Achalasia and Hiatal Hernia: A Rare Association and a Therapeutic Challenge.

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.

Predictive factors of radiofrequency ablation failure in the treatment of dysplastic Barrett's esophagus.

INTRODUCTION: Radiofrequency ablation (RFA) has become the recommended endoscopic treatment for flat dysplastic Barrett's esophagus. However, the outcomes of this treatment are variable across European countries. Our aim was to report the results of a French high-volume center, and to investigate factors associated with treatment failure. METHODS: We conducted a single-center retrospective study from a prospectively collected database from 2011 to 2020, including all consecutive patients treated with RFA for flat dysplastic Barrett's esophagus. The primary endpoint was the failure rate of esophageal radiofrequency treatment, defined as either persistence of intestinal metaplasia at the end of treatment, or neoplastic progression during RFA. RESULTS: 96 patients treated with a median of four RFA sessions for a mean C5M6 Barrett's esophagus were included in the analysis. Complete eradication of intestinal metaplasia and dysplasia were achieved in 59% and 79% of patients, respectively, resulting in a treatment failure rate of 41%. Ten patients experienced neoplastic progression during treatment. We recorded 14% of post-RFA esophageal strictures, all successfully treated by endoscopic dilatation. Univariate analysis identified the length of Barrett's esophagus and the absence of hiatal hernia as predictive factors for treatment failure, however not confirmed in multivariate analysis. CONCLUSION: In our experience, RFA of flat dysplastic Barrett's esophagus had a 41% treatment failure rate. The length of the Barrett's segment might be associated with treatment failure. Although our results confirm a role for RFA in the management of dysplastic Barrett's esophagus, the treatment failure rate was higher than expected. This suggest that endoscopists, even in high-volume centers, should receive specific training in RFA.

Endoscopic submucosal dissection for early esophagogastric junction adenocarcinomas: a systematic review.

Background: Esophagogastric junction adenocarcinomas (EGJAs) include esophageal and gastric cardia adenocarcinomas (GCAs). These tumors are currently regarded as a single entity, with similar surgical and oncological therapies, although they originate from different organs. Endoscopy allows an early-stage diagnosis, where both subtypes can be differentiated. With this review we aimed to describe the outcomes of endoscopic submucosal dissection for the treatment of esophageal adenocarcinomas (EAs) and GCAs. Methods: We identified studies by screening PubMed, Embase and Web of Science. We included all 19 studies that mentioned at least one of the following criteria of interest: en bloc; R0 resection; local recurrences; and/or overall survival. Results: We found an en bloc resection rate superior to 90% for both tumors. R0 resections rates were over 60% for most EAs, vs. 83% for most GCAs. We recorded less than 13% and 20% early and late adverse events for EA, and 10% and 7% for GCA. The local recurrence rate was 8% for EA and 3% for GCA. The overall survival was over 90%. Conclusions: Endoscopic submucosal dissection is safe and effective for esophageal and GCAs. These data support the extension of the use of endoscopic submucosal dissection to all EGJAs, including early EAs.

Outcomes of endoscopic submucosal dissection for early esophageal and gastric cardia adenocarcinomas.

OBJECTIVES: Adenocarcinomas of the esophagus and of the gastric cardia are regarded as a same clinical entity in oncology. For endoscopic resection however, endoscopic mucosal resection is recommended for esophageal adenocarcinoma, while endoscopic submucosal dissection (ESD) is advocated for gastric adenocarcinomas. Our aim was to compare the outcomes of ESD in both types of esophagogastric junction adenocarcinomas. METHODS: Between March 2015 and December 2019, we included all patients who underwent an ESD for early adenocarcinoma of the esophagogastric junction at a French tertiary referral center. Esophageal and gastric cardia adenocarcinomas were compared in terms of clinical, procedural and histological outcomes. RESULTS: 57 esophageal and 19 gastric cardia adenocarcinomas were included in the analysis, for a total of 76 patients. The median (IQR) size of the resections was 40 (40-57.5) and 50 (35-55)mm, p=0.96, respectively. En bloc resection was achieved in 100% and 89% for adenocarcinomas of the esophagus and the gastric cardia, p=0.06. Late adverse events occurred in 14% and 5.3%, respectively, p=0.44, with no severe adverse event. Curative resection rates were 67% and 63% for adenocarcinomas of the esophagus and the gastric cardia, respectively, p=0.89. CONCLUSION: ESD is a safe treatment for T1 adenocarcinomas of the esophagogastric junction, curative in two thirds of the patients, in tumors arising from the esophagus or from the stomach. ESD should be considered for the routine resection of esophageal adenocarcinomas.

