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Journal of Investigative Medicine : the... Feb 2021Several published studies have evaluated the safety and effectiveness of oral and intravenous tacrolimus for the management of patients with inflammatory bowel disease... (Review)
Review
Several published studies have evaluated the safety and effectiveness of oral and intravenous tacrolimus for the management of patients with inflammatory bowel disease (IBD). However, little is known about the effectiveness of topical tacrolimus in this patient population. The aim of this systematic review was to evaluate the current state of literature to evaluate the safety and effectiveness of rectal administration of topical tacrolimus, in the form of suppository, ointment, and/or enema in patients with ulcerative proctitis, perianal Crohn's disease (CD), and chronic refractory pouchitis. Electronic database searches were conducted in international databases since their inception until February 2020. Study subjects were categorized into three groups: topical tacrolimus for patients with proctitis, perianal CD, and chronic refractory pouchitis. The primary end point of this study was the remission rate. Secondary end points were response rate and the incidence of AEs. Eleven studies were included in the final assessment in this systematic review. This provided information from 188 patients. Tacrolimus was administered topically as suppositories, ointment, or enema. Clinical remission was achieved in 57.1%, 57.14%, and 70.0% in patients with proctitis, fistulizing perianal CD, and chronic pouchitis. The most commonly reported side effect was perianal itching and burning. Reversible nephrotoxicity occurred in a single patient. No clear correlation was found between blood levels and clinical outcomes. Topical tacrolimus is effective for a subset of patients with IBD. The adverse effects were minimal and tolerable. Well-designed randomized clinical trials are warranted to establish the appropriate dose and administration method.
PubMed: 33622709
DOI: 10.1136/jim-2020-001699 -
Clinical Colorectal Cancer Mar 2021Prediction of outcome in patients with colorectal cancer (CRC) is challenging as a result of lack of a robust biomarker and heterogeneity between and within tumors. The...
Prediction of outcome in patients with colorectal cancer (CRC) is challenging as a result of lack of a robust biomarker and heterogeneity between and within tumors. The aim of this review was to assess the current possibilities and limitations of radiomics (on computed tomography [CT], magnetic resonance imaging [MRI], and positron emission tomography [PET]) for the prediction of treatment outcome and long-term outcome in CRC. Medline/PubMed was searched up to August 2020 for studies that used radiomics for the prediction of response to treatment and survival in patients with CRC (based on pretreatment imaging). The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and Radiomics Quality Score (RQS) were used for quality assessment. A total of 76 studies met the inclusion criteria and were included for further analysis. Radiomics analyses were performed on MRI in 41 studies, on CT in 30 studies, and on F-FDG-PET/CT in 10 studies. Heterogeneous results were reported regarding radiomics methods and included features. High-quality studies (n = 13), consisting mainly of MRI-based radiomics to predict response in rectal cancer, were able to predict response with good performance. Radiomics literature in CRC is highly heterogeneous, but it nonetheless holds promise for the prediction of outcome. The most evidence is available for MRI-based radiomics in rectal cancer. Future radiomics research in CRC should focus on independent validation of existing models rather than on developing new models.
Topics: Disease-Free Survival; Fluorodeoxyglucose F18; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prognosis; Rectal Neoplasms; Rectum; Risk Assessment; Treatment Outcome
PubMed: 33349519
DOI: 10.1016/j.clcc.2020.11.001 -
JAMA Network Open Dec 2020Standard therapy for locally advanced rectal cancer includes concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A). An alternative... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Standard therapy for locally advanced rectal cancer includes concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A). An alternative strategy known as total neoadjuvant therapy (TNT) involves administration of CRT plus neoadjuvant chemotherapy before surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases. A comparison of these 2 approaches has not been systematically reviewed previously.
OBJECTIVE
To determine the differences in rates of pathologic complete response (PCR), disease-free and overall survival, sphincter-preserving surgery, and ileostomy between patients receiving TNT vs standard CRT plus A.
DATA SOURCES
MEDLINE (via PubMed) and Embase (via OVID) were searched from inception through July 1, 2020, for the following terms: anal/anorectal neoplasms OR anal/anorectal cancer AND total neoadjuvant treatment OR total neoadjuvant therapy. Only studies in English were included.
