Do we still need a diverticuloscope for the flexible endoscopic septotomy of Zenker's diverticulum?

BACKGROUND AND AIM: Zenker's diverticulum (ZD) is the most common type of diverticulum in the esophagus. The endoscopic septotomy of the diverticular wall has become a widely accepted treatment modality, but the recurrence rate is unclear. Our aim was to assess short-term and long-term success rates after flexible endoscopic septotomy for the treatment of ZD. METHODS: All consecutive patients treated at our department for a ZD between November 2014 and September 2018 were included. Endoscopic septotomy was conducted using a diverticuloscope or a distal attachment cap. Data were retrospectively analyzed from a prospectively collected database. We collected data concerning patients, endoscopic procedures, and short-term clinical outcomes. All patients were reached by phone between October and December 2018 to assess long-term results. RESULTS: Seventy-seven patients were referred to our department for a ZD. Sixty patients were treated using a diverticuloscope and 17 patients with a distal attachment cap. For all 77 patients, the myotomy was technically successful. Three patients treated with a diverticuloscope reported complications. Initial treatment success was 93%. After a mean (±SEM) follow up of 23 ± 2 months, 66% of patients had persistent clinical remission. The rate of long-term treatment success was 72% in treatment-naïve and 50% in previously treated patients (P = 0.13). Treatment success was 68% in patients treated with the diverticuloscope versus 60% in the group treated with a cap (P = 0.75). CONCLUSION: The flexible endoscopic septotomy for the treatment of ZD is a safe and effective treatment of ZD, with or without a diverticuloscope.

Three-Dimensional High-Resolution Esophageal Manometry Study of the Esophagogastric Junction in Patients with Achalasia.

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.

Addition of an antiangiogenic therapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers.

Background The prognosis of patients with metastatic carcinoma of the biliary tract (mBTC) is poor and a systemic therapy with gemcitabine and platinum-based is the gold standard. The addition of bevacizumab to the chemotherapy might increase patients' survival. Our aim was to assess and compare the efficacy of GEMOX (gemcitabine and oxaliplatin regimen) plus bevacizumab to GEMOX alone in mBTC. Methods Patients with mBTC who received the GEMOX-bevacizumab (n = 32; Group A) or GEMOX (n = 25; Group B) regimen as first-line treatment were compared. Treatment was repeated every two weeks until disease progression or unacceptable adverse effects occurred. The primary evaluation criterion was the progression-free survival (PFS). Results A quarter of patients (8/32) from Group A and a fifth of patients (13/25) from Group B had an objective response. The median PFS was 6.48 months and 3.72 months in Group A and B, respectively (p = 0.049). The median OS was 11.31 months and 10.34 months in Group A and B, respectively. Grade 3/4 sepsis was identified in 9.4% and 12% in Group A and B, respectively, (p = 0.64). Conclusion In mBTC, the addition of bevacizumab to GEMOX increased the progression-free survival and was associated with manageable toxicity. These data pave the way for further evaluation of antiangiogenic agents in mBTC.

Clinical efficacy of anti-migration features in fully covered metallic stents for anastomotic biliary strictures after liver transplantation: comparison of conventional and anti-migration stents.

