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Susa Valley, located in the Italian Western Alps, has served as a meeting point for cultural, spiritual, and commercial exchange for a long period of history. The valley's role as one of the main connecting routes between south and southwestern Europe resulted in its acquisition of a rich traditional ecological knowledge. However, like other Italian mountainous valleys, this valley has suffered from abandonment and depopulation in the past 50 years. Our study aims to investigate the current ethnobotanical medicinal knowledge in the valley and to compare our findings with a study conducted over 50 years ago in the same area. In 2018, we conducted 30 in-depth semi-structured interviews on medicinal plants and food-medicines used in the Susa Valley. We documented 36 species, of which 21 species were used for medical purposes and 15 species were used as food-medicine. The comparison with the previous study on medicinal herbs conducted in 1970 in the valley demonstrated a significant decrease in both the knowledge and use of medicinal plants, which could be attributed to socioeconomic, cultural, and possibly environmental changes that occurred in the past half-century. Our study highlights several promising species for future use as nutraceuticals, food, and medicinal products, such as Taraxacum officinale , Urtica dioica , and Artemisia genipi .

Temporal lobe epilepsy is a brain network disorder characterized by alterations at both the structural and the functional levels. It remains unclear how structure and function are related and whether this has any clinical relevance. In the present work, we adopted a novel methodological approach investigating how network structural features influence the large-scale dynamics. The functional network was defined by the spatio-temporal spreading of aperiodic bursts of activations (neuronal avalanches), as observed utilizing high-density electroencephalography in patients with temporal lobe epilepsy. The structural network was modelled as the region-based thickness covariance. Loosely speaking, we quantified the similarity of the cortical thickness of any two brain regions, both across groups and at the individual level, the latter utilizing a novel approach to define the subject-wise structural covariance network. In order to compare the structural and functional networks (at the nodal level), we studied the correlation between the probability that a wave of activity would propagate from a source to a target region and the similarity of the source region thickness as compared with other target brain regions. Building on the recent evidence that large-waves of activities pathologically spread through the epileptogenic network in temporal lobe epilepsy, also during resting state, we hypothesize that the structural cortical organization might influence such altered spatio-temporal dynamics. We observed a stable cluster of structure-function correlation in the bilateral limbic areas across subjects, highlighting group-specific features for left, right and bilateral temporal epilepsy. The involvement of contralateral areas was observed in unilateral temporal lobe epilepsy. We showed that in temporal lobe epilepsy, alterations of structural and functional networks pair in the regions where seizures propagate and are linked to disease severity. In this study, we leveraged on a well-defined model of neurological disease and pushed forward personalization approaches potentially useful in clinical practice. Finally, the methods developed here could be exploited to investigate the relationship between structure-function networks at subject level in other neurological conditions., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Although relatively specific anatomo-electro-clinical features of temporal lobe epilepsy (TLE) with bilateral ictal involvement (bitemporal epilepsy-BTLE) have been described, differentiating between BTLE and unilateral TLE (UTLE) remains challenging. Surgery is often the treatment of choice for drug-resistant UTLE, whereas its use is more controversial in BTLE. It is currently unclear whether neuropsychological assessment can contribute to the differential diagnosis. We retrospectively reviewed the neuropsychological evaluation of 46 consecutive patients with refractory TLE. Eighteen patients were diagnosed with BTLE on the basis of ictal electro-clinical data, in particular a video EEG recording of at least one seizure simultaneously involving the two temporal lobes without the possibility of lateralizing its onset or at least two different seizures independently arising from the two temporal lobes. Twenty-eight patients were classified as UTLE. Presurgery evaluation data were used in this study. Compared with UTLE, BTLE was associated with a lower intelligence quotient (IQ) and more severe impairment in long-term memory, the latter remaining significant even after controlling for IQ. No significant differences were found between right and left UTLE. In conclusion, BTLE and UTLE are associated with relatively distinct neuropsychological profiles, further supporting their classification as different disorders within the TLE spectrum.

