A tertiary care prospective of epidemiology and etiopathogenesis of esophageal carcinoma from Northern India

Background: Esophageal cancer is considered to be a one of the most lethal malignancy. Indian population have seen a lot of changes in the epidemiology of this deadly cancer. However very few studies have been done from northern India regarding the epidemiology and etiopathogenesis of this disease. Majority of esophageal cancers (about 90%) are either squamous cell or Adenocarcinoma. Any factor that causes chronic irritation and inflammation of the esophageal mucosa appears to increase the incidence of the esophageal. The aim of the study was to perform an epidemiological study and determine the various factors that are implicated in the pathogenesis of carcinoma esophagus.Methods: This study was conducted in the department of general surgery, Government Medical College, Jammu, as an observational prospective study. It took into account the patients from 2015 to 2020. A total of 23 patients of carcinoma oesophagus who presented to Outdoor patient wing of department of surgery were included in the study. After detailed history, examination and investigations, the various variables were extracted and data was processed.Results: In this study, the majority of people were from rural areas in their seventh decade of life with males: female ratio of 3:1. The majority of people complained of dysphagia and weight loss. The site of tumor was Gastroesophageal junction.Conclusions: This study emphasised the need of health education in our population, especially in young adults to lessen the risk factors for carcinoma esophagus.

Features of therapeutic correction of GERD: focus on cytoprotection (with a clinical case)

Тo date, the possible links of the pathogenesis of this disease have been well studied and described, which predetermine certain approaches to the treatment of various variants of gastroesophageal reflux disease (GERD). Effective drug therapy for GERD includes proton pump inhibitors (PPI). However, PPI monotherapy is not always effective. One approach is to increase the PPI dose. At the same time, combination therapy with the addition of drugs that affect the protective properties of the esophageal mucosa seems to be more rational. It is known that in the development of GERD, the violation of cytoprotection of the esophageal mucosa is one of the key links in pathogenesis. Consequently, the issue of combination therapy of PPIs with drugs that increase the protective properties of the mucous barrier along with acid suppression becomes relevant. An example of such an approach is the appointment of rebamipide, the action of which is to regulate the synthesis of prostaglandins through COX-2 mediated mechanisms, influence on endothelial growth factor, increase the expression of tight intercellular contact proteins in epithelial cells of the mucous membrane, reduce the level of interleukin-8 and free oxygen radicals, directed to protect the mucous membrane of the gastrointestinal tract and restore its natural barrier properties. The effectiveness of the combination of PPI and rebamipide contributes to a greater regression of complaints in patients with GERD and a lower frequency of disease relapses than with PPI monotherapy. This article provides a review of the literature on the features of GERD therapy, primarily with an emphasis on the correction of the cytoprotective properties of the esophageal mucosa, including against the background of the use of nonsteroidal anti-inflammatory drugs (NSAID), and a clinical case analysis with a discussion of rational pharmacological correction.

Scutellariae Radix and Citri Reticulatae Pericarpium Mixture Regulate PPARγ/RXR Signaling in Reflux Esophagitis

Objective. Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach contents reflux into the esophagus, causing complications such as mucosal damage. GERD is a very common disease and is on the rise worldwide. The aim of this study was to assess the impact of a Scutellariae Radix and Citri Reticulatae Pericarpium mixture (SC) on esophageal mucosal injury in rats with chronic acid reflux esophagitis (CARE). Methods. After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks: normal rats (Normal, n = 8), CARE-induced rats were treated with distilled water (Control, n = 8), CARE-induced rats were treated with vitamin E 30 mg/kg body weight (VitE, n = 8), CARE-induced rats were treated with SC 100 mg/kg body weight (SC100, n = 8), and CARE-induced rats were treated with SC 200 mg/kg body weight (SC200, n = 8). Results. SC treatment significantly reduced the degree of esophageal mucosal damage, significantly reduced levels of MDA and MPO, and inhibited the activation of the NF-κB inflammatory pathway by activating the PPARγ/RXR pathway. In addition, SC treatment significantly regulated the expression of arachidonic acid-related proteins (COX-1, COX-2, and PGE2) and modulated the MMP/TIMP proteins in reflux esophagitis. Conclusion. Consequently, SC improved the damage to the esophageal mucosa. Also, the anti-inflammatory effects of the SC suggested the inhibition of NF-κB pathway through the activation of the PPARγ/RXR pathway, thereby reducing the expression of inflammation-related cytokines.

