Anal disorders in pregnant and postpartum women: epidemiological, diagnostic and therapeutic aspects in 10 maternities of Bamako in Mali.

Bowel transit disturbances favored by pregnancy and injuries during childbirth would be triggering or aggravating factors for anal pathologies. The objective of this work was to study the epidemiology, diagnosis, and treatment of anal pathologies during pregnancy and 6 weeks after delivery. We carried out a prospective, multi-centric, and analytical study in 10 obstetric units in Bamako from June 1st, 2019, to May 31st, 2020. After informed consent, we enrolled all first-trimester pregnant women admitted to the hospitals and who were followed up through the postpartum. We conducted a rectal examination in each participant and an anoscope in those with an anal symptom. Hemorrhoidal diseases were diagnosed in the case of external hemorrhoids (thrombosis or prolapse) or internal hemorrhoids. During the study period, we followed up 1,422 pregnant women and we found 38.4% (546) with anal pathologies (hemorrhoidal diseases in 13% (192), anal fissure in 10.5% (150) and anal incontinence in 8.6% (123). Risk factors for the hemorrhoidal disease were age of patient ≥30 years old aRR=5.77, 95% CI 4.57-7.34; p=0.000; a existence of chronic constipation aRR=2.61, 95% CI 1.98-3.44; p=0.000; newborn weight >3500 g aRR= 1.61, 95% CI 1.25-2.07; p=0.000 and fetal expulsion time >20 minutes aRR= 6.04, 95% CI 5.07-7.27; p=0.000. The clinical signs observed were constipation, anal pain, bleeding, and pruritus. The treatment was based on counseling on hygiene and diet, the use of laxatives, local topicals, and analgesics along perineal rehabilitation. Anal pathologies were common during pregnancy and 6 weeks after delivery. Pregnant women must be screened systematically for such pathologies. Early diagnostic and appropriate treatment would reduce serious complications.

Impact of screening programme to prevent anal cancer in high-risk patients with HIV.

INTRODUCTION: We assessed the impact of a nationwide screening programme to reduce the risk of anal cancer in a large cohort of high-risk patients with HIV. METHODS: From a large database from one referral centre, all high-risk patients with HIV (men who have sex with men, history of anal or genital warts, or previous cervix human papillomavirus-related lesions) who were eligible to enter the French anal cancer screening programme (2011-2020) were retrospectively included. Adherence to the screening programme was defined as no interval >18 months between two visits. Standardized management included perianal visualization and standard anoscopy with biopsies of macroscopic abnormalities. RESULTS: Overall, 700 patients with HIV were included (median follow-up 8.4 years [interquartile range 4.3-9.2] and 1491.6 patient-years), and 336 had one or more proctology visit. A total of 13 patients were diagnosed with anal squamous cell carcinomas. The risk of anal cancer was higher with anal intra-epithelial neoplasia grade 3 (AIN3; hazard ratio [HR] 44.5 [95% confidence interval {CI} 11.2-176.6], p < 0.001), AIN2 (HR 11.9 [95% CI 2.1-66.9], p = 0.005), or high-grade dysplasia (HR 23.4 [95% CI 7.9-69.1], p < 0.001) than with low-grade dysplasia or no lesion. Among the patients who were strictly adherent to the screening programme (4.6% [32/700]), we did not report any AIN or anal cancer, but we also did not observe any significant reduction in the risk of anal cancer (p = 0.51), AIN3 (p = 0.28), high-grade dysplasia (p = 0.19), or any AIN lesions (p = 0.10) compared with non-adherent patients. In contrast, screened patients were more likely to be diagnosed with anal warts (HR 3.71 [95% CI 2.14-6.42], p < 0.001). CONCLUSION: Macroscopic high-grade dysplasia lesions are associated with a higher risk of developing anal cancer. Despite finding no cases of cancer during the screening programme, we also did not demonstrate a clear benefit from our screening programme for the prevention of anal cancer in high-risk patients with HIV.

