Early experience with laparoscopic extralevator abdominoperineal excision within an enhanced recovery setting: analysis of short-term outcomes and quality of life.

INTRODUCTION: Conventional abdominoperineal excision for low rectal cancer has a higher local recurrence and reduced survival compared to anterior resection. An extralevator abdominoperineal excision (ELAPE) may improve outcome through removal of increased tissue in the distal rectum. Experience with ELAPE is limited and no studies have reported on quality of life (QOL) following this procedure. We describe a minimally invasive approach to ELAPE within an enhanced recovery programme, and present short-term results and QOL analyses. METHODS: All laparoscopic ELAPEs were included in a prospective database. Demographics, intra-operative and post-operative outcomes were evaluated. Postoperative QOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and QLQ-CR29. RESULTS: Thirteen laparoscopic ELAPEs were performed over a two-year period. All were enrolled in an enhanced recovery programme. The median age was 76. The median tumour height was 20 mm (range: 0-50 mm) from the dentate line and all patients received neoadjuvant treatment. The median duration of surgery was 300 minutes (range: 120-488 minutes), the mean blood loss was 150 ml and one procedure was converted to open surgery. There was no circumferential resection margin involvement or tumour perforation. The median duration of use of intravenous fluid, patient controlled analgesia and urinary catheterisation was 2, 2 and 2.5 days respectively and the median length of hospital stay was 7.5 days. Two patients developed perineal wound dehiscence. QOL analysis revealed high global health status (90.8), physical (91.3), emotional (98.3) and social functioning (100) scores, which compared favourably with EORTC reference values and published QOL scores following conventional abdominoperineal excision. CONCLUSIONS: Laparoscopic ELAPE within an enhanced recovery setting is a feasible and safe approach with acceptable short-term outcomes and post-operative quality of life.

CD40 ligation for immunotherapy of solid tumours.

Tumour vaccines provide an important focus of current cancer research and are often based on the premise that although T-cells do respond naturally to certain tumours, this is usually weak and therefore ineffective at controlling disease. An integral and necessary part of a T-cell immune response involves triggering of CD40 on antigen-presenting cells (APC) by its ligand, CD154, on responding T helper (Th) cells. Furthermore, cytotoxic responses to tumours may fail because the Th-cell response is inadequate and unable to provide CD40 stimulation of APC. Growing evidence shows that stimulating APC with soluble CD40L or an agonistic anti-CD40 mAb can, at least in part, replace the need for Th cells and generate APC that are capable of priming cytotoxic T lymphocytes (CTL). The aim of this study was to investigate whether a range of solid tumours (CD40(-)) could be treated with anti-CD40 mAb. It was found that this treatment was effective, and correlated with the intrinsic immunogenicity and aggressiveness of the tumours. The mAb could be delivered locally or at a distal site, but increased antigen load provided by irradiated tumour cells added little to the effectiveness of the treatment. T-cells were required since cytokine (interferon-gamma) and CTL activity were demonstrated following treatment and the therapeutic efficacy was lost in nude mice. In addition, depletion of CD8(+) cells abrogated protection whilst depletion of CD4(+) cells had no effect. This study demonstrates that solid CD40(-) tumours are sensitive to anti-CD40 mAb therapy and that the response bypasses the need for Th cells.

Monocyte-derived giant cell formation in patients with breast cancer.

Recent reports of monocyte-derived giant cell formation in breast cancer and associated retroviral findings have attracted much interest in the scientific literature and with the media, revitalising hypotheses of a viral role in the aetiology of the disease. We describe an assay developed to investigate further the giant cell forming phenomenon and report results which conflict with earlier work. We observed a smaller proportion of patients with breast cancer forming giant cells than in previous reports. Conversely, a much larger proportion of controls formed giant cells. Using our assay to calculate a fusion index the formation of giant cells, as defined in earlier work, was found to be a poor indicator of the degree of cell fusion in our samples. We discuss our experiences with the assay and suggest the calculation of a fusion index as a more comparable and quantitative measurement of cell fusion.

Local audit in vascular surgery.

A 2-year audit of the Southampton Vascular Unit showed marked discrepancies in workload from nationally accepted figures. All forms of reconstructive surgery except emergency aortic aneurysm grafting were performed more frequently than expected. The vascular population is elderly and at high risk from major surgery. Mortality was appreciable in all major vascular procedures and usually cardiac or renal related. The elderly population and resulting workload is likely to increase in the near future. The role of local audit in vascular surgery is emphasised.

Ultrasound mammography in the management of breast cancer.

In this centre, ultrasound mammography has been shown to be more accurate in elucidating the nature of palpable breast lesions than X-ray mammography. A prospective study was devised to determine whether this accuracy could be translated into improved management of patients with breast carcinoma. A total of 223 patients with palpable breast masses were assessed by clinical examination, imaging (X-ray and ultrasound mammography) and aspiration cytology. Each was scored on a five-point scale and treatment was planned according to the total score. According to the protocol, an adequate total score would permit definitive surgery avoiding frozen section. By using sonography rather than radiology, the number of correct diagnoses could be improved by 25 per cent. This was because the greater sensitivity of ultrasound (92.8 per cent) compared to X-ray mammography (82.5 per cent) was reflected in a higher total score, which was sufficient to allow definitive surgical treatment without prior histological confirmation of diagnosis.

