Global prevalence of claudin 18 isoform 2 in tumors of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

BACKGROUND: Limited data exist for global prevalence of claudin 18 isoform 2 (CLDN18.2) positivity and association of CLDN18.2 status with clinical and tumor characteristics in patients with locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. We report prevalence of CLDN18.2 positivity (phase 3; SPOTLIGHT, NCT03504397; GLOW, NCT03653507) and concordance of CLDN18.2 status between a subset of pair-matched tumor samples (phase 2, ILUSTRO, NCT03505320; phase 1, NCT03528629) from clinical studies of zolbetuximab. METHODS: Tumor samples from patients with LA unresectable or mG/GEJ adenocarcinoma were tested for CLDN18.2 status by immunohistochemistry. Human epidermal growth factor receptor 2 (HER2) expression was tested per central or local assessment. RESULTS: Across SPOTLIGHT and GLOW, the prevalence of CLDN18.2 positivity (≥ 75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 38.4%. Prevalence was similar in gastric versus GEJ adenocarcinoma samples and regardless of collection method (biopsy versus resection) or collection site (primary versus metastatic). CLDN18.2 positivity was most prevalent in patients with diffuse-type tumors. In ILUSTRO and the phase 1 study, concordance of CLDN18.2 positivity was 61.1% between archival (i.e., any time before treatment) and baseline (i.e., ≤ 3 months before first treatment) samples, and concordance of any CLDN18 staining (≥ 1% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 88.9%. CONCLUSIONS: CLDN18.2 was a highly prevalent biomarker in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 positivity remained relatively stable over time in many patients. Biomarker testing for CLDN18.2 should be considered in standard clinical practice in these patients.

The Bittersweet Reality: The Cardiovascular Risk of Artificial Sweeteners.

Artificial sweeteners are increasingly popular as alternatives to sugar. Approximately 41% of the American adult population reports regular consumption of low-calorie sweeteners. People are not even aware they are ingesting artificial sweeteners as they are now in chewing gum, toothpaste, various food products, baked goods, and even pharmaceutical products. Some of these sweeteners are sweeter than sugar, some less sweet than sugar, and some are natural sweeteners. With the goal of increasing palatability, many products have multiple additives to create the perfect taste. Despite their widespread use and perceived benefits, there is increasing concern in the academic community about the long-term safety of these artificial sweeteners and their role in increasing the burden of cardiovascular diseases, including coronary heart disease, stroke, and heart failure. There is general agreement about the cardiovascular risk of added sugars to a diet. Public health authorities have recommended limiting added sugar consumption. Replacing sugar with these artificial sweeteners has become increasingly popular, but safety remains a question. While multiple well-designed randomized clinical trials are needed for the conclusion, review of the current literature gives us pause about the cardiovascular risk and long-term safety of these additives.

Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of two articles. The first article is about a clinical trial called SPOTLIGHT and it was published in the medical journal The Lancet in in April of 2023. The second article is about a clinical trial called GLOW and it was published in the medical journal Nature Medicine in July of 2023. WHAT ARE THE KEY TAKEAWAYS?: Until recently, chemotherapy was the first treatment given to people with stomach cancer or gastroesophageal junction (or GEJ) cancer that is locally advanced unresectable or metastatic. When cancer cells have high amounts of the protein CLDN18.2 but do not have high amounts of the protein HER2, the cancer is known as CLDN18.2-positive (or CLDN18.2+) and HER2-negative (or HER2-). New medicines to treat cancer are being developed. These medicines attach to proteins on cancer cells to help the body recognize and kill cancer cells.The clinical trials SPOTLIGHT and GLOW included participants with CLDN18.2+ and HER2- stomach or GEJ cancer that was locally advanced unresectable or metastatic. These trials looked at whether adding a medicine called zolbetuximab to chemotherapy as the first treatment for cancer helped people live longer before their tumors grew bigger or new tumors grew, after starting the trial. These studies also looked at whether adding zolbetuximab to chemotherapy helped people live longer after starting the trial. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: In SPOTLIGHT and GLOW, on average, participants assigned to zolbetuximab plus chemotherapy lived 1.4 to 1.9 months longer before their tumors grew bigger or new tumors grew, after starting the trial, than participants assigned to a placebo plus chemotherapy. On average, participants assigned to zolbetuximab plus chemotherapy also lived 2.2 to 2.7 months longer, after starting the trial, than participants assigned to a placebo plus chemotherapy. These results suggest that zolbetuximab plus chemotherapy could be a new first treatment for people with CLDN18.2+ and HER2- stomach or GEJ cancer that is locally advanced unresectable or metastatic.Clinical Trial Registration: NCT03504397 (SPOTLIGHT); NCT03653507 (GLOW).