Planned cesarean delivery vs planned vaginal delivery: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: There are over 145 million births worldwide, with over 30 million cesarean deliveries yearly. There are limited data comparing the perinatal and maternal outcomes between planned cesarean delivery and planned vaginal delivery. This study aimed to evaluate perinatal and maternal morbidity and mortality by meta-analysis of randomized controlled trials that randomly assigned patients to either planned cesarean delivery or planned vaginal delivery. DATA SOURCES: Scopus, PubMed, CINAHL, Cochrane Library, and the World Health Organization clinical trial databases were searched from inception through August 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared planned cesarean delivery with planned vaginal delivery at any gestational age and for any delivery indication were included. METHODS: Two authors independently extracted data. PRISMA guidelines were used for data extraction and quality assessment. The primary outcome was perinatal mortality. The summary measures were reported as relative risks or as mean differences with 95% confidence intervals. Pooled odds ratios and 95% confidence intervals were calculated using Mantel-Haenszel random-effects models for outcomes. RESULTS: In 15 primary randomized controlled trials, 3265 patients were randomized to planned cesarean delivery and 3353 to planned vaginal delivery. The incidence of perinatal deaths was not different (1.3% vs 1.3%; relative risk, 0.71; 95% confidence interval, 0.33-1.52). Planned cesarean delivery was associated with lower neonatal incidences of low umbilical artery pH (0.3% vs 2.4%; relative risk, 0.18; 95% confidence interval, 0.05-0.67), birth trauma (0.3% vs 0.7%; relative risk, 0.46; 95% confidence interval, 0.22-0.96), tube feeding requirement (2.5% vs 7.1%; relative risk, 0.36; 95% confidence interval, 0.19-0.66), and hypotonia (0.4% vs 3.5%; relative risk, 0.11; 95% confidence interval, 0.03-0.47), compared to planned vaginal delivery. Chorioamnionitis was less frequent in the planned cesarean delivery group (0.3% vs 1.0%; relative risk, 0.27; 95% confidence interval, 0.08-0.98). Wound infection was more common in the planned cesarean delivery group (1.9% vs 1.1%; relative risk, 1.61; 95% confidence interval, 1.04-2.52). Lower rates were observed in the planned cesarean delivery group for urinary incontinence at both ≤3 months (8.7% vs 12.2%; relative risk, 0.71; 95% confidence interval, 0.59-0.85) and 1 to 2 years (16.9% vs 22%; relative risk, 0.77; 95% confidence interval, 0.67-0.88) and for a painful perineum at 2 years (4% vs 6.2%; relative risk, 0.64; 95% confidence interval, 0.47-0.87) compared to planned vaginal delivery. Among singleton pregnancies, planned cesarean delivery was associated with a lower rate of perinatal death (0.69% vs 1.81%; relative risk, 0.45; 95% confident interval, 0.21-0.93). CONCLUSION: Planned cesarean delivery and planned vaginal delivery were associated with similar rates of perinatal and maternal mortality in this meta-analysis of randomized controlled trials. Planned cesarean delivery was associated with significant decreases in adverse neonatal outcomes such as low umbilical artery pH, birth trauma, tube feeding requirement, and hypotonia, and significant decreases in chorioamnionitis, urinary incontinence, and painful perineum. Planned vaginal delivery was associated with significant decreases in need for general anesthesia and wound infection. Further randomized trials are needed to assess the risks and benefits of planned cesarean delivery vs planned vaginal delivery in lower-risk patients and in the general population.

Anogenital symptoms and lesions in a series of 20 patients infected with monkeypox virus.

AIM: Monkeypox virus (MPXV) has been spreading in many European countries, the USA and Canada since May 2022. General symptoms, skin and anoperineal lesions have been reported. Anal pain is often reported, but anal canal lesions have yet to be described in these patients. The aim of this study was to describe anoperineal lesions in patients infected with MPXV undergoing systematic margin and anal canal examination at a tertiary care centre in France. METHOD: In this prospective descriptive study, systematic anal examination was performed in 20 patients diagnosed with MPXV infection at Bichat Hospital, Paris, France between 6 and 11 July 2022. Anal swabs were also obtained from all these patients for polymerase chain reaction testing for MPXV. RESULTS: All the patients were men that have sex with men (MSM). Sixteen patients had anal symptoms: 13 reported anal pain, and the other anal symptoms described were anal bleeding (n = 12), pruritus (n = 11), dyschezia (n = 10), tenesmus (n = 13), burning (n = 3), swelling (n = 9) and discharge of mucus (n = 9). Proctological examination detected: (i) anal margin lesions in 14 patients (vesicles, n = 8; pustules, n = 6; ulceration, n = 6); (ii) anal canal lesions in 16 patients (ulceration, n = 13; ulcers, n = 4; pustules, n = 1), seven of whom presented anal hypertonia; and (iii) rectal lesions in 12 patients (congested rectum, n = 6; erythema, n = 10; ulcers, n = 2; not seen in one case). the presence of mucus was noted in 10 patients and the presence of blood in six patients. CONCLUSION: This is the first study to describe anal canal lesions in patients infected with MPXV. Most of the observed lesions were ulceration, accounting for the pain reported.