BACKGROUND AND AIMS: Anastomotic biliary strictures (ABSs) are one of the most frequent adverse events that occur after orthotopic liver transplantation (OLT). Multiple plastic stents (MPS) have been validated for this indication. More recently, fully covered self-expandable metallic stents (FCSEMSs) have been used with positive outcomes, but also have a higher rate of migration, which may limit success. Our primary objective was to compare stent migration rates observed with standard FCSEMSs (Std-FCSEMSs) and so-called anti-migration FCSEMSs (Am-FCSEMSs), which are newly designed with reversed proximal side flaps. Secondary objectives were to compare rates of stricture resolution and procedure-related morbidity. METHODS: We conducted a retrospective analysis of a subset of patients (FCSEMSs for post-OLT ABS) from 2 prospectively maintained databases of (1) OLT patients, and (2) ERCP and stent placement. Between January 2009 and January 2016, consecutive patients presenting with ABS after OLT referred to Cochin Hospital (Paris, France) for ERCP and receiving a FCSEMS were included. Exclusion criteria were any other cause of biliary stricture (ie, malignant stricture, ischemic origin), and biliary fistulae. RESULTS: One hundred twenty-five FCSEMSs (57 Am-FCSEMSs, 52 type 1 Std-FCSEMSs, and 16 type 2 Std-FCSEMSs) were used in 75 patients for ABS after OLT, with a planned stent placement period of 6 months in all patients. Patient characteristics and rates of previous endoscopic treatment or timing of ABS occurrence after OLT were not different between the groups. The rate of FCSEMS complete migration was 16% (20/125), consisting of 1.7% (1/57) for Am-FCSEMSs and 28% (19/68) for type 1 and 2 Std-FCSEMSs (P < .0001). All attempted stent removals (100% of patients) were successful. First follow-up ERCP after each FCSEMS highlighted a stricture resolution rate of 78.4% (98/125), including 93% (53/57) for Am-FCSEMSs and 66.2% (45/68) for type 1 and 2 Std-FCSEMSs (P < .001). After a median follow-up of 28 months after stent removal (range, 12-66 months), stricture recurrence was observed in 12.3% (range, 11%-17%) of patients treated with Am-FCSEMSs against 55.9% (range, 54%-56%) of those receiving Std-FCSEMSs (P < .0001). CONCLUSIONS: In patients with ABS after OLT, the use of Am-FCSEMSs significantly decreased the risk of stent migration, improved stricture resolution at the time of stent removal, and reduced the rate of stricture recurrence during follow-up. Endoscopic removal success and procedure-related morbidity were similar for both standard and anti-migration stents.

Tumour growth increased following antiangiogenic interruption: the challenge of tumour evaluation.

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.

Experience with the use of a hemostatic powder in 152 patients undergoing urgent endoscopy for gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: In the recent years, topical hemostatic powders have been used for the management of upper gastrointestinal bleeding. The aim of this study was to report on the use of an hemostatic powder (Hemospray®), outside regular hours, by on-call endoscopists during urgent endoscopic procedures. MATERIAL AND METHODS: In this retrospective multicenter cohort study, consecutive patients having undergone an urgent endoscopy with the use of Hemospray® from November 2015 to December 2018 in the Paris and suburbs area were included. We collected clinical, biological and endoscopic variables. The outcomes such as the recurrence, repeat endoscopy and hemostatic treatment need, complications and survival were also collected. RESULTS: A total of 152 patients (mean 65 years old, 70.4% male) were included. Amongst the 31 endoscopists, 11 were "more experienced", and performed 48% of the endoscopies. The most common causes of bleeding were peptic ulcer (47.7%), malignancy (22.2%) and esophagitis (12.4%). Most bleedings originated from the upper GI tract (95.0%). Hemospray® was used as a salvage therapy in 60.8% of cases. Other hemostatic techniques were used in 52.9% of cases. Immediate bleeding cessation was noted in 79.0% of cases, recurrence in 39.9% of cases, and 26.4% of patients benefited from a repeat endoscopic hemostasis. 34 (23.0%) patients required a non-endoscopic treatment. At day 30, the survival rate was 71.6%. One complication was reported (perforation). CONCLUSIONS: Hemostatic powder application by on-call endoscopists outside regular hours is technically feasible, but comes with a high risk of rebleeding in severely ill patients.

Intraoperative high-resolution esophageal manometry during peroral endoscopic myotomy.

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.

Per-oral endoscopic myotomy for esophageal diverticula with or without esophageal motility disorders.

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.

Endoscopic full-thickness resection of early colorectal neoplasms using an endoscopic submucosal dissection knife: a retrospective multicenter study.

Background and study aims Endoscopic full-thickness resection allows resection of early gastrointestinal neoplasms not amenable to conventional endoscopic resection techniques, due to their location, presence of submucosal fibrosis, or suspected deep mural invasion. It is typically achieved using a dedicated over-the-scope device (full-thickness resection device or FTRD). The aim of our study was to evaluate the feasibility, safety, and clinical outcomes of endoscopic full-thickness resection using an endoscopic submucosal dissection (ESD) knife. Patients and methods Consecutive patients who underwent full-thickness endoscopic resection at six tertiary care centers from August 2010 to June 2017 were retrospectively included. We conducted a comparative analysis of patient characteristics, technical success, adverse events, and time to discharge between patients treated by a full-thickness resection using an ESD knife. Results Twenty-one procedures were performed using an ESD knife. En-bloc resection and R0 resection rates were 95.2 % and 65 %, respectively. Clinical symptoms of perforation occurred in 66.7 %. There was no need for surgery or additional endoscopic procedures. Conclusion Endoscopic full-thickness resection of early colorectal neoplasms using an ESD knife might be feasible and safe. It allows complete resection of lesions with no limitation in size. The technique may be preferable to an other-the-scope resection device in lesions larger than 20 mm, and to surgery in selected cases of low-risk T1 colorectal carcinomas, non-lifting adenomas, submucosal tumors, or technically challenging lesion locations.

