Publications by authors named "Romain Coriat"

260 Publications

Successful treatment of hemorrhagic radiation esophagitis with radiofrequency ablation.

Endoscopy 2022 May 13. Epub 2022 May 13.

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

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http://dx.doi.org/10.1055/a-1824-5000DOI Listing
May 2022

Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers.

Int J Mol Sci 2022 Apr 17;23(8). Epub 2022 Apr 17.

Hepato-Gastroenterology Department, Poitiers University Hospital, 86000 Poitiers, France.

Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI.
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http://dx.doi.org/10.3390/ijms23084427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032866PMC
April 2022

Observational Study in a Real-World Setting of Targeted Therapy in the Systemic Treatment of Progressive Unresectable or Metastatic Well-Differentiated Pancreatic Neuroendocrine Tumors (pNETs) in France: OPALINE Study.

Adv Ther 2022 Jun 13;39(6):2731-2748. Epub 2022 Apr 13.

Service d'Oncologie Médicale Hôpital Edouard Herriot, GHC, Hospices Civils de Lyon, Lyon, France.

Introduction: Approval of sunitinib and everolimus for the treatment of progressive, unresectable or metastatic well-differentiated pancreatic neuroendocrine tumors (pNETs) was obtained in France in 2011 and 2012, respectively. OPALINE was set up as an observational study to evaluate the efficacy of sunitinib and everolimus compared to usual pNET treatments of chemotherapies and somatostatin analogues that had been previously recommended by the health authorities.

Methods: The OPALINE study assessed the efficacy of everolimus and sunitinib in terms of survival, disease progression and tolerance. Patients (N = 144) were enrolled from May 2015 to September 2017, and their disease characteristics were analyzed from diagnosis to 2 years post-enrollment.

Results: At inclusion most patients had comorbidities, and about 95% presented metastases. Patients received on average 3.2 lines of treatment from diagnosis to inclusion and two lines throughout the 2-year follow-up. Seventy-nine patients (59.0%) received at least one targeted therapy (TT) during their care path. For these patients, the overall survival (OS) was approximatively 176.5 months (95% CI: 97.2-not evaluable), with a 2-year survival rate estimated at 93.6% (SD 2.6%). Similar survival rates were observed whether the TTs were prescribed sooner or later in the treatment path. The main reasons for discontinuation of TTs were disease progression (54 patients) and adverse events (26 patients). Most patients receiving TTs did not change their dose during the follow-up reflecting the good treatment tolerability over time. No new safety alert was reported for everolimus and sunitinib during this study.

Conclusion: Given their good tolerance and positive impact on estimated OS, the two TTs have an important role to play in the care path of patients with pNETs.

Clinicaltrials:

Gov National Clinical Trial Number: NCT02264665.
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http://dx.doi.org/10.1007/s12325-022-02103-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123044PMC
June 2022

Prognosis and chemosensitivity of non-colorectal alimentary tract cancers with microsatellite instability.

Dig Liver Dis 2022 Apr 6. Epub 2022 Apr 6.

Hepato-Gastroenterology Department, Poitiers University Hospital, University of Poitiers, 2 rue de la Milétrie, Poitiers 86000, France. Electronic address:

Background: Data on outcomes of microsatellite instable and/or mismatch repair deficient (dMMR/MSI) digestive non-colorectal tumors are limited.

Aims: To evaluate overall survival (OS) of patients with dMMR/MSI digestive non-colorectal tumor.

Methods: All consecutive patients with a dMMR/MSI digestive non-colorectal tumor were included in this French retrospective multicenter study.

Results: One hundred and sixteen patients were included with a mean age of 63.6 years and 32.6% with a Lynch syndrome. Most tumors were oesophago-gastric (54.3%) or small bowel (32.8%) adenocarcinomas and at a localized stage at diagnosis (86.7%). In patients with localized tumors and R0 resection, median OS was 134.0 ± 64.2 months. Median disease-free survival (DFS) was 100.3 ± 65.7 months. Considering oesophago-gastric tumors, median DFS was improved when chemotherapy was added to surgery (not reached versus 22.8 ± 10.0 months, p = 0.03). In patients with advanced tumors treated by chemotherapy, median OS was 14.2 ± 1.9 months and median progression-free survival was 7.4 ± 1.6 months.

Conclusion: dMMR/MSI digestive non-colorectal tumors are mostly diagnosed at a non-metastatic stage with a good prognosis. Advanced dMMR/MSI digestive non-colorectal tumors have a poor prognosis with standard chemotherapy.
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http://dx.doi.org/10.1016/j.dld.2022.03.011DOI Listing
April 2022

Sequential Treatment With Trifluridine/Tipiracil and Regorafenib in Refractory Metastatic Colorectal Cancer Patients: An AGEO Prospective "Real-World Study".

Clin Colorectal Cancer 2022 Jun 14;21(2):132-140. Epub 2022 Feb 14.

Hôpital Européen Georges Pompidou, Université de Paris, Paris, France. Electronic address:

Introduction: Regorafenib (R) and trifluridine/tipiracil (FTD/TPI) are of proven efficacy in metastatic colorectal cancer (mCRC) patient's refractory to standard therapies. However, it remains unclear which drug should be administered first.

