Summary Background The TME trial investigated the value of preoperative short-term radiotherapy in combination with total mesorectal excision (TME). Long-term results are reported after a median follow-up of 12 years. Methods Between Jan 12, 1996, and Dec 31, 1999, 1861 patients with resectable rectal cancer without evidence of distant disease were randomly assigned to TME preceded by 5 × 5 Gy radiotherapy or TME alone (ratio 1:1). Randomisation was based on permuted blocks of six with stratification according to centre and expected type of surgery. The primary endpoint was local recurrence, analysed for all eligible patients who underwent a macroscopically complete local resection. Findings 10-year cumulative incidence of local recurrence was 5% in the group assigned to radiotherapy and surgery and 11% in the surgery-alone group (p Interpretation For all eligible patients, preoperative short-term radiotherapy reduced 10-year local recurrence by more than 50% relative to surgery alone without an overall survival benefit. For patients with a negative resection margin, the effect of radiotherapy was irrespective of the distance from the anal verge and led to an improved cancer-specific survival, which was nullified by an increase in other causes of death, resulting in an equal overall survival. Nevertheless, preoperative short-term radiotherapy significantly improved 10-year survival in patients with a negative circumferential margin and TNM stage III. Future staging techniques should offer possibilities to select patient groups for which the balance between benefits and side-effects will result in sufficiently large gains. Funding The Dutch Cancer Society, the Dutch National Health Council, and the Swedish Cancer Society.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(11)70097-3.pdf

Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial

The saimie paper suggests how susceptible individuals could reduce their total intake of aluminium. In presenting the cpidemiological evidence for a link betveen aluminium and Alzheimcr's, Nart'n suggests that although definite proof is still lacking, there is more than enough positixe evidence to fuel further epidemiological investigation. It states that such investigations might specificallx address the issue of the confounding cffect of silicon and an assessment of exposure to spccific

https://jech.bmj.com/content/jech/47/6/511.4.full.pdf

Methodology for Genetic Studies of Twins and Families

Background
Pelvic organ prolapse may occur in up to 50% of parous women. A variety of urinary, bowel and sexual symptoms may be associated with the prolapse.

Objectives
To determine the effects of the many different surgeries used in the management of pelvic organ prolapse.

Search methods
We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In Process and handsearching of journals and conference proceedings, healthcare-related bibliographic databases, handsearched conference proceedings (searched 20 August 2012), and reference lists of relevant articles. We also contacted researchers in the field.

Selection criteria
Randomised or quasi-randomised controlled trials that included surgical operations for pelvic organ prolapse.

Data collection and analysis
Trials were assessed and data extracted independently by two review authors. Six investigators were contacted for additional information with five responding.

Main results
Fifty-six randomised controlled trials were identified evaluating 5954 women. For upper vaginal prolapse (uterine or vault) abdominal sacral colpopexy was associated with a lower rate of recurrent vault prolapse on examination and painful intercourse than with vaginal sacrospinous colpopexy. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living and increased cost of the abdominal approach. In single studies the sacral colpopexy had a higher success rate on examination and lower reoperation rate than high vaginal uterosacral suspension and transvaginal polypropylene mesh.

Twenty-one trials compared a variety of surgical procedures for anterior compartment prolapse (cystocele). Ten compared native tissue repair with graft (absorbable and permanent mesh, biological grafts) repair for anterior compartment prolapse. Native tissue anterior repair was associated with more recurrent anterior compartment prolapse than when supplemented with a polyglactin (absorbable) mesh inlay (RR 1.39, 95% CI 1.02 to 1.90) or porcine dermis mesh inlay (RR 2.08, 95% CI 1.08 to 4.01), however there was no difference in post-operative awareness of prolapse after absorbable mesh (RR 0.96, 95% CI 0.33 to 2.81) or a biological graft (RR 1.21, 95% CI 0.64 to 2.30). Data on morbidity and other clinical outcomes were lacking. Standard anterior repair was associated with more anterior compartment prolapse on examination than for any polypropylene (permanent) mesh repair (RR 3.15, 95% CI 2.50 to 3.96). Awareness of prolapse was also higher after the anterior repair as compared to polypropylene mesh repair (28% versus 18%, RR 1.57, 95% CI 1.18 to 2.07). However, the reoperation rate for prolapse was similar at 14/459 (3%) after the native tissue repair compared to 6/470 (1.3%) (RR 2.18, 95% CI 0.93 to 5.10) after the anterior polypropylene mesh repair and no differences in quality of life data or de novo dyspareunia were identified. Blood loss (MD 64 ml, 95% CI 48 to 81), operating time (MD 19 min, 95% CI 16 to 21), recurrences in apical or posterior compartment (RR 1.9, 95% CI 1.0 to 3.4) and de novo stress urinary incontinence (RR 1.8, 95% CI 1.0 to 3.1) were significantly higher with transobturator meshes than for native tissue anterior repair. Mesh erosions were reported in 11.4% (64/563), with surgical interventions being performed in 6.8% (32/470).