Purpose: This study aims to describe micronutrient intake according to food processing degree and to investigate the association between the dietary share of ultra-processed foods and micronutrient inadequacies in a representative sample of Portuguese adult and elderly individuals., Methods: Cross-sectional data from the National Food, Nutrition and Physical Activity Survey (2015/2016) were used. Food consumption data were collected through two 24-h food recalls, and food items were classified according to the NOVA system. Linear regression models were used to assess the association between the micronutrient density and the quintiles of ultra-processed food consumption-crude and adjusted. Negative Binomial regressions were performed to measure the prevalence ratio of micronutrient inadequacy according to ultra-processed food quintiles., Results: For adults, all evaluated vitamins had significantly lower content in the fraction of ultra-processed foods compared to unprocessed or minimally processed foods, except vitamin B2. For the elderly, out of ten evaluated vitamins, seven presented significantly less content in ultra-processed foods compared to non-processed ones. The higher energy contribution of ultra-processed foods in adults was associated with a lower density of vitamins and minerals. This association was not observed in the elderly. For adults, compared with the first quintile of ultra-processed food consumption, the fifth quintile was positively associated with inadequate intakes of vitamin B6 (PR 1.51), vitamin C (PR 1.32), folate (PR 1.14), magnesium (PR 1.21), zinc (PR 1.33), and potassium (PR 1.19)., Conclusion: Our results corroborate the importance of public health actions that promote a reduction in the consumption of ultra-processed foods., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

This study aimed to identify dietary patterns (DPs) and their associations with sociodemographic factors and diet quality in Portuguese adults and the elderly. Cross-sectional data were obtained from the National Food, Nutrition and Physical Activity Survey (2015-2016), with two non-consecutive dietary 24 h recalls. Food items were classified according to the NOVA system and its proportion (in grams) in the total daily diet was considered to identify DPs by latent class analysis, using age and sex as concomitant variables. Multinomial logistic and linear regressions were performed to test associations of DPs with sociodemographic characteristics and diet quality, respectively. Three DPs were identified: "Traditional" (higher vegetables, fish, olive oil, breads, beer and wine intake), "Unhealthy" (higher pasta, sugar-sweetened beverages, confectionery and sausages intake) and "Diet concerns" (lower intake of cereals, red meat, sugar-sweetened and alcoholic beverages). "Unhealthy" was associated with being younger and lower intake of dietary fiber and vitamins and the highest free sugars and ultra-processed foods (UPF). "Diet concerns" was associated with being female and a more favorable nutrient profile, but both DPs presented a higher contribution of UPF than the "Traditional" DP. These findings should be considered for the design of food-based interventions and public policies for these age groups in Portugal.

Considering the nature, extent, and purpose of food processing, this study aims to identify dietary patterns (DPs) and their associations with sociodemographic factors and diet quality in Portuguese children and adolescents. Cross-sectional data were obtained from the National Food, Nutrition and Physical Activity Survey (2015-2016) of the Portuguese population. Dietary intake was obtained from two non-consecutive days and food items were classified according to the NOVA system. The proportion (in grams) of foods in the total daily diet was considered to identify DPs by latent class analysis, with age and sex as concomitant variables. Associations of DPs with sociodemographic characteristics were assessed using multinomial logistic regression. Linear regressions adjusted by sociodemographic characteristics tested associations of DPs with diet quality. DPs identified were: "Unhealthy" (higher sugar-sweetened beverages, industrial breads, and sausages intake), "Traditional" (higher vegetables, fish, olive oil, breads, ultra-processed yogurts, and sausages intake), and "Dairy" (higher intake of milk, yogurt, and milk-based beverages). "Unhealthy" was associated with older ages and lower intake of dietary fibre and vitamins and the highest free sugars and ultra-processed foods (UPF), although all DPs presented significant consumption of UPF. These findings should be considered for the design of food-based interventions and school-feeding policies in Portugal.

