Publications by authors named "Lola-Jade Palmieri"

16 Publications

  • Page 1 of 1

Management of esophageal strictures after endoscopic resection for early neoplasia.

Therap Adv Gastroenterol 2021 18;14:1756284820985298. Epub 2021 Jan 18.

Department Gastroenterology and Digestive Oncology, Cochin Hospital, 27 Rue du Faubourg Saint Jacques, 75014 Paris, France.

Background: Endoscopic resection of extensive esophageal neoplastic lesions is associated with a high rate of esophageal stricture. Most studies have focused on the risk factors for post-endoscopic esophageal stricture, but data on the therapeutic management of these strictures are scarce. Our aim is to describe the management of esophageal strictures following endoscopic resection for early esophageal neoplasia.

Methods: We included all patients with an endoscopic resection for early esophageal neoplasia followed by endoscopic dilatation at a tertiary referral center. We recorded the demographic, endoscopic, and histological characteristics, and the outcomes of the treatment of the strictures.

Results: Between January 2010 and December 2019, we performed 166 endoscopic mucosal resections and 261 endoscopic submucosal dissections for early esophageal neoplasia, and 34 (8.0%) patients developed an esophageal stricture requiring endoscopic treatment. The indication for endoscopic resection was Barrett's neoplasia in 15/34 (44.1%) cases and squamous cell neoplasia (SCN) in 19/34 (55.9%) cases. The median [(interquartile range) (IQR)] number of endoscopic dilatations was 2.5 (2.0-4.0). Nine of 34 (26.5%) patients required only one dilatation, and 22/34 (65%) had complete dysphagia relief following three endoscopic treatment sessions. The median number of dilatations was significantly higher for SCN [3.0 (2-7); range 1-17;  = 0.02], and in the case of circumferential resection [4.0 (3.0-7.0);  = 0.03]. Endoscopic dilatation allowed a sustained dysphagia relief in 33/34 (97.0%) patients after a mean follow-up of 25.3 ± 22 months.

Conclusion: Refractory post-endoscopic esophageal stricture is a rare event. After a median of 2.5 endoscopic dilatations, 97.0% of patients were permanently relieved of dysphagia. Circumferential endoscopic esophageal resections should be considered when indicated.
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http://dx.doi.org/10.1177/1756284820985298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816530PMC
January 2021

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

Cancers (Basel) 2020 Dec 2;12(12). Epub 2020 Dec 2.

Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.

: 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. : 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. : 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. : 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.
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http://dx.doi.org/10.3390/cancers12123598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761405PMC
December 2020

The Role of Interventional Radiology for the Treatment of Hepatic Metastases from Neuroendocrine Tumor: An Updated Review.

J Clin Med 2020 Jul 20;9(7). Epub 2020 Jul 20.

Department of Radiology, Cochin Hospital, AP-HP, 27 rue du Faubourg Saint- Jacques, 75014 Paris, France.

Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall survival. These treatment options are proposed in patients with NELM not responding to systemic therapies and without extrahepatic progression. Currently, available data suggest that TAE should be preferred to TACE in patients with NELM from extrapancreatic origin because of similar efficacy and better patient tolerance. TACE is more effective in patients with pancreatic NELM and SIRT has shown promising results along with good tolerance. However, large randomized controlled trials are still lacking in this setting. Available literature mainly consists in small sample size and retrospective studies with important technical heterogeneity. The purpose of this review is to provide an updated overview of the currently reported endovascular interventional radiology procedures that are used for the treatment of NELM.
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http://dx.doi.org/10.3390/jcm9072302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408651PMC
July 2020

Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms.

J Clin Med 2020 Jun 15;9(6). Epub 2020 Jun 15.

Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France.

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.
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http://dx.doi.org/10.3390/jcm9061860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355438PMC
June 2020

Reasons for chemotherapy discontinuation and end-of-life in patients with gastrointestinal cancer: A multicenter prospective AGEO study.

