Exercise-induced amplification of mitogen-stimulated oxidative burst in whole blood is strongly influenced by neutrophil counts during and following exercise.

This study characterized the effect of moderate- or vigorous-intensity exercise on leukocyte counts, using fingertip sampling, and mitogen-stimulated oxidative burst, measured in whole blood with a point-of-care test. In a randomized crossover design, 13 healthy adults (mean ± SD age: 22 ± 2 years; seven male, six female) cycled for 30-min, once at 52 ± 5% V˙ O2peak and on another occasion at 74 ± 9% V˙ O2peak . Blood was sampled at baseline, immediately post-exercise, and 15- and 60-min post-exercise. The leukocyte differential and mitogen-stimulated Reactive Oxygen Species (ROS) production were assessed. Lymphocytes increased immediately post-exercise and decreased below pre-exercise levels 15- and 60-min later. Lymphocyte mobilization immediately post-exercise was 59 ± 36% greater with vigorous- compared to moderate-intensity exercise (p < 0.01). Neutrophils increased immediately after exercise (38 ± 19%, p < 0.01) remaining elevated 60-min later (50 ± 34%, p < 0.01; averaged across intensities) and did not differ between intensities (p = 0.259). Mitogen-stimulated ROS production was amplified immediately (+32 ± 37%, p < 0.01) and 60-min post-exercise (+56 ± 57%, p < 0.01; averaged across intensities) compared to rest and did not differ with intensity (p = 0.739). Exercise-induced amplification of ROS production was abolished when correcting for neutrophil, monocyte and platelet counts and correlated most strongly with neutrophil mobilization immediately (r = 0.709, p < 0.01) and 60-min after vigorous exercise (r = 0.687, p < 0.01). Leukocyte kinetics can be assessed using fingertip blood sampling in exercise settings. Exercise-induced amplification of oxidative burst is detectable with a point-of-care test, but results are strongly influenced by neutrophil counts, which may not be routinely quantified.

Minimal access rectal cancer surgery: an observational study of patient outcomes from a district general hospital with over a decade of experience with robotic rectal cancer surgery.

AIM: Robotic surgery for colorectal cancer has become established more slowly than in other specialities. The aim of this study was to assess the risks and benefits of the use of robotic rectal cancer surgery in comparison with laparoscopic surgery within the confines of a subspecialist rectal cancer service in a district general hospital. METHOD: Outcomes from consecutive patients undergoing minimal access rectal cancer surgery between July 2008 and January 2020 were analysed. Comparisons were made between short-term outcomes including conversion rates, anastomotic leakage and pathological outcomes as well as long-term survival and cancer recurrence. RESULTS: A total of 337 patients were included in the analysis, 204 (60.5%) of whom underwent robotic surgery. Demographic characteristics and use of neoadjuvant chemoradiotherapy were similar between groups. However, patients having robotic surgery had significantly lower tumours than in the laparoscopic group (7.6 cm vs. 9.8 cm, p = 0.003). Conversion to open surgery in the robotic group was significantly less likely (9.8% vs. 22.6%, p = 0.001). Operative mortality, clinical leakage and major complications were similar between groups. While asymptomatic 'radiological' leaks were significantly more common following robotic surgery (13.7% vs. 5.3%, p = 0.017) this did not affect the long-term stoma closure rate. Pathological outcomes were similar with the exception of shorter mean distal resection margins (25.9 mm vs. 32.8 mm, p = 0.001) for the robotic group of patients. There was no statistical difference in 5-year survival between groups (78.7% robotic vs. 85.4% laparoscopic, p = 0.263) nor local recurrence (2.0% robotic vs. 3.8% laparoscopic, p = 0.253). CONCLUSIONS: These results illustrate how the selective use of robotic surgery by a dedicated rectal cancer team can achieve low rates of cancer recurrence and low permanent stoma rates.

Preclinical evaluation of the versius surgical system, a new robot-assisted surgical device for use in minimal access general and colorectal procedures.