Management of esophageal strictures after endoscopic resection for early neoplasia.

BACKGROUND: Endoscopic resection of extensive esophageal neoplastic lesions is associated with a high rate of esophageal stricture. Most studies have focused on the risk factors for post-endoscopic esophageal stricture, but data on the therapeutic management of these strictures are scarce. Our aim is to describe the management of esophageal strictures following endoscopic resection for early esophageal neoplasia. METHODS: We included all patients with an endoscopic resection for early esophageal neoplasia followed by endoscopic dilatation at a tertiary referral center. We recorded the demographic, endoscopic, and histological characteristics, and the outcomes of the treatment of the strictures. RESULTS: Between January 2010 and December 2019, we performed 166 endoscopic mucosal resections and 261 endoscopic submucosal dissections for early esophageal neoplasia, and 34 (8.0%) patients developed an esophageal stricture requiring endoscopic treatment. The indication for endoscopic resection was Barrett's neoplasia in 15/34 (44.1%) cases and squamous cell neoplasia (SCN) in 19/34 (55.9%) cases. The median [(interquartile range) (IQR)] number of endoscopic dilatations was 2.5 (2.0-4.0). Nine of 34 (26.5%) patients required only one dilatation, and 22/34 (65%) had complete dysphagia relief following three endoscopic treatment sessions. The median number of dilatations was significantly higher for SCN [3.0 (2-7); range 1-17; p = 0.02], and in the case of circumferential resection [4.0 (3.0-7.0); p = 0.03]. Endoscopic dilatation allowed a sustained dysphagia relief in 33/34 (97.0%) patients after a mean follow-up of 25.3 ± 22 months. CONCLUSION: Refractory post-endoscopic esophageal stricture is a rare event. After a median of 2.5 endoscopic dilatations, 97.0% of patients were permanently relieved of dysphagia. Circumferential endoscopic esophageal resections should be considered when indicated.

Outcomes of esophagectomy after noncurative endoscopic resection of early esophageal cancer.

BACKGROUND: Current guidelines recommend performing esophagectomy after endoscopic resection for early esophageal cancer when the risk of lymph node metastasis or residual cancer is found to be significant and endoscopic treatment is therefore noncurative. Our aim was to assess the safety and oncological outcomes of esophagogastric resection in this specific clinical setting. PATIENTS AND METHODS: A retrospective review from 2012 to 2018 was performed at four tertiary referral centers. All patients had a noncurative endoscopic resection of a clinical T1 esophageal cancer, followed by esophagectomy. Outcome measures were the rates of T0N0 specimens, overall survival, disease-free and cancer-specific survival, postoperative morbidity and mortality. RESULTS: A total of 30 patients (13 with squamous cell carcinoma and 17 with adenocarcinoma) were included. The reasons for noncurative endoscopic resection were: positive vertical margins (n = 12), squamous cell carcinoma with muscularis mucosae or submucosal layer invasion (n = 3 and 9), adenocarcinoma with deep submucosal invasion (n = 11), poorly differentiated tumor (n = 6) and lymphovascular invasion (n = 6). Overall, 63% of the esophagi were T0N0: most residual lesions were T1a metachronous lesions, and four (13%) patients had advanced pT status (n = 3) or lymph node metastases (n = 2). Overall survival, disease-free survival and cancer-specific survival were 83%, 75%, and 90% respectively. A total of 43% of patients had severe postoperative complications, and postoperative mortality was 7%. CONCLUSION: In this cohort, esophagectomy allowed the resection of residual advanced cancer or lymph node metastases in 13% of cases, at the cost of 43% severe morbidity and 7% mortality. Therefore, the possibility of close follow up needs to be balanced with a highly morbid surgical management in these patients.

