Gilles Boschetti - Academia.edu (original) (raw)

Papers by Gilles Boschetti

European Journal of Gastroenterology Hepatology, Aug 1, 2010

Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular... more Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular carcinoma (HCC), with proved effectiveness on survival, but no complete response. We encountered a case of complete and durable response after gemcitabine plus oxaliplatine (GEMOX) in a patient with metastatic HCC. The use of GEMOX was considered because the patient was young, without other liver disease, with bone and hepatic lesions, a rapidly progressive disease, and a poorly differentiated component on histological aspect. After 12 cycles of GEMOX, complete response occurs with disappearance of metastases and normalization of serum level of alpha-fetoprotein. This is the first case report of complete response of HCC to GEMOX. That is why the association of chemotherapy and molecular targeted therapies is a promising direction of research. Our report shows that another important challenge remains in the identification of predictive factors of response to standard chemotherapy or molecular targeted agents.

European Journal of Immunology, 2015

Intestinal dendritic cells (DCs) orchestrate gut immune homeostasis by dampening pro-inflammatory... more Intestinal dendritic cells (DCs) orchestrate gut immune homeostasis by dampening pro-inflammatory T-cell responses and inducing anti-inflammatory IgA responses. Although no specific DC subset has been strictly assigned so far to govern IgA response, some candidate subsets emerge. In particular, plasmacytoid DCs (pDCs), which notoriously promote anti-viral immunity and T-cell tolerance to innocuous antigens (Ags), contribute to IgA induction in response to intestinal viral infection and promote T-cell-independent IgA responses in vitro. Here, using two transgenic mouse models, we show that neither short-term nor long term pDC depletion alters IgA class switch recombination in Peyer's patches and frequency of IgA plasma cells in intestinal mucosa at steady state, even in the absence of T-cell help. In addition, pDCs are dispensable for induction of intestinal IgA plasma cells in response to oral immunization with T-cell-dependent or T-cell-independent Ags, and are not required for proliferation and IgA switch of Ag-specific B cells in GALT. These results show that pDCs are dispensable for non-infectious IgA responses, and suggest that various DC subsets may play redundant roles in the control of intestinal IgA responses. This article is protected by copyright. All rights reserved.

Neurogastroenterology & Motility, 2013

The effects of bacterial fermentation on human colonic motor activity could be explained by colon... more The effects of bacterial fermentation on human colonic motor activity could be explained by colonic acidification or short-chain fatty acid (SCFA) production. We compared in healthy volunteers the colonic motor effects of intracolonic infusion of neutral or acidic saline solutions and then of neutral or acidic solutions containing an SCFA mixture. 20 healthy volunteers swallowed a probe (with an infusion catheter, 6 perfused catheters and a balloon connected to a barostat) that migrated into the colon. Colonic motor activity was recorded in fasting basal state (1 h), during (3 h) and after (2 h) intracolonic infusion in a random order on two consecutive days of 750 mL of NaCl at pH 7.0 (neutral saline) or 4.5 (acidic saline) in 10 volunteers (first experiment) and of an SCFA mixture (acetic acid 66%, propionic acid 24% and butyric acid 10%; 100 mM) at pH 7.0 or 4.5 in 10 other volunteers (second experiment). We determined for each hour a global motility index (reflecting phasic activity recorded by all catheters), the mean balloon volume (reflecting tonic activity), and the mean number of high-amplitude-propagated contractions (HAPCs). Intracolonic infusion of neutral or acidic solutions containing saline or an SCFA mixture did not change the global motility index, the barostat balloon volume, or the HAPC number compared with basal values. Under our experimental conditions, these findings suggest that the stimulation of colonic motor activity induced by carbohydrate fermentation is not explained by the acidification of the colonic contents or the resulting production of SCFAs.

European Journal of Gastroenterology & Hepatology, 2010

Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular... more Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular carcinoma (HCC), with proved effectiveness on survival, but no complete response. We encountered a case of complete and durable response after gemcitabine plus oxaliplatine (GEMOX) in a patient with metastatic HCC. The use of GEMOX was considered because the patient was young, without other liver disease, with bone and hepatic lesions, a rapidly progressive disease, and a poorly differentiated component on histological aspect. After 12 cycles of GEMOX, complete response occurs with disappearance of metastases and normalization of serum level of alpha-fetoprotein. This is the first case report of complete response of HCC to GEMOX. That is why the association of chemotherapy and molecular targeted therapies is a promising direction of research. Our report shows that another important challenge remains in the identification of predictive factors of response to standard chemotherapy or molecular targeted agents.