The clinical trials SPOTLIGHT and GLOW showed that, on average, participants with stomach or GEJ cancer assigned to zolbetuximab plus chemotherapy lived 2.2 to 2.7 months longer than participants assigned to a placebo plus chemotherapy.

Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer.

BACKGROUND: In the KEYNOTE-590 study, first-line pembrolizumab plus chemotherapy provided statistically significant improvement in overall survival, progression-free survival, and objective response rate compared with chemotherapy, with a manageable safety profile in patients with advanced esophageal cancer. Prespecified health-related quality-of-life (HRQoL) outcomes are reported. MATERIALS AND METHODS: Change from baseline to week 18 in the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/QoL (GHS/QoL) and QLQ-Esophageal cancer module (OES18) dysphagia, pain, and reflux scales were evaluated. RESULTS: The HRQoL analysis included 730 patients who received treatment and completed ≥1 HRQoL assessment. Least squares mean (LSM) change from baseline to week 18 was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 reflux scales. The QLQ-OES18 dysphagia (LSM difference, -5.54; 95% CI, -10.93 to -0.16) and pain (LSM difference, -2.94; 95% CI, -5.86 to -0.02) scales favored pembrolizumab plus chemotherapy over placebo plus chemotherapy. Median time to confirmed deterioration (TTD) was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 dysphagia and reflux scales. Compared with chemotherapy, pembrolizumab plus chemotherapy prolonged median TTD, as seen on the QLQ-OES18 pain scale (HR, 0.69; 95% CI, 0.51 to 0.95). CONCLUSION: The use of pembrolizumab plus chemotherapy maintained HRQoL at week 18 relative to baseline and was comparable with placebo plus chemotherapy. These HRQoL results together with published reports of efficacy, support the use of pembrolizumab plus chemotherapy as first-line therapy for advanced/metastatic esophageal cancer. CLINICALTRIALS.GOV ID: NCT03189719.

LEAP-014: first-line lenvatinib + pembrolizumab + chemotherapy in advanced/metastatic esophageal squamous cell carcinoma.

Treatment options for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) are improving. Current guidelines recommend first-line pembrolizumab plus chemotherapy for patients with unresectable or metastatic ESCC, which has led to improvements in survival outcomes. Antiangiogenic therapy combined with immune checkpoint inhibitors can act synergistically to convert the immunosuppressive tumor microenvironment to an immune supportive microenvironment, thus enhancing antitumor immune responses. In preclinical models, the antiangiogenic agent lenvatinib combined with an anti-PD-1 agent showed synergistic antitumor activity. We describe the design and rationale for the randomized, open-label, phase III LEAP-014 study of lenvatinib in combination with pembrolizumab plus chemotherapy in patients with advanced or metastatic ESCC. Overall survival and progression-free survival are the dual primary end points.Clinical Trial Registration: NCT04949256 (ClinicalTrials.gov).

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GPR75: A Newly Identified Receptor for Targeted Intervention in the Treatment of Obesity and Metabolic Syndrome.

Metabolic syndrome increases the risk of stroke, cardiovascular disease, and diabetes. The morbidity and mortality associated with this constellation of risk factors are equally alarming when considering the economic and global significance that this epidemic has on an institutional and patient level. Despite several current treatments available, there needs to be a continuous effort to explore more specific and effective druggable entities for preventative and therapeutic interventions. Within this context, the G-protein coupled receptor, GPR75, is an attractive pharmacological target. GPR75 and its association with its ligand, 20-hydroxyeicosatetraenoic acid, have been shown to promote hypertension, inflammation, obesity, and insulin resistance. This review will help shed light on this novel signaling pathway and offer a perspective on a promising new direction of targeting different aspects of the metabolic syndrome involving GPR75. Gene targeting of GPR75 is more effective than current pharmacologic therapies without the known side effects.

Nanotechnology: The Future for Diagnostic and Therapeutic Intervention in Cardiovascular Diseases is Here.

With advances in technology and medicine over the last 3 decades, cardiovascular medicine has evolved tremendously. Nanotechnology provides a promising future in personalized precision medicine. In this review, we delve into the current and prospective applications of nanotechnology and nanoparticles in cardiology. Nanotechnology has allowed for point-of-care testing such as high-sensitivity troponins, as well as more precise cardiac imaging. This review is focused on 3 diseases within cardiology: coronary artery disease, heart failure, and valvular heart disease. The use of nanoparticles in coronary stents has shown success in preventing in-stent thrombosis, as well as using nanosized drug delivery medications to prevent neointimal proliferation in a way that spares systemic toxicity. In addition, by using nanoparticles as drug delivery systems, nanotechnology can be utilized in the delivery of goal-directed medical therapy in heart failure patients. It has also been shown to improve cell therapy in this patient population by helping in cell retention of grafts. Finally, the use of nanoparticles in the manufacturing of bioprosthetic valves provides a promising future for the longevity and success of cardiac valve repair and replacement.