STUDY SELECTION
Randomized clinical trials or prospective/retrospective cohort studies comparing outcomes in patients with locally advanced rectal cancer who received TNT vs CRT plus A.
DATA EXTRACTION AND SYNTHESIS
Data regarding the first author, publication year, location, sample size, and rates of PCR, sphincter-preserving surgery, ileostomy, and disease-free and overall survival were extracted using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
Rates of PCR, sphincter-preserving surgery, ileostomy, and disease-free and overall survival.
RESULTS
After reviewing 2165 reports, 7 unique studies including a total of 2416 unique patients, of whom 1206 received TNT, were selected. The median age for the patients receiving TNT ranged from 57 to 69 years, with 58% to 73% being male. The pooled prevalence of PCR was 29.9% (range, 17.2%-38.5%) in the TNT group and 14.9% (range, 4.2%-21.3%) in the CRT plus A group. Total neoadjuvant therapy was associated with a higher chance of achieving a PCR (odds ratio [OR], 2.44; 95% CI, 1.99-2.98). No statistically significant difference in the proportion of sphincter-preserving surgery (OR, 1.06; 95% CI, 0.73-1.54) or ileostomy (OR, 1.05; 95% CI, 0.76-1.46) between recipients of TNT and CRT plus A was observed. Only 3 studies presented data on disease-free survival, and pooled analysis showed significantly higher odds of improved disease-free survival in patients who received TNT (OR, 2.07; 95% CI, 1.20-3.56; I2 = 49%). Data on overall survival were not consistently reported.
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that TNT is a promising strategy in locally advanced rectal cancer, with superior rates of PCR compared with standard therapy. However, the long-term effect on disease recurrence and overall survival needs to be explored in future studies.
Topics: Chemoradiotherapy; Humans; Ileostomy; Neoadjuvant Therapy; Neoplasm Micrometastasis; Neoplasm Staging; Proctectomy; Rectal Neoplasms; Survival Analysis
PubMed: 33326026
DOI: 10.1001/jamanetworkopen.2020.30097 -
World Journal of Gastrointestinal... Nov 2020Endoscopic retrograde cholangiopancreatography (ERCP) is the primary therapeutic procedure for the treatment of diseases affecting the biliary tree and pancreatic duct....
BACKGROUND
Endoscopic retrograde cholangiopancreatography (ERCP) is the primary therapeutic procedure for the treatment of diseases affecting the biliary tree and pancreatic duct. Although the therapeutic success rate of ERCP is high, the procedure can cause complications, such as acute pancreatitis [post-ERCP pancreatitis (PEP)], bleeding and perforation.
AIM
To assess the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in preventing PEP during follow-up.
METHODS
Databases such as MEDLINE, EMBASE and Cochrane Central Library were searched. Only randomized controlled trials (RCTs) comparing the efficacy of NSAIDs and placebo for the prevention of PEP were included. Outcomes evaluated included the incidence of PEP, severity of pancreatitis, route of administration, types, dose, and timing of administration of NSAIDs.
RESULTS
Twenty-six RCTs were considered eligible with a total of 8143 patients analyzed. Overall, 4020 patients used NSAIDs before ERCP and 4123 did not use NSAIDs (control group). Ultimately, 298 cases of post-ERCP acute pancreatitis were diagnosed in the NSAID group and 484 cases in the placebo group. The risk of PEP was lower in the NSAID group risk difference (RD): -0.04; 95% confidence interval (CI): -0.07 to - 0.03; number needed to treat (NNT), 25; < 0.05. NSAID use effectively prevented mild pancreatitis compared to placebo use (2.5% 4.1%; 95%CI: -0.05 to -0.01; NNT, 33; < 0.05), but information on moderate PEP and severe PEP could not be fully elucidated. Only rectal administration reduced the incidence of PEP with RD: -0.06; 95%CI: -0.08 to -0.04; NNT, 17; < 0.05). Furthermore, only the use of diclofenac or indomethacin was effective in preventing PEP, at a dose of 100 mg, which must be administered before performing ERCP.