Scandinavian journal of gastroenterology, 2016

Background Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensi... more Background Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensive colonic involvement or ileocolitis in Crohn's disease (CD). To our knowledge, no specific report of isolated ileitis associated with PSC in CD patients has been published in CD patients. Aim and methods We report three cases of patients with isolated Crohn's ileitis associated with PSC and in whom colonic inflammation was never documented. Results Patients were followed up 10-23 years and each patient underwent 6-7 ileocolonoscopies: inflammation was located only in the terminal ileum, which was confirmed on surgical specimens in two patients. Small-duct PSC led to diagnosis of CD ileitis in one patient, while small and large-ducts PSC were evidenced after CD diagnosis in the other 2. PSC were regularly followed for 9-10 years. Conclusions Our three cases of PSC with isolated CD ileitis and long-term follow-up without any sign of colonic involvement argue against the concept t...

Hepato Gastro Oncologie Digestive, Jun 1, 2013

Hepato Gastro Oncologie Digestive, Jun 1, 2012

R esum e La d ecouverte d'une nouvelle population de lymphocytes T CD4 + dits « Th17 » capables d... more R esum e La d ecouverte d'une nouvelle population de lymphocytes T CD4 + dits « Th17 » capables de produire diff erentes cytokines pro-inflammatoires comme l'interleukine (IL)-17, l'IL-21 et l'IL-22 et la mise en evidence du rôle-cl e de l'IL-23 dans la survie de ces lymphocytes ont boulevers e le sch ema classique de la r eponse immunitaire impliqu ee en cas de maladies inflammatoires chroniques de l'intestin (MICI). Une fr equence accrue de lymphocytes (LT) Th17 et des taux elev es d'IL-17 et d'IL-23 dans l'intestin ont en effet et e identifi es dans les principaux mod eles murins de colite et au cours des pouss ees de MICI chez l'homme. L'importance de l'axe IL-23/Th17 a et e confort ee par l'identification r ecente de l'implication d'un polymorphisme g en etique du r ecepteur de l'IL-23 en cas de maladie de Crohn. L'orientation de la r eponse immunitaire vers la g en eration de LT Th17 est tr es largement d ependante du microenvironnement tissulaire en cytokines puisque la pr esence concomitante de TGFb et d'IL-6 favorise la diff erenciation de lymphocytes T CD4 + naïfs en cellules produisant l'IL-17 tandis que le TGFb seul stimulera pr ef erentiellement leur diff erenciation en LT r egulateurs. L'efficacit e chez l'animal et des donn ees prometteuses chez l'homme de nouvelles bioth erapies bloquant l'axe IL-23/Th17 ouvrent de nouvelles perspectives th erapeutiques en cas de MICI.

Journal of Crohn's & colitis, Jan 19, 2015

Evidence from mouse colitis models indicates that cytotoxic CD8(+) T cells (CTL) play a key role ... more Evidence from mouse colitis models indicates that cytotoxic CD8(+) T cells (CTL) play a key role in the initiation of gut lesions. We investigated whether changes in CD8(+) CTL in blood or lamina propria (LP) of the neoterminal ileum were associated with postoperative endoscopic recurrence of Crohn's disease (CD). Thirty-seven CD patients with ileocolonic resection were endoscopically followed up at six and twelve months post-surgery. CD8(+) T cells were analyzed by flow cytometry in blood and ileal LP. Granzyme B- and perforin-producing CD8(+) T cells were significantly increased at 6 months in blood and in ileum LP in patients with endoscopic recurrence, as compared to those in remission. At a cutoff point of 45% of CD8(+) CTL, the overall accuracies of the frequency of blood granzyme B(+) or perforin(+) CD8(+) T cells to identify patients with postoperative endoscopic recurrence were 77% and 83%, respectively. Interestingly, patients with endoscopic recurrence at 12 months we...