Risk Factors for Anal Continence Impairment Following a Second Delivery after a First Traumatic Delivery: A Prospective Cohort Study.

Postpartum anal incontinence is common. After a first delivery (D1) with perineal trauma, follow-up is advised to reduce the risk of anal incontinence. Endoanal sonography (EAS) may be considered to evaluate the sphincter and in case of sphincter lesions to discuss cesarean section for the second delivery (D2). Our objective was to study the risk factors for anal continence impairment following D2. Women with a history of traumatic D1 were followed before and 6 months after D2. Continence was measured using the Vaizey score. An increase ≥2 points after D2 defined a significant deterioration. A total of 312 women were followed and 67 (21%) had worse anal continence after D2. The main risk factors for this deterioration were the presence of urinary incontinence and the combined use of instruments and episiotomy during D2 (OR 5.12, 95% CI 1.22-21.5). After D1, 192 women (61.5%) had a sphincter rupture revealed by EAS, whereas it was diagnosed clinically in only 48 (15.7%). However, neither clinically undiagnosed ruptures nor severe ruptures were associated with an increased risk of continence deterioration after D2, and cesarean section did not protect against it. One woman out of five in this population had anal continence impairment after D2. The main risk factor was instrumental delivery. Caesarean section was not protective. Although EAS enabled the diagnosis of clinically-missed sphincter ruptures, these were not associated with continence impairment. Anal incontinence should be systematically screened in patients presenting urinary incontinence after D2 as they are frequently associated.

Prospective and multicentre study of radiofrequency treatment in anal fistula.

BACKGROUND: The most effective treatment for anal fistula is fistulotomy, but it involves a risk of anal incontinence. To reduce this morbidity, sphincter-sparing treatments have been developed, but their success in real life is often less than 50%. The aim is to determine the clinical healing rate 6 months after radiofrequency treatment. METHODS: We planned to evaluate 50 patients from three French proctology centres. Treatment efficacy was evaluated at 6 and 12 months by means of clinical and magnetic resonance imaging examination. We evaluated morbidity and healing prognostic factors. RESULTS: Fifty patients with a mean age of 51 years (22-82) were included. Eleven patients had a low trans-sphincteric fistula (LTS), 21 patients had a high trans-sphincteric fistula (HTS), eight had a complex fistula and nine had Crohn's disease fistula. After 6 months, 17 patients (34.7%) had a clinically healed fistula, including five (45.5%) with LTS fistula, seven (33.3%) with HTS fistula, one (12.5%) with complex fistula, four (44.4%) with Crohn's disease, with no significant difference between these fistula types (p: 0.142). At 12 months, the healing rate was identical. MRI in 15 out of 17 clinically healed patients showed a deep remission of 73.3% at 12 months. Energy power was associated with the success of the treatment. There was an 8.2% incidence of post-surgical complications with 4.1% being abscesses (one required surgical management). Postoperative pain was minor. No new cases or deterioration of continence have been shown. CONCLUSION: Radiofrequency is effective in 34.7% of the cases as an anal fistula treatment in this first prospective study, with low morbidity and no effect on continence. Clinical healing was deep (MRI) in three-quarters at 1 year. The increase in energy power during the procedure seems to be a key point to be analysed to optimise results.

Prognostic role of HPV integration status and molecular profile in advanced anal carcinoma: An ancillary study to the epitopes-HPV02 trial.

Squamous Cell Carcinoma of the Anal canal (SCCA) is a rare disease associated with a Human Papillomavirus (HPV) infection in most cases, predominantly the HPV16 genotype. About 15% of SCCA are diagnosed in metastatic stage and some will relapse after initial chemoradiotherapy (CRT). Treatment of patients by Docetaxel, Cisplatin and 5-fluorouracil (DCF) has been recently shown to improve their complete remission and progression-free survival. The aim of this retrospective study was to explore the impact of HPV infection, HPV DNA integration, TERT promoter mutational status and somatic mutations of oncogenes on both progression-free (PFS) and overall survivals (OS) of patients treated by DCF. Samples obtained from 49 patients included in the Epitopes-HPV02 clinical trial, diagnosed with metastatic or non-resectable local recurrent SCCA treated by DCF, were used for analyses. Median PFS and OS were not associated with HPV status. Patients with episomal HPV had an improved PFS compared with SCCA patients with integrated HPV genome (p=0.07). TERT promoter mutations were rarely observed and did not specifically distribute in a subset of SCCA and did not impact DCF efficacy. Among the 42 genes investigated, few gene alterations were observed, and were in majority amplifications (68.4%), but none were significantly correlated to PFS. As no biomarker is significantly associated with patients' survival, it prompts us to include every patient failing CRT or with metastatic disease in DCF strategy.