[Ineffective esophageal motility]. / Le syndrome de motricité œsophagienne inefficace.

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.

Contribution of magnetic resonance imaging to the management of esophageal diseases: A systematic review.

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.

[What is the REAL long-term risk of proton pump inhibitors?] / Quel est le VRAI risque au long cours des inhibiteurs de la pompe à protons ?

Proton pump inhibitors (PPIs) are among the most prescribed drugs in the world. While their efficacy in acute management is indisputable, it has long been suggested that PPI therapy is safe in the long term. In recent years, there has been growing and justified concern about the long-term risks of PPIs. The majority of reported side effects are based on observational studies with a low level of evidence. Concerning digestive risks, PPIs seem to increase the risk of Salmonella and Campylobacter infections. However, the link between PPIs and Clostridium difficile infection is not established. Long-term PPIs may be responsible for an increased risk of gastric cancer according to several recent studies. With regard to extra-digestive risks, PPIs are associated with a moderate increase in the risk of chronic renal failure via an interstitial nephritis mechanism. PPIs also provide martial deficiency and may be associated with vitamin B12 and magnesium deficiency in some patients. Other adverse reactions have been suggested without any causal relationship being established (i.e., dementia or bone fractures, cardiovascular risk). In this review we will discuss the different long-term adverse effects of PPIs and their level of evidence.

Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator.

By using the differential in level of oxidative status between normal and cancer cells, SuperOxide Dismutase (SOD) mimetics can have anti-tumor efficacy and prevent oxaliplatin-induced peripheral neuropathy. Our objective was to evaluate the neuroprotective efficacy of MAG, a new SOD mimic. In vitro, the effects of MAG alone or with oxaliplatin were studied on colon cancer cells (HT29 and CT26) and on normal fibroblast cells (NIH3T3). The cell viability (by crystal violet) as well as the production of reactive forms of oxygen and glutathione (by spectrofluorimetric assay) was measured. In vivo, efficacy on tumor growth was assessed in mice grafted with CT26 colon cancer cells. The effects on induced neurotoxicity were measured by specific behavioral Von Frey nociception, cold-plate tests, specific functional neuromuscular assay and electron microscopy. In vitro, MAG induced a production of hydrogen peroxide in all cells. At 24 h-incubation, MAG exhibits a cytotoxic activity in all cell lines. A cytotoxic additive effect of MAG and oxaliplatin was observed through oxidative burst. In vivo, oxaliplatin-treated mice associated with MAG did not counteract oxaliplatin's antitumoral efficacy. After 4 weeks of treatment with oxaliplatin combined with MAG, behavioral and functional tests showed a decrease in peripheral neuropathy induced by oxaliplatin in vivo. Electron microscopy analyses on sciatic nerves revealed an oxaliplatin-induced demyelination which is prevented by the association of MAG to this chemotherapy. In conclusion, MAG prevents the appearance of sensitive axonal neuropathy and neuromuscular disorders induced by oxaliplatin without affecting its antitumor activity.

[Therapeutic advances in the management of biliary tract carcinoma]. / Les progrès dans la prise en charge des cholangiocarcinomes.

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.

[Focus on Achalasia]. / Prise en charge de l'achalasie.

The pathophysiology of achalasia is largely unknown, and involves the destruction of ganglion cell in the esophageal myenteric plexus. High-resolution esophageal manometry is the key investigation. Endoscopic pneumodilatation and laparoscopic Heller myotomy have comparable short-term success rates, around 90%. The main complication after pneumodilatation is esophageal perforation, occurring in about 1% of cases. Peroral endoscopic myotomy is a promising treatment modality, however with frequent post-procedural gastroesophageal reflux.

