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Journal of Bone Oncology Nov 2018The most serious complication of hereditary multiple exostoses(HME) is chondrosarcoma transformation. Numerous authors have suggested that screening might allow early...
BACKGROUND
The most serious complication of hereditary multiple exostoses(HME) is chondrosarcoma transformation. Numerous authors have suggested that screening might allow early chondrosarcoma detection. However, literature-quoted incidences of malignant transformation are highly variable.
METHODS
A systematic review of malignant transformation by sex, exostosin-1 mutation(EXT1), age and site was conducted searching Medline, Embase and CINHAL. Three HME screening strategies were then developed and compared using cost per life-year gained and incremental cost-effectiveness ratio (ICER).
RESULTS
18 papers with 852 chondrosarcomas were identified. The incidence of chondrosarcoma transformation averaged 4%, 75.2% occurring between ages 20-40 and 56.2% at the pelvis and proximal femur. Screening model: In the general HME population, plain radiographs provided cost per life-year gain of £19,013 compared to £53,392 in MRIs. ICER in MRIs compared to X-rays was £80,218. However, for every generation of HME patients screened over 20 years, X-ray radiation induced 0.65 cancers. Psychological effects of false-positives were marginal. Screening only higher-risk groups (males or EXT1) reduced cost but benefited fewer patients.
CONCLUSIONS
Our results suggest that annual MRI screening for all HME patients between age 20-40 may be of value. However, the extent of anatomical imaging is subject to debate; it is possible that focused imaging protocols which scan from cervical spine to proximal femur may improve cost-effectiveness.
PubMed: 30591865
DOI: 10.1016/j.jbo.2018.09.011 -
The Cochrane Database of Systematic... Nov 2018This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery.
OBJECTIVES
To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE.
SEARCH METHODS
We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies.
SELECTION CRITERIA
We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation.
DATA COLLECTION AND ANALYSIS
Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis.
MAIN RESULTS
We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I = 28%; seven studies, n = 1728; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis (M-H OR 0.30, 95% CI 0.08 to 1.11; I = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (HM-H OR 1.10, 95% CI 0.67 to 1.81; I = 0%; seven studies, n = 2239; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity.
AUTHORS' CONCLUSIONS
Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.
Topics: Abdomen; Anticoagulants; Drug Administration Schedule; Heparin, Low-Molecular-Weight; Humans; Pelvis; Postoperative Care; Postoperative Complications; Postoperative Hemorrhage; Pulmonary Embolism; Randomized Controlled Trials as Topic; Venous Thromboembolism
PubMed: 30481366
DOI: 10.1002/14651858.CD004318.pub3 -
The Lancet. Gastroenterology &... Dec 2018In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential... (Meta-Analysis)
Meta-Analysis
Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis.
BACKGROUND
In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth.
METHODS
We updated search results of a recent systematic review by searching MEDLINE and Embase from Jan 1, 2016, to May 5, 2017, and used expert knowledge to identify published studies reporting on local regrowth in patients with rectal cancer managed by watch and wait after clinical complete response to neoadjuvant chemoradiotherapy. We restricted studies to those that defined clinical complete response using criteria equivalent to São Paulo benchmarks (ie, absence of residual ulceration, stenosis, or mass within the rectum on clinical and endoscopic examination). The primary outcome was 2-year cumulative incidence of local regrowth, estimated with a two-stage random-effects individual participant data meta-analysis. We assessed the effects of clinical and treatment factors using Cox frailty models, expressed as hazard ratios (HRs). From these models, we derived percentage differences in mean θ as an approximation of the effect of measured covariates on between-centre heterogeneity. This study is registered with PROSPERO, number CRD42017070934.