Patients And Methods: This French observational study was prospectively conducted in 11 centers between June 2017 and September 2019. All consecutive patients with chemorefractory mCRC and receiving FTD/TPI and/or R were eligible. The aim was to evaluate the efficacy and tolerability of FTD/TPI and/or R in real-world setting with adjusted analysis.

Results: A total of 237 mCRC patients (25% R and 75% FTD/TPI) were enrolled. As compared to R, FTD/TPI patients were significantly older and with more metastatic sites. Median OS and PFS were respectively 6.2 and 2.4 months in the FTD/TPI and 6.6 and 2.1 months in the R group. After matching 46 paired patients according to a propensity score, a trend to a longer OS (P = .58), and a significantly longer PFS (P = .048) were observed in the FTD/TPI group. In the 24% of patients receiving the R/T or T/R sequence, median OS from first treatment was similar. Tolerability profiles were similar to published data and dose reductions were more frequent in the R group.

Conclusion: Efficacy and safety results in this real-world prospective study are in line with phase III trials. In a matched population, PFS was significantly longer in the FTD/TPI group. Despite a limited number of patients, clinical outcomes seemed similar in patients treated with the T/R or R/T sequence.
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http://dx.doi.org/10.1016/j.clcc.2021.12.003DOI Listing
June 2022

Impact of Delaying the Addition of Anti-EGFR in First Line of RAS Wild-Type Metastatic Colorectal Cancer: A Propensity-Weighted Pooled Data Analysis.

Cancers (Basel) 2022 Mar 10;14(6). Epub 2022 Mar 10.

Gastroenterology and Digestive Oncology Department, Cochin Hospital, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France.

The first-line therapy of patients with RAS wild-type (WT) non-resectable metastatic colorectal cancer (mCRC) is usually 5-fluorouracil-based chemotherapy with either bevacizumab or an anti-epidermal growth factor receptor (EGFR). The addition of anti-EGFR antibodies is commonly delayed in clinical practice because of late RAS testing results. Our objective was to evaluate the impact on overall survival (OS) of a delayed anti-EGFR introduction strategy. This study pooled the data of two large retrospective studies. Patients with RAS WT non-resectable mCRC, treated in first line by a doublet chemotherapy with an anti-EGFR introduced with a delay of 2 to 4 cycles, were compared to an anti-EGFR and to an anti-VEGF that was introduced immediately. Patients numbering 305 in the delayed anti-EGFR group, 401 in the immediate anti-EGFR group, and 129 in the immediate anti-VEGF group were analyzed. After propensity scoring, there was no difference between the characteristics of the three groups. Median OS was 28.6 months (95% CI: 23.5-34.1) in the immediate anti-EGFR group, 35.1 (95% CI: 29.9-43.5) in the delayed anti-EGFR group, and 32.4 (95% CI: 25.4-44.8) in the immediate anti-VEGF group. There was no significant difference concerning median OS ( = 0.24) or progression-free survival ( = 0.56). This study suggests that delaying the introduction of an anti-EGFR has no deleterious impact on survival compared to the immediate introduction of an anti-VEGF or of an anti-EGFR.
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http://dx.doi.org/10.3390/cancers14061410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946276PMC
March 2022

Perihilar cholangiocarcinoma: What the radiologist needs to know.

Diagn Interv Imaging 2022 Mar 18. Epub 2022 Mar 18.

Department of Digestive, Pancreatic, Hepato-biliary and Endocrine Surgery, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014, Paris, France; Université Paris Cité, Faculté de Médecine, 75006 Paris, France.

Perihilar cholangiocarcinoma (PHC) is a common and highly intractable malignancy of the main biliary tree confluence. PHC is associated with a poor prognosis because of its insidious local spread that makes it challenging to diagnose and assess. Surgical resection remains the standard curative treatment (up to 50% 5-year overall survival after negative-margin resection). More aggressive surgical approaches have recently emerged, pushing the boundaries of PHC resectability at the cost of a higher morbidity. As such, adequate preoperative preparation (i.e., biliary drainage, venous embolization) is now regarded as a critical issue to increase the number of patients amenable to extended liver resection. Thorough imaging plays a pivotal role in the preoperative setting in both PHC resectability assessment and patient preparation to surgery. Despite recent improvement in PHC imaging, its assessment remains challenging and only 50-60% of patients who are scheduled to undergo surgery are ultimately amenable to curative resection. Therefore, a knowledge of available diagnostic and interventional imaging techniques is important to improve PHC management. Herein, we review the various imaging techniques and preoperative radiological interventions such as biliary drainage, portal vein embolization and liver venous deprivation that are available in PHC management focusing on the anatomical and oncological considerations that are crucial to prepare and guide curative surgical resection.
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http://dx.doi.org/10.1016/j.diii.2022.03.001DOI Listing
March 2022

Endoscopic ultrasound guided fine needle biopsy in patients with suspected gastric linitis plastica.