The Interplay of Microbiome Dysbiosis and Cardiovascular Disease.

The intricate ecosystem of the mammalian gut, which hosts a diverse microbiome, plays a vital role in various physiological functions. Trillions of bacteria within the gut contribute to host metabolism, immune modulation, energy homeostasis, and more. Emerging research highlights the gut microbiota's significant impact on cardiovascular diseases (CVDs), with intestinal dysbiosis identified as a risk factor for conditions such as obesity and diabetes, both linked to atherosclerosis. Chronic inflammation, pivotal in atherosclerosis, is influenced by the gut microbiome, where microbial signals, such as lipopolysaccharides, can translocate from the gut to trigger inflammatory responses. Diet has major effects on the gut microbiota, with the Western diet, rich in saturated fats, contributing to dysbiosis and elevated cardiovascular risks. Probiotics and prebiotics offer therapeutic potential in CVD management. Probiotics, or live microorganisms, exhibit antioxidant, anti-inflammatory, and cholesterol-lowering effects. Probiotics are most effective when given with prebiotics, with the former acting on the latter as substrate. Understanding the dynamic interplay between diet, gut microbiota, and CVD provides insights into preventive and therapeutic strategies.

Titin: The Missing Link in Cardiac Physiology.

Titin, an extraordinary protein known for its colossal size and multifaceted roles, is a cornerstone in the structural and functional dynamics of striated muscle tissues, including the heart and skeletal muscles. Its sheer enormity, with a molecular weight exceeding 3000 kDa, is paralleled only by the immense influence it exerts on muscle physiology. This review will delve into the remarkable structural organization of Titin and the genetics of this molecule, including the common mutations resulting in various cardiomyopathies. We will delve deeper into its role in dilated cardiomyopathy, familial restrictive cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction cardiomyopathy. This review culminates by discussing the prospects of therapeutic strategies targeting Titin. While these interventions remain primarily theoretical, the possibilities are intriguing. Patients with Titin truncation mutations present unique challenges, but innovative approaches like gene therapy or preemptive treatments with drugs such as angiotensin-converting enzyme inhibitors or beta-blockers offer hope. This multi-pronged approach highlights the significance of understanding Titin's multifaceted role and its potential as a target for future therapeutic interventions.

Diagnostic performances of Nonhyperemic Pressure Ratios and Coronary Angiography-Based Fractional Flow Reserve against conventional Wire-Based Fractional Flow Reserve.

BACKGROUND: Nonhyperemic pressure ratios (NHPRs) have been proposed as alternatives to fractional flow reserve (FFR) without induction of hyperemia. More recently, imaging based-FFR estimation, especially coronary angiography-derived FFR (Angio-FFR) measurement, is proposed to estimate wire-based FFR. However, little is known about the diagnostic performance of these indices against conventional FFR. AIMS: We aimed to assess and compare the diagnostic performance of both NHPRs and coronary Angio-FFR against wire-based conventional FFR. METHODS: PubMed and Embase databases were systematically searched for peer-reviewed original articles up to 08/2022. The primary outcomes were the pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver-operating characteristic curve of those indices. RESULTS: A total of 6693 records were identified after a literature search, including 37 reports for NHPRs and 34 for Angio-FFR. Overall, NHPRs have a lower diagnostic performance in estimating wire-based FFR with an AUC of 0.85 (0.81, 0.88) when compared with Angio-FFR of 0.95 (0.93, 0.97). When all four modalities of NHPRs (iFR, Pd/Pa, DPR, RFR) were compared, those had overlapping AUCs without major differences among each other. Similarly, when the two most commonly used Angio-FFR (QFR, FFR angio ) were compared, those had overlapping AUCs without major differences among each other. CONCLUSION: Angio-FFR may offer a better estimation of wire-based FFR than NHPRs. Our results support a wider use of Angio-FFR in the cardiac catheterization laboratory to streamline our workflow for coronary physiologic assessment. CLASSIFICATIONS: FFR,, stable ischemic disease and non-ST elevation acute coronary syndrome.

The history of forensic neuropsychiatry.

