Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.

BACKGROUND: In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). PATIENTS AND METHODS: Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. RESULTS: From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. CONCLUSIONS: Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. CLINICAL TRIAL NUMBER: NCT02034981.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort.

BACKGROUND: HER2 mutations have been identified as oncogenic drivers in lung cancers and are found in 1-2% of lung adenocarcinomas. There is, to date, no standard of care for these patients. We thus aim to study the therapeutic outcomes of patients harboring HER2 mutations and establish the efficacy of various drug regimens. PATIENTS AND METHODS: This retrospective cohort study in European centers assessed patients with advanced non-small-cell lung cancer (NSCLC), a known HER2 exon-20 insertion, treated with chemotherapy and/or HER2-targeted drugs. RESULTS: We identified 101 eligible patients from 38 centers: median age 61 years (range: 30-87), 62.4% women, 60.4% never-smokers. All tumors were adenocarcinomas. Concomitant EGFR mutations, ALK translocations, and ROS translocations were observed in 5, 1, and 1 patients, respectively. The median number of treatment lines was 3 (range: 1-11). The median overall survival was 24 months. Overall response rate (ORR) and the median progression-free survival (PFS) with conventional chemotherapy (excluding targeted therapies) were 43.5% and 6 months in first-line (n = 93), and 10% and 4.3 months in second-line (n = 52) therapies. Sixty-five patients received HER2-targeted therapies: trastuzumab = 57, neratinib = 14, afatinib = 9, lapatinib = 5, T-DM1 = 1. ORR was 50.9% and PFS was 4.8 months with trastuzumab or T-DM1. CONCLUSION: This series shows the chemosensitivity of HER2-driven NSCLC, and the potential interest of HER2-targeted agents. Our results should help to define the best therapeutic strategy for these patients and to orient future clinical trials.

Efficacy of sacral nerve stimulation for poor functional results of J-pouch ileoanal anastomosis.

PURPOSE: Ileoanal anastomoses (J-pouches) are an alternative to permanent ostomy. The functional outcomes associated with the use of J-pouches are usually good, but continence disorders persist in a significant number of cases and have a negative impact on quality of life. The aim of this study was to assess the efficacy of sacral nerve stimulation (SNS) for poor functional results after J-pouch ileoanal anastomosis. METHODS: Patients suffering from severe fecal incontinence (FI) following coloproctectomy underwent a staged implant SNS procedure. Demographic data and functional results for FI episodes, urgencies per week, frequency of stools, ability to defer defecation, and Wexner scores were obtained at specified intervals. Patients also completed quality-of-life assessments. RESULTS: Four female patients were included in this analysis. All 4 experienced active and passive FI at baseline and subsequently underwent test stimulation with a 75 % success rate. Three received definitive implants. These 3 patients experienced improvement in functional outcomes at 1, 3, and 6 month assessments. Improvements in quality of life were also noted. CONCLUSIONS: Our preliminary study suggests that SNS is effective for the treatment of poor functional results following J-pouch ileoanal anastomosis; however, larger studies with long-term follow-up are needed for confirmation of our findings.

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

Management of lung cancer patients' quality of life in clinical practice: a Delphi study.

BACKGROUND: The assessment of health-related quality of life (HRQoL) has seen exponential growth in oncology clinical trials. However, the measurement of HRQoL has yet to be optimised in routine clinical practice. This study aimed at exploring the operationalisation of HRQoL in clinical practice with the goal of reaching a consensus from a panel of physicians. MATERIALS AND METHODS: Physicians involved in the management of lung cancer patients in France were recruited to participate in a Delphi study. The study involved three rounds of iterated queries to gain consensus on management aspects of HRQoL, including timing of discussion on HRQoL, which specific domains of HRQoL should be discussed, and what was the most appropriate method of assessment. The threshold adopted for consensus was at least 70% agreement among physicians. A scientific committee reviewed results following each round of the Delphi study. RESULTS: A representative panel of 60 physicians participated in this study. Consensus was obtained for HRQoL management at all time points in the patient care pathway. Panellists agreed that HRQoL discussions should occur during routine visits and hospitalisation. The involvement of patients' relatives was also recognised as important, except when discussing side-effects and involvement of a multidisciplinary team. There was a lack of consensus on a systematic assessment for all patients at each visit and no consensus on how HRQoL should be measured in clinical practice. CONCLUSIONS: HRQoL discussions are considered an integral part in the management of lung cancer patients, and are deemed key to success in patient-physician interaction. Further research is required to harmonise how best to implement HRQoL assessment.