Clin Res Hepatol Gastroenterol 2022 Mar 14;46(5):101903. Epub 2022 Mar 14.

Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 27 rue du Faubourg St Jacques, 75014 Paris, France; Faculté de Médicine Paris Centre, Université de Paris, 75006 Paris, France.

Background: Gastric linitis plastica (GLP) is a diffuse infiltrating type of gastric adenocarcinoma. It is associated with a poor prognosis and a five-year survival of 3-10%. The infiltrating profile of this tumor explains the low yield of the superficial mucosal biospies. The objective of this study was to investigate the role of endoscopic ultrasound-fine needle biopsy (EUS-FNB) in the diagnosis of GLP.

Methods: We performed a retrospective analysis including all patients who had an EUS-FNB, at a tertiary referral center, over the last 3 years. The primary outcome was the sensitivity of EUS-FNB in patients with suspected GLP.

Results: Between January 2017 and December 2020, 34 patients had an EUS-FNB for suspected GLP. Ten patients had a diagnostic of GLP. This diagnosis was obtained by EUS-FNB in 90% (9/10) of the cases. Eight patients had at least one previous esophagogastroduodenoscopy (EGD) with negative mucosal biopsies. Gastric EUS-FNB helped diagnose other serious conditions in 47% (16/34) of cases with inconclusive mucosal biopsies.

Conclusion: Gastric EUS-FNB in patients with suspected GLP and normal endoscopic mucosal biopsies may lead to a positive diagnosis of GLP in 90% of cases without notable adverse events. This technique should be considered as a second step in the setting of suspicion of GLP after inconclusive mucosal biopsies.
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http://dx.doi.org/10.1016/j.clinre.2022.101903DOI Listing
March 2022

The Role of Magnetic Resonance Imaging in the Management of Esophageal Cancer.

Cancers (Basel) 2022 Feb 23;14(5). Epub 2022 Feb 23.

Department of Gastroenterology and Digestive Oncology, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France.

Esophageal cancer (EC) is the eighth more frequent cancer worldwide, with a poor prognosis. Initial staging is critical to decide on the best individual treatment approach. Current modalities for the assessment of EC are irradiating techniques, such as computed tomography (CT) and positron emission tomography/CT, or invasive techniques, such as digestive endoscopy and endoscopic ultrasound. Magnetic resonance imaging (MRI) is a non-invasive and non-irradiating imaging technique that provides high degrees of soft tissue contrast, with good depiction of the esophageal wall and the esophagogastric junction. Various sequences of MRI have shown good performance in initial tumor and lymph node staging in EC. Diffusion-weighted MRI has also demonstrated capabilities in the evaluation of tumor response to chemoradiotherapy. To date, there is not enough data to consider whole body MRI as a routine investigation for the detection of initial metastases or for prediction of distant recurrence. This narrative review summarizes the current knowledge on MRI for the management of EC.
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http://dx.doi.org/10.3390/cancers14051141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909473PMC
February 2022

MiR-31-3p do not predict anti-EGFR efficacy in first-line therapy of RAS wild-type metastatic right-sided colon cancer.

Clin Res Hepatol Gastroenterol 2022 Feb 18;46(5):101888. Epub 2022 Feb 18.

Department of Gastroenterology, Rennes University Hospital, University Hospital of Pontchaillou, 2 rue Henri Le Guilloux, Rennes 35033 Cedex 09, France; INSERM U1242 "Chemistry Oncogenesis Stress Signaling", Rennes 1 University, Rennes, France. Electronic address:

Background: Low miR-31-3p expression was identified as predictive of anti-EGFR efficacy in RAS-wt mCRC. Primary tumor side was also proposed as a predictive factor of anti-EGFR benefit. This retrospective multicentric study evaluated the predictive role of miR-31-3p in right-sided RAS-wt mCRC patients treated with first-line CT+anti-EGFR or CT+bevacizumab (Beva).

Methods: Seventy-two right-sided RAS-wt mCRC patients treated in first-line with CT+anti-EGFR (n = 43) or Beva (n = 29) were included. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were analyzed and stratified according to tumor miR-31-3p expression level and targeted therapy (TT).

Results: BRAF V600E mutation was more frequent in high vs low miR-31-3p expressers (60.6% vs 15.4%, P < 0.001). PFS was significantly longer with CT+Beva than with CT+anti-EGFR (13 vs 7 months; P = 0.024). Among low miR-31-3p expressers, PFS, OS and RR were not significantly different between the two groups, while in high miR-31-3p expressers, only PFS was longer in the CT+Beva group (11 vs 6 months; P = 0.03). In patients treated with CT+anti-EGFR, low miR-31-3p expressers had a significantly longer OS (20 vs 13 months; P = 0.02) than high miR-31-3p expressers. ORR was not significantly different between the two groups of treatment, in both low and high miR-31-3p expressers. MiR-31-3p expression status was statistically correlated between primary tumors and corresponding metastases.