Annales Médico-psychologiques, revue psychiatrique, 2015

The American Journal of Gastroenterology, 2015

The American Journal of Gastroenterology, 2015

Fecal calprotectin (fCal) is widely used as marker of gut inflammation and is strongly associated... more Fecal calprotectin (fCal) is widely used as marker of gut inflammation and is strongly associated with the severity of endoscopic lesions in Crohn's disease (CD). We analyzed the relationships between levels of fCal and high-sensitivity C-reactive protein (hsCRP) and the presence and severity of postoperative endoscopic recurrence in asymptomatic CD patients (Harvey-Bradshaw index≤3). Blood and fecal samples were collected in consecutive asymptomatic CD patients (Harvey-Bradshaw index 0.85±0.19, mean±s.e.m.) who had undergone an ileocolonic resection. hsCRP and fCal were measured and a routine ileocolonoscopy was performed within 18 months (median 7 months) from resection, to detect endoscopic recurrence according to the Rutgeerts score. Eighty-six patients were included in this prospective multicenter observational cohort. fCal concentrations differed significantly in patients with endoscopic recurrence when compared with those in endoscopic remission (mean±s.e.m.: 473±78 μg/g vs. 115±18 μg/g; P<0.0001). The area under the receiver operating characteristic (ROC) curve to discriminate between patients in endoscopic remission and recurrence was 0.86 for fCal and lower for hsCRP (0.70). The best cutoff point for fCal to distinguish between endoscopic remission and recurrence was 100 μg/g as determined by the ROC curve, and its sensitivity, specificity, positive and negative predictive values (NPVs), as well as overall accuracy were 95%, 54%, 69%, 93%, and 77%, respectively. Measurement of fCal concentrations is a promising and useful tool for monitoring asymptomatic CD patients after ileocolonic resection. Taking into account the high NPV of fCal, a threshold below 100 μg/g could avoid systematic ileocolonoscopies in 30% of patients from this population.Am J Gastroenterol advance online publication, 17 March 2015; doi:10.1038/ajg.2015.30.

Gastrointestinal endoscopy, 2015

World journal of gastroenterology : WJG, Jan 14, 2015

In recent years, a second pathway for colonic carcinogenesis, distinct from the adenomatous pathw... more In recent years, a second pathway for colonic carcinogenesis, distinct from the adenomatous pathway, has been explored. This is referred to as serrated pathway and includes three types of polyp, characterised by a serrated appearance of the crypts: hyperplastic polyps (HP), sessile serrated adenomas (SSA) or lesions, and traditional serrated adenomas. Each lesion has its own genetic, as well as macroscopic and microscopic morphological features. Because of their flat aspect, their detection is easier with chromoendoscopy (carmin indigo or narrow-band imaging). However, as we show in this review, the distinction between SSA and HP is quite difficult. It is now recommended to resect in one piece as it is possible the serrated polyps with a control in a delay depending on the presence or not of dysplasia. These different types of lesion are described in detail in the present review in general population, in polyposis and in inflammatory bowel diseases patients. This review highlights t...

European Journal of Gastroenterology Hepatology, Aug 1, 2010

Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular... more Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular carcinoma (HCC), with proved effectiveness on survival, but no complete response. We encountered a case of complete and durable response after gemcitabine plus oxaliplatine (GEMOX) in a patient with metastatic HCC. The use of GEMOX was considered because the patient was young, without other liver disease, with bone and hepatic lesions, a rapidly progressive disease, and a poorly differentiated component on histological aspect. After 12 cycles of GEMOX, complete response occurs with disappearance of metastases and normalization of serum level of alpha-fetoprotein. This is the first case report of complete response of HCC to GEMOX. That is why the association of chemotherapy and molecular targeted therapies is a promising direction of research. Our report shows that another important challenge remains in the identification of predictive factors of response to standard chemotherapy or molecular targeted agents.

European Journal of Immunology, 2015

Intestinal dendritic cells (DCs) orchestrate gut immune homeostasis by dampening pro-inflammatory... more Intestinal dendritic cells (DCs) orchestrate gut immune homeostasis by dampening pro-inflammatory T-cell responses and inducing anti-inflammatory IgA responses. Although no specific DC subset has been strictly assigned so far to govern IgA response, some candidate subsets emerge. In particular, plasmacytoid DCs (pDCs), which notoriously promote anti-viral immunity and T-cell tolerance to innocuous antigens (Ags), contribute to IgA induction in response to intestinal viral infection and promote T-cell-independent IgA responses in vitro. Here, using two transgenic mouse models, we show that neither short-term nor long term pDC depletion alters IgA class switch recombination in Peyer's patches and frequency of IgA plasma cells in intestinal mucosa at steady state, even in the absence of T-cell help. In addition, pDCs are dispensable for induction of intestinal IgA plasma cells in response to oral immunization with T-cell-dependent or T-cell-independent Ags, and are not required for proliferation and IgA switch of Ag-specific B cells in GALT. These results show that pDCs are dispensable for non-infectious IgA responses, and suggest that various DC subsets may play redundant roles in the control of intestinal IgA responses. This article is protected by copyright. All rights reserved.