Eosinophilic esophagitis in children: Updates and practical aspects of management for allergists in a non‐tertiary care private practice setup

Background: Eosinophilic esophagitis (EoE) is a chronic immune and/or antigen-mediated disease characterized by eosinophilic infiltration of mucosa (≥15 eosinophils per high power field) without any secondary etiology. Non‐immunoglobulin E mediated mechanisms predominate in EoE. Objective: This review concentrated on a stepwise approach for the allergist working in non‐tertiary care private practice. Methods: A medical literature search that focused on several areas of the latest developments in the diagnosis and management of EoE was conducted. Results: There has been a steady increase in the prevalence and incidence of EoE. Clinical symptoms can vary from dysphagia to failure to thrive, depending on the age at presentation; some children develop adaptive behaviors to compensate for dysphagia, such as food preferences and slow eating. The diagnosis is based on a high index of clinical suspicion and is confirmed with endoscopy with biopsies after ruling out other causes of esophageal eosinophilia. Treatment options may include dietary therapy, pharmacologic therapies, or combination therapy. Therapeutic options may also include endoscopic dilation for stricturing disease. Conclusion: Providers should be aware of recent recommendation changes in the diagnostic workup, the role of skin-prick testing, and role of the proton-pump inhibitor as first-line therapy for EoE. Also, clinicians should be aware of the emerging role of empiric dietary therapy as a preferable therapeutic option when compared with the testing-directed diet and the elemental diet. Furthermore, topical glucocorticoid therapies are available, and new developing therapies are being investigated. Reevaluation of esophageal mucosa with biopsies is required approximately 2 months after therapy for a response and after a change in therapies to confirm continued resolution.

Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease

: Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.

Combination of Endoscopic Resection and Radiofrequency Ablation for the Treatment of Esophageal Squamous Cell Neoplasia With Multiple Lugol-Voiding Lesions

BackgroundLocal recurrence of esophageal squamous cell neoplasia (ESCN) and metachronous ESCN was associated with severe background esophageal multiple Lugol-voiding lesions (LVLs) even though the primary early ESCNs were treated with endoscopic resection (ER). The aim of this study is to explore the feasibility and effectiveness of combination treatments of ER and radiofrequency ablation (RFA) in patients with early ESCNs with synchronous multiple LVLs.MethodsA total of 329 patients with early ESCNs and synchronous multiple LVLs received ER combined with RFA from September 2010 to September 2020. Clinical and pathological features and treatment outcomes were retrospectively reviewed using medical records. Factors associated with background esophageal multiple LVLs before combined treatment were analyzed.ResultsThe proportion of complete response (CR) was 96.7% after primary RFA, while 90.3% patients achieved CR for the last endoscopic examinations regardless if inside or outside the treatment area (TA). Degeneration of background esophageal multiple LVLs occurred in 70.2% of patients. The grade of background esophageal multiple LVLs before combined treatment was closely related to gender, smoking, and drinking. The incidence of metachronous ESCNs outside the TA of ER and local recurrence in the TA of ER was 3.9% and 1.2%, respectively.ConclusionsProphylactic RFA treatment of multiple LVLs together with ER treatment of the primary ESCNs may be effective in reducing the incidence of metachronous ESCNs and local recurrence through improving the background esophageal mucosa.