Objective: The aim of the present study is to investigate with noninvasive methods the modulation of dynamic functional connectivity during interictal epileptiform discharge (IED)., Method: We reconstructed the cortical source of the EEG recorded IED of 17 patients with focal epilepsy. We then computed dynamic connectivity using the time resolved phase locking value (PLV). We derived graph theory indices (i.e. degree, strength, local efficiency, clustering coefficient and global efficiency). Finally, we selected the atlas node with the maximum activation as the IED cortical source investigating the graph indices dynamics in theta, alpha, beta and gamma frequency bands., Results: We observed IED-locked modulations of the graph indexes depending on the frequency bands. We detected a modulation of the strength, clustering coefficient, local and global efficiency both in theta and in alpha bands, which also displayed modulations of the degree index. In the beta band only the global efficiency was modulated by the IED, while no effects were detected in the gamma band. Finally, we found a correlation between alpha and theta local efficiency, as well as alpha global efficiency, and the epilepsy duration., Significance: Our findings suggest that the neural synchronization is not limited to the IED cortical source, but implies a phase synchronization across multiple brain areas. We hypothesize that the aberrant electrical activity originating from the IED locus is spread amongst the other network nodes throughout the low frequency bands (i.e. theta and alpha). Moreover, IED-dependent increase in the global efficiency indicates that the IED interfere with the whole network functioning. We finally discussed possible application of this methodology for future investigation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Familial Hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol (LDL-C) and high atherosclerosis risk. The impact of different dietary patterns on atherosclerosis biomarkers has been poorly studied in FH. This study verified the association of adherence to a Mediterranean diet with biomarkers of dyslipidemia and low-grade inflammation in molecularly proven FH adults from Brazil (BR) and Spain (SP)., Methods and Results: In this cross-sectional study adherence to the Mediterranean diet was assessed by a validated score and generalized estimating equations were used to evaluate its association with plasma LDL-C, apolipoprotein-B (ApoB) and high sensitivity C-reactive protein (hs-CRP) concentrations. We included 92 (mean age 45 years, 58.7% females) and 98 FH individuals (mean age 46.8 years, 60.2% females) respectively from BR and SP. FH causing variants did not differ between countries. LDL-C, ApoB and hs-CRP concentrations were higher in BR than in SP: 179 (135-250) and 161 (133-193) mg/dL; 141 (109-181) and 103 (88-134) mg/dL; and 1.6 (0.8-4.0) and 0.8 (0.4-1.5) mg/L respectively (all p < 0.001). Most of BR had low adherence (n = 77, 83.7%), while the majority of SP were divided into moderate (n = 35, 35.7%) and strong adherence to the Mediterranean diet (n = 37, 37.8%), p < 0.001. There was a significant inverse association of adherence to the Mediterranean diet score with higher LDL-C, ApoB, and hs-CRP after adjusting for socio economic parameters, caloric and fatty acid intakes as well as pharmacological lipid lowering therapies., Conclusions: Higher adherence to a Mediterranean diet was associated with better dyslipidemia and low-grade inflammation profiles in FH., Competing Interests: Declaration of competing interest RDS has received honoraria related to consulting, research and or speaker activities from: Abbott, Amgen, Aché, Astra Zeneca, Esperion, GETZ Pharma, Kowa, Libbs, Merck, MSD, Novo-Nordisk, Novartis, PTC Therapeutics, Pfizer, and Sanofi. Others none to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background Evidence that a vegetarian diet rich in antioxidants contributes to cardiovascular health are growing, however, the underlying molecular mechanisms remain unknown. HO-1 (heme-oxygenase-1), a marker of adaptive response, is protective against oxidative stress and has shown cardioprotective effects. Therefore, we evaluated circulating HO-1 levels and the effect of plasma from omnivorous and vegetarians in endothelial cells (human umbilical vein endothelial cells) on modulating NRF2 (nuclear factor erythroid 2-like 2)/HO-1 and nitric oxide production. Methods and Results From 745 participants initially recruited, 44 omnivorous and 44 vegetarian men matched by age and absence of cardiovascular risk factors and diseases were included in this study. Circulating HO-1 was measured using ELISA and human umbilical vein endothelial cells were incubated with plasma from omnivorous and vegetarians. Higher circulating HO-1 concentrations were found in omnivorous compared with vegetarians. Plasma from omnivorous and not from vegetarians induced NRF2/HO-1 and nitric oxide production in human umbilical vein endothelial cells, and increased reactive oxygen species production and caspase activity after incubation with stressor stimulus. Conclusions We suggest that HO-1 induction in omnivorous may indicate a pro-oxidative status since HO-1 is activated under oxidative stress a state not seen in vegetarians.