Significant advances in various disciplines of neurosciences, such as neurology, neuropsychiatry, neuroimaging, and neurogenetics, have caused an exciting field to emerge in the field of forensic neuropsychiatry called neurolaw. The resurgence of interest in this field has paralleled the renaissance of neuropsychiatry in the last few decades. This historical review of the practice of forensic neuropsychiatry provides an insight into the past with the hope that it will guide the future development of this field.

Forensic neuropsychiatric aspects of epilepsy.

Epilepsy may be associated with automatisms that are classed as 'insane 'as they are deemed to have originated within the mind. 'Sane automatism' is said to occur from external factors, such as physical trauma, while 'insane automatism' is said to be innate to the individual experiencing them. To claim automatism within the context of a criminal matter requires a detailed evaluation of the behavior demonstrated and a questioning of the volitional and purposeful nature of this behavior. It is insufficient to rely upon past behavior in association with these seizures to justify the defense of automatism within a specific event. Epilepsy is often considered to be associated with an increase in violence. Proper epidemiological research, both in long-term, large population control studies and hospital-based studies, has suggested that epilepsy, per se, is not associated with an increase in violence when compared to the population at large and controlled for other familial and environmental factors.

Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review.

Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues. Those receptors rely on the beta klotho (KLB) coreceptors, a transmembrane protein, to activate the FGF21 signaling pathway and FGF21's associated transcription factors. PGZ, through its extended half-life of 55 to 100 hours, has evidenced significant improvements in metabolic functions. Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis. This emerging pharmaceutical compound has shown promise in treating liver fibrosis and inflammation linked to nonalcoholic steatohepatitis. The ENTRIGUE trial, a phase 2 clinical trial of PGZ, has demonstrated a 57% reduction in triglyceride level compared to placebo; a 45% reduction in liver hepatic steatosis; improved insulin sensitivity; reductions in nonhigh-density lipoprotein-cholesterol; and reductions in apolipoprotein B-100.

Cardiovascular Manifestations of Hemochromatosis: A Review of Pathophysiology, Mechanisms, and Treatment Options.

Hemochromatosis is a genetic disorder characterized by excessive absorption and accumulation of iron in the body. It is one of the most common inherited disorders. The excess iron deposition can cause damage to various organs, including the liver, heart, pancreas, and joints. If left untreated, hemochromatosis can lead to serious complications such as cirrhosis, diabetes, heart failure, and increased risk of certain cancers. Iron overload in hemochromatosis significantly affects the cardiovascular system, leading to morbidity and mortality. This article reviews the current literature describing the pathogenesis and various cardiovascular manifestations of hemochromatosis, including dilated cardiomyopathy, conduction abnormalities, heart failure, cardiac fibrosis, myocardial infarction, and valvular heart disease. This article aims to provide a detailed understanding of the cardiovascular manifestations associated with hemochromatosis and their underlying mechanisms through a review of current literature in publicly available databases.

Chemotherapy and Immune Checkpoint Blockade for Gastric and Gastroesophageal Junction Adenocarcinoma.

Importance: Combining immune checkpoint blockade (ICB) with chemotherapy improves outcomes in patients with metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma; however, whether this combination has activity in the perioperative setting remains unknown. Objective: To evaluate the safety and preliminary activity of perioperative chemotherapy and ICB followed by maintenance ICB in resectable G/GEJ adenocarcinoma. Design, Setting, and Participants: This investigator-initiated, multicenter, open-label, single-stage, phase 2 nonrandomized controlled trial screened 49 patients and enrolled 36 patients with resectable G/GEJ adenocarcinoma from February 10, 2017, to June 17, 2021, with a median (range) follow-up of 35.2 (17.4-73.0) months. Thirty-four patients were deemed evaluable for efficacy analysis, with 28 (82.4%) undergoing curative resection. This study was performed at 4 referral institutions in the US. Interventions: Patients received 3 cycles of capecitabine, 625 mg/m2, orally twice daily for 21 days; oxaliplatin, 130 mg/m2, intravenously and pembrolizumab, 200 mg, intravenously with optional epirubicin, 50 mg/m2, every 3 weeks before and after surgery with an additional cycle of pembrolizumab before surgery. Patients received 14 additional doses of maintenance pembrolizumab. Main Outcomes and Measures: The primary end point was pathologic complete response (pCR) rate. Secondary end points included overall response rate, disease-free survival (DFS), overall survival (OS), and safety. Results: A total of 34 patients (median [range] age, 65.5 [25-90] years; 23 [67.6%] male) were evaluable for efficacy. Of these patients, 28 (82.4%) underwent curative resection, 7 (20.6%; 95% CI, 10.1%-100%) achieved pCR, and 6 (17.6%) achieved a pathologic near-complete response. Of the 28 patients who underwent resection, 4 (14.3%) experienced disease recurrence. The median DFS and OS were not reached. The 2-year DFS was 67.8% (95% CI, 0.53%-0.87%) and the OS was 80.6% (95% CI, 0.68%-0.96%). Treatment-related grade 3 or higher adverse events for evaluable patients occurred in 20 patients (57.1%), and 12 (34.3%) experienced immune-related grade 3 or higher adverse events. Conclusion and Relevance: In this trial of unselected patients with resectable G/GEJ adenocarcinoma, capecitabine, oxaliplatin, and pembrolizumab resulted in a pCR rate of 20.6% and was well tolerated. This trial met its primary end point and supports the development of checkpoint inhibition in combination with perioperative chemotherapy in locally advanced G/GEJ adenocarcinoma. Trial Registration: ClinicalTrials.gov Identifier: NCT02918162.

Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer.

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed ("inside-out" (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.

Assessment of Prevalence of Hypertension and its Risk Factors among Adult Tribal Population Residing in Lohandiguda Block of Bastar District of Chhattisgarh.

Background: Hypertension is known as the silent killer. It comprehends the top rank in non-infectious disease amongst adults; accountable for the deaths every year across the world. It is essential to consider the individual impact of risk factors and their impact on hypertension. This study thus elicited the socio-demographic characteristics, the prevalence of hypertension and associated risk factors, and its impact on adults with hypertension. To estimate the hypertension prevalence and its associated risk factors among adult tribal populations aged 25-60 years residing in Lohandiguda block of Bastar district of Chhattisgarh. Material and Methods: A community-based cross-sectional analytical study was used and the setting was done at the field practice area under the three primary health centers of Lohandiguda block, Bastar district of Chhattisgarh. It was carried out among 330 adult tribes residing for ≥1 year in the present locality. Data was collected by door-to-door visits through pre-designed, pretested, semi-structured questionnaire via face-to-face interview method and anthropometric measurement was done by using standard guidelines. The sampling method was multistage sampling. IBM SPSS STATISTICS-20.0 (IBM Corp., Armonk, NY, USA) software. Results: The overall prevalence of pre-hypertension and hypertension among tribal subjects was 34.9% and 47.3%, respectively. Of total hypertensive 27.3% were having stage-1 hypertension, 13.9% were having stage-2 hypertension and 6.0% were already diagnosed cases. Risk factors found in multivariate analysis are occupation (unemployed 0.012), frequency of smokeless tobacco used per day (0.,017) and central obesity (0.000). Conclusions: As hypertension is a multi-factorial disease the study found strong predictors like occupation, frequency of smokeless tobacco per day and having central obesity with significant difference.

Supracarinal lymph node positivity in esophageal squamous cell carcinoma (ESCC) and factors predicting metastasis in supracarinal compartment nodes: Should a total mediastinal node dissection be the standard of care?

Background: Adequate lymphadenectomy in middle- and lower-third esophagus cancer is still a matter of debate. This study aims to find out the extent of histopathological supracarinal lymph nodes positivity rate to establish an adequate lymph node dissection in esophageal squamous cell carcinoma cases operated up-front or after neoadjuvant chemotherapy (CT) + radiotherapy (RT) and its short-term oncological outcome. Materials and Methods: After approval from institutional board review, a retrospective study was conducted from April 2017 to September 2019. A total of 76 patients having mid- or lower-third carcinoma esophagus were operated at our institute for partial/total esophagectomy with extended two-field lymph node dissection were followed. Intraoperative nodal stations were harvested separately and lebeled individually according to the Japanese Esophageal Classification and sent for histopathological examination. Results: The patients had an average age of 52 years. Histologically all were squamous cell carcinoma (SCC). Forty-four patients received preoperative concurrent RT plus drug therapy, whereas 18 cases were operated up-front. Fourteen patients were operated after palliative treatment (CT/RT). The average total lymph node yield was 22 nodes (range 3-69). In 26 patients (34.2%), lymph nodes were positive (N+ disease). Supracarinal nodes were positive in 20 cases (26.31%). The average supracarinal lymph node yield was 10.33 nodes (range 2-32). Five patients (6.5%) had only supracarinal lymph nodes positive on histopathological examination. Seventeen patients had a complete pathological response rate (pCR). Conclusion: In cases of mid-third esophageal carcinoma, extended two fields with supracarinal lymphadenectomy is strongly recommended even after the patient has received neoadjuvant treatment, although the same for lower-third/gastroesophageal (GE) junction tumors should be considered.