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1.
J Neurogastroenterol Motil ; 29(4): 455-459, 2023 Oct 30.
Article En | MEDLINE | ID: mdl-37634895

Background/Aims: Achalasia and hiatal hernia are rarely associated. The aim of the current study is to explore the clinical and manometric findings in patients with achalasia and hiatal hernia, and to determine if the presence of a hiatal hernia should influence therapeutic management in patients with achalasia. Methods: This retrospective single center analysis included a group of patients with achalasia and hiatal hernia (study group) and a group of matched patients with achalasia but no hiatal hernia (control group). We recorded demographic, clinical, endoscopic, and manometric parameters and compared initial presentation and treatment outcomes between the groups. Results: Between 2015 and 2022, achalasia was diagnosed in 294/1513 (19.4%) patients. Concomitant hiatal hernia was identified in 13/294 (4.4%) patients. Compared to patients with achalasia and no hiatal hernia, patients in the study group had lower Eckardt scores at baseline (5.4 ± 2.0 vs 7.8 ± 2.4; P = 0.005) but similar integrated relaxation pressure. Following treatment, patients in the study and control group had similar clinical success and prevalence of gastroesophageal reflux symptoms. Conclusions: Hiatal hernia is rarely associated with achalasia. The presence of a hiatal hernia should not influence treatment decisions in patients with achalasia.

2.
Clin Res Hepatol Gastroenterol ; 46(7): 101921, 2022.
Article En | MEDLINE | ID: mdl-35390539

BACKGROUND: Little is known about small bowel capsule endoscopy (SBCE) outcomes in patients with surgically altered anatomy. AIMS: To assess the feasibility and diagnostic yield of orally ingested SBCE to investigate obscure gastrointestinal bleeding (OGIB) in patients with surgically altered gastric anatomy, compared to native gastric anatomy. METHODS: 207 patients with OGIB were selected from an open, multicenter, retrospective cohort (SAGA study) and match-paired according to age, gender and bleeding type (overt/occult) to 207 control patients from a randomized controlled trial (PREPINTEST). Primary outcomes were the diagnostic yield (P1 or P2 findings), completion rate, adverse events rate, and small bowel transit time (SBTT). RESULTS: The diagnostic yield was not statistically different between groups (44.9% in SAGA vs 42.5% in control patients). Inflammatory/ulcerated lesions were significantly more frequent in patients with SAGA (43.0% vs 29.3%). The median SBTT was significantly longer in the SAGA group than in control patients (283 vs 206 minutes), with a significantly lower completion rate (82.6% vs 89.9%); Adverse events were scarce (0.5% vs 0.0%). CONCLUSION: Patients with surgically altered gastric anatomy should benefit from SBCE investigation for OGIB as much as non-operated patients.


Capsule Endoscopy , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/pathology , Humans , Intestine, Small/pathology , Intestine, Small/surgery , Retrospective Studies , Stomach/surgery
3.
Endosc Int Open ; 9(9): E1355-E1360, 2021 Sep.
Article En | MEDLINE | ID: mdl-34466359

Background and study aims 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. Patients and methods 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. Results 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. Conclusions 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.