The association of components of a low saturated fat (SFA) and of a Mediterranean diet was tested with atherosclerosis biomarkers in 190 familial hypercholesterolemia adults (FH) from Brazil (BR) and Spain (SP). Median blood LDL-C, Apolipoprotein B (apoB), and C reactive protein (hs-CRP) concentrations were higher in BR than in SP: 179.0 vs.161 mg/dL; 141 vs. 103 mg/dL; and 1.6 vs. 0.8 mg/L respectively (all p < 0.001). In BR there was lower median total fat (22.3 vs. 38.3%) and SFA (8.1 vs. 12.5%) but higher cholesterol (283.3 mg vs.188.9 mg) and carbohydrate (57.1 vs. 42.5%) consumption (all p < 0.001). Inverse associations were encountered between fibers, mono, and polyunsaturated fats and their ratios to SFA with LDL-C and ApoB (all p < 0.001). There was a direct association respectively of cholesterol with lipid biomarkers and of carbohydrates and trans-fatty acids with hs-CRP while other fats showed inverse relations with the latter (p < 0.001).

Telomere length is considered to be a biomarker of biological aging and age-related disease. There are few studies that have evaluated the association between telomere length and diet, and none of them have evaluated the impact of a vegetarian diet on telomere length and its correlation with cardiovascular biomarkers in apparently healthy subjects. Therefore, our objectives were to evaluate leukocyte telomere length (LTL) in vegetarians and omnivorous subjects and its association with classical cardiovascular risk biomarkers. From the total of 745 participants initially recruited, 44 omnivorous and 44 vegetarian men apparently healthy were selected for this study and LTL was measured in 39 omnivorous and 41 vegetarians by Real-Time Quantitative PCR reaction. Although telomere length was not different between omnivorous and vegetarians, we found a strong negative correlation between LTL and IMT (intima-media thickness) in omnivorous, but not in vegetarian group. In addition, omnivorous who were classified with short telomere length had higher carotid IMT compared to vegetarians. Our data suggest that telomere length can be a marker of subclinical atherosclerosis in the omnivorous group.

Objective: To evaluate the frequency of food consumption in apparently healthy men and their association with cardiovascular risk factors and biomarkers of subclinical atherosclerosis., Methods: In this observational study, 88 men had their food standard obtained through the food frequency questionnaire (FFQ). Associations of dietary patterns with cardiovascular risk factors, such as anthropometric data, laboratory and clinical evaluations, carotid-femoral arterial stiffness (IMT) and pulse wave velocity were evaluated., Results: The highest values were observed, for most of the risk factors evaluated, with the highest frequency of weekly consumption of dairy products, meats, sweets, fats, cold meats, sodas, milk and white chocolate; and lower frequency of weekly consumption of fruits, cereals, vegetables, legumes, oilseeds, and soy. There was no significant difference for coffee and dark chocolate., Conclusions: A diet with high consumption of animal products has a higher correlation with cardiovascular risk factors; the opposite is true for the consumption of plant-based food, associated with the profile of more favorable biomarkers for cardiovascular health and better biochemical and structural parameters.

