Esophageal and pharyngeal strictures: report on 1,862 endoscopic dilatations using the Savary-Gilliard technique

Treatment of symptomatic pharyngeal and esophageal strictures requires endoscopic dilatation. The Savary-Gilliard bougienage was developed by our department and has been used since 1980 for this purpose. We report our experience using this technique. The records of patients seen from January 1, 1963 to December 31, 2005, who had pharyngeal and esophageal strictures needing dilatation, were reviewed. The prevalence of different etiologies, and the incidence of complications using the Savary-Gilliard dilators were assessed. Efficiency of dilatation was assessed over a 17-year segment of this period, using number of dilatations and time intervals between dilatations until resolution of symptoms as outcome measures. Of the 2,652 pharyngeal and esophageal strictures reviewed, 90% were of organic origin (45% benign and 55% malignant stenoses), and 10% were of functional etiology. The most common etiologies were peptic strictures before the era of proton pump inhibitors, and postoperative anastomotic strictures thereafter. A total of 1,862 dilatations using the Savary-Gilliard technique were analyzed. Complication and mortality rates were 0.18 and 0.09% for benign and 4.58 and 0.81% for malignant etiologies, respectively. The number of dilatations per stricture and the time interval between different sessions were dependent on the type of strictures, varying from 1 to 23 dilatations and 7days to 16years, respectively. Pharyngeal and esophageal dilatations using the Savary-Gilliard technique were safe when used together with fluoroscopy. Overall, the efficiency of the dilatation procedure was good, but some types of strictures (e.g., caustic, post-surgical and/or post radiotherapy) were refractory to treatment and required repeated dilatation

p53 mutation in histologically normal mucosa of the aero-digestive tract is not a marker of increased risk for second primary carcinoma in head and neck cancer patients

Head and neck cancer patients are at high risk for developing second primary tumors. This is known as field cancerization of the aero-digestive tract. In a previous study, we showed that patients with multiple primary tumors were more likely to have p53 mutations in histologically normal mucosae than patients presenting with an isolated tumor. Based on this observation, we postulated that p53 mutations in normal tissue samples of patients bearing a single primary tumor could have a clinical value as a biomarker for the risk of developing second primary tumors. Thirty-five patients presenting with a single primary tumor were followed-up for a median of 51 months (range 1 month to 10.9 years) after biopsies of histologically normal squamous cell mucosa had been analyzed for p53 mutations with a yeast functional assay at the time of the primary tumor. During this follow-up, recurrences and non-sterilization of the primary tumor, occurrence of lymph node metastases, and of second primary tumors were evaluated. Sixteen (45.7%) patients were found to have p53 mutations in their normal squamous cell mucosa, and 19 (54.3%) patients showed no mutation. No relationship was found between p53 mutations and the occurrence of evaluated events during follow-up. Notably, the rate of second primary tumors was not associated with p53 mutations in the normal squamous mucosa. The correlation between p53 mutations in histologically normal mucosae and the incidence of second primary tumors is generally low. The benefit of analyzing p53 mutations in samples of normal squamous cell mucosa in every patient with a primary tumor of the head and neck is doubtfu

Stricture prevention after extended circumferential endoscopic mucosal resection by injecting autologous keratinocytes in the sheep esophagus

Background: During the past decades, endoscopic mucosal resection (EMR) has been developed to treat early intramucosal esophageal cancers and dysplastic Barrett's esophagus. The primary drawback of this method is severe postsurgical esophageal stricture formation. The purpose of this preclinical study was to assess strategies for prevention of this major complication by injecting autologous keratinocytes in the EMR mucosal defect in the sheep model. Methods: Circumferential, 6-cm-long EMRs were performed in the esophagus of nine sheep. Autologous keratinocytes were harvested 2weeks before EMR and cultured. Circumferential resection consisted of two opposite hemicircumferential mucosectomies allowing a widespread resection of 24cm2. Immediately after EMR, autologous keratinocytes were endoscopically injected in the mucosal defect. Animals were sacrificed after 6months. Results: Circumferential EMRs were successfully performed in all animals. There were no intra- or postoperative complications. None of the animals developed strictures. All animals were sacrificed at 6months as planned. Histological examinations showed fibrotic changes in 10% (range 0-25%) of the circumferential muscularis propria interna layer and 7.2% (range 0-25%) in the muscularis propria externa layer at the midportion of the EMR. No circumferential transmural fibrosis was identified. Conclusions: Prevention of stricture formation after extensive (6-cm long) circumferential EMR of the sheep esophagus can be achieved by injecting autologous keratinocytes into the wound of the resected mucosal segmen

MAGE-A3 and MAGE-A4 specific CD4+ T cells in head and neck cancer patients: detection of naturally acquired responses and identification of new epitopes