4.
Clin Res Hepatol Gastroenterol ; 45(6): 101612, 2021 11.
Article En | MEDLINE | ID: mdl-33740610

OBJECTIVE: The detection of lesions during small bowel (SB) capsule endoscopy (CE) depends on the cleanliness of the intestine. Quality reporting and comparison of different preparation methods require reliable scores. Three scores known as quantitative index (QI), qualitative evaluation (QE), and overall adequacy assessment (OAA), have been proposed to assess SB cleanliness, and are sometimes used in clinical practice and in clinical trials. However, none of these scores has received any external validation. The aim of our study was to re-assess the reproducibility of these three specific scores. METHODS: One-hundred-and-fifty-five complete third-generation SB-CE video recordings were extracted from a multicenter randomized controlled trial (PREPINTEST) which evaluated three modalities of SB preparation for CE. Three experts independently read the 155 SB-CE video recordings twice, in a random order, over 48 -h periods at 6-week intervals, using the QI, QE and OAA scores. Cohen's linearly weighted kappa coefficients were calculated to assess intra-observer and inter-observer agreements. RESULTS: Intra-observer reproducibility was fair to moderate, with kappa coefficients between 0.37 and 0.46 for QI, 0.41 and 0.51 for QE, 0.41 and 0.50 for OAA. Inter-observer reproducibility was fair to substantial according to kappa coefficients between experts varying from 0.40 to 0.64, 0.29 to 0.65, and 0.52 to 0.71, for QI, QE and OAA, respectively. CONCLUSIONS: QI, QE and OAA scores, currently used for evaluation of the quality of the preparation of SB-CE, are not sufficiently reproducible. Other scores or methods are therefore needed for SB-CE cleanliness assessment.


Capsule Endoscopy , Intestine, Small , Video Recording , Humans , Intestine, Small/diagnostic imaging , Prospective Studies , Reproducibility of Results
5.
Endoscopy ; 53(9): 932-936, 2021 09.
Article En | MEDLINE | ID: mdl-33137834

BACKGROUND: Cleanliness scores in small-bowel capsule endoscopy (SBCE) have poor reproducibility. The aim of this study was to evaluate a neural network-based algorithm for automated assessment of small-bowel cleanliness during capsule endoscopy. METHODS: 600 normal third-generation SBCE still frames were categorized as "adequate" or "inadequate" in terms of cleanliness by three expert readers, according to a 10-point scale, and served as a training database. Then, 156 third-generation SBCE recordings were categorized in a consensual manner as "adequate" or "inadequate" in terms of cleanliness; this testing database was split into two independent 78-video subsets for the tuning and evaluation of the algorithm, respectively. RESULTS: Using a threshold of 79 % "adequate" still frames per video to achieve the best performance, the algorithm yielded a sensitivity of 90.3 %, specificity of 83.3 %, and accuracy of 89.7 %. The reproducibility was perfect. The mean calculation time per video was 3 (standard deviation 1) minutes. CONCLUSION: This neural network-based algorithm allowing automatic assessment of small-bowel cleanliness during capsule endoscopy was highly sensitive and paves the way for automated, standardized SBCE reports.


Capsule Endoscopy , Algorithms , Humans , Intestine, Small/diagnostic imaging , Neural Networks, Computer , Reproducibility of Results
6.
Sci Rep ; 10(1): 14198, 2020 08 26.
Article En | MEDLINE | ID: mdl-32848175

Peroral endoscopic myotomy is an accepted treatment of achalasia. Some of the treatment failures can be attributable to an insufficient length of the myotomy on the gastric side, because of a more technically challenging submucosal dissection. We assessed the feasibility and the impact of an intraoperative esophageal manometry during the peroral endoscopic myotomy procedure. A high-resolution manometry catheter was introduced through the nostril before the endoscope, and left in place during the peroral endoscopic myotomy procedure. The lower esophageal sphincter pressure was recorded throughout the peroral endoscopic myotomy. The myotomy was extended on the gastric side until the lower esophageal sphincter pressure dropped below 10 mmHg. We included 10 patients (mean age = 55 years old, 3 men) treated by peroral endoscopic myotomy for type I (3/10), type II (3/10), type III achalasia (3/10) or esophagogastric junction outflow obstruction (1/10). Manometric recording was possible in all patients. The median (IQR) lower esophageal sphincter resting pressure was 23 (17-37) mmHg before myotomy, 15 (13-19) mmHg at the end of the tunnel, and 7 (6-11) mmHg at the end of the myotomy. In 4 patients out of 10, the myotomy was extended on the base of the intraoperative manometry findings. High-resolution esophageal manometry is feasible during the peroral endoscopic myotomy procedure, and leads to increase the length of the gastric myotomy in 4 out of 10 patients. However, the cumbersome nature of intraoperative high-resolution manometry during peroral endoscopic myotomy and the high frequency of gastro-esophageal reflux disease after extended gastric myotomy suggest to limit this technique to selected patients refractory to a first myotomy.