[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.

[Acute severe colitis]. / La colite aiguë grave.

Acute severe colitis is a potentially life-threatening medical and surgical emergency requiring hospitalization and intensive monitoring. The diagnosis of severe acute colitis is based on clinical and biological criteria. Colectomy should be discussed at each stage of management and is indicated immediately in case of complications. Thromboembolic prevention with low molecular weight heparin is essential in any patient with severe acute colitis. The first-line medical treatment is intravenous corticosteroid at a dose of 0.8mg/kg/day of prednisone equivalent. In case of failure, a second line of medical treatment can be attempted in the absence of complications. The two possible treatments are infliximab and ciclosporin.

[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.

Best practices to optimize intraoperative photography.

BACKGROUND: Intraoperative photography is used extensively for communication, research, or teaching. The objective of the present work was to define, using a standardized methodology and literature review, the best technical conditions for intraoperative photography. MATERIALS AND METHODS: Using either a smartphone camera, a bridge camera, or a single-lens reflex (SLR) camera, photographs were taken under various standard conditions by a professional photographer. All images were independently assessed blinded to technical conditions to define the best shooting conditions and methods. RESULTS: For better photographs, an SLR camera with manual settings should be used. Photographs should be centered and taken vertically and orthogonal to the surgical field with a linear scale to avoid error in perspective. The shooting distance should be about 75 cm using an 80-100-mm focal lens. Flash should be avoided and scialytic low-powered light should be used without focus. The operative field should be clean, wet surfaces should be avoided, and metal instruments should be hidden to avoid reflections. For SLR camera, International Organization for Standardization speed should be as low as possible, autofocus area selection mode should be on single point AF, shutter speed should be above 1/100 second, and aperture should be as narrow as possible, above f/8. For smartphone, use high dynamic range setting if available, use of flash, digital filter, effect apps, and digital zoom is not recommended. CONCLUSIONS: If a few basic technical rules are known and applied, high-quality photographs can be taken by amateur photographers and fit the standards accepted in clinical practice, academic communication, and publications.

Inhibition of MAPK and VEGFR by Sorafenib Controls the Progression of Endometriosis.

INTRODUCTION: Sorafenib is a strong multikinase inhibitor targeting 2 different pathways of endometriosis pathogenesis: RAF kinase and vascular endothelial growth factor receptor (VEGFR). We investigate whether Sorafenib could control the growth of endometriotic lesions both in vitro and in vivo. METHODS: Stromal primary cells were extracted from endometrial and endometriotic biopsies from patients with (n = 10) and without (n = 10) endometriosis. Proliferation, apoptosis, mitogen-activated protein kinases, and VEGFR-2 autophosphorylation were explored with and without Sorafenib treatment. Human endometriotic lesions were implanted in 30 nude mice randomized according to Sorafenib or placebo treatment. RESULTS: Treating endometriotic cells with Sorafenib abrogated the phosphorylation of extracellular signal-regulated kinase in stromal cells of women with endometriosis compared to controls. In addition, this study highlights the antiangiogenic role of Sorafenib which translates as a decreased phosphorylated VEGFR-2-VEGFR-2 ratio in endometriosis. Using a xenogenic mouse model of endometriosis, we confirmed that Sorafenib regulates the endometriosis activity in vivo by targeting endometriosis-related proliferation and inflammation. CONCLUSION: Our data suggest that Sorafenib controls the growth of endometriotic lesions in vitro and in vivo.

Increased serum oxidative stress markers in women with uterine leiomyoma.

