Abnormalities in CD4+CD25+Foxp3+ regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the α chain of the interleukin-7 receptor, allows an unambiguous flow cytometry–based distinction to be made between CD127lo T reg cells and CD127hi conventional T cells within the CD25+CD45RO+RA− effector/memory and CD45RA+RO− naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25+CD127lo cells comprised 6.35 ± 0.26% of CD4+ T cells, of which 2.05 ± 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127lo phenotype were highly correlated within the CD4+CD25+ population. Moreover, both effector/memory and naive CD25+CD127lo cells manifested suppressive activity in vitro, whereas CD25+CD127hi cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases.

Importance: Laparoscopic procedures are generally thought to have better outcomes than open procedures. Because of anatomical constraints, laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection. Objective: To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance. Design, setting, and participants: Randomized, noninferiority, phase 3 trial (Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March 2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. Interventions: Open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238). Main outcomes and measures: The primary end point was a composite of oncological factors indicating an adequate surgical resection, with a noninferiority boundary of Δ = -8%. Successful resection was defined as meeting all the following criteria: (1) complete total mesorectal excision, (2) a clear circumferential margin (≥1 mm), and (3) a clear distal resection margin (≥1 mm). Pathologists used standardized reporting and were blinded to the method of surgery. Results: A successful resection was achieved in 194 patients (82%) in the laparoscopic surgery group and 208 patients (89%) in the open surgery group (risk difference of -7.0% [95% CI, -12.4% to ∞]; P = .38 for noninferiority). The circumferential resection margin was clear in 222 patients (93%) in the laparoscopic surgery group and in 228 patients (97%) in the open surgery group (risk difference of -3.7% [95% CI, -7.6% to 0.1%]; P = .06), the distal margin was clear in 236 patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the open surgery group (risk difference of -0.4% [95% CI, -1.8% to 1.0%]; P = .67), and total mesorectal excision was complete in 206 patients (87%) in the laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk difference of -5.4% [95% CI, -10.9% to 0.2%]; P = .06). The conversion rate from laparoscopic to open surgery was 9%. Conclusions and relevance: Among patients with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established. Although the overall quality of surgery was high, these findings do not provide sufficient evidence for the routine use of laparoscopic surgery. Longer follow-up of recurrence and survival is currently being acquired. Trial registration: anzctr.org Identifier: ACTRN12609000663257.

Purpose: To compare the local recurrence (LR) rate between short-course (SC) and long-course (LC) neoadjuvant radiotherapy for rectal cancer. Patients and Methods: Eligible patients had ultrasound- or magnetic resonance imaging–staged T3N0-2M0 rectal adenocarcinoma within 12 cm from anal verge. SC consisted of pelvic radiotherapy 5 × 5 Gy in 1 week, early surgery, and six courses of adjuvant chemotherapy. LC was 50.4 Gy, 1.8 Gy/fraction, in 5.5 weeks, with continuous infusional fluorouracil 225 mg/m² per day, surgery in 4 to 6 weeks, and four courses of chemotherapy. Results: Three hundred twenty-six patients were randomly assigned; 163 patients to SC and 163 to LC. Median potential follow-up time was 5.9 years (range, 3.0 to 7.8 years). Three-year LR rates (cumulative incidence) were 7.5% for SC and 4.4% for LC (difference, 3.1%; 95% CI, −2.1 to 8.3; P = .24). For distal tumors (< 5 cm), six of 48 SC patients and one of 31 LC patients experienced local recurrence (P = .21). Five-year distant recurrence rates were 27% for SC and 30% for LC (log-rank P = 0.92; hazard ratio [HR] for LC:SC, 1.04; 95% CI, 0.69 to 1.56). Overall survival rates at 5 years were 74% for SC and 70% for LC (log-rank P = 0.62; HR, 1.12; 95% CI, 0.76 to 1.67). Late toxicity rates were not substantially different (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer G3-4: SC, 5.8%; LC, 8.2%; P = .53). Conclusion: Three-year LR rates between SC and LC were not statistically significantly different; the CI for the difference is consistent with either no clinically important difference or differences in favor of LC. LC may be more effective in reducing LR for distal tumors. No differences in rates of distant recurrence, relapse-free survival, overall survival, or late toxicity were detected.

Review from JAMA — Association Between Compensation Status and Outcome After Surgery — A Meta-analysis — ContextCompensation, whether through workers’ compensation or through litigation, has been associated with poor outcome after surgery; however, this association has not been examined by meta-analysis.ObjectiveTo investigate the association between compensation status and outcome after surgery.Data SourcesWe searched MEDLINE (1966-2003), EMBASE (1980-2003), CINAHL, the Cochrane Controlled Trials Register, and reference lists of retrieved articles and textbooks, and we contacted experts in the field.Study SelectionThe review included any trial of surgical intervention in which compensation status was reported and results were compared according to that status. No restrictions were placed on study design, language, or publication date. Studies were selected by 2 unblinded independent reviewers.Data ExtractionTwo reviewers independently extracted data on study type, study quality, surgical procedure, outcome, country of origin, length and completeness of follow-up, and compensation type.Data SynthesisTwo hundred eleven studies satisfied the inclusion criteria. Of these, 175 stated that the presence of compensation (workers’ compensation with or without litigation) was associated with a worse outcome, 35 found no difference or did not describe a difference, and 1 described a benefit associated with compensation. A meta-analysis of 129 studies with available data (n = 20 498 patients) revealed the summary odds ratio for an unsatisfactory outcome in compensated patients to be 3.79 (95% confidence interval, 3.28-4.37 by random-effects model). Grouping studies by country, procedure, length of follow-up, completeness of follow-up, study type, and type of compensation showed the association to be consistent for all subgroups.ConclusionsCompensation status is associated with poor outcome after surgery. This effect is significant, clinically important, and consistent. Because data were obtained from observational studies and were not homogeneous, the summary effect should be interpreted with caution. Compensation status should be considered a potential confounder in all studies of surgical intervention. Determination of the mechanism for this association requires further study.