Conclusion: In this study, miR-31-3p couldn't identify a subgroup of patients with right-sided RAS-wt mCRC who might benefit from anti-EGFR and suggest that Beva is the TT of choice in first-line treatment of these patients.
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http://dx.doi.org/10.1016/j.clinre.2022.101888DOI Listing
February 2022

Endoscopic management of anastomotic leak after esophageal or gastric resection for malignancy: a multicenter experience.

Therap Adv Gastroenterol 2021 23;14:17562848211032823. Epub 2021 Jul 23.

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

Background: Most anastomotic leaks after surgical resection for esophageal or esophagogastric junction malignancies are treated endoscopically with esophageal stents. Internal drainage by double pigtail stents has been used for the endoscopic management of leaks following bariatric surgery, and recently introduced for anastomotic leaks after resections for malignancies. Our aim was to assess the overall efficacy of the endoscopic treatment for anastomotic leaks after esophageal or gastric resection for malignancies.

Methods: We conducted a multicenter retrospective study in four digestive endoscopy tertiary referral centers in France. We included consecutive patients managed endoscopically for anastomotic leak following esophagectomy or gastrectomy for malignancies between January 2016 and December 2018. The primary outcome was the efficacy of the endoscopic management on leak closure.

Results: Sixty-eight patients were included, among which 46 men and 22 women, with a mean ± SD age of 61 ± 11 years. Forty-four percent had an Ivor Lewis procedure, 16% a tri-incisional esophagectomy, and 40% a total gastrectomy. The median time between surgery and the diagnosis of leak was 9 (6-13) days. Endoscopic treatment was successful in 90% of the patients. The efficacy of internal drainage and esophageal stents was 95% and 77%, respectively ( = 0.06). The mortality rate was 3%. The only predictive factor of successful endoscopic treatment was the initial use of internal drainage ( = 0.002).

Conclusion: Endoscopic management of early postoperative leak is successful in 90% of patients, preventing highly morbid surgical revisions. Internal endoscopic drainage should be considered as the first-line endoscopic treatment of anastomotic fistulas whenever technically feasible.
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http://dx.doi.org/10.1177/17562848211032823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832292PMC
July 2021

A step toward a better understanding of hepatocellular progression after transarterial embolization.

Diagn Interv Imaging 2022 Mar 11;103(3):125-126. Epub 2022 Feb 11.

Department of Body and Interventional Imaging, Hôpital Cochin, AP-HP, 75014 Paris, France; Université de Paris, Faculté de Médecine, 75006 Paris, France.

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http://dx.doi.org/10.1016/j.diii.2022.01.013DOI Listing
March 2022

Re: "Does surgery provide a survival advantage in nondisseminated poorly differentiated gastroenteropancreatic neuroendocrine neoplasms".

Surgery 2022 05 25;171(5):1443-1444. Epub 2022 Jan 25.

Gastroenterology and Digestive Oncology Unit, Hôpital Cochin, APHP Centre, Paris, France; Unité INSERM, Université de Paris, Paris, France.

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http://dx.doi.org/10.1016/j.surg.2021.08.050DOI Listing
May 2022

Multimodal Management of Grade 1 and 2 Pancreatic Neuroendocrine Tumors.

Cancers (Basel) 2022 Jan 15;14(2). Epub 2022 Jan 15.

Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France.

Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.
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http://dx.doi.org/10.3390/cancers14020433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773540PMC
January 2022

Endoscopic management of non-ampullary duodenal adenomas.

Endosc Int Open 2022 Jan 14;10(1):E96-E108. Epub 2022 Jan 14.

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

Duodenal polyps are found in 0.1 % to 0.8 % of all upper endoscopies. Duodenal adenomas account for 10 % to 20 % of these lesions. They can be sporadic or occur in the setting of a hereditary predisposition syndrome, mainly familial adenomatous polyposis. Endoscopy is the cornerstone of management of duodenal adenomas, allowing for diagnosis and treatment, primarily by endoscopic mucosal resection. The endoscopic treatment of duodenal adenomas has a high morbidity, reaching 15 % in a prospective study, consisting of bleeding and perforations, and should therefore be performed in expert centers. The local recurrence rate ranges from 9 % to 37 %, and is maximal for piecemeal resections of lesions > 20 mm. Surgical resection of the duodenum is flawed with major morbidity and considered a rescue procedure in cases of endoscopic treatment failures or severe endoscopic complications such as duodenal perforations. In this paper, we review the existing evidence on endoscopic diagnosis and treatment of non-ampullary duodenal adenomas.
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http://dx.doi.org/10.1055/a-1723-2847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759941PMC
January 2022

Updates on the Treatment of Pancreatic Diseases: Focus on Surgery, Electrochemotherapy and Rituximab.

J Clin Med 2022 Jan 3;11(1). Epub 2022 Jan 3.

Gastroenterology and Digestive Oncology Unit, AP-HP Centre, Cochin Hospital, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France.

The pancreas plays an important role in the human body with its two main endocrine and exocrine functions [...].
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http://dx.doi.org/10.3390/jcm11010239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745851PMC
January 2022

Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study.

J Clin Oncol 2022 01 18;40(3):262-271. Epub 2021 Oct 18.

Gustave Roussy, Université Paris Saclay, Villejuif, France.