Fine needle aspiration cytology of breast masses: an evaluation of its accuracy and reasons for diagnostic failure.

A study of 1458 patients who had undergone breast aspiration cytology was conducted to determine the diagnostic accuracy of the technique. The effect of tumour histology and size on the unsatisfactory aspirate and false negative rate was examined. Seven hundred and thirty one patients (50%) had histological diagnoses. The sensitivity of aspiration cytology for malignancy was 64% for the first aspiration, but was 91% in patients who had had 3 aspirates. The specificity was 56%, this low figure was almost entirely due to inadequate or unsatisfactory cytological preparations. The positive and negative predictive values of aspiration cytology were 99.4% and 85% respectively demonstrating high diagnostic accuracy given a satisfactory aspirate. Invasive lobular carcinoma yielded a significantly higher unsatisfactory rate than invasive ductal carcinoma (P less than 0.001) and fibroadenoma yielded a significantly lower unsatisfactory rate than fibroadenosis (P less than 0.001). Mass size influenced the unsatisfactory rate for invasive ductal carcinoma (P less than 0.05) and fibroadenoma, but not for invasive lobular carcinoma or fibroadenosis. Only 2 of the 32 false negatives were due to misinterpretation, the remainder resulted from the aspiration needle missing the mass. We conclude that aspiration cytology is an accurate preoperative diagnostic procedure for the evaluation of breast masses. Unsatisfactory or negative aspirates should be regarded as 'non-results' if there is clinical or radiological suspicion of malignancy.

Mastalgia; is this commonly associated with operable breast cancer?

A detailed analysis by questionnaire of breast pain in 460 newly referred patients at a specialized breast clinic revealed that only 1.5% of patients with pain had an early breast cancer. Of all 44 cancers 8 were painful but only 4 considered early. All these had nipple retraction. We conclude that although breast pain is rarely associated with cancer, localized pain must be fully investigated to exclude this diagnosis.

Seat belt injury to the female breast.

Six women who sustained injury to a breast from seatbelt straps during road traffic accidents are presented. In three the breast contained a carcinoma. In view of the overlap of the appearance of fat necrosis and carcinoma by clinical and radiological examination all such lesions should be biopsied to exclude carcinoma as the history of the lesion can be dangerously misleading.

The accuracy of ultrasound in the diagnosis of breast disease.

The accuracy of breast ultrasound using all purpose static beta-scanning equipment has been compared with mammography. Ultrasound was found to be both more sensitive (93%:82%) and specific (95%:89%) in a large retrospective series of 1000 patients undergoing investigation for symptomatic breast disease. In a smaller prospective and consecutive series of 142 patients undergoing surgery where histological proof was obtained ultrasound was also found to be more sensitive (91%:81%) and specific (81%:69%). In both studies, the greater accuracy of ultrasound was attributed to its ability to diagnose lesions hidden in X-ray dense breasts and where mammography had revealed featureless asymmetical densities of uncertain nature. In these instances ultrasound may have a significant role to play as an adjunct to mammography in the preoperative assessment of breast lesions.

The preparation of freeze-thaw density gradients with homogeneous solute concentrations.

A simple and effective method is described for preparing freeze-thaw density gradients which is free of the problems of uneven solute distribution. It consists of blending aqueous freeze-thaw gradients with hypertonic diluent. The routine application of this system for separations of murine lymphosarcoma cell populations is described.

Correlations between clonogenicity and prognostic factors in human breast cancer.

The pursuit of more effective systemic treatments in breast cancer has been limited by a failure to maintain or grow tumour cells in vitro. This study reports our experience in obtaining clonogenic growth in 54 primary breast cancers obtained at mastectomy. Of 47 assays free of infection, clonogenic growth was achieved in 22 (41 per cent). Only 5 of 23 oestrogen receptor positive tumours grew compared to 14 of 21 oestrogen receptor negative tumours chi 2 = 9.03; P less than 0.01). None of the 5 cytosolic receptor positive tumours contained a nuclear receptor for oestrogen. Growth was not related to tumour stage, menopausal status, age or histological grade. Receptor negative tumours had higher thymidine labelling indices, but these were no different to the tumours grown in the assay.

The errors of thymidine labelling in breast cancer.

The site to site error and reproducibility of counting error have been assessed in the routine thymidine labelling of breast cancer. Despite modifications of technique designed to minimize these errors both were found to be inaccurate to within 0.5 labelling index %. Since the majority of tumours had labelling indices below 2% this measurement is not a critical determinant of tumour behaviour.

Use of blood in elective general surgery: an area of wasted resources.

A prospective audit of the blood bank was carried out in Portsmouth to examine how efficiently blood was used in elective general surgery. The routine crossmatching of blood was found to be unnecessary for certain procedures such as cholecystectomy, thyroidectomy, mastectomy, and vagotomy. The most efficient use of blood was seen in vascular surgery despite the greater risk of severe haemorrhage. Completed detailed questionnaires returned by members of surgical teams in Wessex supported the Portsmouth data as being fairly typical and confirmed that substantial and unintentional overordering occurred, apparently due to poor communication, lack of discussion, and "force of habit." The place of a "half hour crossmatch" as a substitute for many routine orders has been explored and seems to be acceptable to most anaesthetists and surgeons. This study, by showing how inefficiently blood is used, has underlined the value of local audit. It also supports the general experience of centres throughout the world who have invoked similar methods and achieved considerable savings without harm to patients.