A fulminant colitis index greater or equal to 8 is not predictive of colectomy risk in infliximab-treated moderate-to-severe ulcerative colitis attacks.

INTRODUCTION: In severe attacks of ulcerative colitis (UC) treated with intravenous corticosteroids, a fulminant colitis index (FCI) greater or equal to 8 has been associated with a greater likelihood of colectomy (72 vs 16% with an FCI<8). This retrospective study aimed to assess the accuracy of such an association in infliximab-treated patients with moderate-to-severe bouts of UC. PATIENTS AND METHODS: The study was based on the medical files of 43 patients who had received at least one infusion of infliximab to treat moderate-to-severe UC (partial Mayo Clinic score). Remission and clinical response were also assessed using the partial Mayo score. The accuracy of an FCI greater or equal to 8 to predict the likelihood of colectomy was assessed by calculating the sensitivity, specificity, positive and negative predictive values, Yule's Q coefficient, Youden's index and statistical significance (Chi(2) test). RESULTS: After treatment with infliximab, 10 patients were in remission (23.3%), 21 (48.8%) had a clinical response, four (9.3%) had treatment failure (without, however, requiring colectomy) and eight (18.6%) had a colectomy. Calculation of the above-mentioned indicators revealed that an FCI greater or equal to 8 was not an indicator of the risk of colectomy in this patient population, and found that only an FCI greater or equal to 16 was statistically significant. However, low values for sensitivity, positive predictive value and Youden's index preclude the clinical application of this latter result. CONCLUSION: In patients treated with infliximab for moderate-to-severe UC attacks, the FCI is not a predictor of colectomy. In such patients, the factors predictive of a response to treatment or likelihood of colectomy, currently acknowledged with corticosteroid treatment, need to be further assessed for infliximab treatment.

Proposals for managing patients with thoracic malignancies during COVID-19 pandemic.

The objective of this document is to formalize a degraded mode management for patients with thoracic cancers in the context of the COVID-19 pandemic. The proposals are based on those of the French High Council for Public Health, on published data outside the context of COVID-19, and on a concerted analysis of the risk-benefit ratio for our patients by a panel of experts specialized on thoracic oncology under the aegis of the French-Language Society of Pulmonology (SPLF)/French-language oncology group. These proposals are evolving (10 April 2020) according to the situations encountered, which will enrich it, and are to be adapted to our institutional organisations and to the evolution of resources during the COVID-19 epidemic. Patients with symptoms and/or COVID-19+ are not discussed in this document and are managed within the framework of specific channels.

[Inflammatory bowel disease: genetic or environmental diseases?]. / Maladies inflammatoires chroniques de l'intestin: maladies génétiques ou de l'environnement?

Pathophysiology of inflammatory bowel diseases depends on the interaction between genetic susceptibility and environmental factors leading to a deregulated immune intestinal response resulting in bowel lesions. Epidemiologic variations of inflammatory bowel diseases with time (incidence, prevalence) and space suggest a role for risk environmental factors, but so far only smoking habits and appendectomy have been identified as influencing the risk of occurrence and the course of the diseases. Studies of monozygotic and dizygotic twins and the existence of familial aggregation are strong evidence for an important, but not exclusive, role for genetic susceptibility. Since the discovery of NOD2/CARD15 mutations, numerous genes have been associated with inflammatory bowel diseases, some of them involved in the regulation of innate immunity and cellular clearance of infectious agents (autophagy). Thus, new hypothesis include a key role of mucosal human microbiota which could be partly influenced by environmental factors generated by modern life. The improvement of life hygiene, the change of food composition and habits, the industrial pollution in developed countries, may influence, directly or by the way of modifying intestinal human microbiota, inflammatory bowel diseases risk occurrence.

[Tumour assessment criteria for immune checkpoint inhibitors]. / Critères d'évaluation de la réponse tumorale aux inhibiteurs des points de contrôle immunitaire.

The development of immune checkpoint inhibitors in thoracic oncology has led to a reconsideration of the rules for radiological tumor assessment. The RECIST criteria are widely used for the assessment of conventional treatments but are not suitable for anti-tumoral immunotherapy. The mechanism of action of this new class of drugs may induce specific patterns of response, which are not fully assessed by the RECIST criteria. Several new criteria have been proposed to better detect these patterns of response. The changes usually include confirmation of progression, new ways of assessing new lesions, and a larger role for clinical assessment. Nevertheless, harmonization and validation of these criteria remains indispensable. In this review, we will detail the different criteria that are currently available, and discuss their strengths and weaknesses.

