Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies.

BACKGROUND & AIMS: The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. METHODS: Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. RESULTS: Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. CONCLUSIONS: Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.

Local Therapy in Advanced Cholangiocarcinoma: A Review of Current Endoscopic, Medical, and Oncologic Treatment Options.

Endoscopic decompression of bile duct stenosis in unresectable cholangiocarcinoma (CC) may be difficult due to localization of the tumor, but it is important for pursuing oncologic treatment afterwards. Besides the initial diagnosis, jaundice and cholangitis are the most important indications for immediate endoscopic treatment. Endoscopic retrograde cholangiopancreatography is the favored approach for biliary access and stent placement. Hilar tumors are more difficult to treat and sometimes need higher endoscopic or radiologic expertise. In general, biliary decompression is accompanied by antibiotic treatment. Oncologic treatment of CC remains difficult, as it has to be interrupted when -infectious complications occur. For chemotherapy, a gemcitabine/cisplatin-based regime is favored. A validated -second-line treatment does not exist. Several therapeutic options are therefore offered to patients, including photodynamic therapy, selective internal radiotherapy, and high-dose radiotherapy. Exact treatment recommendations do not exist due to tumor rarity and lack of randomized controlled trials. In the present article, we take a look at current endoscopic, medical, and oncologic challenges from the endoscopist's point of view.

Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study.

The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.

Diet and Risk of Cholecystectomy: A Prospective Study Based on the French E3N Cohort.

OBJECTIVES: This study aimed to examine the relationship between diet and cholecystectomy risk, using three approaches, in a large French cohort. METHODS: In a prospective cohort study in French women who completed a food-frequency questionnaire at baseline, we analyzed diet with three approaches: food groups, dietary patterns obtained by factor analysis, and the Mediterranean diet score. The primary outcome was cholecystectomy. We used Cox proportional hazards regression to assess the relationship between diet and cholecystectomy risk, adjusting for the main potential confounders. RESULTS: During 1,033,955 person years of follow-up, we identified 2,778 incident cases of cholecystectomy. Higher intakes of legumes, fruit, vegetable oil, and wholemeal bread were associated with decreased cholecystectomy risk. Two dietary patterns were identified by factor analysis: "Western" (essentially processed meat, pizza, pies, high-alcohol beverages, French fries, sandwiches…) and "Mediterranean" (essentially fruits, vegetables, seafood, and olive oil). The "Mediterranean" pattern was inversely associated with cholecystectomy risk in the subgroup of postmenopausal women who ever used menopausal hormone therapy (hazard ratio for quartile 4 vs. 1=0.79, 95% confidence interval (CI): 0.65-0.95; P for linear trend=0.008). High adherence to the Mediterranean diet was associated with decreased risk of cholecystectomy (hazard ratio for a 6-9 score vs. 0-3=0.89, 95% CI: 0.80-0.99; P for linear trend=0.02). CONCLUSIONS: Adherence to a diet rich in fruit, vegetables, legumes, and olive oil was associated with a reduction in cholecystectomy risk in French women. Further studies in different settings are requested.

Hemorrhoidal disease: Epidemiological study and analysis of predictive factors for surgical management.

INTRODUCTION: There are very few French studies on hemorrhoidal disease and its management. PATIENTS AND METHODS: Prospective single-center study from July to December 2021 including 472 patients. RESULTS: Bleeding, prolapse and pain were the main reasons for consultation. Treatment modalities were medical (44%),±instrumental (72%), and surgical (17%). After treatment, the bleeding score and prolapse score decreased significantly (P=0.002 and P≤0.0001, respectively), but improvement was more marked in the surgery group with a better rate of "very good satisfaction" (73% vs. 54%, P=0.003). Factors associated with likelihood of surgical treatment were: age>44years, hypertrophic perianal skin tags, high scores (Bristol>5, bleeding>5, prolapse>2), severe impact on quality of life, smoking and reading during bowel movements. We have developed an online application, which aims to assess the risk of requiring hemorrhoidal surgery. CONCLUSION: Less than 20% of patients who present with hemorrhoidal disease require surgical treatment, but it is associated with better effectiveness despite more complex postoperative consequences that sometimes motivate patient refusal. We have highlighted factors associated with surgical management, which can guide the practitioner in their therapeutic choices.

[Anal fistulas: Sparing the sphincter]. / Fistules anales, épargner le sphincter.