Purpose: Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown.

Methods: In this open-label, randomized phase II-III study, patients with locally advanced or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate ≥ 59%, 73% expected).

Results: A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events ≥ grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one).

Conclusion: mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.
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http://dx.doi.org/10.1200/JCO.21.00679DOI Listing
January 2022

Contrast extravasation on computed tomography angiography in patients with hematochezia or melena: Predictive factors and associated outcomes.

Diagn Interv Imaging 2022 Mar 14;103(3):177-184. Epub 2021 Oct 14.

Department of Radiology A, Hôpital Cochin, APHP, Paris 75014, France; Faculté de Médecine, Université de Paris, Paris 75006, France.

Purpose: The purpose of this study was to identify variables associated with extravasation on computed tomography angiography (CTA) in patients with hematochezia/melena and compare the outcome of patients with extravasation on CTA to those without extravasation.

Material And Methods: Ninety-four patients (51 men, 43 women; mean age, 69 ± 16 [SD] years) who underwent CTA within 30 days of hematochezia/melena were included. Variables associated with extravasation on CTA were searched using univariable and multivariable analyses. Outcomes of patients with visible extravasation on CTA were compared with those without visible extravasation.

Results: One hundred and one CTA examinations were included. Extravasation was observed on 26/101 CTA examinations (26%). At multivariable analysis the need for vasopressor drugs (odds ratio [OR], 7.6; P = 0.040), high transfusion requirements (> 2 blood units) (OR, 7.1; P = 0.014), CTA performed on the day of a hemorrhagic event (OR, 46.2; P = 0.005) and repeat CTA (OR, 27.8; P = 0.011) were independently associated with extravasation on CTA. Extravasation on CTA was followed by a therapeutic procedure in 25/26 CTAs (96%; 26 patients) compared to 13/75 CTAs (17%; 68 patients) on which no extravasation was present (P < 0.001). No patients (0/26; 0%) with contrast extravasation on CTA died while 8 patients (8/61; 13%) without contrast extravasation died, although the difference was not significant (P = 0.099).

Conclusion: Extravasation on CTA in the setting of hematochezia or melena is especially seen in clinically unstable patients who receive more than two blood units. Presence of active extravasation on CTA leads to more frequent application of a therapeutic procedure; however, this does not significantly affect patient outcome.
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http://dx.doi.org/10.1016/j.diii.2021.09.006DOI Listing
March 2022

Clinical impact of routine CT esophagogram after peroral endoscopic myotomy (POEM) for esophageal motility disorders.

Endosc Int Open 2021 Sep 16;9(9):E1355-E1360. Epub 2021 Aug 16.

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

Per oral endoscopic myotomy (POEM) of the lower esophageal sphincter has become a major treatment for esophageal motility disorders, especially achalasia. POEM can result in esophageal bleeding or perforation and pleural and mediastinal effusion. Early routine computed tomography (CT) esophagogram is frequently performed to assess these adverse events (AEs) before resuming oral food intake. We sought to evaluate the value of routine CT esophagogram on postoperative day (POD) 1 after POEM. This single-center retrospective study was performed in a tertiary referral center for interventional digestive endoscopy. We included consecutive patients with POEM and routine CT esophagogram on POD 1 between July 2018 and July 2019. Fifty-eight patients were included in the study, 79 % of whom had achalasia. Twenty patients (34 %) presented post-endoscopic AEs, including two patients with severe AEs requiring intensive care admission (one compressive pneumothorax and one mediastinitis); no deaths occurred. Of the 58 CT esophagograms performed, only one was normal. The 57 others (98 %) showed at least one abnormal finding: pneumoperitoneum or retroperitoneal air (91 %), pneumomediastinum (78 %), pleural effusion (34 %), pneumothorax (14 %), pneumonia (7 %), pericardial effusion (2 %), and mediastinal collection (2 %). CT esophagograms revealed AEs and modified therapeutic management in eight patients of 58 (14 %), all of whom had clinical symptoms prior to CT. POD 1 CT esophagogram after POEM for esophageal motility disorders diagnosed clinically meaningful AEs in 14 % of patients, all associated with persistent clinical symptoms. Routine use of CT esophagogram after POEM in asymptomatic patients is questionable.
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http://dx.doi.org/10.1055/a-1512-9638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367446PMC
September 2021

Amplatzer occluders for refractory esophago-respiratory fistulas: a case series.

Endosc Int Open 2021 Sep 16;9(9):E1350-E1354. Epub 2021 Aug 16.

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

Endoscopic management of esophagorespiratory fistulas (ERF) is challenging and currently available options (stents, double pigtail, endoscopic vacuum therapy) are not very effective. We report the feasibility and efficacy of endoscopic placement of Amplatzer cardiovascular occluders for this indication. This was a single-center, prospective study (June 2019 to September 2020) of all patients with non-malignant ERF persistent after conventional management with esophageal and/or tracheal stents. The primary outcome was the technical feasibility of Amplatzer placement. Secondary outcomes were clinical success defined by effective ERF occlusion and resolution of respiratory symptoms allowing oral food intake. Endoscopic placement of Amplatzer occluders was feasible in 83 % of patients (5/6), with a 50 % (3/6) clinical success rate at 9 months. The mortality rate was 33 % (2/6). An Amplatzer cardiac or vascular occluder is a feasible and safe treatment option for refractory ERF, with a 50 % short-term clinical success.
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http://dx.doi.org/10.1055/a-1490-9001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367450PMC
September 2021

Neuroendocrine Carcinomas of the Digestive Tract: What Is New?