FINDINGS
We obtained individual participant data from 11 studies, including 602 patients enrolled between March 11, 1990, and Feb 13, 2017, with a median follow-up of 37·6 months (IQR 25·0-58·7). Ten of the 11 datasets were judged to be at low risk of bias. 2-year cumulative incidence of local regrowth was 21·4% (random-effects 95% CI 15·3-27·6), with high levels of between-study heterogeneity (I=61%). We noted wide between-centre variation in patient, tumour, and treatment characteristics. We found some evidence that increasing cT stage was associated with increased risk of local regrowth (random-effects HR per cT stage 1·40, 95% CI 1·00-1·94; p=0·048). In a subgroup of 459 patients managed after 2008 (when pretreatment staging by MRI became standard), 2-year cumulative incidence of local regrowth was 19% (95% CI 13-28) for stage cT1 and cT2 tumours, 31% (26-37) for cT3, and 37% (21-60) for cT4 (random-effects HR per cT stage 1·50, random-effects 95% CI 1·03-2·17; p=0·0330). We estimated that measured factors contributed 4·8-45·3% of observed between-centre heterogeneity.
INTERPRETATION
In patients with rectal cancer and clinical complete response after chemoradiotherapy managed by watch and wait, we found some evidence that increasing cT stage predicts for local regrowth. These data will inform clinician-patient decision making in this setting. Research is needed to determine other predictors of a sustained clinical complete response.
FUNDING
None.
Topics: Aged; Chemoradiotherapy; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Remission Induction; Watchful Waiting
PubMed: 30318451
DOI: 10.1016/S2468-1253(18)30301-7 -
Journal of Ovarian Research Feb 2018Pelvic masses are a common gynecologic problem, and majority of them are diagnosed as ovarian tumors finally. Sometimes, it is hard to distinguish the origin of these... (Review)
Review
BACKGROUND
Pelvic masses are a common gynecologic problem, and majority of them are diagnosed as ovarian tumors finally. Sometimes, it is hard to distinguish the origin of these pelvic masses. The following case is a solitary neurofibroma arising from the right-side obturator nerve, which was impressed as a right-side ovarian tumor initially. We reported this case, and also performed a PRISMA-driven systematic review to summary the similar cases in the literature. This review includes image, molecular and pathological findings and outcome of neurofibroma.
CASE PRESENTATION
A 33-year-old woman with a regular menstrual period denied any symptoms or signs. During her physical check-up, image examination revealed a right-side heterogeneous pelvic mass; it was suggestive of a complex of right-side ovarian tumor. A provisional diagnosis of retroperitoneal pelvic mass, probably a benign ovarian tumor, was made. Excision of the right-side pelvic mass was performed. We sent the specimens for frozen pathology, which indicated neurofibroma and lipomatous tumor and that the possibility of liposarcoma cannot be excluded. A segment of the obturator nerve was attached to the tumor and was severed. A right-side obturator nerve tear during tumor excision was observed, and a neurosurgeon was consulted for obturator nerve grafting and repair. The patient complained of mild weakness and paresthesia affecting the right leg, and we consulted a rehabilitation doctor for neuron injury. The patient's recovery was uneventful, and she was discharged eight days after the drain was removed. Further rehabilitation treatment was arranged.
CONCLUSION
A neurofibroma is an uncommon pelvic retroperitoneal tumor, and it can be misdiagnosed as an adnexal mass. To our knowledge, this is a rare case of a solitary neurofibroma arising from the obturator nerve. It usually does not have any neurological deficit. We present this case to demonstrate that pelvic neurofibroma can be mistaken for an adnexal mass. This fact should be borne in mind during the diagnosis process.
Topics: Adnexal Diseases; Adult; Biopsy; Diagnosis, Differential; Disease Management; Female; Histocytochemistry; Humans; Neurofibroma; Obturator Nerve; Physical Examination; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Workflow
PubMed: 29426349
DOI: 10.1186/s13048-018-0386-z -
The Cochrane Database of Systematic... Dec 2017About one-third of women have urinary incontinence and up to one-tenth have faecal incontinence after childbirth. Pelvic floor muscle training (PFMT) is commonly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About one-third of women have urinary incontinence and up to one-tenth have faecal incontinence after childbirth. Pelvic floor muscle training (PFMT) is commonly recommended during pregnancy and after birth for both prevention and treatment of incontinence.This is an update of a review previously published in 2012.
OBJECTIVES
To determine the effectiveness of pelvic floor muscle training (PFMT) in the prevention or treatment of urinary and faecal incontinence in pregnant or postnatal women.