CONCLUSION
Rectal administration of diclofenac and indomethacin significantly reduced the risk of developing mild PEP. Additional RCTs are needed to compare the efficacy between NSAID routes of administration in preventing PEP.
PubMed: 33269056
DOI: 10.4253/wjge.v12.i11.469 -
Journal of Gastroenterology and... Jun 2021Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde... (Meta-Analysis)
Meta-Analysis
Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.
BACKGROUND AND AIMS
Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP.
METHODS
We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents.
RESULTS
The NMA included 24 studies evaluating 14 regimens in 11 321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin + lactated Ringer's solution, followed by diclofenac + nitrate and indomethacin + normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group.
CONCLUSIONS
Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.
Topics: Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Diclofenac; Drug Therapy, Combination; Female; Humans; Indomethacin; Male; Nitrates; Pancreatitis; Postoperative Complications; Ringer's Lactate; Treatment Outcome
PubMed: 33068012
DOI: 10.1111/jgh.15303 -
AJR. American Journal of Roentgenology Sep 2021Scarce evidence exists on the diagnostic benefit of enteric contrast administration for abdominopelvic CT performed in the setting of penetrating trauma. The purpose... (Comparative Study)
Comparative Study Meta-Analysis
Scarce evidence exists on the diagnostic benefit of enteric contrast administration for abdominopelvic CT performed in the setting of penetrating trauma. The purpose of this systematic review and meta-analysis is to compare the diagnostic accuracy of CT using enteric contrast material with that of CT not using enteric contrast material in penetrating traumatic abdominopelvic injury in adults. A protocol was registered a priori (PROSPERO CRD42019139613). MEDLINE and EMBASE databases were searched until June 25, 2019. Studies were included that evaluated the diagnostic accuracy of abdominopelvic CT either with or without enteric (oral and/or rectal) contrast material in patients presenting with penetrating traumatic injury. Relevant study data metrics and risk of bias were assessed. Bivariate random-effects meta-analyses and meta-regression modeling were performed to assess and compare diagnostic accuracies. From an initial sample of 829 studies, 12 studies were included that reported on 1287 patients with penetrating injury (389 with confirmed bowel, mesenteric, or other abdominopelvic organ injury). The enteric contrast material group (seven studies; 506 patients; 124 patients with confirmed penetrating injury) showed a sensitivity of 83.8% (95% CI, 73.7-90.5%) and specificity of 93.8% (95% CI, 83.6-97.8%). The group without enteric contrast administration (six studies; 781 patients; 265 patients with confirmed penetrating injury) showed a sensitivity of 93.0% (95% CI, 86.8-96.4%) and a specificity of 90.3% (95% CI, 81.4-95.2%). No statistically significant difference was identified for sensitivity ( = .07) or specificity ( = .37) between the groups with and without enteric contrast material according to meta-regression. Nine of 12 studies showed risk of bias in at least one QUADAS-2 domain (most frequently limited reporting of blinding of radiologists or lack of blinding of radiologists, insufficient clinical follow-up for the reference standard, and limited reporting of sampling methods). The use of enteric contrast material for CT does not provide a significant diagnostic benefit for penetrating traumatic injury. Eliminating enteric contrast administration for CT in penetrating traumatic injury can prevent delays in imaging and surgery and reduce cost.
Topics: Abdomen; Abdominal Injuries; Adult; Contrast Media; Humans; Pelvis; Radiographic Image Enhancement; Reproducibility of Results; Sensitivity and Specificity; Tomography, X-Ray Computed; Wounds, Penetrating
PubMed: 32997519
DOI: 10.2214/AJR.20.24636 -
British Journal of Cancer Dec 2020It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a non-linear dose-dependent relationship is present.
DESIGN
Three electronic databases and a trial platform were searched for all relevant studies, from inception until February 2020, without restrictions. Random-effects meta-analyses provided pooled effect-sizes (ES) with 95% confidence intervals (CI). Dose-response analyses modelling the relationship between number of days exposed to antibiotics and CRC risk were extended to non-linear multivariable random-effects models.