Cancers (Basel) 2021 Jul 27;13(15). Epub 2021 Jul 27.

Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint Jacques, 75014 Paris, France.

Neuroendocrine carcinomas (NEC) are rare tumors with a rising incidence. They show poorly differentiated morphology with a high proliferation rate (Ki-67 index). They frequently arise in the lung (small and large-cell lung cancer) but rarely from the gastrointestinal tract. Due to their rarity, very little is known about digestive NEC and few studies have been conducted. Therefore, most of therapeutic recommendations are issued from work on small-cell lung cancers (SCLC). Recent improvement in pathology and imaging has allowed for better detection and classification of high-grade NEN. The 2019 World Health Organization (WHO) classification has described a new entity of well-differentiated grade 3 neuroendocrine tumors (NET G-3), with better prognosis, that should be managed separately from NEC. NEC are aggressive neoplasms often diagnosed at a metastatic state. In the localized setting, surgery can be performed in selected patients followed by adjuvant platinum-based chemotherapy. Concurrent chemoradiotherapy is also an option for NEC of the lung, rectum, and esophagus. In metastatic NEC, chemotherapy is administered with a classic combination of platinum salts and etoposide in the first-line setting. Peptide receptor radionuclide therapy (PRRT) has shown positive results in high-grade NEN populations and immunotherapy trials are still ongoing. Available therapies have improved the overall survival of NEC but there is still an urgent need for improvement. This narrative review sums up the current data on digestive NEC while exploring future directions for their management.
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http://dx.doi.org/10.3390/cancers13153766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345167PMC
July 2021

Impact of the COVID-19 pandemic on the management of cancer patients: the experience of the cancer outpatients department of a university hospital in Paris.

Clin Med (Lond) 2021 Sep 2;21(5):e552-e555. Epub 2021 Aug 2.

Cochin Hospital, Paris, France.

Cancer patients are a highly vulnerable group in the COVID-19 pandemic and it has been necessary for oncology units to adapt to this unexpected situation. We present our management of outpatients with cancer during the pandemic. We applied two major adaptations: extending the intervals between injections for maintenance therapy and protocol adaptation for patients with comorbidities. Between 17 March and 30 April 2020, 406 patients were treated in our outpatients department. Protocols were adapted for 94 (23.1%) patients. Among them, 49% had an extended interval between treatment administrations, 22.3% had modified protocols to reduce toxicity, 20.2% had therapeutic interruptions and 5.3% did not receive their treatment because of a COVID-19 infection. Overall, protocol adaptations concerned more than 20% of the patients. This pandemic was an opportunity for oncologists to re-examine the risk versus benefit balance of administering immunosuppressive treatment and highlighted that oncology daily routine should not be applied automatically.
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http://dx.doi.org/10.7861/clinmed.2020-0666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439500PMC
September 2021

Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives.

Ther Adv Med Oncol 2021 6;13:17588359211018539. Epub 2021 Jul 6.

Gastroenterology and Digestive Oncology Department, Cochin Hospital, APHP. Centre, Paris, France.

Major breakthroughs have been achieved in the management of metastatic pancreatic ductal adenocarcinoma (PDAC) with FOLFIRINOX (5-fluorouracil + irinotecan + oxaliplatin) and gemcitabine plus nab-paclitaxel approved as a first-line therapy, although the prognosis is still poor. At progression, patients who maintain a good performance status (PS) can benefit from second-line chemotherapy. To address the concern of achieving tumor control while maintaining a good quality of life, maintenance therapy is a concept that has now emerged. After a FOLFIRINOX induction treatment, maintenance with 5-fluorouracil (5-FU) seems to offer a promising approach. Although not confirmed in large, prospective trials, gemcitabine alone as a maintenance therapy following induction treatment with gemcitabine plus nab-paclitaxel could be an option, while a small subset of patients with a germline mutation of breast cancer gene ( can benefit from the polyadenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib. The rate of PDAC with molecular alterations that could lead to a specific therapy is up to 25%. The Food and Drug Administration (FDA) recently approved larotrectinib for patients with any tumors harboring a neurotrophic tyrosine receptor kinase ( gene fusion, and pembrolizumab for patients with a mismatch repair deficiency in a second-line setting, including PDAC. Research focused on targeted therapy and immunotherapy is active and could improve patients' outcomes in the near future.
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http://dx.doi.org/10.1177/17588359211018539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264726PMC
July 2021

Pembrolizumab with Capox Bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: The FFCD 1703-POCHI trial.

Dig Liver Dis 2021 Oct 30;53(10):1254-1259. Epub 2021 Jun 30.

