The high rate of negative appendicectomy among female patients and the increased incidence of perforation in elderly patients reinforce the validity of the judicious use of laparoscopy in these populations. There are still a number of unusual histologies found in appendicectomy specimens supporting the continued use of routine histology.

BackgroundA wealth of evidence obtained using mouse models indicates that CD4+CD25+FOXP3+ regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4+ T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients.Methodology and Principal FindingsTreg were identified and characterized as CD4+CD25+FOXP3+ using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4+ T cell responses, as observed by IFNγ release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group.Conclusions/SignificanceCollectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy.

BackgroundThere is indirect evidence that T cell responses can control the metastatic spread of colorectal cancer (CRC). However, an enrichment of CD4+Foxp3+ regulatory T cells (Tregs) has also been documented.ObjectiveTo evaluate whether CRC promotes Treg activity and how this influences anti-tumour immune responses and disease progression.MethodsA longitudinal study of Treg activity on a cohort of patients was performed before and after tumour resection. Specific CD4+ T cell responses were also measured to the tumour associated antigens carcinoembryonic antigen (CEA) and 5T4.ResultsTregs from 62 preoperative CRC patients expressed a highly significant increase in levels of Foxp3 compared to healthy age-matched controls (p=0.007), which returned to normal after surgery (p=0.0075). CD4+ T cell responses to one or both of the tumour associated antigens, CEA and 5T4, were observed in approximately two-thirds of patients and one third of these responses were suppressed by Tregs. Strikingly, in all patients with tumour recurrence at 12 months, significant preoperative suppression was observed of tumour-specific (p=0.003) but not control CD4+ T cell responses.ConclusionThese findings demonstrate that the presence of CRC drives the activity of Tregs and accompanying suppression of CD4+ T cell responses to tumour-associated antigens. Suppression is associated with recurrence of tumour at 12 months, implying that Tregs contribute to disease progression. These findings offer a rationale for the manipulation of Tregs for therapeutic intervention.

In rectal cancer, preoperative staging should identify early tumours suitable for treatment by surgery alone and locally advanced tumours that require therapy to induce tumour regression from the potential resection margin. Currently, local staging can be performed by digital rectal examination (DRE), endoluminal ultrasound (EUS) or magnetic resonance imaging (MRI). Each staging method was compared for clinical benefit and cost-effectiveness. The accuracy of high-resolution MRI, DRE and EUS in identifying favourable, unfavourable and locally advanced rectal carcinomas in 98 patients undergoing total mesorectal excision was compared prospectively against the resection specimen pathological as the gold standard. Agreement between each staging modality with pathology assessment of tumour favourability was calculated with the chance-corrected agreement given as the kappa statistic, based on marginal homogenised data. Differences in effectiveness of the staging modalities were compared with differences in costs of the staging modalities to generate cost effectiveness ratios. Agreement between staging and histologic assessment of tumour favourability was 94% for MRI (k ¼ 0.81, s.e. ¼ 0.05; k W ¼ 0.83), compared with very poor agreements of 65% for DRE (k ¼ 0.08, s.e. ¼ 0.068, k W ¼ 0.16) and 69% for EUS (k ¼ 0.17, s.e. ¼ 0.065, k W ¼ 0.17). The resource benefits resulting from the use of MRI rather than DRE was d67164 and d92244 when MRI was used rather than EUS. Magnetic resonance imaging dominated both DRE and EUS on cost and clinical effectiveness by selecting appropriate patients for neoadjuvant therapy and justifies its use for local staging of rectal cancer patients.

Persistent symptoms after cholecystectomy are common, occurring in up to 40 per cent of patients. Severe pain persists in 10 per cent of cases. A total of 450 patients were studied, 200 after open cholecystectomy and 250 after the laparoscopic operation. Patient notes were reviewed and a postal questionnaire was circulated. Responses were obtained from 155 patients (77.5 per cent) undergoing open cholecystectomy and 205 (82.0 per cent) having the laparoscopic operation. Mean (s.d.) follow-up was 32(23) months after open cholecystectomy and 15(7) months after the laparoscopic procedure. Right upper quadrant pain was more common after open cholecystectomy (9.7 versus 3.4 per cent, P < 0.05). Indigestion and heartburn were equally prevalent in the two groups. Some 59.4 per cent of patients were free from symptoms after open cholecystectomy compared with 63.4 per cent following the laparoscopic operation; there was symptomatic improvement in 30.3 and 31.7 per cent respectively. Symptoms were the same or worse in 10.3 per cent of patients after open cholecystectomy compared with 4.9 per cent after the laparoscopic operation (P < 0.05). Patients report significantly less right upper quadrant pain after laparoscopic than after open cholecystectomy.