[Curative treatment for esophageal cancer: results of a multidisciplinary consensus]. / Traitement curatif du cancer de l'oesophage: consensus multidisciplinaire multicentrique.

The management of patients with resectable cancer of the esophagus or gastroesophageal junction is currently not standardized. A multi- disciplinary regional consensus has been developed and is presented in this article. The standard workup includes an upper endoscopy, ultrasonography and a CT-scan. For locally advanced tumors, surgery should be associated with either preoperative radiochemotherapy orperioperative chemotherapy after discussion in multidisciplinary tumor board. Before the operation, smoking and alcohol cessation is imperative and nutritional status should be optimized. Nowadays, surgery is well standardized and generally performed minimally invasive accesses. After surgery, clinical and oncological follow-up is necessary.

[Shared decision making in the colorectal cancer screening program in the canton of Vaud]. / Programme cantonal vaudois de dépistage du cancer colorectal: information et décision partagée.

The colorectal cancer screening program of the canton of Vaud aims to facilitate screening for this cancer for the population aged 50 to 69 years old. The two screening modalities offered are fecal immunochemical testing (FIT) and colonoscopy. The decision to undergo screening and the screening modality is based on an individual medical encounter with a primary care physician. Both screening modalities are reimbursed through basic health coverage in Switzerland. The participation to the screening program allows the exemption of the deductible for the medical encounter and the chosen screening modality. A copay of 10% is maintained for all costs. Communication tools were developed on the basis of recommendations in the literature to facilitate shared decision-making in a medical encounter.

Lack of Mycobacterium tuberculosis-specific interleukin-17A-producing CD4+ T cells in active disease.

Protective immunity to Mycobacterium tuberculosis (Mtb) is commonly ascribed to a Th1 profile; however, the involvement of Th17 cells remains to be clarified. Here, we characterized Mtb-specific CD4(+) T cells in blood and bronchoalveolar lavages (BALs) from untreated subjects with either active tuberculosis disease (TB) or latent Mtb infection (LTBI), considered as prototypic models of uncontrolled or controlled infection, respectively. The production of IL-17A, IFN-γ, TNF-α, and IL-2 by Mtb-specific CD4(+) T cells was assessed both directly ex vivo and following in vitro antigen-specific T-cell expansion. Unlike for extracellular bacteria, Mtb-specific CD4(+) T-cell responses lacked immediate ex vivo IL-17A effector function in both LTBI and TB individuals. Furthermore, Mtb-specific Th17 cells were absent in BALs, while extracellular bacteria-specific Th17 cells were identified in gut biopsies of healthy individuals. Interestingly, only Mtb-specific CD4(+) T cells from 50% of LTBI but not from TB subjects acquired the ability to produce IL-17A following Mtb-specific T-cell expansion. Finally, IL-17A acquisition by Mtb-specific CD4(+) T cells correlated with the coexpression of CXCR3 and CCR6, currently associated to Th1 or Th17 profiles, respectively. Our data demonstrate that Mtb-specific Th17 cells are selectively undetectable in peripheral blood and BALs from TB patients.

DNA/NYVAC vaccine regimen induces HIV-specific CD4 and CD8 T-cell responses in intestinal mucosa.

In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpox-specific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed α4ß7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.

[Prevention of colorectal cancer]. / Prévention du cancer colorectal.

Colorectal cancer (CRC) is a public health problem. It is one of the most common cancers and mortality rate is around 50%. This article reports on the various methods of primary prevention testing for the population at average risk of developing CRC. Given its slow evolution through pre-cancerous lesions, it is appropiate to identify patients at medium risk and monitore those at high risk. Current screening methods show very different efficiencies. The most efficient are invasive and limit public support. New non-invasive tests based on fecal and blood biomarkers are being developed and will probably help to improve CRC screening in the future in an attempt to lower mortality rate.

Biomarkers of human gastrointestinal tract regions.

Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations. We analyzed the gene expression signature of antrum, duodenum, jejunum, ileum, and transverse colon biopsies using a biostatistical method based on a multivariate and univariate approach to identify region-selective genes. One hundred sixty-six genes were found responsible for distinguishing the five regions considered. Nineteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion and six novel genes. Moreover, by crossing these genes with those retrieved from an existing data set of gene expression in the intestine of ulcerative colitis and Crohn's disease patients, we identified genes that might be biomarkers of Crohn's and/or ulcerative colitis in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. This study furnishes the first map of gene expression along the healthy human gastrointestinal tract. Furthermore, the approach implemented here, and validated by retrieving known gene profiles, allowed the identification of promising new leads in both healthy and disease states.

Acinar cell carcinoma of the pancreas with thyroid-like follicular features: first description of a new diagnostic challenging subtype.

Acinar cell carcinomas (ACCs) of the pancreas are a heterogeneous group of neoplasms showing a wide spectrum of morphological features including acinar, solid, glandular, and trabecular architecture. In addition, uncommon cytological aspects have recently been described and include oncocytic, spindle, clear, and pleomorphic cell types. This wide histological spectrum represents a challenge in the diagnostic task for pathologists. Molecular mechanisms involved in the onset and progression of ACCs are not completely known, but, in general, they differ from those observed in ductal adenocarcinomas or neuroendocrine neoplasms of the pancreas and frequently include alterations in the APC/ß-catenin pathway. In the present paper, we describe a new variant of ACC showing thyroid-like follicular features and CTNNB1 mutation. This phenotype needs to be included in the spectrum of morphological presentation of ACC.

Combined written and oral information prior to gastrointestinal endoscopy compared with oral information alone: a randomized trial.

BACKGROUND: Little is known about how to most effectively deliver relevant information to patients scheduled for endoscopy. METHODS: To assess the effects of combined written and oral information, compared with oral information alone on the quality of information before endoscopy and the level of anxiety. We designed a prospective study in two Swiss teaching hospitals which enrolled consecutive patients scheduled for endoscopy over a three-month period. Patients were randomized either to receiving, along with the appointment notice, an explanatory leaflet about the upcoming examination, or to oral information delivered by each patient's doctor. Evaluation of quality of information was rated on scales between 0 (none received) and 5 (excellent). The analysis of outcome variables was performed on the basis of intention to treat-analysis. Multivariate analysis of predictors of information scores was performed by linear regression analysis. RESULTS: Of 718 eligible patients 577 (80%) returned their questionnaire. Patients who received written leaflets (N = 278) rated the quality of information they received higher than those informed verbally (N = 299), for all 8 quality-of-information items. Differences were significant regarding information about the risks of the procedure (3.24 versus 2.26, p < 0.001), how to prepare for the procedure (3.56 versus 3.23, p = 0.036), what to expect after the procedure (2.99 versus 2.59, p < 0.001), and the 8 quality-of-information items (3.35 versus 3.02, p = 0.002). The two groups reported similar levels of anxiety before procedure (p = 0.66), pain during procedure (p = 0.20), tolerability throughout the procedure (p = 0.76), problems after the procedure (p = 0.22), and overall rating of the procedure between poor and excellent (p = 0.82). CONCLUSION: Written information led to more favourable assessments of the quality of information and had no impact on patient anxiety nor on the overall assessment of the endoscopy. Because structured and comprehensive written information is perceived as beneficial by patients, gastroenterologists should clearly explain to their patients the risks, benefits and alternatives of endoscopic procedures. TRIAL REGISTRATION: Current Controlled trial number: ISRCTN34382782.

[Acid related diseases progress in 2007]. / Maladies peptiques.

The treatment of reflux disease did not changed. PPI treatment remains the first line treatment and surgery a second line treatment. The effect of surgery in reflux disease reduces and, after ten years, a part of the operated patients needs PPI again. The triple therapy is the treatment of choice of Helicobacter pylori infection. Patients with persistent Helicobacter pylori infection, after a first treatment, should be treated with a sequential treatment. PPI are effective in the prevention of gastroduodenal lesions and in the treatment of dyspeptic symptoms during NSAID treatment. IPP should be given to all patients presenting dyspeptic symptoms under NSAID or COX-2 administration.

[Colorectal cancer screening: follow-up of patients with adenomatous and colorectal cancer]. / Dépistage du cancer colorectal; surveillance après résection de polypes coliques ou d'un cancer colorectal.