Tissue Type Differences in ABCB1 Expression and Paclitaxel Tissue Pharmacokinetics in Patients With Esophageal Cancer

Background: Data from previous work suggests that there is no correlation between systemic (plasma) paclitaxel exposure and efficacy in patients treated for esophageal cancer. In this trial, we investigated ATP-binding cassette efflux transporter expression and intratumoral pharmacokinetics of paclitaxel to identify changes which could be a first sign of chemoresistance.Methods: Patients with esophageal cancer treated with paclitaxel and carboplatin (± concomitant radiotherapy) were included. During the first and last cycle of weekly paclitaxel, blood samples and biopsies of esophageal mucosa and tumor tissue were taken. Changes in paclitaxel exposure and expression of ABCB1 (P-glycoprotein) over time were studied in both tumor tissue and normal appearing esophageal mucosa.Results: ABCB1 was significantly higher expressed in tumor tissue compared to esophageal tissue, during both the first and last cycle of paclitaxel (cycle 1: p < 0.01; cycle 5/6: p = 0.01). Interestingly, ABCB1 expression was significantly higher in adenocarcinoma than in squamous cell carcinoma (p < 0.01). During the first cycle, a trend towards a higher intratumoral paclitaxel concentration was observed compared to the esophageal mucosa concentration (RD:43%; 95%CI: −3% to 111% p = 0.07). Intratumoral and plasma paclitaxel concentrations were significantly correlated during the first cycle (AUC0–48 h: r = 0.72; p < 0.01).Conclusion: Higher ABCB1 expression in tumor tissue, and differences between histological tumor types might partly explain why tumors respond differently to systemic treatment. Resistance by altered intratumoral paclitaxel concentrations could not be demonstrated because the majority of the biopsies taken at the last cycle of paclitaxel did contain a low amount of tumor cells or no tumor.

Genetic Alterations of Esophageal Squamous Cell Carcinoma in Korean Patients

Background: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers in Korea, although its incidence is lower in Korea than in China and Japan. There are no data on genetic alterations associated with ESCC in Korea. Our study is the first report of the mutational landscape of ESCC in a Korean cohort.Methods: We performed whole exome sequencing analysis of 43 ESCC tumor samples and germline DNA from normal esophageal mucosa or whole blood. Using electronic medical records, the patients’ clinical characteristics were reviewed carefully.Results: We found a mutually exclusive mutation pattern in NFE2L2–ZNF750 gene pairs. Non-silent variants of KMT2D (MLL2) were associated with a poor prognosis. An analysis to identify potentially druggable genes revealed NOTCH1 as a potential therapeutic target. We observed a high frequency of C:G → T:A transitions regardless of smoking history. In our cohort, deconstruction of the mutation signature revealed enrichment of COSMIC single base substitution (SBS) 13, SBS 39, SBS 2, SBS 40, and SBS 1.Conclusion: We did not find a Korean-specific signature of genetic alterations, but our data suggest that KMT2D is a molecular prognostic marker. Further studies need to examine the role of KMT2D in ESCC prognosis due to our small sample size.

Anti-Inflammation and Protective Effects of Anethum graveolens L. (Dill Seeds) on Esophageal Mucosa Damages in Reflux Esophagitis-Induced Rats

Anethum graveolens L. (dill seeds) are important medicinal and functional foods in Europe and central and south Asia, often used as a seasoning in daily diets. Anethum graveolens L. seeds (AGS) are used to treat indigestion and have shown physiological activities such as those against hypoglycemia and gastroesophageal disease. This study explored the protective effects of AGS extract on mucosal damages and inflammation in reflux esophagitis rats. AGS inhibited cellular inflammation including NO production and the expression of inflammatory proteins (iNOS and COX2 etc.), cytokines (IL-1β and TNF-α) and nuclear transfer factor related to NF-κB signaling caused by LPS stimulation in vitro. Furthermore, reflux esophagitis-induced rats were used to observe the anti-inflammatory effect of AGS. Tissue staining and inflammation-related protein expression of rats with acute reflux esophagitis indicated that AGS improved this inflammatory response, such as COX-2 and TNF-α in mucosa. In conclusion, AGS have good physiological activity and the possibility of being used as a medicinal food and a functional resource for the prevention and therapy of gastroesophageal diseases.