Clin Res Hepatol Gastroenterol 2021 Jan 11;45(1):101431. Epub 2020 May 11.

Department of hepatogastroenterology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75013 Paris, France.

Background: Previous research on chemotherapy discontinuation has mainly focused on predictive factors and outcomes. Few data are available on the reasons for chemotherapy discontinuation. The main objective was to identify the reasons for chemotherapy discontinuation in patients with gastrointestinal cancer. The secondary objectives were to describe the announcement of chemotherapy discontinuation and the time between chemotherapy discontinuation and death.

Methods: This prospective multicenter French cohort included patients with advanced gastrointestinal cancer, for whom chemotherapy was discontinued between May 2016 and January 2018.

Results: One hundred and fourteen patients were analyzed. The first cause of chemotherapy discontinuation was the impairment of general condition (asthenia, cachexia). Complications such as sepsis, jaundice or occlusion, were the second most frequent cause. Progression was observed at chemotherapy discontinuation in two-thirds of cases. The announcement of the chemotherapy discontinuation was made formally in 74% of cases, with a follow-up by a palliative care team initiated in 50% of cases. Sixty-nine percent of the patients received chemotherapy during the last three months of life and 26% during the last month. The median time between chemotherapy discontinuation and death was 65 days (IQR: 36.5-109): 44% of patients died at the hospital, 39% in a palliative care unit and 16% at home.

Conclusion: Impairment of general condition was the major reason for chemotherapy discontinuation in patients with gastrointestinal cancers. Complications such as jaundice, sepsis or occlusion, were important reasons for discontinuation and could explain our shorter time between chemotherapy discontinuation and death, compared to other oncology sub-specialties.
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http://dx.doi.org/10.1016/j.clinre.2020.03.029DOI Listing
January 2021

Oral therapies in digestive oncology (Review).

Oncol Rep 2020 Jun 20;43(6):1719-1728. Epub 2020 Mar 20.

Department of Gastroenterology, Cochin Teaching Hospital, 75014 Paris, France.

Targeted therapy and oral chemotherapy indications are increasing in the realm of digestive oncology. Oral intake of cancer agents is sometimes compulsory (no i.v. equivalent) or is preferred by the patient or the physician. Although oral chemotherapy facilitates the treatment of oncology patients, the treatment diversity, risk of pharmaceutical interactions and monitoring of side effects are potentially challenging and need to be fully acknowledged by the physician. We offer here a literature review of the indications, doses, side effects and monitoring of every oral therapy indicated in Digestive Oncology. We suggest a prescription algorithm including therapeutic education by the physician or a trained nurse, and pharmaceutical counseling.
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http://dx.doi.org/10.3892/or.2020.7555DOI Listing
June 2020

Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study).

Oncologist 2020 02 2;25(2):e266-e275. Epub 2019 Oct 2.

Department of Gastroenterology, Cochin Hospital, Paris, France.

Background: Patients with RAS wild-type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti-epidermal growth factor receptor (EGFR) combined with first-line, 5-fluorouracil-based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti-EGFR. Our objective was to compare both strategies in a routine practice setting.

Materials And Methods: This multicenter, retrospective, propensity score-weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5-FU-based chemotherapy, with either delayed anti-EGFR or immediate anti-vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression-free survival (PFS) and objective response rate (ORR).

Results: A total of 262 patients (129 in the anti-VEGF group and 133 in the anti-EGFR group) were included. Patients receiving an anti-VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13-26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69-1.08, p = .2024). The delayed introduction of anti-EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61-0.90, p = .0024). ORR was significantly higher in the anti-EGFR group (66.7% vs. 45.6%, p = .0007).

Conclusion: Delayed introduction of anti-EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti-VEGF.

Implications For Practice: For RAS/RAF wild-type metastatic colorectal cancer, patients may receive 5-fluorouracil-based chemotherapy plus either bevacizumab or an anti-epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti-EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti-EGFR on survival, compared with the introduction of an anti-vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti-EGFR while waiting for RAS status.
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http://dx.doi.org/10.1634/theoncologist.2019-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011620PMC
February 2020

Early esophageal signet ring cell carcinoma: A contraindication to endoscopic resection?