Esophageal Achalasia/surgery , Esophagus/surgery , Manometry , Myotomy/statistics & numerical data , Natural Orifice Endoscopic Surgery , Adult , Aged , Female , Humans , Intraoperative Care , Male , Middle Aged , Prospective Studies , Young Adult
7.
Endosc Int Open ; 8(3): E415-E420, 2020 Mar.
Article En | MEDLINE | ID: mdl-32118115

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. With a mean number of 50,000 SB frames per video, SBCE reading is time-consuming and tedious (30 to 60 minutes per video). We describe a large, multicenter database named CAD-CAP (Computer-Assisted Diagnosis for CAPsule Endoscopy, CAD-CAP). This database aims to serve the development of CAD tools for CE reading. Materials and methods Twelve French endoscopy centers were involved. All available third-generation SB-CE videos (Pillcam, Medtronic) were retrospectively selected from these centers and deidentified. Any pathological frame was extracted and included in the database. Manual segmentation of findings within these frames was performed by two pre-med students trained and supervised by an expert reader. All frames were then classified by type and clinical relevance by a panel of three expert readers. An automated extraction process was also developed to create a dataset of normal, proofread, control images from normal, complete, SB-CE videos. Results Four-thousand-one-hundred-and-seventy-four SB-CE were included. Of them, 1,480 videos (35 %) containing at least one pathological finding were selected. Findings from 5,184 frames (with their short video sequences) were extracted and delimited: 718 frames with fresh blood, 3,097 frames with vascular lesions, and 1,369 frames with inflammatory and ulcerative lesions. Twenty-thousand normal frames were extracted from 206 SB-CE normal videos. CAD-CAP has already been used for development of automated tools for angiectasia detection and also for two international challenges on medical computerized analysis.

8.
Dig Dis Sci ; 65(4): 1092-1098, 2020 04.
Article En | MEDLINE | ID: mdl-31541368

BACKGROUND: A novel three-dimensional high-resolution esophageal manometry provides a dynamic 360° representation of the pressure at the esophagogastric junction. AIMS: To describe the three-dimensional high-resolution esophageal manometry patterns of achalasia. METHODS: We retrospectively included all consecutive patients who underwent three-dimensional high-resolution esophageal manometry before and after treatment (pneumatic dilatation or per-oral endoscopic myotomy) for achalasia between November 2016 and July 2017. The distribution of the pressures at the esophagogastric junction on three-dimensional high-resolution esophageal manometry was determined. RESULTS: Eighteen patients were included. Mean integrated relaxation pressure was 20.7 mmHg, and median (range) Eckardt score was 7 (4-10). Nine patients were treated by pneumatic dilatation and seven by myotomy. Nine patients underwent three-dimensional high-resolution esophageal manometry after treatment. Before treatment, the esophagogastric junction pressure distribution was best observed at end expiration and during the 4 s of the integrated relaxation pressure measurement. During the integrated relaxation pressure, the lower esophageal sphincter was asymmetric in 12 patients with a high-pressure zone between the left and the posterior side of the esophagogastric junction. After treatment, five patients had a residual high-pressure point on the left or the posterior side of the esophagogastric junction. CONCLUSIONS: Three-dimensional high-resolution esophageal manometry allows a simple assessment of the pressure topography at the EGJ. In patients with achalasia, we found the esophagogastric junction pressure to be asymmetric with a peak pressure on the greater curvature side. Three-dimensional high-resolution esophageal manometry has the potential to guide initial and redo treatments.