Neurogastroenterology & Motility, 2013

The effects of bacterial fermentation on human colonic motor activity could be explained by colon... more The effects of bacterial fermentation on human colonic motor activity could be explained by colonic acidification or short-chain fatty acid (SCFA) production. We compared in healthy volunteers the colonic motor effects of intracolonic infusion of neutral or acidic saline solutions and then of neutral or acidic solutions containing an SCFA mixture. 20 healthy volunteers swallowed a probe (with an infusion catheter, 6 perfused catheters and a balloon connected to a barostat) that migrated into the colon. Colonic motor activity was recorded in fasting basal state (1 h), during (3 h) and after (2 h) intracolonic infusion in a random order on two consecutive days of 750 mL of NaCl at pH 7.0 (neutral saline) or 4.5 (acidic saline) in 10 volunteers (first experiment) and of an SCFA mixture (acetic acid 66%, propionic acid 24% and butyric acid 10%; 100 mM) at pH 7.0 or 4.5 in 10 other volunteers (second experiment). We determined for each hour a global motility index (reflecting phasic activity recorded by all catheters), the mean balloon volume (reflecting tonic activity), and the mean number of high-amplitude-propagated contractions (HAPCs). Intracolonic infusion of neutral or acidic solutions containing saline or an SCFA mixture did not change the global motility index, the barostat balloon volume, or the HAPC number compared with basal values. Under our experimental conditions, these findings suggest that the stimulation of colonic motor activity induced by carbohydrate fermentation is not explained by the acidification of the colonic contents or the resulting production of SCFAs.

European Journal of Gastroenterology & Hepatology, 2010

Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular... more Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular carcinoma (HCC), with proved effectiveness on survival, but no complete response. We encountered a case of complete and durable response after gemcitabine plus oxaliplatine (GEMOX) in a patient with metastatic HCC. The use of GEMOX was considered because the patient was young, without other liver disease, with bone and hepatic lesions, a rapidly progressive disease, and a poorly differentiated component on histological aspect. After 12 cycles of GEMOX, complete response occurs with disappearance of metastases and normalization of serum level of alpha-fetoprotein. This is the first case report of complete response of HCC to GEMOX. That is why the association of chemotherapy and molecular targeted therapies is a promising direction of research. Our report shows that another important challenge remains in the identification of predictive factors of response to standard chemotherapy or molecular targeted agents.

Scandinavian journal of gastroenterology, 2016

Background Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensi... more Background Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensive colonic involvement or ileocolitis in Crohn's disease (CD). To our knowledge, no specific report of isolated ileitis associated with PSC in CD patients has been published in CD patients. Aim and methods We report three cases of patients with isolated Crohn's ileitis associated with PSC and in whom colonic inflammation was never documented. Results Patients were followed up 10-23 years and each patient underwent 6-7 ileocolonoscopies: inflammation was located only in the terminal ileum, which was confirmed on surgical specimens in two patients. Small-duct PSC led to diagnosis of CD ileitis in one patient, while small and large-ducts PSC were evidenced after CD diagnosis in the other 2. PSC were regularly followed for 9-10 years. Conclusions Our three cases of PSC with isolated CD ileitis and long-term follow-up without any sign of colonic involvement argue against the concept t...

Hepato Gastro Oncologie Digestive, Jun 1, 2013

Hepato Gastro Oncologie Digestive, Jun 1, 2012

R esum e La d ecouverte d'une nouvelle population de lymphocytes T CD4 + dits « Th17 » capables d... more R esum e La d ecouverte d'une nouvelle population de lymphocytes T CD4 + dits « Th17 » capables de produire diff erentes cytokines pro-inflammatoires comme l'interleukine (IL)-17, l'IL-21 et l'IL-22 et la mise en evidence du rôle-cl e de l'IL-23 dans la survie de ces lymphocytes ont boulevers e le sch ema classique de la r eponse immunitaire impliqu ee en cas de maladies inflammatoires chroniques de l'intestin (MICI). Une fr equence accrue de lymphocytes (LT) Th17 et des taux elev es d'IL-17 et d'IL-23 dans l'intestin ont en effet et e identifi es dans les principaux mod eles murins de colite et au cours des pouss ees de MICI chez l'homme. L'importance de l'axe IL-23/Th17 a et e confort ee par l'identification r ecente de l'implication d'un polymorphisme g en etique du r ecepteur de l'IL-23 en cas de maladie de Crohn. L'orientation de la r eponse immunitaire vers la g en eration de LT Th17 est tr es largement d ependante du microenvironnement tissulaire en cytokines puisque la pr esence concomitante de TGFb et d'IL-6 favorise la diff erenciation de lymphocytes T CD4 + naïfs en cellules produisant l'IL-17 tandis que le TGFb seul stimulera pr ef erentiellement leur diff erenciation en LT r egulateurs. L'efficacit e chez l'animal et des donn ees prometteuses chez l'homme de nouvelles bioth erapies bloquant l'axe IL-23/Th17 ouvrent de nouvelles perspectives th erapeutiques en cas de MICI.