ANAL FISTULAS: SPARING THE SPHINCTER. Fistulotomy is the most used treatment for anal fistula. It is very effective with a cure rate of over 95% but carries a risk of incontinence. This has led to the development of various sphincter sparing techniques. The injection of biological glue or paste and the insertion of a plug have disappointing results and are expensive. The rectal advancement flap is still practised because of its cure rate of around 75% but it may result in some incontinence. Intersphincteric ligation of the fistula track and laser treatment are widely practised in France with cure rates between 60 and 70%. Video-assisted anal fistula treatment as well as injections of adipose tissue, stromal vascular fraction, platelet-enriched plasma and/or mesenchymal stem cells are emerging techniques for which even better results are expected.

FISTULES ANALES, ÉPARGNER LE SPHINCTER. La fistulotomie est le traitement le plus souvent utilisé dans la fistule anale. Elle est très efficace, avec un taux de guérison supérieur à 95 %, mais expose à un risque d'incontinence. Cela a conduit au développement de diverses techniques d'épargne sphinctérienne. L'injection de colle ou de pâte biologique ainsi que la mise en place d'un plug ont des résultats finalement décevants et un coût élevé. Le lambeau rectal d'avancement est encore pratiqué en raison de son taux de guérison aux alentours de 75 %, mais il peut se solder par quelques troubles séquellaires de la continence. La ligature intersphinctérienne du trajet fistuleux et le laser sont largement pratiqués en France, avec des taux de guérison oscillant entre 60 et 70 %. Le traitement vidéo-assisté du trajet fistuleux ainsi que les injections périfistuleuses de tissu adipeux, de fraction vasculaire stromale, de plasma enrichi en plaquettes et/ou de cellules souches mésenchymateuses sont des techniques émergentes dont on espère de meilleurs résultats encore.

[Management of secondary lesions in ano-perineal Crohn's disease]. / Prise en charge des lésions secondaires de la maladie de Crohn anopérinéale.

MANAGEMENT OF SECONDARY LESIONS IN ANO-PERINEAL CROHN'S DISEASE. Anoperineal involvement in Crohn's disease is common and affects around 1/3 of patients during their disease. It constitutes a pejorative factor with an increased risk of permanent colostomy and proctectomy and is associated with a major deterioration in quality of life. Secondary anal lesions in Crohn's disease are fistulas and abscesses. They are difficult to treat and often recurrent. A multidisciplinary medico-surgical management in several stages is essential. The classic sequence is based on a first phase of drainage of fistulas and abscesses, a second phase of medical treatment based primarily on anti-TNF alpha and finally a third phase of surgical closure of the fistula tract(s). Conventional closure techniques such as biologic glue, plug, advancement flap and intersphincteric ligation of the fistula tract have limited effectiveness, are not always feasible, require technical skills and some have an impact on anal continence. In recent years, we have witnessed a real enthusiasm generated by the arrival of cell therapy. This has not spared proctology since adipose-derived allogeneic mesenchymal stem cells have had Marketing Authorisation and have been reimbursed in France since 2020 in the treatment of complex anal fistulas in Crohn's disease after failure of at least one biologic therapy. This new treatment offers an additional alternative in patients often in a situation of therapeutic impasse. Preliminary results in real life are satisfactory with a good safety profile. However, it will be necessary to confirm these results in the longer term and to work to determine the profile of the patients who could benefit the most from this expensive therapy.

PRISE EN CHARGE DES LÉSIONS SECONDAIRES DE LA MALADIE DE CROHN ANOPÉRINÉALE. L'atteinte anopérinéale de la maladie de Crohn est fréquente ; elle affecte environ un tiers des patients durant leur maladie. Elle constitue un facteur péjoratif responsable d'une majoration du risque de colostomie définitive et de proctectomie, et est associée à une altération majeure de la qualité de vie. Les lésions anales secondaires de la maladie de Crohn sont des fistules et des abcès. Elles sont difficiles à traiter et souvent récidivantes. Une prise en charge multidisciplinaire médico-chirurgicale en plusieurs étapes s'impose. La séquence classique se fonde sur une phase de drainage des fistules et des abcès, une phase de traitement médical fondé en priorité sur les anti-TNF alpha et enfin une phase de fermeture chirurgicale du (ou des) trajet(s) fistuleux. Les techniques de fermeture classiques comme la colle biologique, le plug, le lambeau d'avancement et la ligature intersphinctérienne du trajet fistuleux ont une efficacité limitée, ne sont pas toujours réalisables, nécessitent des compétences techniques et ont, pour certaines, un impact sur la continence anale. Ces dernières années, l'arrivée de la thérapie cellulaire suscite un véritable enthousiasme. Cet engouement n'a pas épargné la proctologie, puisque les cellules souches mésenchymateuses (CSM) allogéniques d'origine adipocytaires ont obtenu une autorisation de mise sur le marché (AMM), sont commercialisées et remboursées en France depuis 2020 dans le traitement des fistules anales complexes de la maladie de Crohn en échec d'au moins une biothérapie. Cette thérapie offre une alternative supplémentaire à des patients souvent en situation d'impasse thérapeutique. Les résultats préliminaires en vraie vie sont satisfaisants, avec un bon profil d'innocuité. Toutefois, il faudra confirmer ces résultats à plus long terme et travailler à identifier le profil des patients qui pourraient bénéficier au mieux de cette thérapie onéreuse.