Esophageal Achalasia/diagnostic imaging , Esophagogastric Junction/diagnostic imaging , Imaging, Three-Dimensional/methods , Manometry/methods , Adult , Aged , Aged, 80 and over , Endoscopy, Digestive System/methods , Esophageal Achalasia/physiopathology , Esophagogastric Junction/physiopathology , Female , Humans , Male , Middle Aged , Retrospective Studies
9.
Clin Res Hepatol Gastroenterol ; 44(1): 82-89, 2020 02.
Article En | MEDLINE | ID: mdl-31080116

INTRODUCTION: Mid-esophageal and epiphrenic diverticula (MED) can be associated with esophageal motility disorders. Per-oral endoscopic myotomy (POEM) is an established treatment for esophageal motility disorders that has also been introduced for the treatment of MED. METHODS: Data were prospectively collected from patients with MED treated with POEM at our institution. When esophageal motility disorders were present, myotomy was performed extending the myotomy to the lower esophageal sphincter (LES) to treat the motility dysfunction associated with the diverticulum. In the absence of esophageal motility disorder, POEM was performed without including the LES in the myotomy to achieve diverticulotomy. RESULTS: Four patients were treated with POEM for MED between April 2017 and March 2018. The patients suffered from distal esophageal spasm, jackhammer esophagus or esophago-gastric junction outflow obstruction. One patient had no esophageal motility disorder. Diverticulum size was 3 cm in one case and 6 cm in the others. Preoperative Eckardt scores ranged from 6 to 8. No life-threatening complications were reported. Intraoperative pneumoperitoneum was described in two cases and one patient experienced aspiration pneumonia. The patients with motility disorders were asymptomatic at 6-8 months follow-up. The patient without documented underlying esophageal motility disorder had an Eckardt score of 3 at 9-months follow-up. Two cases of gastro-esophageal reflux were successfully managed with proton pump inhibitors. CONCLUSIONS: In the case of MED and esophageal motility disorder, POEM permitted treatment of the underlying cause of the diverticulum, achieving favorable early clinical outcomes. In the absence of motility disorder, POEM was feasible with promising early outcomes, and could be a valid alternative to surgical diverticulectomy in selected patients.


Diverticulum, Esophageal/complications , Diverticulum, Esophageal/surgery , Esophageal Motility Disorders/complications , Esophageal Sphincter, Lower/surgery , Esophagoscopy , Myotomy , Aged , Female , Humans , Male , Prospective Studies
10.
Presse Med ; 48(9): 897-903, 2019 Sep.
Article Fr | MEDLINE | ID: mdl-31471090

Ineffective esophageal motility is the most frequent esophageal motility disorder. It is currently defined by 50% or more ineffective esophageal contractions and a normal lower esophageal sphincter relaxation on high-resolution esophageal manometry. Although reported in patients without symptoms, it is typically associated with gastro-esophageal reflux disease, and might be a consequence of the reflux. Ineffective esophageal motility can account for a certain degree of dysphagia, and is associated with a more severe gastroesophageal reflux. Todate, no specific endoscopic or pharmacologic treatment is available, and proton pump inhibitor are advisable when gastro-esophageal reflux is associated.


Esophageal Motility Disorders/etiology , Gastroesophageal Reflux/complications , Asymptomatic Diseases , Deglutition Disorders/etiology , Eosinophilic Esophagitis/complications , Esophageal Motility Disorders/drug therapy , Gastroesophageal Reflux/drug therapy , Humans , Proton Pump Inhibitors/therapeutic use , Scleroderma, Systemic/complications , Syndrome
11.
Eur J Radiol ; 120: 108684, 2019 Nov.
Article En | MEDLINE | ID: mdl-31563109