Background: Recent studies have shown a lower prevalence of metabolic syndrome (MSyn) in vegetarians (VEG) despite the inconclusive evidence from others., Objective: To verify the association between diet and other lifestyle characteristics and the prevalence of MSyn, cardiovascular risk factors (CRF), and Framingham Risk Score (FRS) in apparently healthy VEG and omnivorous (OMN) men., Methods: In this cross-sectional study, 88 apparently healthy men ≥ 35 years, 44 VEG and 44 OMN, were assessed for anthropometric data, blood pressure, blood lipids, glucose, C-reactive protein (CRP) and FRS. To test the association between lifestyle and MSyn, Student t test, chi-square test, and multiple logistic regression model were used. A significance level of 5% was considered in all statistical analyses., Results: Several CRF were significantly lower in VEG than in OMN: body mass index, systolic blood pressure, diastolic blood pressure, fasting serum total cholesterol, LDL-cholesterol, apolipoprotein b, glucose, and glycated hemoglobin (all p < 0.05). The FRS mean was lower in VEG than in OMN (2.98 ± 3.7 vs 4.82 ± 4.8, p = 0.029). The percentage of individuals with MSyn was higher among OMN than among VEG (52.3 vs.15.9%) (p < 0.001). The OMN diet was associated with MSyn (OR: 6.28 95%CI 2.11-18.71) and alterations in most MSyn components in the multiple regression model independently of caloric intake, age and physical activity., Conclusion: The VEG diet was associated with lower CRF, FRS and percentage of individuals with MSyn.

In epileptic encephalopathies (EE), interictal epileptiform discharges (IEDs) contribute to cognitive impairment. The EE process has been studied in a patient affected by epilepsy with occipital calcification and celiac disease (CEC syndrome) by combining the administration of brain area stimulus specific (visual and auditory) reaction times (RT) during continuous EEG monitoring with the off-line reconstruction of auditory and visual evoked potentials (EP). Visual RT and VEP were abnormal only if recorded concomitantly to the IEDs. Auditory RT and EP were normal. When the EE process is going on, IEDs transiently disrupt aspects of cortical functioning, contributing to the cognitive impairment.

Background: Dietary habits play an important role in the development of atherosclerosis, the most important cause of morbidity and mortality in the world. The objective of this study was to verify if vegetarian (VEG) diet could be related a better profile of subclinical vascular disease evaluated by arterial stiffness and functional and structural properties of carotid arteries, compared to omnivorous (OMN) diet., Methods: In this cross-sectional study, 44 VEG and 44 OMN apparently healthy men ≥35years of age, in order to not have confounding risk factors of subclinical atherosclerosis, were assessed for anthropometric data, blood pressure, blood lipids, glucose, C reactive protein (CRP), and arterial stiffness determined by carotid-femoral pulse wave velocity (PWV). Also, carotid intima-media thickness (c-IMT) and distensibility were evaluated., Results: VEG men had lower body mass index, systolic and diastolic blood pressures, fasting serum total cholesterol, LDL and non-HDL-cholesterol, apolipoprotein B, glucose and glycated hemoglobin values in comparison with OMN individuals (all p values <0.05). Markers of vascular structure and function were different between VEG and OMN: PWV 7.1±0.8m/s vs. 7.7±0.9m/s (p<0.001); c-IMT 593±94 vs. 661±128μm (p=0.003); and relative carotid distensibility 6.39±1.7 vs. 5.72±1.8% (p=0.042), respectively. After a multivariate linear regression analysis, a VEG diet was independently and negatively associated with PWV (p value 0.005)., Conclusions: A VEG diet is associated with a more favorable cardiovascular diseases biomarker profile and better vascular structural and functional parameters., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Nocturnal frontal lobe epilepsy (NFLE) is an epileptic syndrome that is primarily characterized by seizures with motor signs occurring almost exclusively during sleep. We describe 2 children with mucopolysaccharidosis (MPS) who were referred for significant sleep disturbance. Long term video-EEG monitoring (LT-VEEGM) demonstrated sleep-related hypermotor seizures consistent with NFLE. No case of sleep-related hypermotor seizures has ever been reported to date in MPS. However, differential diagnosis with parasomnias has been previously discussed. The high frequency of frontal lobe seizures causes sleep fragmentation, which may result in sleep disturbances observed in at least a small percentage of MPS patients. We suggest monitoring individuals with MPS using periodic LT-VEEGM, particularly when sleep disorder is present. Moreover, our cases confirm that NFLE in lysosomal storage diseases may occur, and this finding extends the etiologic spectrum of NFLE., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