SEARCH METHODS
We searched the Cochrane Incontinence Specialised Register (16 February 2017) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised or quasi-randomised trials in pregnant or postnatal women. One arm of the trial included PFMT. Another arm was no PFMT, usual antenatal or postnatal care, another control condition, or an alternative PFMT intervention.
DATA COLLECTION AND ANALYSIS
Review authors independently assessed trials for inclusion and risk of bias. We extracted data and checked them for accuracy. Populations included: women who were continent (PFMT for prevention), women who were incontinent (PFMT for treatment) at randomisation and a mixed population of women who were one or the other (PFMT for prevention or treatment). We assessed quality of evidence using the GRADE approach.
MAIN RESULTS
The review included 38 trials (17 of which were new for this update) involving 9892 women from 20 countries. Overall, trials were small to moderate sized, and the PFMT programmes and control conditions varied considerably and were often poorly described. Many trials were at moderate to high risk of bias. Other than two reports of pelvic floor pain, trials reported no harmful effects of PFMT.Prevention of urinary incontinence: compared with usual care, continent pregnant women performing antenatal PFMT may have had a lower risk of reporting urinary incontinence in late pregnancy (62% less; risk ratio (RR) for incontinence 0.38, 95% confidence interval (CI) 0.20 to 0.72; 6 trials, 624 women; low-quality evidence). Similarly, antenatal PFMT decreased the risk of urinary incontinence in the mid-postnatal period (more than three to six months' postpartum) (29% less; RR 0.71, 95% CI 0.54 to 0.95; 5 trials, 673 women; moderate-quality evidence). There was insufficient information available for the late (more than six to 12 months') postnatal period to determine effects at this time point.Treatment of urinary incontinence: it is uncertain whether antenatal PFMT in incontinent women decreases incontinence in late pregnancy compared to usual care (RR 0.70, 95% CI 0.44 to 1.13; 3 trials, 345 women; very low-quality evidence). This uncertainty extends into the mid- (RR 0.94, 95% CI 0.70 to 1.24; 1 trial, 187 women; very low-quality evidence) and late (RR 0.50, 95% CI 0.13 to 1.93; 2 trials, 869 women; very low-quality evidence) postnatal periods. In postnatal women with persistent urinary incontinence, it was unclear whether PFMT reduced urinary incontinence at more than six to 12 months' postpartum (RR 0.55, 95% CI 0.29 to 1.07; 3 trials; 696 women; very low-quality evidence).Mixed prevention and treatment approach to urinary incontinence: antenatal PFMT in women with or without urinary incontinence (mixed population) may decrease urinary incontinence risk in late pregnancy (26% less; RR 0.74, 95% CI 0.61 to 0.90; 9 trials, 3164 women; low-quality evidence) and the mid-postnatal period (RR 0.73, 95% CI 0.55 to 0.97; 5 trials, 1921 women; very low-quality evidence). It is uncertain if antenatal PFMT reduces urinary incontinence risk late postpartum (RR 0.85, 95% CI 0.63 to 1.14; 2 trials, 244 women; low-quality evidence). For PFMT begun after delivery, there was considerable uncertainty about the effect on urinary incontinence risk in the late postnatal period (RR 0.88, 95% CI 0.71 to 1.09; 3 trials, 826 women; very low-quality evidence).Faecal incontinence: six trials reported faecal incontinence outcomes. In postnatal women with persistent faecal incontinence, it was uncertain whether PFMT reduced incontinence in the late postnatal period compared to usual care (RR 0.68, 95% CI 0.24 to 1.94; 2 trials; 620 women; very low-quality evidence). In women with or without faecal incontinence (mixed population), antenatal PFMT led to little or no difference in the prevalence of faecal incontinence in late pregnancy (RR 0.61, 95% CI 0.30 to 1.25; 2 trials, 867 women; moderate-quality evidence). For postnatal PFMT in a mixed population, there was considerable uncertainty about the effect on faecal incontinence in the late postnatal period (RR 0.73, 95% CI 0.13 to 4.21; 1 trial, 107 women, very low-quality evidence).There was little evidence about effects on urinary or faecal incontinence beyond 12 months' postpartum. There were few incontinence-specific quality of life data and little consensus on how to measure it. We found no data on health economics outcomes.