BACKGROUND: Uterine leiomyomas (fibroids) are the most common gynaecological benign tumors in premenopausal women. Evidences support the role of oxidative stress in the development of uterine leiomyoma. We have analysed oxidative stress markers (thiols, advanced oxidized protein products (AOPP), protein carbonyls and nitrates/nitrites) in preoperative sera from women with histologically proven uterine leiomyoma. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a laboratory study in a tertiary-care university hospital. Fifty-nine women with histologically proven uterine leiomyoma and ninety-two leiomyoma-free control women have been enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Preoperative serum samples were obtained from all study participants to assay serum thiols, AOPP, protein carbonyls and nitrates/nitrites. Concentrations of serum protein carbonyl groups and AOPP were higher in leiomyoma patients than in the control group (p=0.005 and p<0.001, respectively). By contrast, serum thiol levels were lower in leiomyoma patients (p<0.001). We found positive correlations between serum AOPP concentrations and total fibroids weight (r=0.339; p=0.028), serum AOPP and serum protein carbonyls with duration of infertility (r=0.762; p=0.006 and r=0.683; p=0.021, respectively). CONCLUSIONS/SIGNIFICANCE: This study, for the first time, reveals a significant increase of protein oxidative stress status and reduced antioxidant capacity in sera from women with uterine leiomyoma.

[Achalasia: role of endoscopic therapy and surgery]. / Achalasie: place du traitement endoscopique et du traitement chirurgical.

Pneumatic dilation of achalasia has a same medium-term efficacy than surgery and is commonly proposed as the first-line treatment. Intra-sphincteric injection of botulinum toxin is reserved for elderly patients with serious comorbidities. Per-endoscopic myotomy is possible but needs to be evaluated by further studies. Laparoscopic Heller's myotomy in first intension is reserved for young patients less than 40 years. Results of Heller's myotomy are not modified by prior endoscopic treatment or by mega-esophagus. Better surgery results are shown in recent and severe achalasia.

CT antegrade colonography to assess proctectomy and temporary diverting ileostomy complications before early ileostomy takedown in patients with low rectal endometriosis.

OBJECTIVE: The purpose of this study is to describe an imaging method based on a CT technique, CT antegrade colonography, for the evaluation of low anastomosis and to evaluate the value of CT antegrade colonography before early ileostomy closure after proctectomy in low rectal endometriosis. MATERIALS AND METHODS: One hundred ninety-five patients referred for low rectal endometriosis underwent proctectomy and were eligible for early ileostomy closure. All patients underwent standard antegrade fluoroscopy (n=77) or CT antegrade colonography (n=118) 8 days after surgery. The negative predictive values, positive predictive values, sensitivity, specificity, and likelihood ratio of standard antegrade fluoroscopy and CT antegrade colonography in detecting anastomotic leakage and abscesses were assessed. The reference standard for positive and negative examinations was based on clinical follow-up, imaging, surgical, or interventional procedure findings. RESULTS: Negative and positive predictive values for detecting anastomotic leakage were 100% (95% CI, 96.8-100%) and 100% (95% CI, 39.8-100%), respectively, for CT antegrade colonography and 98.6% (95% CI, 92.4-100%) and 100% (95% CI, 54.1-100%), respectively, for standard antegrade fluoroscopy. The negative and positive predictive values for detecting abscess were 100% (95% CI, 96.8-100%) and 100% (95% CI, 47.8-100%), respectively, for CT antegrade colonography and 97.3% (95% CI, 90.8-99.7%) and 100% (95% CI, 2.5-100%), respectively, for standard antegrade fluoroscopy. CONCLUSION: CT antegrade colonography may play a major role in the evaluation of low anastomosis protected by an ileostomy after proctectomy in low rectal endometriosis, leading to the development of a new strategy with early restoration of the intestinal continuity.

[Intestinal endometriosis]. / Localisations digestives de l'endométriose.

Endometriosis affects 6 to 10 % of all women of childbearing age. Intestinal involvement is defined by muscularis infiltration and has been estimated to occur in 8 % to 12 % of women with endometriosis. The most common sites are rectum, sigmoid and ileocaecal junction. In most cases, intestinal endometriosis is associated with deep infiltrating endometriosis, multifocal and aggressive form of endometriosis, responsible for refractory pelvic pain and infertility. The symptoms are nonspecific but are characterized by cyclic exacerbation of pain. The preoperative work-up includes a rectal endoscopic ultrasonography, a transvaginal ultrasonography, a pelvic magnetic resonance imaging and a multidetector CT scan. There is currently no cure other than surgical removal of lesions. Medical treatments are based on a hormone used to block ovarian function.

