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Cancer Treatment Reviews Nov 2011Results from recent phase III trials in anal cancer failed to show any benefit for neoadjuvant chemotherapy (NACT) with cisplatin, or cisplatin-based consolidation... (Review)
Review
INTRODUCTION
Results from recent phase III trials in anal cancer failed to show any benefit for neoadjuvant chemotherapy (NACT) with cisplatin, or cisplatin-based consolidation chemotherapy compared to chemoradiation alone for loco-regional control, disease-free survival (DFS) and overall survival (OS).
AIMS
This systematic review examines evidence for efficacy and toxicity of chemotherapy and chemoradiotherapy in anal cancer.
RESULTS
In total, for chemoradiation, 103 retrospective/observational studies, four phase I/II studies, 16 phase II prospective studies, two randomised phase II studies, and six phase III trials of chemoradiation in anal cancer were identified. Only three phase II chemotherapy studies in metastatic disease were identified. Few retrospective studies were consistent in their use of chemotherapy or radiation doses, and long-term follow-up (> 3 years) was rare.
CONCLUSIONS
In anal cancer T3/T4 lesions fare badly (3 year DFS 40-68%). Cisplatin appears an effective drug, but novel strategies have not allowed progress from the schedule of chemoradiation using MMC, infusional 5FU and radiotherapy--the paradigm developed by Nigro over 30 years ago. Different cytotoxic agents such as capecitabine, oxaliplatin and docetaxel, and biologically targeted agents--either an EGFR monoclonal antibody or an oral tyrosine kinase inhibitor, which exploits this pathway, might offer an alternative. In particular, the role of EGFR inhibition following chemoradiation should be explored.
Topics: Antineoplastic Agents; Anus Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Humans
PubMed: 21450408
DOI: 10.1016/j.ctrv.2011.02.003 -
Colorectal Disease : the Official... Feb 2016There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare... (Review)
Review
AIM
There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment.
METHOD
An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence.
RESULTS
The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies from immunomodulation and photodynamic therapy to targeted destruction of areas of HGAIN/AIN II/III using infrared coagulation, electrocautery, cryotherapy or surgical excision but with little consensus between the guidelines. Recommendations on surveillance strategies are similarly discordant, ranging from 6-monthly physical examination to annual anoscopy ± biopsy. Over 50% of the recommendations are based on Level 3 or Level 4 evidence and many were compiled using studies that were more than 10 years old.
CONCLUSION
Despite concordance regarding diagnosis, there is significant variation in the guidelines over recommendations on the treatment and surveillance of patients with HGAIN/AIN II/III. All three sets of guidelines are based on low level, outdated evidence originating from the 1980s and 1990s.
Topics: Anus Neoplasms; Carcinoma in Situ; Disease Management; Guideline Adherence; Humans; Population Surveillance; Practice Guidelines as Topic; Terminology as Topic
PubMed: 26559167
DOI: 10.1111/codi.13215 -
European Journal of Pediatrics Jun 2021Group A Streptococcus has been associated with a perianal infection. We conducted a systematic review of the literature on childhood streptococcal perianitis in three...