Clin Res Hepatol Gastroenterol 2020 10 6;44(5):e98-e102. Epub 2020 Feb 6.

Gastroenterology and Digestive Oncology Department, Cochin Hospital, 75014 Paris, France; University of Paris, Paris, France.

Introduction: Endoscopic resection is a standard-of-care for early esophageal neoplasia. Early gastric signet ring cell carcinoma (SRCC) can be safely managed by endoscopic resection, if the early SRCC is limited to the mucosa and less than 15mm, with a low lymph node metastasis rate. It is not known if esophageal signet ring cell carcinoma is amenable to endoscopic resection.

Methods: We retrospectively collected demographic, procedural, oncologic and follow-up data from all patients with esophageal SRCC resected endoscopically at our institution, and compared them to those of patients with endoscopically resected poorly differentiated esophageal adenocarcinomas.

Results: Between 2016 and 2018, 170 endoscopic resections were performed for esophageal neoplasms, among which 7 patients with SRCC and 6 patients with poorly differentiated early adenocarcinomas were identified. The histologically complete (R0) resection rate was 28.6% (2/7) for SRCC vs. 100% for poorly differentiated adenocarcinomas (P=0.04). The presence of lymphovascular invasion or deep submucosal invasion led to curative resection rates of 14.2% (1/7) and 66.6% (4/6) for SRCC and poorly differentiated adenocarcinomas, respectively (P=0.1).

Conclusion: Endoscopic resection of early esophageal SRCC is neither histologically complete, nor curative in the majority of cases. These data argue against upfront endoscopic resection when SRCC is evidenced on esophageal biopsies.
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http://dx.doi.org/10.1016/j.clinre.2020.01.004DOI Listing
October 2020

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

J Clin Med 2019 Nov 7;8(11). Epub 2019 Nov 7.

Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.

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.
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http://dx.doi.org/10.3390/jcm8111907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912565PMC
November 2019

Potential Areas of Interest in a Trial of Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin for Hepatocellular Carcinoma.

JAMA Oncol 2019 Oct 10. Epub 2019 Oct 10.

Department of Gastroenterology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

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http://dx.doi.org/10.1001/jamaoncol.2019.4052DOI Listing
October 2019

[Identification and management of patients with Lynch syndrome].

Presse Med 2019 Sep 24;48(9):904-914. Epub 2019 Sep 24.

AP-HP, hôpital Cochin, service de gastro-entérologie, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Université de Paris, 12, rue de l'École-de-Médecine, 75006 Paris, France.

About 5% of colorectal cancer (CRC) cases occurred in the context of an underlying hereditary predisposition syndrome. Lynch syndrome is the main causes of hereditary CRC but is also associated with a higher risk of other cancers (such as endometrial cancer and ovarian cancer). It is the consequence of constitutional mutation in a MisMatch Repair (MMR) gene, involved in DNA repair: MLH1, MSH2, MSH6 or PMS2; or of the EPCAM gene (MSH2 promotor). If a mutation predisposing to Lynch Syndrome is identified in an individual, special monitoring should be initiated, adapted to estimated cancer risk. Clinical criteria (Amsterdam II and Bethesda) have been validated to identify the patients who should be referred for genetic counseling in order to initiate constitutional DNA testing. Furthermore, the French National Cancer Institute (INCa) systematically recommend tumoral testing looking for MMR system failure in case of CRC diagnosed under 60, endometrial cancer diagnosed under 50 or whatever the age in patients diagnosed with CRC or endometrial cancer harbouring personal or familal history of Lunch Syndrome cancers. In this review, we will discuss how to detect Lynch syndrome (identification of the index case and family screening) and how to monitor it in 2019.
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http://dx.doi.org/10.1016/j.lpm.2019.07.011DOI Listing
September 2019

Major pitfalls of protein kinase inhibitors prescription: A review of their clinical pharmacology for daily use.