The treatment of Barrett's esophagus is still controversial. Actually, the only method to prevent the development to cancer is endoscopic surveillance, which ensures good results in terms of long-term survival. An ideal treatment capable of destroying columnar metaplasia, followed by squamous epithelium regeneration could potentially result in a decrease of the incidence of adenocarcinoma. Recently most ablative techniques were used, such as photodynamic therapy, ablation therapy with Nd-YAG laser or argon plasma coagulation and endoscopic mucosal resection. We started a prospective study in January 1998, enrolling 94 patients affected by Barrett's esophagus and candidates for antireflux repair in order to assess the effectiveness and the results of endoscopic coagulation with argon plasma combined with surgery in the treatment of uncomplicated Barrett's esophagus. All patients underwent endoscopic treatment with argon plasma; we observed complete response in 68 patients (72.34%), 27 of them (39.7%) underwent antireflux surgery and the other 41 continued medical therapy. Post-operatively 19 patients (70%) underwent regular surveillance endoscopies and in two cases metaplasia recurred. The final objective of these combined treatments should be the complete eradication of metaplastic mucosa. Our experience was that argon plasma coagulation combined with antireflux surgery or proton pump inhibitor therapy gave satisfactory results, even if follow-up is too short to evaluate the potential evolution of metaplasia to cancer. For this reason, we recommend that this technique should be done only in specialized centres and that these patients continue their endoscopic surveillance program.

Study Aim: Aim of this study was to assess symptomatic and objective outcome in patients undergoing laparoscopic Heller myotomy after unsuccessful endoscopic treatment, compared to patients having primary surgery., Patients and Method: Between November 1992 and December 1998, 92 patients with esophageal achalasia underwent laparoscopic Heller myotomy and Dor fundoplication. Intraoperative endoscopy was routinely performed. Sixty patients had primary surgery (PS); 32 patients had surgery after unsuccessful pneumatic dilatation (PD) (n = 22), or botulinum toxin (Botox) injection (n = 10)., Results: The mean operative time and the incidence of postoperative dysphagia were similar in the two groups. The incidence of intraoperative mucosal tears was 5% in the PS group and 12.5% in the PD/Botox group (P = NS). Mucosal tears occurred more frequently during the first 30 operations (17% vs 3.2%, P < 0.05). Median follow-up was 28 months (range 4-76). An abnormal esophageal acid exposure was documented in 2 patients in the PS group (7.7%), and in two patients in the PD/Botox group (13.3%) (P = NS). Lower esophageal sphincter pressure significantly decreased in both groups (P < 0.01). The mean percentage of radionuclide residual activity in the esophagus at 1 and 10 minutes significantly decreased in both groups (P < 0.01)., Conclusion: There is only a trend, although not statistically significant, towards an increased risk of complications and adverse effects in patients previously treated by PD and/or Botox. The higher incidence of mucosal tears during the first 30 operations suggests the effect of the learning curve.

Background: Anedoctal reports suggest a detrimental effect of pneumatic dilation and botulinum toxin injection in patients who are potential candidates for Heller myotomy., Aims: To assess symptomatic and objective outcome in patients undergoing Heller myotomy as a primary procedure or after failed endoscopic treatment., Patients: Between November 1992 and December 1998, 92 patients with oesophageal achalasia were treated. Sixty patients had primary surgery; 32 patients had surgery after unsuccessful pneumatic dilation (n = 22), or botulinum toxin injection (n = 10)., Methods: Laparoscopic Heller myotomy plus Dor fundoplication with routine intraoperative endoscopy. Operative records, symptoms, and results of radiological, manometric and scintigraphic assessment in the two groups of patients were compared., Results: The mean operative time, the rate of intraoperative mucosal tears and the incidence of postoperative dysphagia were similar in the two groups. Mucosal tears occurred more frequently during the first 30 operations (p < 0.05). Median follow-up was 28 months (range 4-76). An abnormal oesophageal acid exposure was documented in 2 patients in the primary surgery group (7.7%), and in 2 patients in the pneumatic dilation/botulinum toxin group (13.3%) (p = ns). Lower oesophageal sphincter pressure significantly decreased in both groups (p < 0.01). The mean percentage of radionuclide residual activity in the oesophagus at 1 and 10 minutes significantly decreased in both groups (p < 0.01)., Conclusions: There was only a trend, although not statistically significant, towards an increased risk of complications and adverse effects in patients previously treated by pneumatic dilation or botulinum toxin. The higher incidence of mucosal tears during the first 30 operations suggests the effect of the learning curve.