Relationship between clinical remission of perianal fistulas in Crohn's disease and serum adalimumab concentrations: A multi-center cross-sectional study.

BACKGROUND: Crohn's disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients. AIM: To study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas. METHODS: This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present's criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events. RESULTS: The study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) µg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) µg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations. CONCLUSION: We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Surgical closure, mainly with glue injection and anti-tumour necrosis factor α, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial.

AIM: In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab. METHODS: This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities. RESULTS: Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000). CONCLUSIONS: Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.

Risk of Fecal Incontinence Following Receptive Anal Intercourse: Survey of 21,762 Men Who Have Sex With Men.

BACKGROUND: The prevalence of receptive anal intercourse (RAI) is increasing. A few studies, with heterogeneous designs, have investigated the associated risk of fecal incontinence (FI). AIM: The primary objective of this study was to determine FI prevalence in a population of men who have sex with men (MSM) engaging in RAI. The secondary objective was to identify risk factors for severe FI. METHODS OUTCOMES: An online survey of 24,308 MSM was performed in 2019. Demographic and socioeconomic data were collected, together with information about RAI sexual practices, and FI defined by: "During the last month, have you experienced any involuntary leakage of stools?" RESULTS CLINICAL IMPLICATIONS: In total, 1,734 (8%) of the 21,762 participants reported FI. Mean age was 35.3 years. The prevalence of FI was correlated with RAI frequency: 12.7% (if RAI ≥ 1 /wk) versus 5.7% (if no RAI). In multivariate analysis, the factors associated with FI were age (OR: 1.01), low socioeconomic status (OR 1.32 to 1.40), HIV-seropositivity (OR: 1.78), high RAI frequency (OR: 1.64), chemsex (OR: 1.67) and fist-fucking (OR: 1.61). STRENGTHS AND LIMITATIONS: Main strengths of our study are population size and assessment of detailed modalities of sexual practices. Main limitations are the use of a convenience non-random sample and the assessment of FI only during the past month. CONCLUSION: This study of a large MSM population, highlights risk factors for FI among RAI practices: RAI ≥ 1 /wk, chemsex, fist-fucking, low socioeconomic status. Garros A, Bourrely M, Sagaon-Teyssier L, et al. Risk of Fecal Incontinence Following Receptive Anal Intercourse: Survey of 21,762 Men Who Have Sex With Men. J Sex Med 2021;18:1880-1890.

What is the optimal treatment for T1N0 anal squamous cell carcinoma? Analysis of current practices in the prospective French FFCD ANABASE cohort.

INTRODUCTION: for localized T1N0 squamous cell carcinoma of the anus (SCCA) standard radiotherapy (RT) may result in overtreatment and alternative strategies are debated. METHODS: T1N0M0 SCCA treated between 2015 and 2020 by local excision (LE) or RT were analyzed from the French prospective FFCD ANABASE cohort. Treatment strategies, recurrence-free and colostomy-free survivals (RFS, CFS) and prognostic factors were reported. RESULTS: among 1135 SCCA patients, 99 T1N0M0 were treated by LE(n = 17,17.2%), or RT (n = 82,82.8%) including RT alone (n = 65,79.2%) or chemo-RT (n = 17, 20.7%). Median follow-up was 27.2 months [0.03-54.44]. Median tumor size were 11.4 mm [0.9-20] and 15.3 mm [2-20] in the LE and RT groups respectively. Mean RT tumor dose was 59.4 Gy [18-69.4 Gy]. One patient in LE group and 9 in RT group had a pelvic recurrence, either local (60%), nodal (10%) or both (30%). RFS and CFS at 24 months were 92.2%[95%CI,83.4-96.4] and 94.6%[95%CI,86.1-98.0], at 36 months 88.1%[95%CI,77.1-94.2] and 88.5%[95%CI,77.0-94.5], in LE and RT group respectively, without any significative difference (HR = 0.57;[95%CI,0.07-4.45];p = 0.60). By univariate analysis, male gender was the only prognostic factor(HR = 5.57;95%CI, 1.76-17.63; p = 0.004). CONCLUSION: this cohort confirms the heterogeneity of T1N0M0 SCCA management, questioning the place of RT alone, reduced dose or RT volume, and the safety of LE.