Crit Rev Oncol Hematol 2019 Sep 16;141:112-124. Epub 2019 Jun 16.

AP-HP, Cochin Hospital, Department of gastroenterology and gastrointestinal oncology, Université Paris Descartes, Paris, France.

Protein kinase inhibitors (PKI) are a growing class of anticancer agents. They are prescribed with flat doses, and their oral administration is associated with interindividual variability in exposure. Patients can be over- or underexposed, due to numerous factors. We reviewed key pharmacokinetic concepts and mechanisms by which PKIs prescription could be altered. Challenging situations that could lead to increased toxicity or to therapeutic failure are described and recommendation for clinicians are proposed. Finally, the interest of therapeutic drug monitoring and indications for its use in daily practice is discussed.
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http://dx.doi.org/10.1016/j.critrevonc.2019.06.006DOI Listing
September 2019

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

Oncology 2019 2;97(4):191-201. Epub 2019 Jul 2.

Department of Gastroenterology, Cochin Teaching Hospital, University Paris Descartes, AP-HP, Paris, France,

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.
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http://dx.doi.org/10.1159/000500832DOI Listing
October 2019

CNCM I-745 Modulates the Fecal Bile Acids Metabolism During Antimicrobial Therapy in Healthy Volunteers.

Front Microbiol 2019 4;10:336. Epub 2019 Mar 4.

Inserm UMR1149, DHU Unity - Paris Diderot University, Paris, France.

CNCM I-745 (SB) is a probiotic yeast used to lower the incidence of antibiotic-associated () infection, though its mechanism of action remains unclear. Cholic acid is a primary bile acid, which triggers the germination and promotes the growth of . The intestinal microbiota transforms primary into secondary bile acids. This study examined (1) the antimicrobial-induced alteration of fecal bile acid content, and (2) whether the concomitant administration of SB influences this transformation. This is an ancillary work from a randomized study, which revealed that SB modulates fecal microbiota dysbiosis during antibiotic treatment. Healthy subjects were randomly assigned to (1) SB only, (2) amoxicillin-clavulanate (AC), (3) SB plus AC, or (4) no treatment. We analyzed fecal concentrations of BA by high performance liquid chromatography/tandem mass spectrometry. Compared to the untreated or the SB-treated groups, AC decreased the percentage of fecal secondary BA significantly (days 3 and 7). When SB and AC were administered concomitantly, this decrease in secondary BA was no longer significant. Following treatment with AC, a significant peak of fecal CA was measured on days 3 and 7, which was prevented by the concomitant administration of SB. AC administered to healthy volunteers altered the microbial transformation of primary BA, decreased secondary BA, and increased CA. The latter was prevented by the concomitant administration of SB and AC, suggesting a potent mechanism protection conferred by SB against post-antimicrobial infection. www.ClinicalTrials.gov, identifier NCT01473368.
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http://dx.doi.org/10.3389/fmicb.2019.00336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407479PMC
March 2019

Tumor-size responses to first-line is a predictor of overall survival in metastatic colorectal cancer.

Eur Radiol 2019 Jul 31;29(7):3871-3880. Epub 2019 Jan 31.

Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Objectives: Early tumor shrinkage (ETS) has been reported to be associated with survival of metastatic colorectal cancer (mCRC) patients. Our aim was to analyze long-term tumor-size evolution, according to early mCRC best responses during the first-line therapy, to evaluate first best response-survival links.

Methods: Sixty-five patients with unresectable mCRCs, treated between 2010 and 2015, were included retrospectively in this descriptive monocenter study and grouped according to their RECIST 1.1 first-line best responses: progressive disease (PD), stable disease with tumor-size evolution between 0 and + 19% (SD+) or 0 and - 29% (SD-), and partial responders (PRs), who were classed PR with ETS (ETS) or without (PR). Tumor-size evolution and best tumor responses to each chemotherapy line were analyzed.