AUTHORS' CONCLUSIONS
Targeting continent antenatal women early in pregnancy and offering a structured PFMT programme may prevent the onset of urinary incontinence in late pregnancy and postpartum. However, the cost-effectiveness of this is unknown. Population approaches (recruiting antenatal women regardless of continence status) may have a smaller effect on urinary incontinence, although the reasons for this are unclear. It is uncertain whether a population-based approach for delivering postnatal PFMT is effective in reducing urinary incontinence. Uncertainty surrounds the effects of PFMT as a treatment for urinary incontinence in antenatal and postnatal women, which contrasts with the more established effectiveness in mid-life women.It is possible that the effects of PFMT might be greater with targeted rather than mixed prevention and treatment approaches and in certain groups of women. Hypothetically, for instance, women with a high body mass index are at risk factor for urinary incontinence. Such uncertainties require further testing and data on duration of effect are also needed. The physiological and behavioural aspects of exercise programmes must be described for both PFMT and control groups and how much PFMT women in both groups do, to increase understanding of what works and for whom.Few data exist on faecal incontinence or costs and it is important that both are included in any future trials. It is essential that future trials use valid measures of incontinence-specific quality of life for both urinary and faecal incontinence.
Topics: Exercise Therapy; Fecal Incontinence; Female; Humans; Pelvic Floor; Postnatal Care; Pregnancy; Pregnancy Complications; Prenatal Care; Randomized Controlled Trials as Topic; Urinary Incontinence
PubMed: 29271473
DOI: 10.1002/14651858.CD007471.pub3 -
Pain Physician Mar 2017Pain is considered as one of the main symptoms of endometriosis. The treatment for endometriosis remains controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pain is considered as one of the main symptoms of endometriosis. The treatment for endometriosis remains controversial.
OBJECTIVES
The aim of this study is to compare the effect of medical or surgical treatments for pain-relief in patients with endometriosis.
STUDY DESIGN
Systematic review and meta-analysis.
SETTING
Published papers about evaluating pain treatment in endometriosis in PubMed, Scopus, and Google Scholar.
METHODS
After searching all studies evaluating pain treatment in endometriosis in PubMed, Scopus, and Google Scholar, there were 23 related studies, containing 1,847 patients enrolled in our study. We used a variety of tests: fixed and random effects models, Q Cochrane test and I2 index, Egger and Begg tests, forest and funnel plots, Trim and fill method, and meta-regression in our analysis.
RESULTS
There was no statistically significant difference in pain improvement between surgical and medical treatment. Interestingly, pain relief was more prominent longer after treatment. Both clinical trials and cross sectional studies showed higher improvement in pain than cohort studies. High quality studies and lower body mass index (BMI) had a greater effect on pain relief. All studies were heterogeneous, but there was no publication bias.
LIMITATIONS
There was a higher probability of risk of bias in blinding, random sequence generation, and selective outcome reporting in clinical trial studies entered in our meta-analysis.
CONCLUSIONS
Our results could not demonstrate the preference of each medical or surgical treatment effect for dysmenorrhea in endometriosis. Additional data is required before a standardized medical protocol can be offered, but we believe this study may encourage clinicians to consider a less invasive alternative for treating their patients' chronic pelvic pain in the near future.Key words: Endometriosis, pain, meta-analysis, therapy, disease management.
Topics: Clinical Trials as Topic; Cross-Sectional Studies; Endometriosis; Female; Humans; Pain Management; Pelvic Pain
PubMed: 28339429
DOI: No ID Found -
International Journal of Surgery Case... 2016To highlight the laparoscopic management as a feasible treatment option for vaginal cuff dehiscence with intestinal evisceration after hysterectomy.
INTRODUCTION
To highlight the laparoscopic management as a feasible treatment option for vaginal cuff dehiscence with intestinal evisceration after hysterectomy.