Group A Streptococcus has been associated with a perianal infection. We conducted a systematic review of the literature on childhood streptococcal perianitis in three databases: Excerpta Medica, National Library of Medicine, and Web of Science. The main purposes were to document the clinical features, the tendency to recur, the association with an asymptomatic streptococcal throat carriage, the accuracy of rapid streptococcal tests, and the mechanism possibly underlying the acquisition of this infection. More than 80% of cases are boys ≤7.0 years of age with defecation disorders, perianal pain, local itch, rectal bleeding, or fissure and a sharply demarcated perianal redness. Perianitis is associated with a streptococcal tonsillopharyngitis in about every fifth case. The time to diagnosis is ≥3 weeks in 65% of cases. Recurrences occur within 3½ months in about 20% of cases. An asymptomatic group A streptococcal throat carriage occurs in 63% of cases. As compared with perianal Streptococcus A culture, the rapid streptococcal tests have a positive predictive value of 80% and a negative predictive value of 96%. It is hypothesized that digital inoculation from nasopharynx to anus underlies perianitis. Many cases are likely caused directly by children, who are throat and nasal carriers of Streptococcus A. Some cases might occur in children, who have their bottoms wiped by caregivers with streptococcal tonsillopharyngitis or carriage of Streptococcus.Conclusion: Perianitis is an infection with a distinctive presentation and a rather long time to diagnosis. There is a need for a wider awareness of this condition among healthcare professionals. What is Known: • Group A Streptococcus may cause perianitis in childhood. • Systemic antimicrobials (penicillin V, amoxycillin, or cefuroxime) are superior to topical treatment. What is New: • The clinical presentation is distinctive (defecation disorders, perianal pain, local itch, rectal bleeding, or fissure and a sharply demarcated perianal redness). • The time to diagnosis is usually ≥3 weeks. Recurrences occur in about 20% of cases.
Topics: Amoxicillin; Anal Canal; Child; Female; Humans; Male; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes
PubMed: 33532889
DOI: 10.1007/s00431-021-03965-9 -
International Journal of Molecular... Mar 2024Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex... (Meta-Analysis)
Meta-Analysis Review
Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms.
Topics: Male; Humans; Homosexuality, Male; Human papillomavirus 16; Papillomavirus Infections; Early Detection of Cancer; Seroepidemiologic Studies; Sexual and Gender Minorities; Biomarkers, Tumor; Carcinoma in Situ; Anus Neoplasms; Papillomaviridae
PubMed: 38542409
DOI: 10.3390/ijms25063437 -
Plastic and Reconstructive Surgery May 2016Abdominoperineal resection and pelvic exenteration for resection of malignancies can lead to large perineal defects with significant surgical-site morbidity.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Abdominoperineal resection and pelvic exenteration for resection of malignancies can lead to large perineal defects with significant surgical-site morbidity. Myocutaneous flaps have been proposed in place of primary closure to improve wound healing. A systematic review was conducted to compare primary closure with myocutaneous flap reconstruction of perineal defects following abdominoperineal resection or pelvic exenteration with regard to surgical-site complications.
METHODS
A comprehensive literature search was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in the MEDLINE, EMBASE, Google Scholar, and Cochrane Library databases. After data extraction from included studies, meta-analysis was performed to compare outcome parameters defining surgical-site complications of flap and primary closure.
RESULTS
Our systematic review yielded 10 eligible studies (one randomized controlled trial and nine retrospective studies) involving 566 patients (226 flaps and 340 primary closures). Eight studies described rectus abdominis myocutaneous flaps and two studies used gracilis flaps. In meta-analysis, primary closure was more than twice as likely to be associated with total perineal wound complications compared with flap closure (OR, 2.17; 95 percent CI, 1.34 to 3.14; p = 0.001). Rates of major perineal wound complications were also significantly higher in the primary closure group (OR, 3.64; 95 percent CI, 1.43 to 7.79; p = 0.005). There was no statistically significant difference between primary and flap closure for minor perineal wound complications, abdominal hernias, length of stay, or reoperation rate.
CONCLUSIONS
This is the first systematic review with meta-analysis comparing primary closure with myocutaneous flap closure for pelvic reconstruction. The authors' results have validated the use of myocutaneous flaps for reducing perineal morbidity following abdominoperineal resection or pelvic exenteration.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Therapeutic, II.
Topics: Anus Neoplasms; Female; Genital Neoplasms, Female; Genital Neoplasms, Male; Gracilis Muscle; Hernia, Abdominal; Humans; Length of Stay; Male; Myocutaneous Flap; Pelvic Exenteration; Perineum; Postoperative Complications; Randomized Controlled Trials as Topic; Plastic Surgery Procedures; Rectus Abdominis; Reoperation; Retrospective Studies; Treatment Outcome; Wound Healing
PubMed: 26796372
DOI: 10.1097/PRS.0000000000002107 -
BMJ Open Oct 2019To generate estimates of comparative clinical effectiveness for interventions used in the treatment of anogenital warts (AGWs) through the systematic review, appraisal... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To generate estimates of comparative clinical effectiveness for interventions used in the treatment of anogenital warts (AGWs) through the systematic review, appraisal and synthesis of data from randomised controlled trials (RCTs).
