DNA and RNA Alterations Associated with Colorectal Peritoneal Metastases: A Systematic Review.

BACKGROUND: As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment. AIM: To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied. METHODS: A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines. RESULTS: Overall, 32 studies with 18,906 patients were included. BRAF mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers. CONCLUSION: An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of BRAF mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required.

The effectiveness of health education interventions on cervical cancer prevention in Africa: A systematic review.

Low levels of knowledge and awareness on cervical cancer play a role in limiting cervical cancer prevention uptake. This systematic review aimed to identify effective educational interventions to increase cervical cancer awareness, knowledge, and subsequently screening or vaccination uptake in African women. A literature search was conducted in Medline and EMBASE databases. We examined original, peer-reviewed English literature published between 2005 and 2020. Nineteen studies examining health education interventions' impact on awareness, knowledge, and screening or vaccination uptake in African women were included. Ten studies were controlled trials, nine performed pre- and post-measurements in one group. Most studies were published between 2015 and 2020 (86%), many were from Nigeria (47%). Studies were mostly set up in communities and schools. The most frequently used intervention was lectures, alone or combined with videos and practical demonstrations. Sixteen studies evaluated knowledge or awareness, and all showed a statistically significant improvement following the intervention. Of the ten studies that evaluated screening uptake, either as the single outcome or combined with knowledge or awareness, six found a significant rise in screening uptake after intervention. Educational interventions increased knowledge and awareness in African women, some boosted uptake of cervical cancer screening, especially when using peer health educators and culturally tailored methods. Innovative approaches such as self-collected HPV testing and mHealth also demonstrated a potential to increase uptake of screening. More research is needed to identify and analyse barriers to screening uptake, which can still be present even after a successful educational intervention.

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review.

For peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been developed to deliver intraperitoneal chemotherapy for a prolonged period, suitable for a larger patient group. These drug delivery systems (DDSs) seem promising in the experimental setting. Many types of DDSs have been explored in a variety of animal models, using different cytostatics. This review aimed to provide an overview of animal studies using DDSs containing cytostatics for the treatment of gastro-intestinal PM and identify the most promising therapeutic combinations. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) guidelines. The 35 studies included revealed similar results: using a cytostatic-loaded DDS to treat PM resulted in a higher median survival time (MST) and a lower intraperitoneal tumor load compared to no treatment or treatment with a 'free' cytostatic or an unloaded DDS. In 65% of the studies, the MST was significantly longer and in 24% the tumor load was significantly lower in the animals treated with cytostatic-loaded DDS. The large variety of experimental setups made it impossible to identify the most promising DDS-cytostatic combination. In most studies, the risk of bias was unclear due to poor reporting. Future studies should focus more on improving the clinical relevance of the experiments, standardizing the experimental study setup, and improving their methodological quality and reporting.

Diagnostic Performance of Electronic Noses in Cancer Diagnoses Using Exhaled Breath: A Systematic Review and Meta-analysis.

Importance: There has been a growing interest in the use of electronic noses (e-noses) in detecting volatile organic compounds in exhaled breath for the diagnosis of cancer. However, no systematic evaluation has been performed of the overall diagnostic accuracy and methodologic challenges of using e-noses for cancer detection in exhaled breath. Objective: To provide an overview of the diagnostic accuracy and methodologic challenges of using e-noses for the detection of cancer. Data Sources: An electronic search was performed in the PubMed and Embase databases (January 1, 2000, to July 1, 2021). Study Selection: Inclusion criteria were the following: (1) use of e-nose technology, (2) detection of cancer, and (3) analysis of exhaled breath. Exclusion criteria were (1) studies published before 2000; (2) studies not performed in humans; (3) studies not performed in adults; (4) studies that only analyzed biofluids; and (5) studies that exclusively used gas chromatography-mass spectrometry to analyze exhaled breath samples. Data Extraction and Synthesis: PRISMA guidelines were used for the identification, screening, eligibility, and selection process. Quality assessment was performed using Quality Assessment of Diagnostic Accuracy Studies 2. Generalized mixed-effects bivariate meta-analysis was performed. Main Outcomes and Measures: Main outcomes were sensitivity, specificity, and mean area under the receiver operating characteristic curve. Results: This review identified 52 articles with a total of 3677 patients with cancer. All studies were feasibility studies. The sensitivity of e-noses ranged from 48.3% to 95.8% and the specificity from 10.0% to 100.0%. Pooled analysis resulted in a mean (SE) area under the receiver operating characteristic curve of 94% (95% CI, 92%-96%), a sensitivity of 90% (95% CI, 88%-92%), and a specificity of 87% (95% CI, 81%-92%). Considerable heterogeneity existed among the studies because of differences in the selection of patients, endogenous and exogenous factors, and collection of exhaled breath. Conclusions and Relevance: Results of this review indicate that e-noses have a high diagnostic accuracy for the detection of cancer in exhaled breath. However, most studies were feasibility studies with small sample sizes, a lack of standardization, and a high risk of bias. The lack of standardization and reproducibility of e-nose research should be addressed in future research.