PRESENTATION OF CASE
We report a rare case of a 49-year-old postmenopausal woman who was admitted to the emergency department with vaginal herniation of approximately 40cm of small bowel 3 months after total laparoscopic hysterectomy, treated laparoscopically exclusively.
DISCUSSION
The patient underwent a laparoscopic reduction of the protruded mass, inspection of the entire small bowel and closure of the vaginal dehiscence. She was discharged home in a good health and the postoperative course remains uneventful 6 months later. Our systematic review of the literature found 116 cases of vaginal evisceration, which were described as early as 1864. There is no consensus on the ideal method of surgical repair. To our knowledge, only 2% (3 cases) were treated totally laparoscopically and 10% by a combined approach (laparoscopic and vaginal). Although the current evidence does not suggest that one approach is preferred to the others, the laparoscopic approach seems to be the new trend for the management of this surgical emergency.
CONCLUSION
Totally laparoscopic repair in experience hands seems to be a safe approach to cure vaginal evisceration after pelvic surgery.
PubMed: 27337703
DOI: 10.1016/j.ijscr.2016.06.004 -
The Cochrane Database of Systematic... May 2016About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis. Although other reviews have assessed the ability of blood tests to diagnose endometriosis, this is the first review to use Cochrane methods, providing an update on the rapidly expanding literature in this field.
OBJECTIVES
To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis. Specific objectives include:1. To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal, ovarian and deep infiltrating pelvic endometriosis, compared to surgical diagnosis as a reference standard.2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses.
SEARCH METHODS
We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as these databases to 20 April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
SELECTION CRITERIA
We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more blood biomarkers with the findings of surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS
Two authors independently collected and performed a quality assessment of data from each study. For each diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis, and we calculated sensitivity and specificity estimates. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient datasets were available. The predetermined criteria for a clinically useful blood test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of ≥ 0.95 and a specificity of ≥ 0.50, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of ≥ 0.50 and a specificity of ≥ 0.95, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).
MAIN RESULTS
We included 141 studies that involved 15,141 participants and evaluated 122 blood biomarkers. All the studies were of poor methodological quality. Studies evaluated the blood biomarkers either in a specific phase of the menstrual cycle or irrespective of the cycle phase, and they tested for them in serum, plasma or whole blood. Included women were a selected population with a high frequency of endometriosis (10% to 85%), in which surgery was indicated for endometriosis, infertility work-up or ovarian mass. Seventy studies evaluated the diagnostic performance of 47 blood biomarkers for endometriosis (44 single-marker tests and 30 combined tests of two to six blood biomarkers). These were angiogenesis/growth factors, apoptosis markers, cell adhesion molecules, high-throughput markers, hormonal markers, immune system/inflammatory markers, oxidative stress markers, microRNAs, tumour markers and other proteins. Most of these biomarkers were assessed in small individual studies, often using different cut-off thresholds, and we could only perform meta-analyses on the data sets for anti-endometrial antibodies, interleukin-6 (IL-6), cancer antigen-19.9 (CA-19.9) and CA-125. Diagnostic estimates varied significantly between studies for each of these biomarkers, and CA-125 was the only marker with sufficient data to reliably assess sources of heterogeneity.The mean sensitivities and specificities of anti-endometrial antibodies (4 studies, 759 women) were 0.81 (95% confidence interval (CI) 0.76 to 0.87) and 0.75 (95% CI 0.46 to 1.00). For IL-6, with a cut-off value of > 1.90 to 2.00 pg/ml (3 studies, 309 women), sensitivity was 0.63 (95% CI 0.52 to 0.75) and specificity was 0.69 (95% CI 0.57 to 0.82). For CA-19.9, with a cut-off value of > 37.0 IU/ml (3 studies, 330 women), sensitivity was 0.36 (95% CI 0.26 to 0.45) and specificity was 0.87 (95% CI 0.75 to 0.99).Studies assessed CA-125 at different thresholds, demonstrating the following mean sensitivities and specificities: for cut-off > 10.0 to 14.7 U/ml: 0.70 (95% CI 0.63 to 0.77) and 0.64 (95% CI 0.47 to 0.82); for cut-off > 16.0 to 17.6 U/ml: 0.56 (95% CI 0.24, 0.88) and 0.91 (95% CI 0.75, 1.00); for cut-off > 20.0 U/ml: 0.67 (95% CI 0.50 to 0.85) and 0.69 (95% CI 0.58 to 0.80); for cut-off > 25.0 to 26.0 U/ml: 0.73 (95% CI 0.67 to 0.79) and 0.70 (95% CI 0.63 to 0.77); for cut-off > 30.0 to 33.0 U/ml: 0.62 (95% CI 0.45 to 0.79) and 0.76 (95% CI 0.53 to 1.00); and for cut-off > 35.0 to 36.0 U/ml: 0.40 (95% CI 0.32 to 0.49) and 0.91 (95% CI 0.88 to 0.94).We could not statistically evaluate other biomarkers meaningfully, including biomarkers that were assessed for their ability to differentiate endometrioma from other benign ovarian cysts.Eighty-two studies evaluated 97 biomarkers that did not differentiate women with endometriosis from disease-free controls. Of these, 22 biomarkers demonstrated conflicting results, with some studies showing differential expression and others no evidence of a difference between the endometriosis and control groups.
