Summary Background Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50%; ...therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival. Methods In this 2×2 factorial trial, we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK. Patients were randomly assigned to one of four groups, to receive either mitomycin (12 mg/m2 on day 1) or cisplatin (60 mg/m2 on days 1 and 29), with fluorouracil (1000 mg/m2 per day on days 1–4 and 29–32) and radiotherapy (50·4 Gy in 28 daily fractions); with or without two courses of maintenance chemotherapy (fluorouracil and cisplatin at weeks 11 and 14). The random allocation was generated by computer and patients assigned by telephone. Randomisation was done by minimisation and stratified by tumour site, T and N stage, sex, age, and renal function. Neither patients nor investigators were masked to assignment. Primary endpoints were complete response at 26 weeks and acute toxic effects (for chemoradiation), and progression-free survival (for maintenance). The primary analyses were done by intention to treat. This study is registered at controlled-trials.com , number 26715889. Findings We enrolled 940 patients: 472 were assigned to mitomycin, of whom 246 were assigned to no maintenance, 226 to maintenance; 468 were assigned to cisplatin, of whom 246 were assigned to no maintenance, 222 to maintenance. Median follow-up was 5·1 years (IQR 3·9–6·9). 391 of 432 (90·5%) patients in the mitomycin group versus 386 of 431 (89·6%) in the cisplatin group had a complete response at 26 weeks (difference −0·9%, 95% CI −4·9 to 3·1; p=0·64). Overall, toxic effects were similar in each group (334/472 71% for mitomycin vs 337/468 72% for cisplatin). The most common grade 3–4 toxic effects were skin (228/472 48% vs 222/468 47%), pain (122/472 26% vs 135/468 29%), haematological (124/472 26% vs 73/468 16%), and gastrointestinal (75/472 16% vs 85/468 18%). 3-year progression-free survival was 74% (95% CI 69–77; maintenance) versus 73% (95% CI 68–77; no maintenance; hazard ratio 0·95, 95% CI 0·75–1·21; p=0·70). Interpretation The results of our trial—the largest in anal cancer to date—show that fluorouracil and mitomycin with 50·4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK. Funding Cancer Research UK.
Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in ...LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival (CFS).
Patients with tumors ≥ 40 mm, or < 40 mm and N1-3M0 were randomly assigned to one of four treatment arms: (A) two ICT cycles (fluorouracil 800 mg/m(2)/d intravenous IV infusion, days 1 through 4 and 29 to 32; and cisplatin 80 mg/m(2) IV, on days 1 and 29), RCT (45 Gy in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), and standard-dose boost (SD; 15 Gy); (B) two ICT cycles, RCT, and high-dose boost (HD; 20-25 Gy); (C): RCT and SD boost (reference arm); and (D) RCT and HD boost.
Two hundred eighty-three of 307 patients achieved full treatment. With a median follow-up period of 50 months, the 5-year CFS rates were 69.6%, 82.4%, 77.1%, and 72.7% in arms A, B, C, and D, respectively. Considering the 2 × 2 factorial analysis, the 5-year CFS was 76.5% versus 75.0% (P = .37) in groups A and B versus C and D, respectively (ICT effect), and 73.7% versus 77.8% in groups A and C versus B and D, respectively (RT-dose effect; P = .067).
Using CFS as our main end point, we did not find an advantage for either ICT or HD radiation boost in LAACC. Nevertheless, the results of the most treatment-intense arm B should prompt the design of further intensification studies.
On initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, ...Cisplatin and Radiotherapy in Carcinoma of the Anal Canal, concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival CFS), CF, and relapse (locoregional failure LRF, distant metastasis) in this patient group.
Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors.
Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS.
CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.
This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice Committee. The paper was approved by the Committee on May 18, ...2003, and by the AGA Governing Board on July 25, 2003.
ABSTRACTInflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes both Crohn disease (CD) and ulcerative colitis. Abdominal pain, rectal bleeding, ...diarrhea, and weight loss characterize both CD and ulcerative colitis. The incidence of IBD in the United States is 70 to 150 cases per 100,000 individuals and, as with other autoimmune diseases, is on the rise. CD can affect any part of the gastrointestinal tract from the mouth to the anus and frequently will include perianal disease. The first description connecting regional enteritis with perianal disease was by Bissell et al in 1934, and since that time perianal disease has become a recognized entity and an important consideration in the diagnosis and treatment of CD. Perianal Crohn disease (PCD) is defined as inflammation at or near the anus, including tags, fissures, fistulae, abscesses, or stenosis. The symptoms of PCD include pain, itching, bleeding, purulent discharge, and incontinence of stool. In this report, we review and discuss the etiology, diagnosis, evaluation, and treatment of PCD.