[MET exon 14 splicing sites mutations: A new therapeutic opportunity in lung cancer]. / Les mutations des sites d'épissage de l'exon 14 de MET. Une nouvelle opportunité thérapeutique dans le cancer du poumon.

The mutations leading to MET exon 14 skipping represent a new class of molecular alterations described in various cancers. These alterations are observed in 2 to 3 % of cases of non-small cell lung cancer (NSCLC). Several cases of NSCLC carrying such alterations and achieving objective response to MET tyrosine kinase inhibitorshave recently been published. This review summarizes the molecular mechanisms responsible for MET exon 14 skipping as well as the consequences of the loss of this exon on receptor activity. We also describe the clinical characteristics of patients with METΔ14 mutations. Finally, we address the issues related to the detection of these mutations in lung cancer, and the need to anticipate resistance to MET inhibitors.

[Protein-losing enteropathy revealing an idiopathic constrictive pericarditis]. / Entéropathie exsudative révélant une péricardite chronique constrictive idiopathique.

INTRODUCTION: The cause of protein-losing enteropathy is sometimes difficult to establish. It can be rarely due to a constrictive pericarditis. EXEGESIS: We report a patient presenting a protein-losing enteropathy revealing a constrictive pericarditis. CONCLUSION: Chronic pericarditis should be evoked in case of unexplained protein-losing enteropathy. Echocardiography can sometimes be normal. Therefore, chest computed tomography scan or cardiac MRI followed by confirmation right heart catheterization should be performed in case of persistent unexplained protein-losing enteropathy.

Successful induction of tolerance to infliximab in patients with Crohn's disease and prior severe infusion reactions.

AIM: To appraise the tolerance and efficacy of an induction of tolerance protocol to infliximab permitting the re-administration of the drug to patients with Crohn's disease having had infusion reactions requiring suspension of treatment. METHODS: Fourteen patients were included in the induction of tolerance protocol. Each infusion of infliximab (5 mg/kg) was divided into 11 escalating 15 min increments over a 3-h time period. The induction of tolerance procedure was repeated for subsequent infusions. RESULTS: Ten patients (71.4%) received all the three infusions for the induction treatment. Nine (64.3%) had a significant response and six (48.8%) still benefited from infliximab infusions. Seven patients (50%) achieved a complete remission, after a mean of 2.5 (two to three) infusions. Four patients (28.6%) had no response and the protocol was stopped. Three patients (21.4%) experienced mild immediate hypersensitivity reactions, which were controlled, two patients (14.2%) experienced severe immediate hypersensitivity reactions, leading to interruption of the treatment and one patient developed a delayed hypersensitivity reaction. CONCLUSION: Our induction of tolerance protocol allows some patients who have experienced severe or repetitive infusion reactions to infliximab to be safely retreated with the drug in a hospitalized setting, with a clinical response achieved in a majority of these patients.

[Pulmonary MALT lymphoma revealing AIDS]. / Lymphome pulmonaire du MALT révélant un sida.

INTRODUCTION: We report the case of a patient with an isolated pulmonary mucosa associated lymphoid tissue (MALT) lymphoma that revealed an acquired immune deficiency syndrome (AIDS). CASE REPORT: A 30 year old man from Central Africa was admitted to hospital with cough, dyspnoea and general weakness. A diagnosis of HIV infection was made promptly. The thoracic CT scan revealed diffuse bilateral ground glass opacities as well as consolidation of the right upper lobe. After a non-diagnostic endoscopy the diagnosis of a low grade B cell MALT lymphoma (CD20+) was made by lung biopsy and confirmed by the presence of the t(11;18) translocation. No extrathoracic lymphoma was found. Treatment with rituximab and triple anti-retroviral therapy led to a rapid and complete remission that was maintained for 3 years after the diagnosis. CONCLUSION: Pulmonary MALT lymphoma may reveal AIDS. A combination of rituximab and anti-retroviral therapy led to complete remission in this patient.

[Systemic treatment of brain metastases from lung cancer]. / Traitement systémique des métastases cérébrales de cancer bronchique.