DESIGN
Systematic review and network meta-analysis of RCTs. Search strategies were developed for MEDLINE, Embase, the Cochrane Library and the Web of Science. For electronic databases, searches were run from inception to March 2018. The systematic review was carried out following the general principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
PARTICIPANTS
People aged ≥16 years with clinically diagnosed AGWs (irrespective of biopsy confirmation).
INTERVENTIONS
Topical and ablative treatments recommended by the British Association for Sexual Health and HIV for the treatment of AGWs, either as monotherapy or in combination versus each other.
OUTCOME MEASURES
Complete clearance of AGWs at the end of treatment and at other scheduled visits, and rate of recurrence.
RESULTS
Thirty-seven RCTs met inclusion criteria. Twenty studies were assessed as being at unclear risk of bias, with the remaining studies categorised as high risk of bias. Network meta-analysis indicates that, of the treatment options compared, carbon dioxide laser therapy is the most effective treatment for achieving complete clearance of AGWs at the end of treatment. Of patient-applied topical treatments, podophyllotoxin 0.5% solution was found to be the most effective at achieving complete clearance, and was associated with a statistically significant difference compared with imiquimod 5% cream and polyphenon E 10% ointment (p<0.05). Few data were available on recurrence of AGWs after complete clearance. Of the interventions evaluated, surgical excision was the most effective at minimising risk of recurrence.
CONCLUSION
Of the studies assessed, as a collective, the quality of the evidence is low. Few studies are available that evaluate treatment options versus each other.
TRIAL REGISTRATION NUMBER
CRD42013005457.
Topics: Administration, Topical; Antineoplastic Agents; Anus Diseases; Catechin; Caustics; Condylomata Acuminata; Cryosurgery; Electrosurgery; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Imiquimod; Laser Therapy; Male; Network Meta-Analysis; Papillomaviridae; Podophyllotoxin; Treatment Outcome; Trichloroacetic Acid
PubMed: 31676644
DOI: 10.1136/bmjopen-2018-027765 -
Herz Mar 2024Exercise-based cardiac rehabilitation has positive benefits for patients with chronic heart failure (CHF), but the choice of exercise intensity has been controversial.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Exercise-based cardiac rehabilitation has positive benefits for patients with chronic heart failure (CHF), but the choice of exercise intensity has been controversial. The aim of this systematic review and meta-analysis was to investigate the effects of different exercise intensities on cardiopulmonary function and quality of life (QoL) of patients with CHF.
METHODS
Randomized controlled trials (RCTs) of different exercise intensities applied to patients with CHF were searched in PubMed, Web of Science, the Cochrane Library, and Embase databases from inception to December 2021. Study selection and data extraction were performed simultaneously by two independent reviewers, using the Physiotherapy Evidence Database Scale (PEDro) for quality assessment of the included literature. The weighted mean differences (WMD) or standardized mean difference (SMD) were calculated by employing a fixed or random effects model. Other statistical analyses included subgroup analysis and sensitivity analysis. Quality of evidence was evaluated by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) method.
RESULTS
Eight RCTs were included. Analyses reported no significant improvement in left ventricular ejection fractions (LVEF; WMD = 0.47, 95% CI [-4.10, 5.03], p = 0.841), peak oxygen uptake (peak VO) (SMD = 0.38, 95% CI [-0.03, 0.80], p = 0.069) and 6‑min walking distance (6MWD) (WMD = 14.10, 95% CI [-9.51, 37.72], p = 0.242). Exercise interventions of varying intensity produced small-to-moderate beneficial effects on QoL (WMD = -4.99, 95% CI [-8.29, -1.68], p = 0.003), which appeared to be attenuated at long-term follow-up (WMD = 2.12, 95% CI [-2.91, 7.16], p = 0.409).