Squamous cell carcinoma of the anus (SCCA) is caused by HPV, and is elevated in persons living with HIV (PLWHIV). We aimed to estimate sex‐ and HIV‐stratified SCCA burden at a country, regional and ...global level. Using anal cancer incidence estimates from 185 countries available through GLOBOCAN 2020, and region/country‐specific proportions of SCCA vs non‐SCCA from the Cancer Incidence in Five Continents (CI5) Volume XI database, we estimated country‐ and sex‐specific SCCA incidence. Proportions of SCCA diagnosed in PLWHIV, and attributable to HIV, were calculated using estimates of HIV prevalence (UNAIDS 2019) and relative risk applied to SCCA incidence. Of 30 416 SCCA estimated globally in 2020, two‐thirds occurred in women (19 792) and one‐third among men (10 624). Fifty‐three percent of male SCCA and 65% of female SCCA occurred in countries with a very high Human Development Index (HDI). Twenty‐one percent of the global male SCCA burden occurred in PLWHIV (n = 2203), largely concentrated in North America, Europe and Africa. While, only 3% of global female SCCA burden (n = 561) occurred in PLWHIV, mainly in Africa. The global age‐standardized incidence rate of HIV‐negative SCCA was higher in women (0.55 cases per 100 000) than men (0.28), whereas HIV‐positive SCCA was higher in men (0.07) than women (0.02). HIV prevalence reached >40% in 22 countries for male SCCA and in 10 countries for female SCCA, mostly in Africa. Understanding global SCCA burden by HIV status can inform SCCA prevention programs (through HPV vaccination, screening and HIV control) and help raise awareness to combat the disease.
What's new?
Squamous cell carcinoma of the anus (SCCA) is the most commonly diagnosed anal cancer subtype for which human papillomavirus (HPV) infection is considered a necessary cause and HIV is a major risk factor. Our study examined SCCA incidence and the contribution of HIV to SCCA among men and women at the country, regional and global level. Analyses show that globally two‐third of SSCA cases occur in women, with the majority of those cases in countries with a high Human Development Index. Men had a higher burden of HIV‐positive SCCA. The findings are relevant for advancing SCCA prevention and screening recommendations.
The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little ...is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable.
VACTERL/VATER Association Solomon, Benjamin D
Orphanet journal of rare diseases,
08/2011, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
VACTERL/VATER association is typically defined by the presence of at least three of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal ...fistula, renal anomalies, and limb abnormalities. In addition to these core component features, patients may also have other congenital anomalies. Although diagnostic criteria vary, the incidence is estimated at approximately 1 in 10,000 to 1 in 40,000 live-born infants. The condition is ascertained clinically by the presence of the above-mentioned malformations; importantly, there should be no clinical or laboratory-based evidence for the presence of one of the many similar conditions, as the differential diagnosis is relatively large. This differential diagnosis includes (but is not limited to) Baller-Gerold syndrome, CHARGE syndrome, Currarino syndrome, deletion 22q11.2 syndrome, Fanconi anemia, Feingold syndrome, Fryns syndrome, MURCS association, oculo-auriculo-vertebral syndrome, Opitz G/BBB syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with hydrocephalus. Though there are hints regarding causation, the aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. New genetic research methods offer promise that the causes of VACTERL association will be better defined in the relatively near future. Antenatal diagnosis can be challenging, as certain component features can be difficult to ascertain prior to birth. The management of patients with VACTERL/VATER association typically centers around surgical correction of the specific congenital anomalies (typically anal atresia, certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae of the congenital malformations. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life. Importantly, patients with VACTERL association do not tend to have neurocognitive impairment.
Basaloid squamous cell carcinoma (SCC) of the anus, previously called cloacogenic carcinoma, is a subtype of SCC. There are very few data on the morphologic variation within basaloid SCC of the anus, ...which may contribute to misdiagnosis. We retrospectively evaluated cases originally diagnosed as basaloid SCC for histologic characterization. We retrieved and reviewed cases of basaloid SCC from 1994 to 2013. Ten (27%) cases were reclassified after review, including basal cell carcinoma (n=6), melanoma (n=2), and neuroendocrine carcinoma (n=2). The final group of basaloid SCC (n=27) showed a female predominance (median age=60 y; range, 42 to 92 y). Morphologically, basaloid SCC could be categorized into 4 groupstransitional carcinoma like (n=10), basaloid with peripheral palisade (n=13), adenoid cystic carcinoma like (n=3), and mucinous microcystic (n=1). In 19 cases the histologic patterns were pure and were mixed in the remainder. CK5/6, p16, and high-risk HPV were positive in all cases (n=27). SOX2 was positive in 18/22 cases. Clinical follow-up was available on 60% of cases; 9 patients (53%) developed local recurrence or metastasis, and 5 (29%) died of disease. Basaloid SCC of the anus is characterized by 4 major histologic patterns and is consistently HPV driven.
PDF