AUTHORS' CONCLUSIONS
Of the biomarkers that were subjected to meta-analysis, none consistently met the criteria for a replacement or triage diagnostic test. A subset of blood biomarkers could prove useful either for detecting pelvic endometriosis or for differentiating ovarian endometrioma from other benign ovarian masses, but there was insufficient evidence to draw meaningful conclusions. Overall, none of the biomarkers displayed enough accuracy to be used clinically outside a research setting. We also identified blood biomarkers that demonstrated no diagnostic value in endometriosis and recommend focusing research resources on evaluating other more clinically useful biomarkers.
Topics: Adult; Autoantibodies; Biomarkers; CA-125 Antigen; CA-19-9 Antigen; Endometriosis; Endometrium; Female; Humans; Interleukin-6; Ovarian Diseases; Pelvis; Peritoneal Diseases; Randomized Controlled Trials as Topic
PubMed: 27132058
DOI: 10.1002/14651858.CD012179 -
The Cochrane Database of Systematic... Mar 2016Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. One potential strategy is to surgically stage all women with suspicious ovarian masses, without any histological information during surgery. This avoids incomplete staging, but puts more women at risk of potential surgical over-treatment.A second strategy is to perform a two-stage procedure to remove the pelvic mass and subject it to paraffin sectioning, which involves formal tissue fixing with formalin and paraffin embedding, prior to ultrathin sectioning and multiple site sampling of the tumour. Surgeons may then base further surgical staging on this histology, reducing the rate of over-treatment, but conferring additional surgical and anaesthetic morbidity.A third strategy is to perform a rapid histological analysis on the ovarian mass during surgery, known as 'frozen section'. Tissues are snap frozen to allow fine tissue sections to be cut and basic histochemical staining to be performed. Surgeons can perform or avoid the full surgical staging procedure depending on the results. However, this is a relatively crude test compared to paraffin sections, which take many hours to perform. With frozen section there is therefore a risk of misdiagnosing malignancy and understaging women subsequently found to have a presumed early-stage malignancy (false negative), or overstaging women without a malignancy (false positive). Therefore it is important to evaluate the accuracy and usefulness of adding frozen section to the clinical decision-making process.
OBJECTIVES
To assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard).
SEARCH METHODS
We searched MEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015) and relevant Cochrane registers.
SELECTION CRITERIA
Studies that used frozen section for intraoperative diagnosis of ovarian masses suspicious of malignancy, provided there was sufficient data to construct 2 x 2 tables. We excluded articles without an available English translation.
DATA COLLECTION AND ANALYSIS
Authors independently assessed the methodological quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) domains: patient selection, index test, reference standard, flow and timing. Data extraction converted 3 x 3 tables of per patient results presented in articles into 2 x 2 tables, for two index test thresholds.