The different methods of colorectal cancer screening are discussed. Our recommendations had not changed: we recommend as colorectal cancer screening a colonoscopy at the age of 50 years in all healthy persons with average risk for colorectal cancer. A 2007 interdisciplinary consensus conference revised the Swiss recommendations for the follow-up of patients with operated colorectal cancer or after polypectomy.

Wireless capsule pH monitoring: does it fulfil all expectations?

pH monitoring has been used as a diagnostic tool in gastro-oesophageal reflux disease (GERD) for many years. Recent studies have shown that wireless capsule pH monitoring is better tolerated and interferes less with daily activities as compared to traditional catheter-based pH monitoring. Moreover, prolonged recording time (48 h instead of 24 h) is possible with wireless pH monitoring. The main secondary effect of wireless capsule pH monitoring is induction of thoracic discomfort in 10-65% of the patients, which can vary from mild foreign body sensation to severe chest pain. Sensitivity and specificity of wireless capsule monitoring is comparable to that of traditional pH monitoring. It has not been proven yet that better tolerability and a longer recording time increases the diagnostic yield of wireless capsule monitoring in GERD.

[Peptic diseases]. / Maladies peptiques.

There are no real therapeutical acquisitions in the year 2006. The latest breakthroughs related to peptic disease treatment are the subject of this article. In particular various therapeutic procedures in reflux disease, including Barrett's oesophagus are developed here. Two important items were emphasized in the treatment of gastric and duodenal ulcers, in particular Helicobacter pylori eradication and the treatment of bleeding ulcer. Prophylaxis of gastrointestinal lesions due to AINS is also approached in detail.

Endoscopic and surgical ampullectomy for non-invasive ampullary tumors: Short-term outcomes.

Non-invasive ampullary tumors, may be treated with endoscopic (EA) or surgical ampullectomy (SA). However, evidence on the morbidity of these techniques remains limited. This pilot study aimed to assess and compare morbidity of EA and SA. Patients undergoing EA or SA for non-invasive ampullary tumors were retrospectively analyzed and compared. Outcomes were postoperative complications graded with Clavien Classification and Comprehensive Complication Index (CCI), and length of stay (LoS). A review of the literature was performed to propose an evidence-based algorithm to treat ampullary tumors. A total of 11 EA and 19 SA were identified and analyzed. EA was associated with shorter intervention (51 vs. 191 min, p < 0.001) and decreased blood loss (0 vs. 100 mL, p < 0.001). Postoperative complications were more frequent after surgery compared to endoscopy (9% vs. 68%, p = 0.002). Surgical patients showed a higher CCI (0 vs. 8.7, p < 0.001). LoS was reduced in patients undergoing endoscopy (0 vs. 14 days, p < 0.001), with comparable readmissions rates (p = 0.126). Necessity of subsequent treatment was more frequent after endoscopic, compared to SA (5 vs. 1, p = 0.016). EA was associated with lower morbidity than SA and appeared as an appropriate first-line treatment for non-invasive ampullary tumors. SA remains a valuable alternative after EA failure.

Repair of challenging non-malignant tracheo- or broncho-oesophageal fistulas by extrathoracic muscle flaps.

OBJECTIVES: Evaluation of complex, acquired, non-malignant tracheo/broncho-oesophageal fistulas (TEF) repaired by extrathoracic pedicled muscle flaps that were, in addition to their interposition between the airways and the gastro-intestinal tract, patched into gastro-intestinal or airway defects if primary closure seemed risky. METHODS: A single institution experience of patients treated between 2003 and 2015. Twenty-two patients required TEF repair following oesophageal surgery (18), Boerhaave syndrome (1), chemotherapy for mediastinal lymphoma (1), carinal resection and irradiation (1) and laryngectomy (1); 64% of them underwent prior radio- or chemotherapy and 50% prior airway or oesophageal stenting. RESULTS: Airway defects were closed by muscle flap patch ( n = 12), lobectomy ( n = 4), airway resection/anastomosis ( n = 2), pneumonectomy ( n = 1), segmentectomy ( n = 2) or primary suture ( n = 1). Gastro-intestinal defects were repaired by oesophageal diversion ( n = 9), muscle flap patch ( n = 8) or primary suture ( n = 5). A muscle flap patch was used to close airway and gastro-intestinal defects in 55% and 36% of cases, respectively. The 90-day postoperative mortality and TEF recurrence rates were 18% and 4.5%. Airway healing and breathing without tracheal appliance was obtained in 95% of patients and gastro-intestinal healing in 77% of those without oesophageal diversion. Five of nine patients with oesophageal diversion underwent intestinal restoration by retrosternal colon transplants. CONCLUSIONS: Complex TEF arising after oesophageal surgery, radio-chemotherapy or failed stenting can be successfully closed using extrathoracic muscle flaps that can, in addition to their interposition between the airway and the gastro-intestinal tract, also be patched into gastro-oesophageal or airway defects if primary closure seems hazardous.