Observed versus modelled lifetime overall survival of targeted therapies and immunotherapies for advanced non-small cell lung cancer patients - A systematic review.

Outcomes used for the effectiveness (median) and cost-effectiveness (mean) on overall survival (OS) are different and can vary from one another. Therefore, we compared median and mean OS gains of targeted therapies and immunotherapies for stage IIIB/IV Non-small cell lung cancer and explored underlying aspect. Eligible trials were searched in PubMed, survival curves were digitized, and parametric survival models fitted to model the mean OS. Twenty-seven trials were found for targeted therapies (n = 17) and immunotherapies (n = 10). Differences between median and mean OS gains in months ranged from -2.8 to 6.8 and -4.9 to 0.3 for two different subgroups of targeted therapies, and -2.4 to 11.4 for immunotherapies. The mean OS gain was substantially larger for most immunotherapy trials, due to relatively long survival. Median and mean OS gains did not differ for targeted therapies. Our findings imply a potential discrepancy between the estimates of effectiveness and cost-effectiveness of cancer treatments.

European association for endoscopic surgery (EAES) consensus statement on single-incision endoscopic surgery.

BACKGROUND: Laparoscopic surgery changed the management of numerous surgical conditions. It was associated with many advantages over open surgery, such as decreased postoperative pain, faster recovery, shorter hospital stay and excellent cosmesis. Since two decades single-incision endoscopic surgery (SIES) was introduced to the surgical community. SIES could possibly result in even better postoperative outcomes than multi-port laparoscopic surgery, especially concerning cosmetic outcomes and pain. However, the single-incision surgical procedure is associated with quite some challenges. METHODS: An expert panel of surgeons has been selected and invited to participate in the preparation of the material for a consensus meeting on the topic SIES, which was held during the EAES congress in Frankfurt, June 16, 2017. The material presented during the consensus meeting was based on evidence identified through a systematic search of literature according to a pre-specified protocol. Three main topics with respect to SIES have been identified by the panel: (1) General, (2) Organ specific, (3) New development. Within each of these topics, subcategories have been defined. Evidence was graded according to the Oxford 2011 Levels of Evidence. Recommendations were made according to the GRADE criteria. RESULTS: In general, there is a lack of high level evidence and a lack of long-term follow-up in the field of single-incision endoscopic surgery. In selected patients, the single-incision approach seems to be safe and effective in terms of perioperative morbidity. Satisfaction with cosmesis has been established to be the main advantage of the single-incision approach. Less pain after single-incision approach compared to conventional laparoscopy seems to be considered an advantage, although it has not been consistently demonstrated across studies. CONCLUSIONS: Considering the increased direct costs (devices, instruments and operating time) of the SIES procedure and the prolonged learning curve, wider acceptance of the procedure should be supported only after demonstration of clear benefits.

Sexual function after treatment for sacrococcygeal teratoma during childhood.

BACKGROUND: Children treated for sacrococcygeal teratoma (SCT) may suffer from sexual dysfunction later in life because of the extended pelvic surgery performed, however, structured evaluations have not been performed yet. METHODS: The Female Sexual Function Index (FSFI), the International Index of Erectile Function (IIEF) and the Body Image Questionnaire (BIQ) were sent to patients (≥18years) treated for SCT in the Dutch pediatric surgical centers after 1970. RESULTS: Forty-five of 76 patients returned the questionnaires; 28 women (median age 27.3years, range 18.3-41.0) and seven men (median age 22.0years, range 19.1-36.5) were eligible for analysis. The FSFI and IIEF results were compared to healthy controls. Female patients scored significantly lower on the desire (p=0.014), arousal (p=0.013) and lubrication domain (p=0.019). FSFI total-scores of female patients were significantly lower compared to controls [median 30.5 (IQR 28.6-31.4) vs. median 32.4 (IQR 30.6-33.45) p≤0.001] but were above the threshold value for sexual dysfunction. Males reported normal erectile function and penetration ability with normal ejaculation. Females had significant lower BIQ results compared to males; BIQ-cosmesis scores were moderately correlated to the FSFI-desire score (r=-0.37, p=0.028). CONCLUSION: SCT resection in girls may result in diminished sexual function at adult age with worse self-perceived body image. The possibility of sexual complaints should be integrated in the surveillance strategies for these patients.

Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease.

OBJECTIVES: Transoral incisionless fundoplication (TIF) was developed in an attempt to create a minimally invasive endoscopic procedure that mimics antireflux surgery. The objective of this trial was to evaluate effectiveness of TIF compared with proton pump inhibition in a population consisting of gastroesophageal reflux disease (GERD) patients controlled with proton pump inhibitors (PPIs) who opted for an endoscopic intervention over lifelong drug dependence. METHODS: Patients with chronic GERD were randomized (2:1) for TIF or continuation of PPI therapy. American Society of Anesthesiologists >2, body mass index >35 kg/m(2), hiatal hernia >2 cm, and esophageal motility disorders were exclusion criteria. Primary outcome measure was GERD-related quality of life. Secondary outcome measures were esophageal acid exposure, number of reflux episodes, PPI usage, appearance of the gastroesophageal valve, and healing of reflux esophagitis. Crossover for the PPI group was allowed after 6 months. RESULTS: A total of 60 patients (TIF n=40, PPI n=20, mean body mass index 26 kg/m(2), 37 male) were included. At 6 months, GERD symptoms were more improved in the TIF group compared with the PPI group (P<0.001), with a similar improvement of distal esophageal acid exposure (P=0.228) compared with baseline. The pH normalization for TIF group and PPI group was 50% and 63%, respectively. All patients allocated for PPI treatment opted for crossover. At 12 months, quality of life remained improved after TIF compared with baseline (P<0.05), but no improvement in esophageal acid exposure compared with baseline was found (P=0.171) and normalization of pH was accomplished in only 29% in conjunction with deteriorated valve appearances at endoscopy and resumption of PPIs in 61%. CONCLUSION: Although TIF resulted in an improved GERD-related quality of life and produced a short-term improvement of the antireflux barrier in a selected group of GERD patients, no long-term objective reflux control was achieved.

The cost-effectiveness of particle therapy in non-small cell lung cancer: exploring decision uncertainty and areas for future research.

PURPOSE: To review and synthesize all available evidence in order to explore the cost-effectiveness of particle therapy (carbon-ions, protons) compared to the best current treatments for non-small-cell lung cancer (NSCLC), and the value of additional research. The present study focuses on stage I NSCLC, as no data is available for more advanced stages. METHODS: A probabilistic decision-analytic Markov model was constructed to synthesize all available evidence. Comparative treatments were carbon-ions, protons, conventional radiotherapy (CRT) and stereotactic radiotherapy (SBRT) for inoperable stage I NSCLC; and carbon-ions and SBRT for operable stage I NSCLC. The expected value of perfect information (EVPI) was calculated to support research decisions. RESULTS: For inoperable stage I NSCLC, carbon-ion therapy costed euro 67.257 per quality-adjusted-life-year gained compared to SBRT. Both treatments dominated protons and CRT. Considerable uncertainty surrounded these results, resulting in a high EVPI. For operable stage I NSCLC SBRT dominated carbon-ion therapy. CONCLUSIONS: Due to the considerable uncertainty in stage I NSCLC, and the lack of data on more advanced stages, it is recommended not to adopt particle therapy as standard treatment in NSCLC yet. More evidence is needed to reduce the decision uncertainty and to support evidence-based treatment decisions. It might be worthwhile to invest in a particle facility for clinical research. Future research should also weigh the investment risk, value of information and costs of delay.

How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons.

PURPOSE: Particle therapy has potentially a better therapeutic ratio than photon therapy. However, investment costs are much higher. This study provides an estimation and comparison of the costs of these therapies. METHODS: Within an extensive analytical framework capital and operational costs, cost per fraction, and four tumor specific treatment costs are calculated for three facilities: combined carbon-ion/proton, proton-only, and photon. RESULTS: Capital costs for the combined, proton-only and photon facilities are: euro 138.6 million, euro 94.9 million, euro 23.4 million. Total costs per year are: euro 36.7 million, euro 24.9 million, euro 9.6 million. Cost per fraction is: euro 1128 (euro 877-1974), euro 743 (euro 578-1300), euro 233 (euro 190-407). Cost ratio particle/photon therapy is 4.8 for the combined and 3.2 for the proton-only facility. Particle treatment costs vary from euro 10,030 (c-ion: lung cancer) to euro 39,610 (proton: head & neck tumors). Cost difference between particle and photon therapies is relatively small for lung and prostate cancer, larger for skull-base chordoma and head & neck tumors. CONCLUSION: Investment costs are highest for the combined carbon-ion/proton facility and lowest for the photon facility. Cost differences become smaller when total costs per year and specific treatment costs are compared. Lower fractionation schedule of particle therapy might further reduce its costs.