RESULTS
Of 6483 identified publications ten were eligible, including 4.1 million individuals and over 73,550 CRC cases. The pooled CRC risk was increased among individuals who ever-used antibiotics (ES = 1.17, 95%CI 1.05-1.30), particularly for broad-spectrum antibiotics (ES = 1.70, 95%CI 1.26-2.30), but not for narrow-spectrum antibiotic (ES = 1.11, 95% 0.93-1.32). The dose-response analysis did not provide strong evidence of any particular dose-response association, and the risk patterns were rather similar for colon and rectal cancer.
DISCUSSION
The antibiotic use associated CRC risk seemingly differs between broad- and narrow-spectrum antibiotics, and possibly within the colorectal continuum. It remains unclear whether this association is causal, requiring more mechanistic studies and further clarification of drug-microbiome interactions.
Topics: Anti-Bacterial Agents; Colonic Neoplasms; Colorectal Neoplasms; Confidence Intervals; Databases as Topic; Dose-Response Relationship, Drug; Gastrointestinal Microbiome; Humans; Rectal Neoplasms; Risk Factors
PubMed: 32968205
DOI: 10.1038/s41416-020-01082-2 -
World Journal of Urology Jun 2021Radiation dose to the rectum in prostate brachytherapy (PBT) can be reduced by the use of polyethylene glycol (PEG) hydrogel spacers. This reduces the rate of rectal...
INTRODUCTION
Radiation dose to the rectum in prostate brachytherapy (PBT) can be reduced by the use of polyethylene glycol (PEG) hydrogel spacers. This reduces the rate of rectal toxicity and allows dose escalation to the prostate. Our objectives were to provide an overview of technique for injection of a PEG hydrogel spacer, reduction in rectal dosimetry, gastrointestinal toxicity and potential complications.
METHODS
We systematically reviewed the role of PEG hydrogel spacers in PBT using the Cochrane and PRISMA methodology for all English-language articles from January 2013 to December 2019. Data was extracted for type of radiotherapy, number of patients, type of PEG-hydrogel used, mean prostate-rectum separation, rectal dosimetry, acute and late GI toxicity, procedure-related complications and the technique used for hydrogel insertion.
RESULTS
Nine studies (671 patients and 537 controls) met our inclusion criteria. Of these 4 used DuraSeal and 5 used SpaceOAR. The rectal spacing achieved varied between 7.7-16 mm. Failure of hydrogel insertion was seen only in 12 patients, mostly related to failure of hydrodissection in patients undergoing salvage PBT. Where reported, the rectal D2 cc was reduced by between 21.6 and 52.6% and the median rectal V75% cc was reduced by between 91.8-100%. Acute GI complications were mostly limited to grade 1 or 2 toxicity (n = 153, 33.7%) with low levels of grade 3 or 4 toxicity (n = 1, 0.22%). Procedure-related complications were limited to tenesmus (0.14%), rectal discomfort (1.19%), and bacterial prostatitis (0.44%).
CONCLUSIONS
PEG hydrogel spacers are safe to insert. Gel insertion is easy, fast and has a low rate of failure. These studies convincingly demonstrate a significant reduction in rectal dosimetry. Although the results of spacers in reducing rectal toxicity is promising, these need to be confirmed in prospective randomised trial.