PURPOSE: Currently available imaging modalities used to investigate the esophagus are irradiating or limited to the analysis of the esophageal lumen. Magnetic resonance imaging (MRI) is a non-invasive and non-radiating imaging technique that provides high degrees of soft tissue contrast. Newly developed fast MRI sequences allow for both morphological and functional assessment of the esophageal body and esophagogastric junction. The purpose of this systematic review was to identify the contribution of MRI to the diagnosis and management of esophageal diseases, such as gastroesophageal reflux, esophageal motility disorders, esophageal neoplasms, and portal hypertension. METHODS: We performed a systematic search of the Medline (via Ovid), EMBASE (via Ovid), PubMed and Cochrane Library databases from inception to December 2018 inclusively, using the MESH major terms "magnetic resonance imaging" AND "esophagus". RESULTS: The initial search retrieved 310 references, of which 56 were found to be relevant for the study. References were analysed and classified in different subheadings: MRI protocols for the esophagus, gastroesophageal reflux disease, achalasia and other esophageal motility disorders, esophageal cancer, portal hypertension and other esophageal conditions. CONCLUSION: MR Esophagography might become a non-invasive, non-irradiating technique of choice following diagnostic esophagogastroduodenoscopy for the assessment of esophageal diseases.


Esophageal Diseases/diagnostic imaging , Magnetic Resonance Imaging/methods , Preoperative Care/methods , Esophageal Diseases/surgery , Esophagogastric Junction/diagnostic imaging , Esophagogastric Junction/surgery , Esophagus/diagnostic imaging , Esophagus/surgery , Humans , Male
13.
Presse Med ; 47(5): 419-422, 2018 May.
Article Fr | MEDLINE | ID: mdl-29622390

Cancers of the bile ducts or cholangiocarcinomas are a rare entity whose incidence is increasing in France. Surgical resection of cholangiocarcinoma remains the only curative therapy. Adjuvant therapy with capecitabine at a fixed dose of 1250mg/m2 twice daily from day 1 to day 14 (21-day cycle) for a 6 months period is now the standard of care after curative surgery. At a metastatic stage, the reference treatment consists of the combination of a platinum salt in addition to gemcitabine. No biomarker has been identified to predict the response to chemotherapy. DNA sequencing of the tumor can identify specific tumor mutations in bile duct cancers that are the focus of targeted studies.


Bile Duct Neoplasms/therapy , Cholangiocarcinoma/therapy , Medical Oncology/trends , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bile Duct Neoplasms/epidemiology , Bile Ducts, Intrahepatic/pathology , Capecitabine/administration & dosage , Cholangiocarcinoma/epidemiology , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , France/epidemiology , Humans , Medical Oncology/methods , Gemcitabine
14.
Oncotarget ; 9(10): 8849-8869, 2018 Feb 06.
Article En | MEDLINE | ID: mdl-29507659

LRP1 (low-density lipoprotein receptor-related protein 1), a multifunctional endocytic receptor, has recently been identified as a hub within a biomarker network for multi-cancer clinical outcome prediction. As its role in colon cancer has not yet been characterized, we here investigate the relationship between LRP1 and outcome. MATERIALS AND METHODS: LRP1 mRNA expression was determined in colon adenocarcinoma and paired colon mucosa samples, as well as in stromal and tumor cells obtained after laser capture microdissection. Clinical potential was further investigated by immunohistochemistry in a population-based colon cancer series (n = 307). LRP1 methylation, mutation and miR-205 expression were evaluated and compared with LRP1 expression levels. RESULTS: LRP1 mRNA levels were significantly lower in colon adenocarcinoma cells compared with colon mucosa and stromal cells obtained after laser capture microdissection. Low LRP1 immunohistochemical expression in adenocarcinomas was associated with higher age, right-sided tumor, loss of CDX2 expression, Annexin A10 expression, CIMP-H, MSI-H and BRAFV600E mutation. Low LRP1 expression correlated with poor clinical outcome, especially in stage IV patients. While LRP1 expression was downregulated by LRP1 mutation, LRP1 promoter was never methylated. CONCLUSIONS: Loss of LRP1 expression is associated with worse colon cancer outcomes. Mechanistically, LRP1 mutation modulates LRP1 expression.