Service d'Hépato-gastroentérologie, CHU de Poitiers et Université de Poitiers, Poitiers, France. Electronic address:

Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI. We formulated the hypothesis that patients with MSS/pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin and bevacizumab-based chemotherapy. POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of Pembrolizumab with Capox Bevacizumab as first-line treatment of MSS/pMMR mCRC with a high immune infiltrate for which we plan to enrol 55 patients. Primary endpoint is progression-free survival (PFS) at 10 months, which is expected greater than 50%, but a 70% rate is hoped for. Main secondary objectives are overall survival, secondary resection rate and depth of response. Patients must have been resected of their primary tumour so as to evaluate two different immune scores (Immunoscore® and TuLIS) and are eligible if one score is "high". The first patient was included on April 20, 2021.
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http://dx.doi.org/10.1016/j.dld.2021.06.009DOI Listing
October 2021

Utility of CT to Differentiate Pancreatic Parenchymal Metastasis from Pancreatic Ductal Adenocarcinoma.

Cancers (Basel) 2021 Jun 22;13(13). Epub 2021 Jun 22.

Department of Radiology, Hôpital Cochin, AP-HP, 75014 Paris, France.

: To report the computed tomography (CT) features of pancreatic parenchymal metastasis (PPM) and identify CT features that may help discriminate between PPM and pancreatic ductal adenocarcinoma (PDAC). : Thirty-four patients (24 men, 12 women; mean age, 63.3 ± 10.2 [SD] years) with CT and histopathologically proven PPM were analyzed by two independent readers and compared to 34 patients with PDAC. Diagnosis performances of each variable for the diagnosis of PPM against PDAC were calculated. Univariable and multivariable analyses were performed. A nomogram was developed to diagnose PPM against PDAC. : PPM mostly presented as single (34/34; 100%), enhancing (34/34; 100%), solid (27/34; 79%) pancreatic lesion without visible associated lymph nodes (24/34; 71%) and no Wirsung duct enlargement (29/34; 85%). At multivariable analysis, well-defined margins (OR, 6.64; 95% CI: 1.47-29.93; = 0.014), maximal enhancement during arterial phase (OR, 6.15; 95% CI: 1.13-33.51; = 0.036), no vessel involvement (OR, 7.19; 95% CI: 1.512-34.14) and no Wirsung duct dilatation (OR, 10.63; 95% CI: 2.27-49.91) were independently associated with PPM. The nomogram yielded an AUC of 0.92 (95% CI: 0.85-0.98) for the diagnosis of PPM vs. PDAC. : CT findings may help discriminate between PPM and PDAC.
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http://dx.doi.org/10.3390/cancers13133103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268077PMC
June 2021

Diagnosis of Infection in a Routine Testing Workflow: Effect of Bacterial Load and Virulence Factors.

J Clin Med 2021 Jun 23;10(13). Epub 2021 Jun 23.

Service de Bactériologie, AP-HP Centre-Université de Paris, Hôpital Cochin, 75014 Paris, France.

Reliable diagnostic methods are mandatory for effective management of infection. Histology and culture are the most common invasive methods in current practice, even if molecular methods are gaining in importance. The performance of these conventional methods varies significantly. We conducted a retrospective study of 1540 adults and 504 children with gastric biopsies taken during endoscopy to assess the impact of bacterial load and the virulence factor on the performance of infection testing. The association between virulence and histology findings was also investigated. With 23S rRNA qPCR confirmed by amplification as the gold standard, culture and histology had lower sensitivity, 74.4% and 73.3%, respectively. However, their sensitivity was enhanced (>90%) in biopsies with high bacterial load (qPCR Ct < 30). Positive status of the strain was associated with high bacterial load (94.9%), thus resulting in more frequent positive culture (94.3%) and histology detection (91.7%) and more severe lesions on histology ( < 0.001). Conversely, the status of the strains was negative in 110/119 (92.4%) of biopsies with low bacterial load (qPCR Ct < 30), 82/90 (91.1%) with negative histology detection and 119/131 (90%) with negative culture findings ( < 0.001). This study highlights the low sensitivity of conventional culture and histology that may lead to false negative diagnosis if used alone. quantification associated with genotyping in routine workflow are essential for a sensitive and reliable diagnosis, to identify patients at high risk and to manage eradication therapies.
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http://dx.doi.org/10.3390/jcm10132755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268826PMC
June 2021

Efficacy and tolerance of gemcitabine and nab-paclitaxel in elderly patients with advanced pancreatic ductal adenocarcinoma.

Pancreatology 2021 May 24. Epub 2021 May 24.

Université de Paris, Department of Gastroenterology and Pancreatology, Beaujon University Hospital (APHP), Clichy, France. Electronic address:

Background: The efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting.

Patients And Methods: We retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years.

Results: The study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8-10.2) and PFS (median, 5.5 months; 95% CI, 4.8-6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis.

Conclusion: GnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.
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http://dx.doi.org/10.1016/j.pan.2021.05.006DOI Listing
May 2021

Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions.

Cancers (Basel) 2021 May 18;13(10). Epub 2021 May 18.