Anal Dysplasia Among Patients With Multiple Human Papillomavirus Anal Lesions: Mosaic or Homogeneity?

PURPOSE: Anal dysplasia is caused by chronic infection with the human papillomavirus and exposes to the risk of anal cancer. The aim of this study was to evaluate the distribution of dysplasia anal grade among patients operated on for multiple anal condylomas with no macroscopic differences. METHODS: This is a cross-sectional study of patients operated on for multiple anal condylomas including a mapping of dysplasia by performing systematically for each patient one biopsy on visible lesion from each of the 4 quadrants on anal margin and in anal canal. All biopsies were read independently by 2 different pathologists. RESULTS: Among 72 patients, 60 were men and 48 were human immunodeficiency virus (HIV)-infected with a median age of 37.5 years. The proportion of high-grade squamous intraepithelial lesion (HSIL) was higher in the anal canal (41.7%) compared to the margin (20.8%) (P = 0.004). HSIL frequency did not differ according to the quadrant (anterior, posterior, right, and left) of the 2 areas. HSIL on anal canal was not associated with HSIL on anal margin and vice versa (P = 0.390). Neither age nor sex was associated to HSIL but HIV positivity increased the risk of HSIL on the anal margin (P = 0.010). CONCLUSION: Anal dysplasia is heterogeneously distributed in the anal canal as well as between anal canal and anal margin. The diagnostic of the grade of dysplasia for a person should require multiple biopsies on the canal and anal margin.

Long-term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease.

AIM: The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short-term efficacy in a randomized controlled trial. No long-term data are available to assess the benefit of this treatment. METHODS: This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end-point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. RESULTS: In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti-tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow-up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end-point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. CONCLUSION: An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease.

Impact of tobacco smoking on the patient's outcome after (chemo)radiotherapy for anal cancer.

PURPOSE: Anal squamous cell carcinoma is associated with multiple risk factors, including infection with human papillomavirus and human immunodeficiency virus, immunosuppression, multiple sex partners, receptive anal sex and tobacco smoking. The aim of our study was to identify prognostic factors associated with poor outcomes after radiotherapy for anal cancer. METHODS: We analysed retrospectively the medical records of 171 patients treated by (chemo)radiotherapy for non-metastatic anal cancer in our institution from 2000 to 2015. Patients and tumour characteristics, treatments (chemotherapy, radiotherapy [RT] and surgery) and outcomes were reported. Colostomy-free survival (CRF), disease-free survival and overall survival (OS) at 5 years were studied. Univariate and multivariate analyses were performed by logistic regression to determine factors associated with poor progression-free survival (PFS). RESULTS: Patients' characteristics were as follows: median age, 62 years (range = 36-89); gender, 45 men (26%) and 126 women (74%); HIV serology, positive: 21 patients (12%); tobacco smoking, 86 patients (50%), among whom 28 patients and 58 patients were current and former smokers, respectively. Tumours were classified as locally limited (T1-2, N0, M0) for 86 patients (50%) and locally advanced (T3-4 or N+, M0) for 85 patients (50%). The median total dose was 64.4 Gy (range = 54-76.6), and 146 patients were treated by concurrent chemoradiotherapy. Factors associated with poor PFS in univariate analysis were as follows: tumour size >4 cm, lymph node involvement, tobacco smoking, no initial surgical excision and anal warts at diagnosis. In multivariate analysis, only tobacco smoking status was significantly associated with poor PFS (hazard ratio = 2.85, 95% confidence interval [1.25-6.50], p = 0.013). Five-year PFS for non-smokers, former smokers and current smokers was 88.1%, 76.7% and 73.8%, respectively (p = 0.038). Tobacco smoking was also associated with poor overall survival (p = 0.03), locoregional relapse-free survival (LRFS; p = 0.05) and CFS (p = 0.02). CONCLUSIONS: Tobacco smoking status is associated with poor OS, LRFS, PFS and CFS in patients treated for anal cancer by high RT dose ± chemotherapy.

PD-1/PD-L1 expression in anal squamous intraepithelial lesions.