Topics: Brachytherapy; Humans; Hydrogels; Injections; Male; Polyethylene Glycols; Prostatic Neoplasms; Radiotherapy Dosage
PubMed: 32840655
DOI: 10.1007/s00345-020-03414-6 -
Journal of Medical Virology Feb 2021Testing is one of the commendable measures for curbing the spread of coronavirus disease (COVID-19). But, it should be done using the most appropriate specimen and an... (Meta-Analysis)
Meta-Analysis
Testing is one of the commendable measures for curbing the spread of coronavirus disease (COVID-19). But, it should be done using the most appropriate specimen and an accurate diagnostic test such as real-time reverse transcription-polymerase chain reaction (qRT-PCR). Therefore, a systematic review was conducted to determine the positive detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different clinical specimens using qRT-PCR. A total of 8136 pooled clinical specimens were analyzed to detect SARS-CoV-2, the majority were nasopharyngeal swabs (69.6%). A lower respiratory tract (LRT) specimens had a positive rate (PR) of 71.3% (95% confidence interval [CI]: 60.3%-82.3%) while no virus was detected in the urinogenital specimens. Bronchoalveolar lavage fluid (BLF) specimen had the PR of 91.8% (95% CI: 79.9%-103.7%), followed by rectal swabs; 87.8% (95% CI: 78.6%-96.9%) then sputum; 68.1% (95% CI: 56.9%-79.4%). A low PR was observed in oropharyngeal swabs; 7.6% (95% CI: 5.7%-9.6%) and blood samples; 1.0% (95% CI: -0.1%-2.1%) whereas no SARS-CoV-2 was detected in urine samples. Feces had a PR of 32.8% (95% CI:1 5.8%-49.8%). Nasopharyngeal swab, a widely used specimen had a PR of 45.5% (95% CI: 31.2%-59.7%). In this study, SARS-CoV-2 was highly detected in LRT specimens while no virus was detected in urinogenital specimens. BLF had the highest PR followed by rectal swab then sputum. Nasopharyngeal swab which is widely used had moderate PR. Low PR was recorded in oropharyngeal swab and blood samples while no virus was found in urine samples. Last, the virus was detected in feces, suggesting SARS-CoV-2 transmission by the fecal route.
Topics: Bronchoalveolar Lavage Fluid; COVID-19; COVID-19 Testing; Feces; Humans; Nasopharynx; Oropharynx; RNA, Viral; Real-Time Polymerase Chain Reaction; SARS-CoV-2; Specimen Handling; Sputum
PubMed: 32706393
DOI: 10.1002/jmv.26349 -
International Journal of Clinical... Sep 2020Neo-adjuvant chemoradiation (NA-CRT) is the standard of management for the locally advanced rectal cancer (LARC), achieving very low rates of local recurrence (LR)....
Neo-adjuvant chemoradiation (NA-CRT) is the standard of management for the locally advanced rectal cancer (LARC), achieving very low rates of local recurrence (LR). However, NA-CRT fails to control distant recurrence and improve survival, whilst it is associated with increased postoperative morbidity and increased acute and late toxicity. In recent years, neo-adjuvant chemotherapy (NACTx) appears in the literature as an alternative to NA-CRT in patients with LARC. In the present study, the authors review all current evidence on the specific subject. Following a systematic search of the literature, 25 studies were identified reporting on short- or long-term outcomes of NACTx for LARC. Seventeen studies were prospective or retrospective series, and 8 comparative. Of the comparative studies, one was a randomized control trial (RCT) comparing NACTx to NA-CRT and to the combination of NACTx/NA-CRT, and another a non-randomized study comparing NACTx to NA-CRT. Chemotherapeutic regimens were 5-fluoropyrimidine and oxaliplatin based. In some of them, irinotecan or/and bevacizumab was added. A pooled analysis showed that NACTx is associated with a mean anastomotic leak rate of 6.8%. In the RCT, postoperative morbidity and overall toxicity was significantly less in the NACTx group. Mean T downstaging (ypStage 0-I) was 49.6%, mean N downstaging 69.6% and mean pathologic complete response (pCR) 10.7%. The RCT showed an inferior pCR rate after NACTx than after NA-CRT, but similar rates of T downstaging. Mean LR was 8.6% and mean distant recurrence 17.2%. Satisfactory survival rates are reported by several studies. NACTx seems to be an alternative to NA-CRT for patients with LARC, associated with low anastomotic leak, adequate tumour downstaging, low LR and rather high survival rates. Further data deriving from high-quality studies are necessary to assess safety and efficacy of NACTx as a substitute to NA-CRT, for at least a subset of patients with LARC.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Humans; Irinotecan; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxaliplatin; Postoperative Complications; Prospective Studies; Rectal Neoplasms; Rectum; Retrospective Studies; Survival Rate
PubMed: 32666388
DOI: 10.1007/s10147-020-01738-2