Outcomes after double switching from originator Infliximab to biosimilar CT-P13 and biosimilar SB2 in patients with inflammatory bowel disease: a 12-month prospective cohort study.

BACKGROUND: There are few data regarding multiple switching from the originator Infliximab to its biosimilars. AIM: To assess outcomes and patient perspectives in a prospective manner after double switching from Infliximab to the biosimilars CT-P13 and SB2. METHODS: A total of 158 consecutive patients with inflammatory bowel disease (IBD) receiving CT-P13 maintenance therapy were switched to SB2 and followed for 54 weeks. Patients were stratified according to previous switch from the originator Infliximab to CT-P13 (double switch group) or not (single switch group). RESULTS: The drug persistence was high (94.9%) after 54 weeks. In total, 17 (10.8%) patients experienced loss of response to SB2, including 10 patients who were managed through dose optimisation and continued treatment. No changes were observed in clinical activity scores, fatigue, biological activity and pharmacokinetical parameters after the switch. The safety profile was in line with the current knowledge of Infliximab. According to the Beliefs about Medicines Questionnaire, the patients' perspectives did not change after switching from CT-P13 to SB2. The primary patient concerns remained after the switch, which were focused on effectiveness and safety rather than on the molecular differences between originator and biosimilars or socioeconomic benefits. There were also no differences in the concerns and beliefs between the double and single switch groups. CONCLUSION: Double switching from the originator Infliximab to CT-P13 and then to SB2 was not associated with an impairment in patient beliefs, while the effectiveness, immunogeniity and safety of anti-TNF therapy remained stable after 54 weeks of follow-up.

Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms.

Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm.

Organ Preservation after Endoscopic Resection of Early Esophageal Cancer with a High Risk of Lymph Node Involvement.

Background: Esophagectomy is recommended after endoscopic resection of an early esophageal cancer when pejorative histoprognostic criteria indicate a high risk of lymph node involvement. Our aim was to analyze the clinical outcomes of a non-surgical, organ preserving management in this clinical setting. Patients and Methods: This retrospective study was performed in two tertiary centers from 2015 to 2020. Patients were included if they had histologically complete resection of an early esophageal cancer, with poor differentiation, lymphovascular invasion or deep submucosal invasion. Endoscopic resection was followed by chemoradiotherapy or follow-up in case of surgical contraindications or patient refusal. Outcome measures were disease-free survival (DFS), overall survival (OS), cancer specific survival (CSS) and toxicity of chemoradiotherapy. Results: Forty-one patients (36 with squamous cell carcinoma and 5 with adenocarcinomas) were included. The estimated high risk of lymph node involvement was based on poor differentiation (10/41; 24%), lympho-vascular invasion (11/41; 27%), muscularis mucosa invasion or deep sub-mucosal invasion (38/41; 93%). Thirteen patients (13/41; 32%) were closely monitored, and 28 (28/41; 68%) were treated by chemoradiotherapy or radiotherapy alone. In the close follow-up group, DFS, OS and CSS were 92%, 92% and 100%, respectively vs. 75%, 79% and 96%, respectively in the chemoradiotherapy group at the end of the follow-up. Serious adverse events related to chemoradiotherapy occurred in 10% of the patients. There were no treatment-related deaths. Conclusions: Our study shows that close follow-up may be an alternative to systematic esophagectomy after endoscopic resection of early esophageal cancer with a predicted high risk of lymph node involvement.

[What is the REAL long-term risk of proton pump inhibitors?] / Quel est le VRAI risque au long cours des inhibiteurs de la pompe à protons ?