INTRODUCTION: Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers. The description of the expression of these molecules has never been performed in anal low-grade/high grade squamous intra-epithelial lesions (LSIL/HSIL respectively). MATERIALS AND METHODS: Patients followed in the AIN3 cohort were routinely sampled. For each selected sample, an immunohistochemical study was performed with anti-CD8, PD-1, PD-L1 antibodies. The presence and distribution of CD8+ lymphocytes, and the presence of PD-1+ lymphocytes and PD-L1+ epithelial cells were assessed. The comparison of these characteristics was performed between the HSIL and LSIL groups. RESULTS: 33 patients were included and 78 samples selected (60 HSIL and 18 LSIL). CD8+ lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial (respectively 90% vs. 60%, p = 0.01; and 62% vs. 33%, p = 0.04). PD-1+ lymphocytes were observed more frequently in HSIL versus LSIL (41% vs 11%, p = 0.03). There was no difference between HSIL and LSIL for PD-L1+ epithelial cells. CONCLUSIONS: Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions. These results highlight the involvement of the PD-1/PD-L1 pathway in the natural history of anal dysplasia.

Correction to: Prevalence of anal symptoms in general practice: a prospective study.

Following publication of the original article [1], the authors reported an error to one of the 'study groups' in the authorship section.

Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families.

BACKGROUND: Abetalipoproteinemia, a recessive disease resulting from deleterious variants in MTTP (microsomal triglyceride transfer protein), is characterized by undetectable concentrations of apolipoprotein B, extremely low levels of low-density lipoprotein cholesterol in the plasma, and a total inability to export apolipoprotein B-containing lipoproteins from both the intestine and the liver. OBJECTIVE: To study lipid absorption after a fat load and liver function in 7 heterozygous relatives from 2 abetalipoproteinemic families, 1 previously unreported. RESULTS: Both patients are compound heterozygotes for p.(Arg540His) and either c.708_709del p.(His236Glnfs*11) or c.1344+3_1344+6del on the MTTP gene. The previously undescribed patient has been followed for 22 years with ultrastructure analyses of both the intestine and the liver. In these 2 families, 5 relatives were heterozygous for p.(Arg540His), 1 for p.(His236Glnfs*11) and 1 for c.1344+3_1344+6del. In 4 heterozygous relatives, the lipid absorption was normal independent of the MTTP variant. In contrast, in 3 of them, the increase in triglyceride levels after fat load was abnormal. These subjects were additionally heterozygous carriers of Asp2213 APOB in-frame deletion, near the cytidine mRNA editing site, which is essential for intestinal apoB48 production. Liver function appeared to be normal in all the heterozygotes except for one who exhibited liver steatosis for unexplained reasons. CONCLUSION: Our study suggests that a single copy of the MTTP gene may be sufficient for human normal lipid absorption, except when associated with an additional APOB gene alteration. The hepatic steatosis reported in 1 patient emphasizes the need for liver function tests in all heterozygotes until the level of risk is established.

Epidemiological and economic burden of potentially HPV-related cancers in France.

Human papillomaviruses (HPV) infection is now known to be responsible for almost all cervical cancers, and for a substantial fraction of Head and Neck cancers (HNCs). However, comprehensive epidemiological and economic data is lacking in France, especially for rarer potentially HPV-related cancers, which include anal, vulvar and vaginal cancers. Using the national comprehensive database of French public and private hospital information (PMSI), we assessed prevalence and incidence of patients with in-hospital diagnosis for potentially HPV-related cancers in 2013, and estimated costs related to their management over a 3-year period after diagnosis in France. Concerning female genital cancers, 7,597, 1,491 and 748 women were hospitalized for cervical, vulvar and vaginal cancer in 2013, respectively, with 3,120, 522 and 323 of them being new cases. A total of 4,153 patients were hospitalized for anal cancer in 2013, including 1,661 new cases. For HNCs, 8,794 and 14,730 patients were hospitalized for oral and oropharyngeal cancer in 2013, respectively; 3,619 and 6,808 were new cases. Within the 3 years after cancer diagnosis, the average cost of hospital care per patient varied from €28 K for anal cancer to €41 K for oral cancer. Most expenditures were related to hospital care, before outpatient care and disability allowance; they were concentrated in the first year of care. The total economic burden associated with HPV-potentially related cancers was about €511 M for the French National Health Insurance over a 3 years period (2011 to 2013), ranging from €8 M for vaginal cancer to €222 M for oropharyngeal cancer. This study reported the most up-to-date epidemiological and economic data on potentially HPV-related cancers in France. These results may be used to evaluate the potential impact of new preventive strategies, namely the generalized organized screening of cervical cancer and the nine-valent HPV vaccine, indicated in the prevention of cervical, vaginal, vulvar and anal cancers.