Multigene Profiling of Circulating Tumor Cells in Esophageal Squamous Cell Carcinoma Identifies Prognostic Cancer Driver Genes Associated with Epithelial-Mesenchymal-Transition Progression and Chemoresistance.

We investigated the clinical significance of CTCs in cancer progression by detecting multiple cancer driver genes associated with epithelial-to-mesenchymal transition (EMT) at the transcript level. The 10-gene panel, comprising CCND1, ECT2, EpCAM, FSCN1, KRT5, KRT18, MET, TFRC, TWIST1, and VEGFC, was established for characterizing CTCs from mouse ESCC xenograft models and clinical ESCC peripheral blood (PB) samples. Correlations between gene expression in CTCs from PB samples (n = 77) and clinicopathological features in ESCC patients (n = 55) were examined. The presence of CTCs at baseline was significantly correlated with tumor size (p = 0.031). The CTC-high patients were significantly correlated with advanced cancer stages (p = 0.013) and distant metastasis (p = 0.029). High mRNA levels of TWIST1 (Hazard Ratio (HR) = 5.44, p = 0.007), VEGFC (HR = 6.67, p < 0.001), TFRC (HR = 2.63, p = 0.034), and EpCAM (HR = 2.53, p = 0.041) at baseline were significantly associated with a shorter overall survival (OS) in ESCC patients. This study also revealed that TWIST1 facilitates EMT and enhances malignant potential by promoting tumor migration, invasion, and cisplatin chemoresistance through the TWIST1-TGFBI-ZEB1 axis in ESCC, highlighting the prognostic and therapeutic potential of TWIST1 in clinical ESCC treatment.

A Prospective Study Evaluating the Feasibility and Accuracy of Post-operative Laryngeal Ultrasonography (LUSG) in Assessment of Vocal Cord Function After Esophagectomy.

BACKGROUND: Vocal cord paresis (VCP) is a serious complication after esophagectomy. Conventional diagnosis of VCP relies on flexible laryngoscopy (FL), which is invasive. Laryngeal ultrasonography (LUSG) is non-invasive and convenient. It has provided accurate VC evaluation after thyroidectomy but it is unclear if it is just as accurate following esophagectomy. This prospective study evaluated the feasibility and accuracy of LUSG in VC assessment on day-1 after esophagectomy. METHODS: Consecutive patients from a tertiary teaching hospital who underwent elective esophagectomy were prospectively recruited. All received pre-operative FL, and post-operative LUSG and FL on Day-1, each performed by a blinded, independent assessor. The primary outcomes were feasibility and accuracy of LUSG in the diagnosis of VCP on Day-1 post-esophagectomy. The accuracy of voice assessment (VA) was analyzed. RESULTS: Twenty-six patients were eligible for analysis. The median age was 70 years (66-73). Majority were male (84.6%). Twenty-five (96.2%) received three-phase esophagectomy. Twenty-four (96%) had same-stage anastomosis at the neck. Three (11.5%) developed temporary and one (3.8%) developed permanent unilateral VCP. Overall VC visualization rate by LUSG was 100%; sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of LUSG were 75.0%, 100%, 100%, 98.0%, 98.1% respectively, and superior to VA. Combining LUSG with VA findings could pick up all VCPs i.e. improved sensitivity and NPV to 100%. CONCLUSION: LUSG is a highly feasible, accurate and non-invasive method to evaluate VC function early after esophagectomy. Post-operative FL may be avoided in patients with both normal LUSG and voice.

Circulating Tumor Cell Enumeration for Serial Monitoring of Treatment Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma.