Invasive pit pattern, macronodule and depression are predictive factors of submucosal invasion in colorectal laterally spreading tumours from a Western population.

BACKGROUND: Laterally spreading tumours are separated in subclasses: granular, homogenous or nodular mixed; and non-granular, flat or pseudodepressed. For every subtype, a proper risk of submucosal invasive cancer has been described in Asian series. OBJECTIVE: The aim of the study was to determine the rate of cancer and submucosal invasive cancer in a Western series of endoscopic-resected laterally spreading tumours and their endoscopic predictive factors. METHODS: A total of 374 laterally spreading tumours ≥20 mm were resected by endoscopy in our single centre between 2012-2016. We analysed endoscopic and pathological data from our prospective database, determining the rates of cancer and submucosal invasive cancer according to the subtype of laterally spreading tumour. RESULTS: The rates of submucosal invasive cancer for granular homogenous, granular nodular mixed, non-granular flat, non-granular pseudodepressed laterally spreading tumours were 4.9%, 15.9%, 3.0% and 19.4%, respectively. Endoscopic mucosal resection was used in 58.0% and endoscopic submucosal dissection in 42.0%. Endoscopic submucosal dissection was associated with a higher rate of en-bloc resection (87.3% vs 26.3%; p < 0.0001), and a lower risk of recurrence (7.6% vs 15.2%; p = 0.026). Adverse event rates were not statistically different (9.5% vs 6.4%, p = 0.26). Predictive endoscopic factors of submucosal invasive cancer were: invasive pit pattern (hazard ratio = 33 (8.81-143.3)), non-granular pseudodepressed laterally spreading tumours (hazard ratio = 11.9 (0.89-146.2)), and granular nodular mixed laterally spreading tumours (hazard ratio = 3.42 (0.99-13.0)). CONCLUSIONS: The risk of submucosal invasive cancer varies according to the laterally spreading tumour subtype. Three factors were associated with submucosal invasion and should justify an endoscopic submucosal dissection: non-granular pseudodepressed laterally spreading tumours, granular nodular mixed laterally spreading tumours subtypes and invasive pit pattern.

[Usefulness of small-bowel capsule endoscopy in gastrointestinal bleeding]. / Intérêt de l'exploration de l'intestin grêle dans les hémorragies digestives.

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.

Niclosamide Inhibits Oxaliplatin Neurotoxicity while Improving Colorectal Cancer Therapeutic Response.

Neuropathic pain is a limiting factor of platinum-based chemotherapies. We sought to investigate the neuroprotective potential of niclosamide in peripheral neuropathies induced by oxaliplatin. Normal neuron-like and cancer cells were treated in vitro with oxaliplatin associated or not with an inhibitor of STAT3 and NF-κB, niclosamide. Cell production of reactive oxygen species and viability were measured by 2',7'-dichlorodihydrofluorescein diacetate and crystal violet. Peripheral neuropathies were induced in mice by oxaliplatin with or without niclosamide. Neurologic functions were assessed by behavioral and electrophysiologic tests, intraepidermal innervation, and myelination by immunohistochemical, histologic, and morphologic studies using confocal microscopy. Efficacy on tumor growth was assessed in mice grafted with CT26 colon cancer cells. In neuron-like cells, niclosamide downregulated the production of oxaliplatin-mediated H2O2, thereby preventing cell death. In colon cancer cells, niclosamide enhanced oxaliplatin-mediated cell death through increased H2O2 production. These observations were explained by inherent lower basal levels of GSH in cancer cells compared with normal and neuron-like cells. In neuropathic mice, niclosamide prevented tactile hypoesthesia and thermal hyperalgesia and abrogated membrane hyperexcitability. The teniacide also prevented intraepidermal nerve fiber density reduction and demyelination in oxaliplatin mice in this mixed form of peripheral neuropathy. Niclosamide prevents oxaliplatin-induced increased levels of IL6, TNFα, and advanced oxidized protein products. Niclosamide displayed antitumor effects while not abrogating oxaliplatin efficacy. These results indicate that niclosamide exerts its neuroprotection both in vitro and in vivo by limiting oxaliplatin-induced oxidative stress and neuroinflammation. These findings identify niclosamide as a promising therapeutic adjunct to oxaliplatin chemotherapy. Mol Cancer Ther; 16(2); 300-11. ©2016 AACR.