Proton pump inhibitors (PPIs) are among the most prescribed drugs in the world. While their efficacy in acute management is indisputable, it has long been suggested that PPI therapy is safe in the long term. In recent years, there has been growing and justified concern about the long-term risks of PPIs. The majority of reported side effects are based on observational studies with a low level of evidence. Concerning digestive risks, PPIs seem to increase the risk of Salmonella and Campylobacter infections. However, the link between PPIs and Clostridium difficile infection is not established. Long-term PPIs may be responsible for an increased risk of gastric cancer according to several recent studies. With regard to extra-digestive risks, PPIs are associated with a moderate increase in the risk of chronic renal failure via an interstitial nephritis mechanism. PPIs also provide martial deficiency and may be associated with vitamin B12 and magnesium deficiency in some patients. Other adverse reactions have been suggested without any causal relationship being established (i.e., dementia or bone fractures, cardiovascular risk). In this review we will discuss the different long-term adverse effects of PPIs and their level of evidence.

Non-Pharmacological Therapeutic Options for Liver Metastases in Advanced Neuroendocrine Tumors.

The incidence of liver metastasis in digestive neuroendocrine tumors is high. Their presence appears as an important prognostic factor in terms of quality of life and survival. These tumors may be symptomatic because of the tumor burden itself and/or the hormonal hyper-secretion induced by the tumor. Surgery is the treatment of choice for resectable tumors and metastasis. Nevertheless, surgery is only possible in a small number of cases. The management of non-resectable liver metastasis is a challenge. The literature is rich but consists predominantly in small retrospective series with a low level of proof. Thus, the choice of one technique over another could be difficult. Local ablative techniques (radiofrequency) or trans-catheter intra-arterial liver-directed treatments (hepatic artery embolization, chemo-embolization, and radio-embolization) are frequently considered for liver metastasis. In the present review, we focus on these different therapeutic approaches in advanced neuroendocrine tumors, results (clinical and radiological), and overall efficacy, and summarize recommendations to help physicians in their clinical practice.

[Management of anorectal bleeding]. / Conduite à tenir devant un saignement anorectal

Management of anorectal bleeding. Anorectal bleeding is a common reason for consultation in general medical practice. The ano-rectal origin is suspected on the characteristics of the bleeding which is often scant and bright red color. Medical history and clinical examination alone are often sufficient to make a diagnosis, since the main causes are hemorrhoids and anal fissure. On the other hand, the estimated risk of anorectal tumours in patients with ano-rectal bleeding has been reported in about 10%. Colonoscopy is therefore necessary at the slightest diagnostic doubt and, anyway, in all patients aged over 45 years.

Conduite à tenir devant un saignement anorectal. Les saignements anorectaux sont un motif de consultation fréquent en médecine générale. L'origine anorectale est suspectée sur les caractéristiques du saignement, qui est habituellement de faible abondance et de couleur rouge vif. L'interrogatoire et l'examen clinique seuls suffisent le plus souvent à poser un diagnostic étiologique, puisque les causes sont dominées par la pathologie hémorroïdaire et la fissure anale. D'un autre côté, la pathologie tumorale anorectale, hantise aussi bien des patients que des médecins, en est la cause dans environ 10 %. La coloscopie reste donc indiquée au moindre doute diagnostique et, de principe, chez tous les patients âgés de plus de 45 ans.

Conditions of prescription of anti-TNF agents in newly treated patients with inflammatory bowel disease in France (2011-2013).

BACKGROUND: Tumour necrosis factor inhibitors (anti-TNFs) are active but expensive drugs that induce and maintain remission in patients with Crohn's disease (CD) and ulcerative colitis (UC). AIMS: To assess the trends in anti-TNF prescription and the conditions of prescription of these drugs in patients with inflammatory bowel disease (IBD) in France. METHODS: Incidence study of anti-TNF use was performed based on French medico-administrative databases (SNIIRAM/PMSI). IBD patients who initiated adalimumab or infliximab between 2011 and 2013 were selected. RESULTS: The number of new anti-TNF users increased from 4571 to 5875 between 2011 and 2013 (+29%). More specifically, the number of patients not treated with immunosuppressants (IS) during the previous 12 months increased from 2100 to 3007 (+43%), among whom 379 patients in 2011 and 570 patients in 2013 started combination therapy (+50%). These trends were observed for both CD and UC. Patients who were naïve of IS were hospitalised more frequently than those treated with IS prior to anti-TNF therapy. CONCLUSION: This study shows a rapid increase in new prescriptions of anti-TNF for both CD and UC in France between 2011 and 2013. These results suggest a change in medical practices, with anti-TNF agents prescribed more often as first-line maintenance treatment.