OBJECTIVE: To evaluate the utility of a new robot-assisted surgical system (the Versius Surgical System, CMR Surgical, Cambridge, UK) for use in minimal access general and colorectal surgery, in a preclinical setting. Robot-assisted laparoscopy has been developed to overcome some of the important limitations of conventional laparoscopy. The new system is designed to assist surgeons in performing minimal access surgery and overcome some of the challenges associated with currently available surgical robots. METHODS: Cadaveric sessions were conducted to evaluate the ability of the system to provide adequate surgical access and reach required to complete a range of general and colorectal procedures. Port and bedside unit positions were recorded, and surgical access and reach were evaluated by the lead surgeon using a visual analogue scale. A live animal (porcine) model was used to assess the surgical device's safety in performing cholecystectomy or small bowel enterotomy. RESULTS: Nine types of procedure were performed in cadavers by nine lead surgeons; 35/38 procedures were completed successfully. The positioning of ports and bedside units reflected the lead surgeons' preferred laparoscopic set-up and enabled good surgical access and reach. Cholecystectomy (n = 6) and small bowel enterotomy (n = 5) procedures performed in pigs were all completed successfully by two surgeons. There were no device-related intra-operative complications. CONCLUSIONS: This preclinical study of a new robot-assisted surgical system for minimal access general and colorectal surgery demonstrated the safety and effectiveness of the system in cadaver and porcine models. Further studies are required to assess its clinical utility.

The majority of colorectal resections require an open approach, even in units with a special interest in laparoscopic surgery.

AIM: Proponents suggest that laparoscopic colorectal resection might be achievable in up to 90% of cases, while keeping conversion rates below 10%. This unselected prospective case series reports on the proportion of patients having a completed laparoscopic colorectal resection in two units where laparoscopic colorectal practice is well established and readily available. METHOD: All patients undergoing elective and emergency colorectal resection during a 6-month period were identified. The underlying pathology and the surgical approach (laparoscopic or open) were recorded. The contraindications to laparoscopic resection were also documented. The need and rationale for conversion to an open approach were recorded. RESULTS: In total, 205 consecutive patients (160 elective and 45 emergency procedures) underwent colorectal resection for malignancy [117 (57%) patients] and benign pathology [88 (43%) patients]. Laparoscopic resection was attempted in 127/205 (62%) patients and 31/127 (24%) of these were converted to open surgery. The main reasons for not attempting laparoscopic resection were locally advanced disease and emergency surgery. The commonest reasons for conversion were advanced disease and to allow completion of rectal dissection and/or cross-stapling of the rectum. CONCLUSION: Despite a special interest in laparoscopic colorectal surgery of the two colorectal units who provided the data for this study, fewer than half (96/205; 47%) of the patients in this consecutive unselected series who were undergoing major colorectal resection had the procedure completed laparoscopically.

Does the laparoscopic colorectal surgery learning curve adversely affect the results of colorectal cancer resection? A 3-year prospective study in a district general hospital.

INTRODUCTION: Laparoscopic colorectal surgery is slowly being adopted across the UK. We present a 3-year prospective study of laparoscopic colorectal cancer resections in a district general hospital. METHOD: Data relating to premorbid, operative and postoperative parameters were recorded for all patients undergoing laparoscopic, open, planned converted (laparoscopic assisted) and unplanned converted resections prospectively from April 2003 to April 2006. RESULTS: A total of 238 colorectal resections were performed, 153 of which were for cancer. Of these 44 (29%) were open, 77 (50%) were laparoscopic and 32 (21%) were converted [26 (17%) planned and six (4%) unplanned]. Blood loss was less in the laparoscopic group compared with the open group (P = 0.02) as was intra-operative fluid replacement (P = 0.01). Time to requiring oral analgesia alone was shorter (P = 0.001) and bowel function returned earlier (P = 0.001) in the laparoscopic group. This is reflected in a trend towards a shorter hospital stay for the laparoscopic group compared with the open group (P = 0.049). The operating time of the laparoscopic group was not significantly longer (P = 0.38). The complication rate was similar between groups (P = 0.31) and the mortality in the laparoscopic group was 1.3%. CONCLUSION: Changing from open to laparoscopic dissection for colorectal cancer is safe even during the initial learning curve. There are clear potential short-term benefits for patients and the technique can be introduced without penalties in terms of reduced surgical throughput.

Radiotherapy for rectal carcinoma: an unusual cause of foreskin phimosis.

