. Median anal squeeze pressures increased with stimulation from 40 (range, 6–156) cmH2O to 64 (range, 16–243) cmH2O. Median rectal compliance did not significantly change with stimulation (prestimulation: 11.5 (range, 7.9–21.8) mL/mmHg, poststimulation: 12.4 (range, 6.2–22) mL/mmHg, P = .941). Rectal wall pressures associated with urge (baseline: 15.4 (range, 11–26.7) mmHg, poststimulation: 19 (range, 11.1–42.7) mmHg, P = .054) and maximal tolerated thresholds (baseline: 21.6 (8.5–31.9) mmHg, poststimulation: 27.1 (14.3–43.3) mmHg, P = .023) significantly increased after stimulation. Rectal Doppler mucosal blood flow did not significantly change with stimulation (baseline: 125.8 (69.9–346.8), poststimulation: 112.4 (50.2–404.1), P = .735). Changes in anal resting pressure and rectal wall pressures with stimulation were evident only in responders; however, changes in anal squeeze pressures were evident in both responders and nonresponders. LIMITATIONS: The study reports results following short-term stimulation in a small but homogenous group of patients. A larger long-term study will follow. CONCLUSION: Temporary sacral nerve stimulation does not change rectal compliance, but is associated with significant changes to the pressure thresholds of rectal distension. This, together with the observation that outcome is not related to sphincter integrity, supports the hypothesis of an afferent-mediated mechanism of action.

The role of 18FDG PET/CT in the management of colorectal liver metastases

INTRODUCTION Surgical resection remains the only potentially curative treatment for colorectal liver metastases (CLM). However, involvement of both the hepatic lobes or extrahepatic disease (EHD) can be a contra-indication for resection. The aim of the present study was to examine the addition of combined positron emission and computed tomography (PET/CT) to CLM staging to assess the effects upon staging and management. METHODS All CLM patients referred to a single centre between January 2005 and January 2009 were prospectively included. All underwent routine staging (clinical examination and computed tomography), followed by a whole body (18) fluoro-deoxy-glucose ((18)FDG)-PET/CT scan and Fong clinical risk score calculation. RESULTS Sixty-four patients were included [63% male with a median age of 63 years (age range 32-79 years)]. The addition of PET/CT led to disease upstaging in 20 patients (31%) and downstaging in two patients (3%). EHD was found in 24% of low-risk patients (Fong score 0-2) as compared with 44% of high-risk patients (Fong score 3-5) (P= 0.133). There was a trend towards a greater influence upon management in patients with a low score (44% vs. 17%; P= 0.080). CONCLUSION The addition of PET/CT led to management changes in over one-third of patients but there was no correlation between alterations in staging or management and the Fong clinical risk score; suggesting that PET/CT should be utilized, where available, in the pre-operative staging of CLM patients.

Integrated (18)F-FDG PET/CT and perfusion CT of primary colorectal cancer: effect of inter- and intraobserver agreement on metabolic-vascular parameters.

OBJECTIVE The purpose of this article is to assess the effect of observers on combined metabolic-vascular parameters in colorectal cancer. SUBJECTS AND METHODS Twenty-five prospective patients (12 men and 13 women; mean age, 66.9 years) with proven primary colorectal adenocarcinoma underwent integrated (18)F-FDG PET/perfusion CT to assess tumor metabolism (mean and maximum standardized uptake value [SUV(mean) and SUV(max), respectively]) and vascularization (blood flow [BF], blood volume [BV], permeability surface-area product, and standardized perfusion value). Intra- and interobserver agreement for PET, perfusion CT, and combined metabolic-flow parameters were determined by Bland-Altman statistics and intraclass correlation coefficients (ICCs). RESULTS The mean tumor size was 3.8 ± 1.6 cm; there were five stage IA/B, six stage IIA/B, eight stage IIIA/B, and six stage IV tumors. Intra- and interobserver agreement for individual parameters was fair to good, with mean differences between observers of -0.74 for SUV(max), -0.16 for SUV(mean), 9.72 for BF, 0.15 for BV, -0.76 for permeability surface-area product, and 0.09 for standardized perfusion value. ICCs were 0.44-0.99 and 0.38-0.89 for intra- and interobserver agreement, respectively. Interobserver agreement was variable for combined metabolic-flow parameters but better for metabolic-flow difference than for metabolic-flow ratio: ICCs were 0.69-0.88 for the metabolic-flow difference and 0.44-0.94 for the metabolic-flow ratio. CONCLUSION Combined parameters to assess the metabolic-flow relationship are influenced by observer variation. Intra- and interobserver agreement are better for the metabolic-flow differences than for the ratios, suggesting that metabolic-flow differences may be a more robust parameter for clinical practice.