Data from three trials compared native tissue repairs with a variety of total, anterior, or posterior polypropylene kit meshes for vaginal prolapse in multiple compartments. While no difference in awareness of prolapse was able to be identified between the groups (RR 1.3, 95% CI 0.6 to 1.7) the recurrence rate on examination was higher in the native tissue repair group compared to the transvaginal polypropylene mesh group (RR 2.0, 95% CI 1.3 to 3.1). The mesh erosion rate was 35/194 (18%), and 18/194 (9%) underwent surgical correction for mesh erosion. The reoperation rate after transvaginal polypropylene mesh repair of 22/194 (11%) was higher than after the native tissue repair (7/189, 3.7%) (RR 3.1, 95% CI 1.3 to 7.3).

Data from three trials compared posterior vaginal repair and transanal repair for the treatment of posterior compartment prolapse (rectocele). The posterior vaginal repair had fewer recurrent prolapse symptoms (RR 0.4, 95% CI 0.2 to 1.0) and lower recurrence on examination (RR 0.2, 95% CI 0.1 to 0.6) and on defecography (MD -1.2 cm, 95% CI -2.0 to -0.3).

Sixteen trials included significant data on bladder outcomes following a variety of prolapse surgeries. Women undergoing prolapse surgery may have benefited from having continence surgery performed concomitantly, especially if they had stress urinary incontinence (RR 7.4, 95% CI 4.0 to 14) or if they were continent and had occult stress urinary incontinence demonstrated pre-operatively (RR 3.5, 95% CI 1.9 to 6.6). Following prolapse surgery, 12% of women developed de novo symptoms of bladder overactivity and 9% de novo voiding dysfunction.

Authors' conclusions
Sacral colpopexy has superior outcomes to a variety of vaginal procedures including sacrospinous colpopexy, uterosacral colpopexy and transvaginal mesh. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living, and increased cost of the abdominal approach.

The use of mesh or graft inlays at the time of anterior vaginal wall repair reduces the risk of recurrent anterior wall prolapse on examination. Anterior vaginal polypropylene mesh also reduces awareness of prolapse, however these benefits must be weighted against increased operating time, blood loss, rate of apical or posterior compartment prolapse, de novo stress urinary incontinence, and reoperation rate for mesh exposures associated with the use of polypropylene mesh.

Posterior vaginal wall repair may be better than transanal repair in the management of rectocele in terms of recurrence of prolapse. The evidence is not supportive of any grafts at the time of posterior vaginal repair. Adequately powered randomised, controlled clinical trials with blinding of assessors are urgently needed on a wide variety of issues, and they particularly need to include women's perceptions of prolapse symptoms. Following the withdrawal of some commercial transvaginal mesh kits from the market, the generalisability of the findings, especially relating to anterior compartment transvaginal mesh, should be interpreted with caution.

/pdf/surgical-management-of-pelvic-organ-prolapse-in-women-4v2ip7dbgk.pdf

Surgical management of pelvic organ prolapse in women

Background
Pelvic floor muscle training is the most commonly used physical therapy treatment for women with stress urinary incontinence (SUI). It is sometimes also recommended for mixed and, less commonly, urgency urinary incontinence.

Objectives
To determine the effects of pelvic floor muscle training for women with urinary incontinence in comparison to no treatment, placebo or sham treatments, or other inactive control treatments.