Phimosis of the foreskin secondary to radiotherapy for a pelvic malignancy has not been previously described in the world literature. However, as radiotherapy is ever more widely used in the treatment of various pelvic malignancies, it is important to ensure that this complication is prevented by the use of appropriate penile shielding.

A personal view on laparoscopic rectal cancer surgery.

Benefits such as reduced morbidity and shorter length of stay have been demonstrated for laparoscopic colon cancer resection, Laparoscopic rectal cancer surgery is thought to be more challenging and it is not clear if it offers the same benefits. There are concerns about oncological outcome and anastomotic technique and complications. In this review we discuss the difficulties and challenges of laparoscopic rectal cancer surgery within the context of our own personal experience and with regard to some of the current literature. We propose that laparoscopic and open rectal cancer surgery both have a role and the challenge is selection of appropriate patients for each technique.

The use of intra-operative endo-anal ultrasound in perianal disease.

INTRODUCTION: Endoanal ultrasound (EAUS) has demonstrated high sensitivity and specificity for the structural imaging of anorectal pathology. This study prospectively assessed the impact of intra-operative EAUS on the surgical management of perianal disease. METHODS: EAUS was performed prior to and after examination under anaesthesia (EUA) in a consecutive series of patients with perianal disease. The impact of EAUS on the surgery performed was identified. RESULTS: Forty-three procedures have been performed in 38 patients (21 male, 17 female; mean age 42.7 years, range 6-76 years) over a three year period. Pathologies encountered were fistula-in-ano (42%), fissure-in-ano (26%), complicated perianal sepsis (16%) and carcinoma (5%). No specific abnormality was identified in 5 symptomatic patients (12%). Four patients with fissures had undergone previous sphincterotomy. In 22 cases (51.2%) the EAUS findings affected the surgical management (extent of muscle above a fistula 9 cases, extent of sphincterotomy 7 cases, site of sepsis identified 2 cases, exclusion of sepsis 2 cases, assessment of cancer resectability 1 case, biopsy of intersphincteric lesion 1 case). CONCLUSION: Intra-operative EAUS accurately identifies perianal disease and influences the surgical procedure performed. While not essential, it is a useful adjunct especially in recurrent perianal sepsis, undiagnosed anorectal pain and anal fissure.

Management of the rectal stump after emergency sub-total colectomy: which surgical option is associated with the lowest morbidity?

OBJECTIVE: To identify the preferred surgical management of the rectal stump after emergency subtotal colectomy (ESC) for acute severe colitis by assessing the morbidity associated with each option. PATIENTS AND METHODS: Consecutive patients undergoing ESC at a district general hospital between 1999 and 2004 were retrospectively audited for pathology, rectal stump complications and length of postoperative hospital stay (POS). RESULTS: Thirty-seven ESCs were performed, 34 were undertaken for disease refractory to medical treatment, 2 for toxic mega colon and 1 for perforation. Thirty-four cases were for ulcerative colitis, 2 Crohn's colitis and 1 infective colitis. Twenty-seven had an intraperitoneal and 10 a subcutaneously placed closed rectal stump. The median POS for patients with a subcutaneously placed stump was shorter than for those with an intraperitoneal stump, 8 and 15 days, respectively (P = 0.04). Two patients had leakage from an intraperitoneal stump, prolonging POS (33 and 193 days). Three of the subcutaneous stumps leaked causing wound infection but not prolonging the POS (6, 7 and 16 days). CONCLUSION: Avoiding a second stoma by closing the rectal stump after ESC has been confirmed as acceptable practice by studies over the last 15 years, reporting no overall increase in complications. The location of a closed rectal stump appears to influence the incidence of pelvic sepsis. The lowest pelvic sepsis rate is associated with subcutaneous placement; despite a higher wound infection rate this option appears to be associated with a lower total morbidity reflected in a shorter POS.

Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer.

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (+/- SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% +/- 3% and 86% +/- 4%, respectively. For the matched comparison group survival was 85% +/- 3% at 5 years and 74% +/- 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P =.04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.

Identifying breast cancer patients at high risk for bone metastases.