Systemic treatment of lung cancer patients with brain metastases is based on clinical (presence of symptomatic intracranial lesions), pathological and molecular characteristics of the disease. The efficacy of standard platinum-based chemotherapy is comparable inside and outside the brain, justifying its use as front-line therapy. The intracranial efficacy of targeted therapies (EGFR tyrosine kinase inhibitors, ALK inhibitors) is demonstrated, and is globally superior to the efficacy of standard chemotherapy, justifying their use as front-line therapy in case of EGFR activating mutation or ALK rearrangement (providing the change in the crizotinib label in France). The concomitant use of whole brain radiotherapy and a systemic treatment (chemotherapy or targeted therapy) is not recommended in the absence of a demonstrated better efficacy and/or acceptable safety profile. Several trials are ongoing to assess new whole brain radiotherapy modalities, new targeted therapies alone or in combination, especially exploring immunotherapy.

Familial and sporadic inflammatory bowel disease: different entities?

The strongest risk factor for developing inflammatory bowel disease (IBD) is having a relative with the disease. Familial IBD may be one homogeneous subgroup, phenotypically different from sporadic IBD. Several observations support a role for familiarity in disease site and behavior, particularly in Crohn's disease (CD), but published findings do not all concur. Early disease onset is often found in children with IBD who have a parent with the disease. Genetic anticipation may explain this finding but other explanations and/or observational biasis are more likely. Location and type may differ between familial and sporadic CD cases: family studies report many cases involving both small bowel and colon, and few cases of colonic disease alone, although such features may be secondary to early age at onset. Most studies found no effect of positive family history on severity and course of CD. In ulcerative colitis (UC), phenotypic differences between familial and sporadic cases appear to be limited, but little data are available for analysis. No difference has been found between familial and sporadic IBD as far as disease markers such as pANCA, ASCA, or intestinal permeability are concerned. In conclusion, the only message available for clinical practice is that the relative risk of IBD in first-degree relatives is increased by a factor of 10-15 compared with the general population. Families should not receive genetic counseling/information about age at onset and disease severity.

Anti-neutrophil cytoplasmic auto-antibodies (ANCA) in ulcerative colitis (UC): no relationship with disease activity.

The relationship between anti-neutrophil cytoplasmic auto-antibodies (ANCA) and disease activity in inflammatory bowel diseases remains controversial. The aim of this study was to highlight the relationship between ANCA presence or titers and disease activity in ulcerative colitis (UC). Three groups of patients with UC were studied: 1) group A included 39 patients who had not undergone colectomy, 2) group B, 43 patients with subtotal colectomy and ileo-rectal anastomosis, 3) group C, 98 patients with proctocolectomy and ileo-anal anastomosis, including 88% with pouchitis and 12% without pouchitis at the time of the study. Determination of ANCA was performed using the standardized indirect immunofluorescence assay. ANCA were positive in 59%, 65%, and 54% of patients from groups A, B, and C, respectively (NS). No relationship between ANCA presence or titers and UC activity could be detected within groups A and B. In group C, 45 of 86 patients (52%) without pouchitis and 8 of 12 patients (67%) with pouchitis, were ANCA positive (NS). These results do not support a relationship between ANCA and UC activity in this cohort of 180 patients.

Pouchitis is associated with mucosal imbalance between interleukin-8 and interleukin-10.

BACKGROUND: Mucosal lesions of pouchitis are characterized by a neutrophil infiltrate. Interleukin (IL)-8 is the main mediator involved in neutrophil recruitment and is down-regulated by IL-10. AIM: To look for an imbalance between IL-8 and IL-10 in patients with pouchitis. PATIENTS/METHODS: 18 patients having an ileoanal pouch for ulcerative colitis were studied. Eleven had pouchitis defined by the pouchitis disease activity index of > or =7 points and 7 had no history of pouchitis. Biopsies taken at the site of inflammation or in the normal mucosa were scored for the histologic lesions, the intensity of neutrophil infiltration, and the presence of crypt abscesses. Mucosal IL-8 and IL-10 mRNA were quantified by competitive polymerase chain reaction. RESULTS: IL-8, IL-10, and IL-10/IL-8 mRNA were similar in patients with or without pouchitis. IL-8 mRNA levels were significantly higher in patients with a histologic score >2 (p = 0.01) and in patients with crypt abscesses (p = 0.01). IL-10/IL-8 mRNA was significantly lower in patients having a histologic score >2 (p = 0.019), a neutrophil infiltration > or =10% (p = 0.013), and crypt abscesses (p = 0.01). CONCLUSION: Histologic lesions of pouchitis are associated with a mucosal imbalance between IL-8 and IL-10. IL-10 could be proposed as a new treatment for pouchitis.