CONCLUSION
High-intensity exercise does not have a significant advantage over moderate-intensity exercise in improving cardiopulmonary function and aerobic capacity in patients with CHF. Beneficial changes in QoL from high-intensity exercise also appeared to decrease during long-term follow-up, indicating a cumulative effect of the efficacy of high-intensity exercise.
Topics: Humans; Exercise Therapy; Exercise; Heart Failure; Quality of Life; Chronic Disease
PubMed: 37552242
DOI: 10.1007/s00059-023-05202-5 -
World Journal of Gastrointestinal... Aug 2019The anorectal leiomyosarcoma (LMS) is an aggressive malignant neoplasm. Owing to the rarity of LMSs, an optimal treatment modality has yet to be determined.
BACKGROUND
The anorectal leiomyosarcoma (LMS) is an aggressive malignant neoplasm. Owing to the rarity of LMSs, an optimal treatment modality has yet to be determined.
AIM
To collect all published data on anorectal LMS characteristics, explore current treatment options, and review recent cases of postradiation LMS.
METHODS
A literature search of the PubMed electronic database was conducted using the MeSH terms "rectal neoplasms", "anus neoplasms" and "gastrointestinal neoplasms" combined with "leiomyosarcoma". The search was limited to English language and human studies. All available case reports and case series of anal or rectal LMSs that were published from the beginning of January 1996 to May 2017 were included if the diagnosis of LMS had been confirmed by histopathologic examination. Data were analyzed using simple statistics (mean, median, and standard deviation). Independent sample -test was used to compare means for continuous variables.
RESULTS
A total of 27 articles reporting on 51 cases of anorectal LMS were identified. Among these cases, 11.7% had undergone previous pelvic radiotherapy (developing LMS at 13-35 years afterwards). Anorectal LMS affected the rectum in 92.2% of the cases, and no sex-based predominance was observed. Surgical resection with negative margins remains the mainstay of treatment, which can be accomplished with wide local excision or radical resection. The local recurrence rate was higher among cases who received wide local excision (30%), as compared to radical resection (20%); however, the overall rate of metastasis was 51.61% regardless of the treatment approach. The use of neoadjuvant radiation lowers the risk of local recurrence compared to adjuvant radiotherapy, and facilitates R0 resection of the tumor. Cases treated with adjuvant chemotherapy showed better rates of distant recurrence and overall survival. Nonetheless, multidisciplinary team discussion is necessary to determine the optimal management plan whilst considering patient- and disease-related factors.
CONCLUSION
A multidisciplinary team approach, considering the underlying patient- and disease- related factors, is necessary for optimal management of these complex tumors.
PubMed: 31523383
DOI: 10.4240/wjgs.v11.i8.334 -
The American Journal of Gastroenterology Apr 2011Crohn's disease is often purely inflammatory at presentation, but most patients develop strictures and fistulae over time (complicated disease). Many studies have... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Crohn's disease is often purely inflammatory at presentation, but most patients develop strictures and fistulae over time (complicated disease). Many studies have suggested that nucleotide-binding oligomerization domain 2 (NOD2) mutations are associated with a varying but increased risk of complicated disease. An accurate and sufficiently powerful predictor of complicated disease could justify the early use of biological therapy in high-risk individuals. We performed a systematic review and meta-analysis to obtain accurate estimates of the predictive power of the identified mutations (such as p.R702W, P.G908R, and p.Leu1007fsX1008) in NOD2 for the risk of complicated disease.
METHODS
An electronic search of MEDLINE, Embase, and Web of Science identified 917 relevant papers. Inclusion required specification of genetic mutations at the individual level and disease phenotypes by Vienna classification (inflammatory (B1), stricturing (B2), and fistulizing (B3)). A total of 49 studies met these criteria, which included 8,893 subjects, 2,897 of whom had NOD2 mutations. Studies were weighted by median disease duration. Studies not providing duration data were weighted at the level of the study with the shortest disease duration (3.9 years).
