Evaluation of quality of life and function at 1 year after transanal endoscopic microsurgery.

AIM: Transanal endoscopic microsurgery (TEM) enables organ preservation after rectal tumour surgery. Its application is being expanded using adjuvant and neoadjuvant treatments. Our objective was to evaluate the changes over time in anorectal function, urinary symptoms and quality of life (QoL) in patients who had TEM surgery for a rectal tumour. METHOD: Between September 2009 and October 2012, a consecutive series of 102 patients underwent TEM at a single institution. Patients were asked to fill out standardized questionnaires at baseline and then at 6, 12, 26 and 52 weeks after surgery. The QoL among these patients was assessed using one generic (EQ-5D) and two disease-specific [European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR29] questionnaires. Anorectal and urinary symptoms were studied using the COlo-REctal Functional Outcome (COREFO) and the International Prostate Symptom Score (I-PSS) questionnaires, respectively. RESULTS: The response rate was 90% (92/102 patients). Postoperative complications occurred in 14% (13/92) of patients. The general QoL (as assessed using the EQ-5D) was lower 6 and 12 weeks after TEM compared with baseline QoL (P < 0.05) but returned towards baseline after 26 weeks. Anorectal function (determined using the COREFO) was worse 6 weeks postoperatively (P < 0.01) but had normalized by 12 weeks. Urinary function (determined using the I-PSS) was not affected at any time point after surgery. The total COREFO score and the American Society of Anesthesiologists (ASA) score were correlated with the deterioration in QoL. CONCLUSION: The study demonstrates that TEM has a temporary and reversible impact on QoL and anorectal function. Intensive interrogation of QoL and function using appropriate questionnaires will help to define the role of organ-preserving surgery for rectal cancer before and after chemoradiotherapy.

The economic impact of anastomotic leakage after anterior resections in English NHS hospitals: are we adequately remunerating them?

AIM: Our aim was to determine the frequency and economic impact of anastomotic leakage (AL) at local and national levels in England. METHOD: All patients who underwent AR in Oxford between 2007 and 2009 were evaluated for AL. Hospital Episode Statistics (HES) data were used to determine reoperation rates after elective AR (n = 23 388) in England between 2000 and 2008. Hospital episode remuneration costs were calculated by the local commissioning department and compared with Department of Health (DH) reference index costs. RESULTS: The frequency of AL following anterior resection was 10.9% (31 out of 285) in Oxford. Laparotomy for leakage was performed in 5.6% of cases. The 30-day hospital mortality rate for all ARs was 2.1%, compared with 3.2% after AL. The national relaparotomy rate (within 28 days) and 30-day hospital mortality in English National Health Service (NHS) trusts following AR were 5.9% and 2.9%, respectively. Institutional remunerated tariffs (£6233 (SD ± 965)) were similar to DH reference costs (£6319 (SD ± 1830)) after uncomplicated AR. However, there was a significant (P = 0.008) discrepancy between the remunerated tariff for AL (£9605 (SD ± 6908)) and the actual cost (£17 220 (SD ± 9642)). AL resulted in an additional annual cost of approximately £1.1 million to £3.5 million when extrapolated nationally. CONCLUSION: The estimated economic burden of anastomotic leakage following AR is approximately double that of the remunerated tariff.

Transversus abdominis plane (TAP) blocks-a review.

INTRODUCTION: Effective post-operative pain management can positively influence patient outcome. Multimodal analgesic regimes are often limited by side-effects. Epidural analgesia may be resource-consuming, restrict mobility and have negative cardiovascular and gastrointestinal consequences. Consequently, there is a need for regional anaesthetic techniques to minimise opioid use, and provide alternatives to epidurals, especially within the context of minimally invasive abdominal surgery and enhanced recovery programmes. This review aims to evaluate the evidence base underlying Transversus abdominis plane (TAP) blockade. METHODS: A literature search was performed using the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) using the parameters 'transversus abdominis plane' and 'TAP'. The references within were then searched for applicable studies. Case reports and correspondence were excluded. FINDINGS: Thirteen studies assessed technique and mechanisms of action. Fourteen clinical studies involved a total of 1250 patients. Seven studies (6 Randomised Controlled Trials, RCTs) demonstrated reductions in post-operative morphine requirements (33.3%-73.1%). Five RCTs demonstrated concomitant improvements in pain scores. Five RCTs demonstrated reduced opioid side effects. The one study assessing functional outcome (a Prospective Controlled Trial, PCT) demonstrated earlier return of gastrointestinal function and hospital discharge. CONCLUSION: The limited evidence to date suggests that TAP blockade is an effective adjunct to multimodal post-operative analgesia following a range of abdominal surgical procedures. Whether TAP blocks are a viable alternative to epidural analgesia remains to be determined. However, it is likely that as this technique grows in popularity its role, particularly that in enhanced recovery programmes, will be better delineated and refined.

Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis.