Technology insight: Photodynamic therapy for cholangiocarcinoma.

Cholangiocarcinoma is, in most cases, rapidly fatal. Curative resection can only be offered to approximately 10% of patients. Even after seemingly curative resection, recurrence frequently occurs. Adjuvant chemotherapy and/or radiotherapy do not reduce the recurrence rate after resection. In the palliative setting, endoscopic or percutaneous biliary drainage is performed to relieve jaundice; however, poor results have been obtained in patients with tumors involving the intrahepatic bile ducts. Biliary drainage alleviates jaundice, but there is no evidence that it prolongs life. Palliative chemotherapy and/or radiotherapy have not been proven to prolong life and relieve jaundice. Photodynamic therapy (PDT) is a relatively new local, minimally invasive procedure that can be used to treat cholangiocarcinoma. PDT uses the physical properties of light-absorbing molecules, so-called photosensitizers, which accumulate within proliferating cells. Activation of the photosensitizer by a non-thermal laser leads to selective photochemical destruction of tumors. In a randomized trial of patients with nonresectable cholangiocarcinoma, PDT prolonged survival time, improved cholestasis and quality of life considerably, and had a favorable side-effect profile. A second randomized trial confirmed the beneficial effect of PDT. For the time being, PDT is recommended for patients with nonresectable disease. The role of PDT before and after surgical resection needs to be assessed.

Training primary care physicians to offer their patients faecal occult blood testing and colonoscopy for colorectal cancer screening on an equal basis: a pilot intervention with before-after and parallel group surveys.

OBJECTIVES: Primary care physicians (PCPs) should prescribe faecal immunochemical testing (FIT) or colonoscopy for colorectal cancer screening based on their patient's values and preferences. However, there are wide variations between PCPs in the screening method prescribed. The objective was to assess the impact of an educational intervention on PCPs' intent to offer FIT or colonoscopy on an equal basis. DESIGN: Survey before and after training seminars, with a parallel comparison through a mailed survey to PCPs not attending the training seminars. SETTING: All PCPs in the canton of Vaud, Switzerland. PARTICIPANTS: Of 592 eligible PCPs, 133 (22%) attended a seminar and 106 (80%) filled both surveys. 109 (24%) PCPs who did not attend the seminars returned the mailed survey. INTERVENTION: A 2 h-long interactive seminar targeting PCP knowledge, skills and attitudes regarding offering a choice of colorectal cancer (CRC) screening options. OUTCOME MEASURES: The primary outcome was PCP intention of having their patients screened with FIT and colonoscopy in equal proportions (between 40% and 60% each). Secondary outcomes were the perceived role of PCPs in screening decisions (from paternalistic to informed decision-making) and correct answer to a clinical vignette. RESULTS: Before the seminars, 8% of PCPs reported that they had equal proportions of their patients screened for CRC by FIT and colonoscopy; after the seminar, 33% foresaw having their patients screened in equal proportions (p<0.001). Among those not attending, there was no change (13% vs 14%, p=0.8). Of those attending, there was no change in their perceived role in screening decisions, while the proportion responding correctly to a clinical vignette increased (88-99%, p<0.001). CONCLUSIONS: An interactive training seminar increased the proportion of physicians with the intention to prescribe FIT and colonoscopy in equal proportions.