Results: Tumor loads of ETS or PR mCRCs tended to remain inferior to their initial values: 60% of patients died with target lesion sums below baseline. For first-line SD+ or PD mCRCs, rapid tumor load increases continued during successive lines: > 80% died with target lesion sums above baseline. ETS mCRCs responded better to subsequent lines (37.5% second-line PR), whereas PD mCRCs remained refractory to other therapies (0% second- and third-line PR). Overall survival rates were significantly (p = 0.03) longer for the ETS group (29.9 [95% CI: 12.6-47.1] months) and shorter for the PD group (17.1 [95% CI: 1.5-37.5] months).

Conclusion: Tumors responding to first-line chemotherapy also responded better to subsequent lines, whereas PD mCRCs remained refractory, which may explain the better survival associated with ETS.

Key Points: • Early shrinking tumors under first-line chemotherapy responded better to subsequent lines, maintaining low tumor loads, potentially explaining the link between early tumor shrinkage and overall survival of metastatic colorectal cancer (mCRC) patients. • mCRCs progressing under first-line chemotherapy remained refractory to other therapies and their tumor loads increased rapidly. • Even outside a clinical trial, an early first CT scan reevaluation with RECIST criteria 8 weeks after starting first-line therapy is crucial to determine long-term mCRC evolution.
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http://dx.doi.org/10.1007/s00330-018-5967-0DOI Listing
July 2019

Inhibitory Effect of Ursodeoxycholic Acid on Germination Is Insufficient to Prevent Colitis: A Study in Hamsters and Humans.

Front Microbiol 2018 22;9:2849. Epub 2018 Nov 22.

INSERM U1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Paris Diderot, Université Paris Diderot, Paris, France.

Bile acids (BA) influence germination and growth of . Ursodeoxycholic acid (UDCA), a BA minor in human, used for cholestatic liver diseases, inhibits germination and growth of , but was never tested with an infectious challenge versus control. We hypothesized that UDCA could prevent CDI. We evaluated the effects of UDCA on and in hamsters, with pharmacokinetics study and with an infectious challenge. Then, we studied CDI incidence in UDCA-treated patients. We evaluated germination and growth of , with 0.01, 0.05, and 0.1% UDCA. We analyzed fecal BA of hamsters receiving antibiotics and UDCA (50 mg/kg/day), antibiotics, or UDCA alone. Then, we challenged with spores of at D6 hamsters treated with UDCA (50 mg/kg/day) from D1 to D13, versus control. In human, we analyzed the database of a cohort on CDI in acute flares of inflammatory bowel disease (IBD). As PSC-IBD patients were under UDCA treatment, we compared PSC-IBD patients to IBD patients without PSC. , UDCA inhibited germination and growth of at 0.05 and 0.1%, competing with 0.1% TCA (with 0.1%: 0.05% ± 0.05% colony forming unit versus 100% ± 0%, < 0.0001). In hamsters, UDCA reached high levels only when administered with antibiotics (43.5% UDCA at D5). Without antibiotics, UDCA was in small amount in feces (max. 4.28%), probably because of UDCA transformation into LCA by gut microbiota. During infectious challenge, mortality was similar in animals treated or not with UDCA (62.5%, = 5/8, = 0.78). UDCA percentage was high, similar and with the same kinetics in dead and surviving hamsters. However, dead hamsters had a higher ratio of primary over secondary BA compared to surviving hamsters. 9% ( = 41/404) of IBD patients without PSC had a CDI, versus 25% ( = 4/12) of PSC-IBD patients treated with UDCA. We confirmed the inhibitory effect of UDCA on growth and germination of , with 0.05 or 0.1% UDCA. However, in our hamster model, UDCA was inefficient to prevent CDI, despite high levels of UDCA in feces. Patients with PSC-IBD treated with UDCA did not have less CDI than IBD patients.
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http://dx.doi.org/10.3389/fmicb.2018.02849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262072PMC
November 2018