15.
Bull Cancer ; 105(3): 228-233, 2018 Mar.
Article Fr | MEDLINE | ID: mdl-29426740

INTRODUCTION: Adapted physical activity (APA) is recognized as an effective supportive care for asthenia and quality of life in oncology. Before an APA program was organized, the feasibility of such a program was evaluated among the patients. METHODS: Descriptive, prospective, semi-qualitative, single-center study over a 3-month period in patients treated with ambulatory chemotherapy for digestive cancer. A self-questionnaire was offered to all patients to evaluate their practice and knowledge about APA. In ten patients, fatigue, anxiety and depression were assessed, before and after 9 weeks of hospital-based APA. The scores were compared by matched Student test. RESULTS: Of the 123 patients treated, 80 questionnaires (65%) were exploitable. Before the diagnosis of cancer, 40 patients (50%) were physically active, 20% after (n=16). The reasons for not practicing were: lack of interest/not the idea (42%), lack of time (34%), do not believe in profit (9%), too expensive (8%). Fifty-three patients (66%) were interested in the program. In 10 patients, the APA program significantly reduced the depression score (P=0.024) and a non-significant improvement in anxiety and fatigue. DISCUSSION: This study shows that patients treated with chemotherapy are unaware of the usefulness of APA and that medical information can improve adherence to such a program. The establishment of an intra-hospital APA program proved to be possible and relevant.


Ambulatory Care/methods , Digestive System Neoplasms/drug therapy , Exercise , Program Development , Adult , Aged , Aged, 80 and over , Anxiety/diagnosis , Depression/diagnosis , Digestive System Neoplasms/psychology , Fatigue/diagnosis , Feasibility Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Surveys and Questionnaires
16.
Presse Med ; 46(10): 903-910, 2017 Oct.
Article Fr | MEDLINE | ID: mdl-28935445

In France, upper gastrointestinal haemorrhages have an estimated annual incidence of 143 cases per 100,000 inhabitants. Classically, two types of digestive hemorrhage are described: acute and chronic digestive hemorrhages. Upper endoscopy is carried out in case of hematemesis or melena. It requires that the patient has been fasting for at least 6hours for solids and 3hours for liquids. The main etiologies of hemorrhagic hemorrhage of the origin are the vascular abnormalities, inflammatory or drug-induced ulcerations, intestinal tumors, Meckel's diverticulum, and Dieulafoy ulcer. The modalities of exploration of the small intestine before digestive hemorrhage are the wireless capsule, a reference examination for the exploration of the small intestine, enteroscopy, therapeutic examination, entero-CT or MRI, and 99mTc-labeled red blood cell scintigraphy. In this review, we will discuss the different etiologies of the digestive haemorrhage of intestinal origin and propose a management algorithm.


Capsule Endoscopy , Gastrointestinal Hemorrhage/pathology , Algorithms , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Humans , Intestine, Small
17.
Anticancer Drugs ; 28(9): 1062-1065, 2017 10.
Article En | MEDLINE | ID: mdl-28682829

Vascular endothelial growth factor inhibitors, led by bevacizumab, are considered the cornerstone of the therapy in metastatic colorectal carcinoma. We present the case of a patient with metastatic colorectal cancer who experienced rapid tumour growth with liver broad invasion after the withdrawal of an antivascular endothelial growth factor therapy, aflibercept. The rebound effect caused by the residual tumour inducing a regrowth after an initial controlled disease has already been stressed in mice and metastatic colorectal cancer patients following bevacizumab interruption. The use of liver volume evaluation was consistent with the Response Evaluation Criteria in Solid Tumours 1.1 criteria evaluation and might be a useful tool in patients with more than a half liver invasion. We describe for the first time the case of a major liver disease progression, confirmed by Response Evaluation Criteria in Solid Tumours 1.1 criteria and liver volume evaluation, after an antiangiogenic interruption in second line.


Adenocarcinoma/blood supply , Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/blood supply , Colorectal Neoplasms/pathology , Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Colorectal Neoplasms/drug therapy , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism
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