Frequent expression of cancer testis antigens (CTA) has been consistently observed in head and neck squamous cell carcinomas (HNSCC). For instance, in 52 HNSCC patients, MAGE-A3 and -A4 CTA were expressed in over 75% of tumors, regardless of the sites of primary tumors such as oral cavity or hypopharynx. Yet, T-cell responses against these CTA in tumor-bearing patients have not been investigated in detail. In this study, we assessed the naturally acquired T-cell response against MAGE-A3 and -A4 in nonvaccinated HNSCC patients. Autologous antigen-presenting cells pulsed with overlapping peptide pools were used to detect and isolate MAGE-A3 and MAGE-A4 specific CD4+ T cells from healthy donors and seven head and neck cancer patients. CD4+ T-cell clones were characterized by cytokine secretion. We could detect and isolate MAGE-A3 and MAGE-A4 specific CD4+ T cells from 7/7 cancer patients analyzed. Moreover, we identified six previously described and three new epitopes for MAGE-A3. Among them, the MAGE-A3111-125 and MAGE-A3161-175 epitopes were shown to be naturally processed and presented by DC in association with HLA-DP and DR, respectively. All of the detected MAGE-A4 responses were specific for new helper epitopes. These data suggest that naturally acquired CD4+ T-cell responses against CT antigens often occur in vivo in HNSCC cancer patients and provide a rationale for the development of active immunotherapeutic approaches in this type of tumo

Eigenfunction Statistics on Quantum Graphs

We investigate the spatial statistics of the energy eigenfunctions on large quantum graphs. It has previously been conjectured that these should be described by a Gaussian Random Wave Model, by analogy with quantum chaotic systems, for which such a model was proposed by Berry in 1977. The autocorrelation functions we calculate for an individual quantum graph exhibit a universal component, which completely determines a Gaussian Random Wave Model, and a system-dependent deviation. This deviation depends on the graph only through its underlying classical dynamics. Classical criteria for quantum universality to be met asymptotically in the large graph limit (i.e. for the non-universal deviation to vanish) are then extracted. We use an exact field theoretic expression in terms of a variant of a supersymmetric sigma model. A saddle-point analysis of this expression leads to the estimates. In particular, intensity correlations are used to discuss the possible equidistribution of the energy eigenfunctions in the large graph limit. When equidistribution is asymptotically realized, our theory predicts a rate of convergence that is a significant refinement of previous estimates. The universal and system-dependent components of intensity correlation functions are recovered by means of an exact trace formula which we analyse in the diagonal approximation, drawing in this way a parallel between the field theory and semiclassics. Our results provide the first instance where an asymptotic Gaussian Random Wave Model has been established microscopically for eigenfunctions in a system with no disorder.Comment: 59 pages, 3 figure

Emergencies after endoscopic procedures

Endoscopy adverse events (AEs), or complications, are a rising concern on the quality of endoscopic care, given the technical advances and the crescent complexity of therapeutic procedures, over the entire gastrointestinal and bilio-prancreatic tract. In a small percentage, not established, there can be real emergency conditions, as perforation, severe bleeding, embolization or infection. Distinct variables interfere in its occurrence, although, the awareness of the operator for their potential, early recognition, and local organized facilities for immediate handling, makes all the difference in the subsequent outcome. This review outlines general AEs’ frequencies, important predisposing factors and putative prophylactic measures for specific procedures (from conventional endoscopy to endoscopic cholangio-pancreatography and ultrasonography), with comprehensive approaches to the management of emergent bleeding and perforation

Quantum ergodicity on graphs

We investigate the equidistribution of the eigenfunctions on quantum graphs in the high-energy limit. Our main result is an estimate of the deviations from equidistribution for large well-connected graphs. We use an exact field-theoretic expression in terms of a variant of the supersymmetric nonlinear sigma-model. Our estimate is based on a saddle-point analysis of this expression and leads to a criterion for when equidistribution emerges asymptotically in the limit of large graphs. Our theory predicts a rate of convergence that is a significant refinement of previous estimates, long-assumed to be valid for quantum chaotic systems, agreeing with them in some situations but not all. We discuss specific examples for which the theory is tested numerically.Comment: 4 pages, 1 figur

A robotic honeycomb for interaction with a honeybee colony

Abstract: Robotic technologies have shown the capability to interact with living organisms and even to form integrated mixed societies comprised of living and artificial agents. Bio-compatible robots, incorporating sensing and actuation capable of generating and responding to relevant stimuli, can be a tool to study collective behaviors previously unattainable with traditional techniques. To investigate collective behaviors of the western honeybee (Apis mellifera), we designed a robotic system capable of observing and modulating the bee cluster using an array of thermal sensors and actuators. We initially integrated the system into a beehive populated with approximately 4,000 bees for several months. The robotic system was able to observe the colony by continuously collecting spatio- temporal thermal profiles of the winter cluster. Furthermore, we found that our robotic device reliably modulated the superorganism’s response to dynamic thermal stimulation, influencing its spatiotemporal re-organization. In addition, after identifying the thermal collapse of a colony, we used the robotic system in a “life-support” mode via its thermal actuators. Ultimately, we demonstrated a robotic device capable of autonomous closed-loop interaction with a cluster comprising thousands of individual bees. Such biohybrid societies open the door to investigation of collective behaviors that necessitate observing and interacting with the animals within a complete social context, as well as for potential applications in augmenting the survivability of these pollinators crucial to our ecosystems and our food supply. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Robotics, Vol. 8, 76, Mar 2023, DOI: 10.1126/scirobotics.add7385 https://doi.org/10.1126/scirobotics.add738