[Surgical treatment of liver metastasis in patients with colorectal cancer]. / Cancers colorectaux : traitement chirurgical des métastases hépatiques.

Half of patients with colorectal cancer have liver metastasis during their illness. Surgical resection of metastases represents the only curative treatment with prolonged survival in more than 50 % of patients. The aim of liver resection is complete excision of the lesions with histological negative margins while preserving sufficient functional liver parenchyma. In patients with diffuse liver disease, the radiofrequency ablation of metastases may be associated with surgical resection. The use of portal vein remobilization and neoadjuvant chemotherapy can also increase the number of patients for curative treatment. Despite this progress, from 50 to 60 % of patients relapse after complete resection of MHCCR. Surgical treatment of recurrent aggressive and effective chemotherapy allows the prolonged survival of these patients. The modern treatment of liver metastasis of colorectal cancers can be envisaged as part of a multidisciplinary approach to increase the number of patients for curative treatment.

Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.

INTRODUCTION AND AIM: Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. METHODS: Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. RESULTS: Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. CONCLUSIONS: Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.

The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice.

Deep infiltrating endometriosis (DIE) is a particular clinical and histological entity of endometriosis responsible for chronic pelvic pain and infertility. Here we characterize the proliferative phenotype of DIE cells, to explore the cellular and molecular mechanisms that could explain their aggressive potential. In addition, the inhibition of mTOR/AKT pathway was tested, as a potential treatment of DIE. Included were 22 patients with DIE and 12 control patients without endometriosis. Epithelial and stromal cells were extracted from biopsies of eutopic endometrium and deep infiltrating endometriotic nodules from patients with DIE. Cell proliferation was determined by thymidine incorporation. Oxidative stress was assayed by spectrofluorometry. The ERK and mTOR/AKT pathways were analyzed in vitro by Western blot and for AKT in vivo in a mouse model of DIE. The proliferation rate of eutopic endometrial cells and of deep infiltrating endometriotic cells from DIE patients was higher than that of endometrial cells from controls. The hyperproliferative phenotype of endometriotic cells was associated with an increase in endogenous oxidative stress, and with activation of the ERK and mTOR/AKT pathways. mTOR/AKT inhibition by temsirolimus decreased endometriotic cell proliferation both in vitro and in vivo in a mouse model of DIE. Blocking the mTOR/AKT pathway offers new prospects for the treatment of DIE.

Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Researchers have suggested that antibiotics could cure acute appendicitis. We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis. METHODS: In this open-label, non-inferiority, randomised trial, adult patients (aged 18-68 years) with uncomplicated acute appendicitis, as assessed by CT scan, were enrolled at six university hospitals in France. A computer-generated randomisation sequence was used to allocate patients randomly in a 1:1 ratio to receive amoxicillin plus clavulanic acid (3 g per day) for 8-15 days or emergency appendicectomy. The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10 percentage points. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT00135603. FINDINGS: Of 243 patients randomised, 123 were allocated to the antibiotic group and 120 to the appendicectomy group. Four were excluded from analysis because of early dropout before receiving the intervention, leaving 239 (antibiotic group, 120; appendicectomy group, 119) patients for intention-to-treat analysis. 30-day postintervention peritonitis was significantly more frequent in the antibiotic group (8%, n=9) than in the appendicectomy group (2%, n=2; treatment difference 5·8; 95% CI 0·3-12·1). In the appendicectomy group, despite CT-scan assessment, 21 (18%) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. In the antibiotic group, 14 (12% [7·1-18·6]) of 120 underwent an appendicectomy during the first 30 days and 30 (29% [21·4-38·9]) of 102 underwent appendicectomy between 1 month and 1 year, 26 of whom had acute appendicitis (recurrence rate 26%; 18·0-34·7). INTERPRETATION: Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis. Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment. FUNDING: French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.