Journal of Crohn's & colitis, Jan 19, 2015

Evidence from mouse colitis models indicates that cytotoxic CD8(+) T cells (CTL) play a key role ... more Evidence from mouse colitis models indicates that cytotoxic CD8(+) T cells (CTL) play a key role in the initiation of gut lesions. We investigated whether changes in CD8(+) CTL in blood or lamina propria (LP) of the neoterminal ileum were associated with postoperative endoscopic recurrence of Crohn's disease (CD). Thirty-seven CD patients with ileocolonic resection were endoscopically followed up at six and twelve months post-surgery. CD8(+) T cells were analyzed by flow cytometry in blood and ileal LP. Granzyme B- and perforin-producing CD8(+) T cells were significantly increased at 6 months in blood and in ileum LP in patients with endoscopic recurrence, as compared to those in remission. At a cutoff point of 45% of CD8(+) CTL, the overall accuracies of the frequency of blood granzyme B(+) or perforin(+) CD8(+) T cells to identify patients with postoperative endoscopic recurrence were 77% and 83%, respectively. Interestingly, patients with endoscopic recurrence at 12 months we...

Annales Médico-psychologiques, revue psychiatrique, 2015

The American Journal of Gastroenterology, 2015

The American Journal of Gastroenterology, 2015

Fecal calprotectin (fCal) is widely used as marker of gut inflammation and is strongly associated... more Fecal calprotectin (fCal) is widely used as marker of gut inflammation and is strongly associated with the severity of endoscopic lesions in Crohn's disease (CD). We analyzed the relationships between levels of fCal and high-sensitivity C-reactive protein (hsCRP) and the presence and severity of postoperative endoscopic recurrence in asymptomatic CD patients (Harvey-Bradshaw index≤3). Blood and fecal samples were collected in consecutive asymptomatic CD patients (Harvey-Bradshaw index 0.85±0.19, mean±s.e.m.) who had undergone an ileocolonic resection. hsCRP and fCal were measured and a routine ileocolonoscopy was performed within 18 months (median 7 months) from resection, to detect endoscopic recurrence according to the Rutgeerts score. Eighty-six patients were included in this prospective multicenter observational cohort. fCal concentrations differed significantly in patients with endoscopic recurrence when compared with those in endoscopic remission (mean±s.e.m.: 473±78 μg/g vs. 115±18 μg/g; P<0.0001). The area under the receiver operating characteristic (ROC) curve to discriminate between patients in endoscopic remission and recurrence was 0.86 for fCal and lower for hsCRP (0.70). The best cutoff point for fCal to distinguish between endoscopic remission and recurrence was 100 μg/g as determined by the ROC curve, and its sensitivity, specificity, positive and negative predictive values (NPVs), as well as overall accuracy were 95%, 54%, 69%, 93%, and 77%, respectively. Measurement of fCal concentrations is a promising and useful tool for monitoring asymptomatic CD patients after ileocolonic resection. Taking into account the high NPV of fCal, a threshold below 100 μg/g could avoid systematic ileocolonoscopies in 30% of patients from this population.Am J Gastroenterol advance online publication, 17 March 2015; doi:10.1038/ajg.2015.30.

Gastrointestinal endoscopy, 2015

World journal of gastroenterology : WJG, Jan 14, 2015

In recent years, a second pathway for colonic carcinogenesis, distinct from the adenomatous pathw... more In recent years, a second pathway for colonic carcinogenesis, distinct from the adenomatous pathway, has been explored. This is referred to as serrated pathway and includes three types of polyp, characterised by a serrated appearance of the crypts: hyperplastic polyps (HP), sessile serrated adenomas (SSA) or lesions, and traditional serrated adenomas. Each lesion has its own genetic, as well as macroscopic and microscopic morphological features. Because of their flat aspect, their detection is easier with chromoendoscopy (carmin indigo or narrow-band imaging). However, as we show in this review, the distinction between SSA and HP is quite difficult. It is now recommended to resect in one piece as it is possible the serrated polyps with a control in a delay depending on the presence or not of dysplasia. These different types of lesion are described in detail in the present review in general population, in polyposis and in inflammatory bowel diseases patients. This review highlights t...