MAIN RESULTS
All studies were retrospective, and the majority reported consecutive sampling of cases. Sensitivity and specificity results were available from 38 studies involving 11,181 participants (3200 with invasive cancer, 1055 with borderline tumours and 6926 with benign tumours, determined by paraffin section as the reference standard). The median prevalence of malignancy was 29% (interquartile range (IQR) 23% to 36%, range 11% to 63%). We assessed test performance using two thresholds for the frozen section test. Firstly, we used a test threshold for frozen sections, defining positive test results as invasive cancer and negative test results as borderline and benign tumours. The average sensitivity was 90.0% (95% confidence interval (CI) 87.6% to 92.0%; with most studies typically reporting range of 71% to 100%), and average specificity was 99.5% (95% CI 99.2% to 99.7%; range 96% to 100%).Similarly, we analysed sensitivity and specificity using a second threshold for frozen section, where both invasive cancer and borderline tumours were considered test positive and benign cases were classified as negative. Average sensitivity was 96.5% (95% CI 95.5% to 97.3%; typical range 83% to 100%), and average specificity was 89.5% (95% CI 86.6% to 91.9%; typical range 58% to 99%).Results were available from the same 38 studies, including the subset of 3953 participants with a frozen section result of either borderline or invasive cancer, based on final diagnosis of malignancy. Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity. Average sensitivity was 94.0% (95% CI 92.0% to 95.5%; range 73% to 100%), and average specificity was 95.8% (95% CI 92.4% to 97.8%; typical range 81% to 100%).Our additional analyses showed that, if the frozen section showed a benign or invasive cancer, the final diagnosis would remain the same in, on average, 94% and 99% of cases, respectively.In cases where the frozen section diagnosis was a borderline tumour, on average 21% of the final diagnoses would turn out to be invasive cancer.In three studies, the same pathologist interpreted the index and reference standard tests, potentially causing bias. No studies reported blinding pathologists to index test results when reporting paraffin sections.In heterogeneity analyses, there were no statistically significant differences between studies with pathologists of different levels of expertise.
AUTHORS' CONCLUSIONS
In a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative).If a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed.The largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients.
Topics: Diagnostic Errors; False Negative Reactions; False Positive Reactions; Female; Frozen Sections; Humans; Intraoperative Period; Neoplasm Staging; Ovarian Neoplasms; Paraffin Embedding; Pelvic Neoplasms; Retrospective Studies; Sensitivity and Specificity
PubMed: 26930463
DOI: 10.1002/14651858.CD010360.pub2 -
International Urogynecology Journal Nov 2015Pelvic organ prolapse (POP) is a common condition with multifactorial etiology. The purpose of this systematic review was to provide an overview of literature on risk... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Pelvic organ prolapse (POP) is a common condition with multifactorial etiology. The purpose of this systematic review was to provide an overview of literature on risk factors for POP and POP recurrence.
METHODS
PubMed and Embase were searched with "pelvic organ prolapse" combined with "recurrence" and combined with "risk factors," with Medical Subject Headings and Thesaurus terms and text words variations until 4 August 2014, without language or publication date restrictions. Only cohort or cross-sectional studies carried out in western developed countries containing multivariate analyses and with a definition of POP based on anatomical references were included. POP recurrence had to be defined as anatomical recurrence after native tissue repair without mesh. Follow-up after surgery should have been at least 1 year. Articles were excluded if POP was not a separate entity or if it was unclear whether the outcome was primary POP or recurrence.
RESULTS
PubMed and Embase revealed 2,988 and 4,449 articles respectively. After preselection, 534 articles were independently evaluated by two researchers, of which 15 met the selection criteria. In 10 articles on primary POP, 30 risk factors were investigated. Parity, vaginal delivery, age, and body mass index (BMI) were significantly associated in at least two articles. In 5 articles on POP recurrence, 29 risk factors were investigated. Only preoperative stage was significantly associated in at least two articles.
CONCLUSION
Parity, vaginal delivery, age, and BMI are risk factors for POP and preoperative stage is a risk factor for POP recurrence.
Topics: Female; Humans; Pelvic Organ Prolapse; Recurrence; Risk Factors
PubMed: 25966804
DOI: 10.1007/s00192-015-2695-8