Department of Gastroenterology and Digestive Oncology, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, Université de Paris, 75014 Paris, France.

Digestive well-differentiated grade 3 neuroendocrine tumors (NET G-3) have been clearly defined since the 2017 World Health Organization classification. They are still a rare category lacking specific data and standardized management. Their distinction from other types of neuroendocrine neoplasms (NEN) not only lies in morphology but also in genotype, aggressiveness, functional imaging uptake, and treatment response. Most of the available data comes from pancreatic series, which is the most frequent tumor site for this entity. In the non-metastatic setting, surgical resection is recommended, irrespective of grade and tumor site. For metastatic NET G-3, chemotherapy is the main first-line treatment with temozolomide-based regimen showing more efficacy than platinum-based regimen, especially when Ki-67 index <55%. Targeted therapies, such as sunitinib and everolimus, have also shown some positive therapeutic efficacy in small samples of patients. Functional imaging plays a key role for detection but also treatment selection. In the second or further-line setting, peptide receptor radionuclide therapy has shown promising response rates in high-grade NEN. Finally, immunotherapy is currently investigated as a new therapeutic approach with trials still ongoing. More data will come with future work now focusing on this specific subgroup. The aim of this review is to summarize the current data on digestive NET G-3 and explore future directions for their management.
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http://dx.doi.org/10.3390/cancers13102448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158108PMC
May 2021

Prognostic transcriptome classes of duodenopancreatic neuroendocrine tumors.

Endocr Relat Cancer 2021 06 21;28(8):563-571. Epub 2021 Jun 21.

Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, F-75014, Paris, France.

Duodenopancreatic neuroendocrine tumors (DPNETs) aggressiveness is heterogeneous. Tumor grade and extension are commonly used for prognostic determination. Yet, grade classes are empirically defined, with regular updates changing the definition of classes. Genomic screening may provide more objective classes and reflect tumor biology. The aim of this study was to provide a transcriptome classification of DPNETs. We included 66 DPNETs, covering the entire clinical spectrum of the disease in terms of secretion, grade, and stage. Three distinct molecular groups were identified, associated with distinct outcomes (log-rank P < 0.01): (i) better-outcome DPNETs with pancreatic beta-cell signature. This group was mainly composed of well-differentiated, grade 1 insulinomas; (ii) poor-outcome DPNETs with pancreatic alpha-cell and hepatic signature. This group included all neuroendocrine carcinomas and grade 3 DPNETs, but also some grade 1 and grade 2 DPNETs and (iii) intermediate-outcome DPNETs with pancreatic exocrine and progenitor signature. This group included grade 1 and grade 2 DPNETs, with some insulinomas. Fibrinogen gene FGA expression was one of the topmost expressed liver genes. FGA expression was associated with disease-free survival (HR = 1.13, P = 0.005) and could be validated on two independent cohorts. This original pathophysiologic insight provides new prognostic classification perspectives.
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http://dx.doi.org/10.1530/ERC-21-0051DOI Listing
June 2021

Colorectal cancer screening programme: is the French faecal immunological test (FIT) threshold optimal?

Therap Adv Gastroenterol 2021 7;14:17562848211009716. Epub 2021 May 7.

Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, Paris, France.

Background: In France, the colorectal cancer organised screening programme uses the faecal immunological test. A positive test ⩾30 μg Hb/g of stool leads to a colonoscopy for identification of potential colorectal lesions. Cut-off values vary from 20 to 47 μg Hb/g of stool in Western countries. We herein question this threshold's relevance in a French population and perform a retrospective observational study using the Parisian database between 1 April 2015 and 31 December 2018.

Methods: Rates of participation, numbers of positive faecal immunological test (FIT), detection rates and positive predictive values for advanced adenomas and/or colorectal cancer were determined. Mean positivity values for colorectal lesions were calculated.

Results: In our population, there were 4.1% positive tests and 67.6% colonoscopy results available with final reports. Positive predictive value for advanced adenomas and colorectal cancer were 30% [95% confidence interval (CI) 29.8-30.3] and 7.4% (95% CI 7.35-7.52), respectively. The mean positivity value for all positive tests in our population was 101.7 µg Hb/g of stool (95% CI 85-118.3). There were 1136 normal colonoscopies (21.4%) with a mean positivity value of 88.6 μg Hb/g of stool. Following a negative test in a first screening campaign, 40.8% of patients in our population performed a second test with a positivity rate of 1.3% and with the encounter of 81 colorectal cancers. The risk of having a positive test during the second screening campaign and finding advanced colorectal lesions significantly increased (all  < 0.001) when comparing negative FIT results ranging between 15 and 29 μg Hb/g of stool to 0 and 14 μg Hb/g of stool from the previous campaign.

Conclusion: Using the current positivity threshold, some patients were considered negative with a delay in colorectal cancer diagnosis, suggesting the threshold could be lowered. Also, the mean positivity value for normal colonoscopies was high, raising the question of upper gastrointestinal bleeding.
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http://dx.doi.org/10.1177/17562848211009716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111528PMC
May 2021
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