RESULTS
The relative risk (RR) of the presence of any NOD2 mutant allele for complicated disease (B2 or B3) was 1.17 (95% confidence interval (95% CI) 1.10-1.24; P<0.001). P.G908R was associated with an RR of complicated disease of 1.33 (95% CI 1.11-1.60; P=0.002). NOD2 did not predict perianal disease (P=0.4). The RR of surgery was 1.58 (95% CI 1.38-1.80; P<0.001). There was substantial heterogeneity across all studies (I(2)=66.7%). On the basis of logistic regression of these data, the sensitivity of any mutation in predicting complicated disease was 36% and specificity was 73%, with the area under the receiver operating characteristic curve 0.56.
CONCLUSIONS
The presence of a single NOD2 mutation predicted an 8% increase in the risk for complicated disease (B2 or B3), and a 41% increase with 2 mutations. Surgery risk is increased by 58% with any NOD2 mutation, whereas perianal disease was unchanged. The predictive power associated with a single NOD2 mutation is weak. The RR of any NOD2 mutations for complicated disease was only 17% across 36 studies. However, the presence of two NOD2 mutations had 98% specificity for complicated disease. These data provide insufficient evidence to support top-down therapy based solely on single NOD2 mutations, but suggest that targeted early-intensive therapy for high-risk patients with two NOD2 mutations might be beneficial, if prospective trials can demonstrate changes in the natural history in this subset of patients.
Topics: Alleles; Anus Diseases; Constriction, Pathologic; Crohn Disease; Digestive System Surgical Procedures; Genetic Predisposition to Disease; Genetic Testing; Genotype; Homozygote; Humans; Intestinal Diseases; Intestinal Fistula; Mutation; Nod2 Signaling Adaptor Protein; Prognosis; Risk; Sensitivity and Specificity
PubMed: 21343918
DOI: 10.1038/ajg.2011.19 -
Annals of Palliative Medicine Sep 2021Surgery is the clinically preferred treatment for high perianal abscesses. Incision and seton drainage improve the cure rate and reduce recurrence. We aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surgery is the clinically preferred treatment for high perianal abscesses. Incision and seton drainage improve the cure rate and reduce recurrence. We aimed to systematically evaluate the clinical effect and safety of incision and seton drainage in the treatment of high perianal abscess.
METHODS
China Knowledge Network (CNKI), WanFang database, VIP database, PubMed, and Cochrane Library were searched and all relevant Chinese and English language documents until July 2021were retrieved. All records that described randomized clinical trials (RCTs) of incision and seton drainage for the treatment of high perianal abscess were eligible. Documents that met the inclusion criteria were evaluated for bias using the Cochrane Collaboration Risk Evaluation Standard, and Revman5.4 software was used to analyze the data.
RESULTS
Fourteen RCTs were included. The results of nine studies showed that the clinical cure rate of the incision-seton group was higher than that of the incision-drainage group (P<0.05). Seven studies showed that the wound healing time of the incision-seton group was shorter than that of the incision-drainage group (P<0.05). Four studies showed that the visual analogue scale (VAS) score of the incision-seton group was lower than that of the incision-drainage group (P<0.05). Five studies showed that the Wexner score of the incision-seton group was lower than that of the incision-drainage group (P<0.05). Six studies showed that the formation rate of anal fistula in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Six studies demonstrated that the recurrence rate of abscess in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Seven studies showed that the incidence of adverse events in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Five studies demonstrated that the length of stay in the incision-seton group was shorter than that of the incision-drainage group (P<0.05).
DISCUSSION
The choice of surgical methods in clinical research has always been controversial. The incision-seton method can effectively and safely treat high perianal abscess. However, the results of this meta-analysis still leave some gaps in the evidence. More large-sample, high-quality, and multi-center RCTs are needed.
Topics: Abscess; Anus Diseases; Drainage; Humans; Rectal Fistula; Recurrence
PubMed: 34628909
DOI: 10.21037/apm-21-2229