Search methods
We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL) (1999 onwards), MEDLINE (1966 onwards) and MEDLINE In-Process (2001 onwards), and handsearched journals and conference proceedings (searched 15 April 2013) and the reference lists of relevant articles.

Selection criteria
Randomised or quasi-randomised trials in women with stress, urgency or mixed urinary incontinence (based on symptoms, signs, or urodynamics). One arm of the trial included pelvic floor muscle training (PFMT). Another arm was a no treatment, placebo, sham, or other inactive control treatment arm.

Data collection and analysis
Trials were independently assessed by two review authors for eligibility and methodological quality. Data were extracted then cross-checked. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions. Trials were subgrouped by diagnosis of urinary incontinence. Formal meta-analysis was undertaken when appropriate.

Main results
Twenty-one trials involving 1281 women (665 PFMT, 616 controls) met the inclusion criteria; 18 trials (1051 women) contributed data to the forest plots. The trials were generally small to moderate sized, and many were at moderate risk of bias, based on the trial reports. There was considerable variation in the interventions used, study populations, and outcome measures. There were no studies of women with mixed or urgency urinary incontinence alone.

Women with SUI who were in the PFMT groups were 8 times more likely than the controls to report that they were cured (46/82 (56.1%) versus 5/83 (6.0%), RR 8.38, 95% CI 3.68 to 19.07) and 17 times more likely to report cure or improvement (32/58 (55%) versus 2/63 (3.2%), RR 17.33, 95% CI 4.31 to 69.64). In trials in women with any type of urinary incontinence, PFMT groups were also more likely to report cure, or more cure and improvement than the women in the control groups, although the effect size was reduced. Women with either SUI or any type of urinary incontinence were also more satisfied with the active treatment, while women in the control groups were more likely to seek further treatment. Women treated with PFMT leaked urine less often, lost smaller amounts on the short office-based pad test, and emptied their bladders less often during the day. Their sexual outcomes were also better. Two trials (one small and one moderate size) reported some evidence of the benefit persisting for up to a year after treatment. Of the few adverse effects reported, none were serious.

The findings of the review were largely supported by the summary of findings tables, but most of the evidence was down-graded to moderate on methodological grounds. The exception was 'Participant perceived cure' in women with SUI, which was rated as high quality.

Authors' conclusions
The review provides support for the widespread recommendation that PFMT be included in first-line conservative management programmes for women with stress and any type of urinary incontinence. Long-term effectiveness of PFMT needs to be further researched.

/pdf/pelvic-floor-muscle-training-versus-no-treatment-or-inactive-6ve912sotz.pdf

Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women

Computational and Mathematical Methods in Medicine

BACKGROUND The use of standardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years, but it is unclear whether this approach results in better outcomes than traditional colporrhaphy. METHODS In this multicenter, parallel-group, randomized, controlled trial, we compared the use of a trocar-guided, transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall (cystocele). The primary outcome was a composite of the objective anatomical designation of stage 0 (no prolapse) or 1 (position of the anterior vaginal wall more than 1 cm above the hymen), according to the Pelvic Organ Prolapse Quantification system, and the subjective absence of symptoms of vaginal bulging 12 months after the surgery. RESULTS Of 389 women who were randomly assigned to a study treatment, 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy. At 1 year, the primary outcome was significantly more common in the women treated with transvaginal mesh repair (60.8%) than in those who underwent colporrhaphy (34.5%) (absolute difference, 26.3 percentage points; 95% confidence interval, 15.6 to 37.0). The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group (P<0.001 for both comparisons). Rates of bladder perforation were 3.5% in the mesh-repair group and 0.5% in the colporrhaphy group (P=0.07), and the respective rates of new stress urinary incontinence after surgery were 12.3% and 6.3% (P=0.05). Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2% of 186 patients in the mesh-repair group. CONCLUSIONS As compared with anterior colporrhaphy, use of a standardized, trocar-guided mesh kit for cystocele repair resulted in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events. (Funded by the Karolinska Institutet and Ethicon; ClinicalTrials.gov number, NCT00566917.).