Objective: To assess the effectiveness of transoral stapled diverticulum esophagostomy in relieving symptoms and decreasing outflow resistance at the pharyngoesophageal junction in patients with Zenker diverticulum., Design: Cohort study. From April 1, 1992, until May 31, 1996, the operation was attempted in 95 patients. The median follow-up was 23 months (range, 13-48 months)., Setting: Tertiary care university hospital., Patients: There were 74 men and 21 women, with a median age of 64 years (age range, 37-92 years). All complained of dysphagia and pharyngo-oral regurgitation, and 18 (20%) suffered from recurrent aspiration pneumonia. The median size of the pouch measured by flexible endoscopy was 4 cm (range, 2.5-8 cm)., Intervention: The septum between the diverticulum and the esophageal lumen was divided under general anesthesia using a linear endostapler introduced through a Weerda endoscope. In most patients, 2 applications of the endostapler with a modified anvil were used. Operative time averaged 23 minutes., Main Outcome Measures: Morbidity, symptom score, patient's satisfaction, videofluorographic barium transit, hypopharyngeal intrabolus pressure, upper esophageal clearance of radioisotope., Results: A switch to open surgery was required in 3 patients (3.1%), due to difficult exposure of the common wall in 2 cases and a mucosal tear in the other. No postoperative morbidity or mortality was recorded. Oral feeding was started the following day and the median hospital stay was 3 days (range, 2-8 days). Five patients complained of persistent symptoms; 3 of them underwent another endosurgical operation, 1 underwent laser treatment by means of flexible endoscopy, and 1 eventually required open surgery. All patients are asymptomatic at the latest follow-up visit. Postoperative radiologic studies showed free flow of barium in all patients. Manometry showed a significant reduction of hypopharyngeal intrabolus pressure over preoperative values (P=.003). Radionuclide studies showed a significant reduction of upper esophageal residual activity at 1 minute compared with preoperative values (P=.006)., Conclusions: Endosurgical approach to hypopharyngeal diverticula larger than 2 cm is safe and effective. Symptom relief, elimination of the pouch, and decreased outflow resistance at the pharyngoesophageal junction can be obtained without morbidity and with a short hospital stay.

The aim of this study was to investigate the biochemical basis of biomechanical and morphological alterations of upper esophageal sphincter, which have been reported in patients with Zenker's diverticulum. 4-L-Hydroxyproline (4-Hyp) (collagen), isodesmosine (Ides), and desmosine (Des) (elastin) contents were measured in samples of cricopharyngeal muscle (CPM) and muscularis propria of the esophagus below the CPM. The specimens were collected from seven patients operated for Zenker's diverticulum and eight cadavers, without esophageal and connective tissue disease, 4-Hyp was assayed colorimetrically, Ides and Des by high-performance liquid chromatography. Mean (+/-SEM) values were compared by Mann-Whitney U test. In patients, collagen content was significantly increased, both in CPM and in the muscularis propria of the esophagus below the CPM (P < 0.05). In CPM, Ides to Des and collagen to elastin ratios were significantly higher in patients than in controls (P < 0.05). Both the CPM and the upper muscular cuff of the esophagus appear to be involved in the pathogenesis of Zenker's diverticulum. This finding supports the extension of the myotomy to the muscularis propria of the esophagus below the CPM. The alterated Ides to Des ratio suggests a primary disease of CPM as a cause of Zenker's diverticulum.