PURPOSE: To identify patient populations at high risk for bone metastases at any time after diagnosis of operable breast cancer, because these patients are potential beneficiaries of treatment with bisphosphonates. PATIENTS AND METHODS: We evaluated data from 6,792 patients who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1993. Median follow-up was 10. 7 years. A total of 1,275 patients (18.7%) presented with node-negative disease, whereas 3,354 patients (49.4%) had one to three and 2,163 patients (31.9%) had four or more involved axillary lymph nodes. We also assessed the incidence of subsequent bone metastases in the cohort of 1,220 patients who had a first event in local or regional sites or soft tissue alone. Median follow-up for this cohort was 7.7 years from first recurrence. RESULTS: For the entire population with operable disease, the cumulative incidence of bone metastases at any time was 8.2% at 2 years from randomization and 27.3% at 10 years. The highest cumulative incidences of bone metastases at any time were among patients who had four or more involved axillary nodes at the time of diagnosis (14.9% at 2 years and 40.8% at 10 years) and among patients who had as their first event a local or regional recurrence or a recurrence in soft tissue, without any other overt metastases (21.1% at 2 years from first recurrence and 36.7% at 10 years). CONCLUSION: Treatments to prevent bone metastases may have a major impact on the course of breast cancer and may be most efficiently studied in populations with several involved axillary nodes at the time of presentation and in populations with local or regional recurrence or recurrence in soft tissue.

Risk of breast cancer in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen contraceptives.

Recent studies have suggested that progestogen-only contraceptives and combined estrogen/progestogen oral contraceptives (COCs) may increase the risk of breast cancer among women less than 35 years of age or among recent users. The authors conducted a case-control study, in which cases of breast cancer (n = 484) [corrected] and controls (n = 1,625) hospitalized for conditions unrelated to contraceptive use were interviewed from 1994 to 1997 in hospitals in greater Cape Town, South Africa. The women were aged 20-54 years, resided in a defined area around Cape Town, and were Black or of mixed racial descent. The relative risk for exposure to injectable progestogen contraceptives (IPCs), mostly depot medroxyprogesterone acetate, was 0.9 (95% confidence interval (CI) 0.7, 1.2). There were no consistent associations within categories of age or recency or duration of use. For exposure to COCs, the overall relative risk was 1.2 (95% CI 1.0, 1.5). Among women below age 35 years, the relative risk was 1.7 (95% CI 1.0, 3.0), and it was unrelated to the duration or recency of use. The findings suggest that IPCs do not increase the risk of breast cancer, and that COCs may increase the risk among women below age 35 years, although bias cannot be excluded.

Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer: the International Breast Cancer Study Group Trial VII.

PURPOSE: Information on the tolerability and efficacy of adjuvant chemoendocrine therapy for older women is limited. We studied these issues using the data collected as part of the International Breast Cancer Study Group Trial VII. PATIENTS AND METHODS: Postmenopausal women with operable, node-positive breast cancer were randomized to receive either tamoxifen alone for 5 years (306 patients) or tamoxifen plus three consecutive cycles of classical cyclophosphamide (100 mg/m(2) orally days 1 to 14), methotrexate (40 mg/m(2) intravenous days 1 and 8), and fluorouracil (600 mg/m(2) intravenous days 1 and 8) every 28 days (CMF; 302 patients). The median follow-up was 8.0 years. RESULTS: Among the 299 patients who received at least one dose of CMF, women 65 years of age or older (n = 76) had higher grades of toxicity compared with women less than 65 years old (n = 223) (P =.004). More women in the older age group compared with the younger women experienced grade 3 toxicity of any type (17% v 7%, respectively), grade 3 hematologic toxicity (9% v 5%, respectively), and grade 3 mucosal toxicity (4% v 1%, respectively). Older patients also received less than their expected CMF dose compared with younger postmenopausal women (P =.0008). The subjective burdens of treatment, however, were similar for younger and older patients based on quality-of-life measures (performance status, coping, physical well-being, mood, and appetite). For older patients, the 5-year disease-free survival (DFS) rates were 63% for CMF plus tamoxifen and 61% for tamoxifen alone (hazards ratio [HR], 1.00; 95% confidence interval [CI], 0.65 to 1.52; P =.99). For younger patients, the corresponding 5-year DFS rates were 61% and 53% (HR, 0.70; 95% CI, 0.53 to 0.91; P =.008), but the test for heterogeneity of CMF effect according to age group was not statistically significant. The reduced effectiveness of CMF among older women could not be attributed to dose reductions according to dose received. CONCLUSION: CMF tolerability and effectiveness were both reduced for older patients compared with younger postmenopausal node-positive breast cancer patients who received tamoxifen for 5 years. The development and evaluation of less toxic and more effective chemotherapy regimens are required for high-risk elderly patients.