/pdf/anterior-colporrhaphy-versus-transvaginal-mesh-for-pelvic-1rro67l7am.pdf

Anterior colporrhaphy versus transvaginal mesh for pelvic-organ prolapse.

BACKGROUND Recent genetic and morphologic studies have challenged the traditional view on the pathogenesis of ovarian cancer; suggesting that ovarian cancer predominantly arises within the fallopian tubes or the uterus. We hypothesize that surgical removal of the fallopian tubes is associated with a reduced risk for ovarian cancer. METHODS In this population-based cohort study, we used data on women with previous surgery on benign indication (sterilization, salpingectomy, hysterectomy, and bilateral salpingo-oophorectomy [BSO], hysterectomy; n = 251465) compared with the unexposed population (n = 5449119) between 1973 and 2009 and analyzed with Cox regression models. The effects of one- and two-sided salpingectomy were considered in a subanalysis. All statistical tests were two-sided. RESULTS There was a statistically significantly lower risk for ovarian cancer among women with previous salpingectomy (HR = 0.65, 95% CI = 0.52 to 0.81) when compared with the unexposed population. In addition, statistically significant risk reductions were observed among women with previous hysterectomy (HR = 0.79, 95% CI = 0.70 to 0.88), sterilization (HR = 0.72, 95% CI = 0.64 to 0.81), and hysterectomy with BSO (HR = 0.06, 95% CI = 0.03 to 0.12). Bilateral salpingectomy was associated with a 50% decrease in risk of ovarian cancer compared with the unilateral procedure (HR = 0.35, 95% CI = 0.17 to 0.73, and 0.71, 95% CI = 0.56 to 0.91, respectively). CONCLUSION Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. These data support the hypothesis that a substantial fraction of ovarian cancer arises in the fallopian tube. Our results suggest that removal of the fallopian tubes by itself, or concomitantly with other benign surgery, is an effective measure to reduce ovarian cancer risk in the general population.

/pdf/ovarian-cancer-risk-after-salpingectomy-a-nationwide-4tbh9woaoj.pdf

Ovarian Cancer Risk After Salpingectomy: A Nationwide Population-Based Study

Epidemiology of urinary incontinence (UI) and other lower urinary tract symptoms (LUTS), pelvic organ prolapse (POP) and anal incontinence (AI)

Background:

Preoperative radiotherapy improves local control and survival in rectal cancer, but there are few reports on long-term morbidity. The aims of this study were to compare long-term morbidity and quality of life in patients undergoing rectal cancer surgery with or without preoperative radiotherapy.



Methods:

A total of 252 patients, randomized within the two Stockholm trials on preoperative radiotherapy in rectal cancer, were alive at a mean of 15 years after surgery. Some 139 of these patients were available for follow-up by questionnaires and clinical examination. Questionnaires regarding medical history and quality of life were completed by all patients. All patients had a clinical examination, and those without a stoma underwent rigid sigmoidoscopy.



Results:

Overall, patients who had preoperative radiotherapy experienced significantly more late complications than those who did not (69 versus 43 per cent; P = 0·002). This morbidity consisted mainly of cardiovascular disease (35 versus 19 per cent; P = 0·032), faecal incontinence (12 of 21 versus 11 of 42 patients having anterior resection; P = 0·013) and urinary incontinence (45 versus 27 per cent; P = 0·023). No significant differences between groups were found for hip or pelvic fractures, small bowel obstruction or global quality of life.



Conclusion:

Preoperative short-course, high-dose radiotherapy in patients with rectal cancer increases the risk of anal and urinary dysfunction, and may lead to increased cardiovascular morbidity, at long-term follow-up. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Daniel Altman

Papers

Anterior colporrhaphy versus transvaginal mesh for pelvic-organ prolapse.

Ovarian Cancer Risk After Salpingectomy: A Nationwide Population-Based Study

Epidemiology of urinary incontinence (UI) and other lower urinary tract symptoms (LUTS), pelvic organ prolapse (POP) and anal incontinence (AI)

Late adverse effects of short-course preoperative radiotherapy in rectal cancer.

Anal incontinence after vaginal delivery: a five-year prospective cohort study.