Development and Clinical Validation of a Blood Test Based on 29-Gene Expression for Early Detection of Colorectal Cancer.

PURPOSE: A blood test for early detection of colorectal cancer is a valuable tool for testing asymptomatic individuals and reducing colorectal cancer-related mortality. The objective of this study was to develop and validate a novel blood test able to differentiate patients with colorectal cancer and adenomatous polyps (AP) from individuals with a negative colonoscopy. EXPERIMENTAL DESIGN: A case-control, multicenter clinical study was designed to collect blood samples from patients referred for colonoscopy or surgery. Predictive algorithms were developed on 75 controls, 61 large AP (LAP) ≥1 cm, and 45 colorectal cancer cases and independently validated on 74 controls, 42 LAP, and 52 colorectal cancer cases (23 stages I-II) as well as on 245 cases including other colorectal findings and diseases other than colorectal cancer. The test is based on a 29-gene panel expressed in peripheral blood mononuclear cells alone or in combination with established plasma tumor markers. RESULTS: The 29-gene algorithm detected colorectal cancer and LAP with a sensitivity of 79.5% and 55.4%, respectively, with 90.0% specificity. Combination with the protein tumor markers carcinoembryonic antigen (CEA) and CYFRA21-2 resulted in a specificity increase (92.2%) with a sensitivity for colorectal cancer and LAP detection of 78.1% and 52.3%, respectively. CONCLUSIONS: We report the validation of a novel blood test, Colox®, for the detection of colorectal cancer and LAP based on a 29-gene panel and the CEA and CYFRA21-1 plasma biomarkers. The performance and convenience of this routine blood test provide physicians a useful tool to test average-risk individuals unwilling to undergo upfront colonoscopy. Clin Cancer Res; 22(18); 4604-11. ©2016 AACR.

Gastric banding interferes with esophageal motility and gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux and progressive esophageal dilatation can develop after gastric banding (GB). HYPOTHESIS: Gastric banding may interfere with esophageal motility, enhance reflux, or promote esophageal dilatation. DESIGN: Before-after trial in patients undergoing GB. SETTING: University teaching hospital. PATIENTS AND METHODS: Between January 1999 and August 2002, 43 patients undergoing laparoscopic GB for morbid obesity underwent upper gastrointestinal endoscopy, 24-hour pH monitoring, and stationary esophageal manometry before GB and between 6 and 18 months postoperatively. MAIN OUTCOME MEASURES: Reflux symptoms, endoscopic esophagitis, pressures measured at manometry, esophageal acid exposure. RESULTS: There was no difference in the prevalence of reflux symptoms or esophagitis before and after GB. The lower esophageal sphincter was unaffected by surgery, but contractions in the lower esophagus weakened after GB, in correlation with preoperative values. There was a trend toward more postoperative nonspecific motility disorders. Esophageal acid exposure tended to decrease after GB, with fewer reflux episodes. A few patients developed massive postoperative reflux. There was no clear correlation between preoperative testing and postoperative esophageal acid exposure, although patients with abnormal preoperative acid exposure tended to maintain high values after GB. CONCLUSIONS: Postoperative esophageal dysmotility and gastroesophageal reflux are not uncommon after GB. Preoperative testing should be done routinely. Low amplitude of contraction in the lower esophagus and increased esophageal acid exposure should be regarded as contraindications to GB. Patients with such findings should be offered an alternative procedure, such as Roux-en-Y gastric bypass.

[Colorectal stent: therapeutic alternative for acute obstruction?]. / Le stent colorectal: atternative thérapeutique en situation d'obstruction aiguë?

A colorectal obstruction generally requires an urgent approach, both diagnostically and therapeutically. This context and a poor general condition make surgery hazardous. An auto-expansive stent is an effective therapeutic alternative, more often used to remove such a benign or malignant colorectal obstruction. In the latter presentation, the stent allows for the removal of the obstacle and for the establishment of a precise diagnosis before surgery. In the case of an incurable tumour or where removal is contra-indicated, a stent can represent a palliative treatment. Success in terms of re-establishment of perfusion, is about 85%. The most frequently encountered complication is perforation and is an indication for urgent surgery. Migration and obstruction of the stent are less frequent.