BACKGROUND: The effect of glycoengineering a membrane specific anti-carcinoembryonic antigen (CEA) (this paper uses the original term CEA for the formally designated CEACAM5) antibody (PR1A3) on its ability to enhance killing of colorectal cancer (CRC) cell lines by human immune effector cells was assessed. In vivo efficacy of the antibody was also tested. METHODS: The antibody was modified using EBNA cells cotransfected with beta-1,4-N-acetylglucosaminyltransferase III and the humanised hPR1A3 antibody genes. RESULTS: The resulting alteration of the Fc segment glycosylation pattern enhances the antibody's binding affinity to the FcgammaRIIIa receptor on human immune effector cells but does not alter the antibody's binding capacity. Antibody-dependent cellular cytotoxicity (ADCC) is inhibited in the presence of anti-FcgammaRIII blocking antibodies. This glycovariant of hPR1A3 enhances ADCC 10-fold relative to the parent unmodified antibody using either unfractionated peripheral blood mononuclear or natural killer (NK) cells and CEA-positive CRC cells as targets. NK cells are far more potent in eliciting ADCC than either freshly isolated monocytes or granulocytes. Flow cytometry and automated fluorescent microscopy have been used to show that both versions of hPR1A3 can induce antibody-dependent cellular phagocytosis (ADCP) by monocyte-derived macrophages. However, the glycovariant antibody did not mediate enhanced ADCP. This may be explained by the relatively low expression of FcgammaRIIIa on cultured macrophages. In vivo studies show the efficacy of glycoengineered humanised IgG1 PR1A3 in significantly improving survival in a CRC metastatic murine model. CONCLUSION: The greatly enhanced in vitro ADCC activity of the glycoengineered version of hPR1A3 is likely to be clinically beneficial.

Detection of circulating tumour cells in peripheral blood with an automated scanning fluorescence microscope.

We have developed an automated, highly sensitive and specific method for identifying and enumerating circulating tumour cells (CTCs) in the blood. Blood samples from 10 prostate, 25 colorectal and 4 ovarian cancer patients were analysed. Eleven healthy donors and seven men with elevated serum prostate-specific antigen (PSA) levels but no evidence of malignancy served as controls. Spiking experiments with cancer cell lines were performed to estimate recovery yield. Isolation was performed either by density gradient centrifugation or by filtration, and the CTCs were labelled with monoclonal antibodies against cytokeratins 7/8 and either AUA1 (against EpCam) or anti-PSA. The slides were analysed with the Ikoniscope robotic fluorescence microscope imaging system. Spiking experiments showed that less than one epithelial cell per millilitre of blood could be detected, and that fluorescence in situ hybridisation (FISH) could identify chromosomal abnormalities in these cells. No positive cells were detected in the 11 healthy control samples. Circulating tumour cells were detected in 23 out of 25 colorectal, 10 out of 10 prostate and 4 out of 4 ovarian cancer patients. Five samples (three colorectal and two ovarian) were analysed by FISH for chromosomes 7 and 8 combined and all had significantly more than four dots per cell. We have demonstrated an Ikoniscope based relatively simple and rapid procedure for the clear-cut identification of CTCs. The method has considerable promise for screening, early detection of recurrence and evaluation of treatment response for a wide variety of carcinomas.

Vascular surgery within general surgery: an analysis of workload 1989-2005.

INTRODUCTION: There is considerable debate as to whether vascular surgery should be a subspecialty separate from general surgery. This study examines the changing relationship between general and vascular surgery in a district general surgical unit over 16 years. PATIENTS AND METHODS: A detailed survey of referrals, admissions and operations to one unit was carried out over 3 months in 2003. This was compared with similar surveys in 1989, 1990 and 1995. In addition a 3-month audit of operations performed was carried out in 2005 following a decision by the Primary Care Trust (PCT) to reduce varicose vein referrals. RESULTS: There was a significant increase in the number of varicose vein and arterial referrals 1989-2003 (P = 0.0001 and P < 0.0001, respectively). This was reflected in increased number of vascular admissions (P < 0.0001). In 1989, 14% of the arterial cases were admitted as emergencies. This figure rose to 52% in 2003 (P < 0.0001). There was a significant increase in the number of arterial operations performed between 1989 and 1995; however, from 1995 to 2003 this number fell P < 0.0001). The number of varicose vein procedures increased significantly 1989-2003 (P < 0.0001), with a significant fall after the PCT decision (P < 0.0001). However, the number of operations carried out in 2005 increased slightly with the proportion of general surgical cases, mostly hernia repairs and laparoscopic cholecystectomies, increasing. CONCLUSIONS: With increasing specialisation comes the risk that reduction in any aspect of a particular specialty may result in that unit becoming unsustainable. In vascular surgery this will inevitably lead to centralisation of services. In a large district general hospital having two general surgeons with a vascular interest, the general surgical component has maintained the workload of the unit following reduction in varicose vein referrals.