Effects of sibutramine alone and with alcohol on cognitive function in healthy volunteers.

AIMS: To investigate the effects of sibutramine in combination with alcohol in a double-blind, randomised, placebo-controlled, four-way crossover study in 20 healthy volunteers. METHODS: On each study day each volunteer received either: sibutramine 20 mg+0.5 g kg-1 alcohol; sibutramine 20 mg+placebo alcohol; placebo capsules+0.5 g kg-1 alcohol; or placebo capsules+placebo alcohol. Alcohol was administered 2 h following ingestion of the study capsules. During each study day, assessments of cognitive performance were made prior to dosing, and at 3, 4.5, 6 and 10 h post dosing. Blood alcohol concentration was estimated using a breath alcometer immediately prior to each cognitive performance test session. Each study day was followed by a minimum 7 day washout period. RESULTS: Alcohol was found to produce statistically significant impairments in tests of attention (maximum impairment to speed of digit vigilance=49 ms) and episodic memory (maximum impairment to speed of word recognition=74 ms). Alcohol also increased body sway (maximum increase 17.4 units) and lowered self rated alertness (maximum decrease 13.6 mm). These effects were produced by an inferred blood alcohol level of 53.2 mg dl-1. Sibutramine was not found to potentiate any of the effects of alcohol. There was a small, yet statistically significant, interaction effect observed on the sensitivity index of the picture recognition task. In this test, the combined effects of sibutramine and alcohol were smaller than the impairments produced by alcohol alone. Sibutramine, when dosed alone, was associated with improved performance on several tasks. Sibutramine improved attention (mean speed of digit vigilance improved by 21 ms), picture recognition speed (improvement at 3=81) and motor control (tracking error at 3 h reduced by 1.58 mm). Also sibutramine improved postural stability (reducing body sway at 3 h by 14.2 units). Adverse events reported were unremarkable and consistent with the known pharmacology of sibutramine and alcohol. CONCLUSIONS: There was little evidence of a clinically relevant interaction of sibutramine with the impairment of cognitive function produced by alcohol in healthy volunteers. The single statistically significant interaction indicated a reduction, rather than a worsening, of alcohol-induced impairment when sibutramine is taken concomitantly. Sibutramine when administered alone is associated with improved performance on several tasks.

Breast cancer incidence and determinants of cancer stage in the Western Cape.

OBJECTIVE: To describe the overall and age-specific incidence rates for breast cancer and determinants of the stage of breast cancer at the time of diagnosis in the Western Cape, South Africa. METHODS: Data were derived from a case-control study of the association between injectable progestagen contraceptives and breast cancer conducted over a 4-year period from January 1994 to December 1997. In all, 485 cases were drawn from a study population consisting of coloured and black women under the age of 55 years, who presented with a first occurrence of invasive breast cancer at two tertiary hospitals in Cape Town. A questionnaire was administered and information on a large number of variables was recorded. RESULTS: The 249 cases who were interviewed during the first 2 years of the study constituted the numerator for estimates of incidence rates. The overall incidence rate was 23.1 per 100,000 women per year. The incidence rate for coloured women was 25.6 per 100,000, almost twice that for black women (14.7 per 100,000). The incidence rate in urban areas was 26.6 per 100,000, almost twice that in the rural areas (16.3 per 100,000). Stages 1 and 2 accounted for 57.8% of the cases. Early stage at diagnosis was significantly associated with a higher educational level, membership of a medical aid, residence in an urban area and a positive family history. CONCLUSION: The data suggest that there is scope for improvement in the detection of the disease through education and access to diagnostic measures, particularly in rural and disadvantaged populations.