We aim to reveal the clinical significance and potential usefulness of dynamic monitoring of CTCs to track therapeutic responses and improve survival for advanced ESCC patients. Peripheral blood (PB) (n = 389) and azygos vein blood (AVB) (n = 13) samplings were recruited prospectively from 88 ESCC patients undergoing curative surgery from 2017 to 2022. Longitudinal CTC enumeration was performed with epithelial (EpCAM/pan-cytokeratins/MUC1) and mesenchymal (vimentin) markers at 12 serial timepoints at any of the pre-treatment, all of the post-treatments/pre-surgery, post-surgery follow-ups for 3-year, and relapse. Longitudinal real-time CTC analysis in PB and AVB suggests more CTCs are released early at pre-surgery and 3-month post-surgery into the circulation from the CTRT group compared to the up-front surgery group. High CTC levels at pre-treatments, 1-/3-month post-surgery, unfavorable changes of CTC levels between all post-treatment/pre-surgery and 1-month or 3-month post-surgery (Hazard Ratio (HR) = 6.662, p < 0.001), were independent prognosticators for curative treatment. The unfavorable pre-surgery CTC status was independent prognostic and predictive for neoadjuvant treatment efficacy (HR = 3.652, p = 0.035). The aggressive CTC clusters were more frequently observed in AVB compared to PB. Its role as an independent prognosticator with relapse was first reported in ESCC (HR = 2.539, p = 0.068). CTC clusters and longitudinal CTC monitoring provide useful prognostic information and potential predictive biomarkers to help guide clinicians in improving disease management.

Transgastric Single-Incision Laparoscopic Resection for a Gastric Submucosal Tumor Located at the Cardia.

INTRODUCTION: Surgical treatment of gastric submucosal tumors (SMTs) located near the gastroesophageal junction can be technically challenging, especially regarding preservation of the integrity and function of the lower esophageal sphincter. We introduce a novel minimally invasive surgery, successfully performed in a patient with a gastric SMT located at the cardia. A 24-year-old lady presenting with acid reflux for 1 year underwent esophagogastroscopy that showed a gastric SMT located at the cardia. Endoscopic ultrasonography showed a 20×19 mm homogeneous hypoechoic lesion originating from the muscularis propria layer. Transgastric single-incision laparoscopic resection of the tumor was performed. CONCLUSION: Transgastric single-incision laparoscopic resection of gastric SMTs is technically feasible and safe. This presents an alternative surgical choice for resection for gastric SMTs located in difficult regions such as the fundus, cardia, or prepyloric antrum.

Clonal relationship and alcohol consumption-associated mutational signature in synchronous hypopharyngeal tumours and oesophageal squamous cell carcinoma.

BACKGROUND: The patients with dual oesophageal squamous cell carcinoma (ESCC) and hypopharyngeal cancer (HPC) have poor prognosis; their underlying genetic pathogenesis is unclear. We hypothesise that development of synchronous ESCC/HPC depends on multicentricity or independent origin, rather than multifocality due to local or lateral spreading. METHOD: Multiple region whole-exome sequencing (M-WES) and clonality analysis were used to assess clonal relationship and spatial inter- or intra-tumour heterogeneity (ITH) in 62 tumour regions from eight dual ESCC/HPC and ten ESCC patients. RESULTS: All synchronous ESCC/HPC patients had COSMIC 16 mutation signatures, compared to only 40% ESCC in the current study (p = 0.013) and public data set (n = 165, p = 0.003). This alcohol consumption-related mutation signature 16, commonly involved in multiple alcohol-related cancers, was significantly associated with drinking and alcohol metabolism-related ADH1B rs1229984. The mutational landscape and copy number profiles were completely distinct between the two primary tumours; clonality analysis further suggested the two primary tumours shared no or only one clone accompanying independent subclone evolution. M-WES strategy demonstrated higher sensitivity and accuracy for detection of mutational prevalence and the late branch mutations among different regions in the ESCC tumours, compared to traditional sequencing analysis based on single biopsy strategy. Patients with high ITH assessed by cancer cell fraction analysis after M-WES were significantly associated with both relapse and survival. CONCLUSIONS: Our hypothesis-generating M-WES ITH assessment data have implications for prognostication. Collectively, our findings support multicentric independent clonal evolution, the field cancerisation theory, and suggest novel insights implicating an aetiologic role of alcohol metabolism in dual ESCC/HPC carcinogenesis.

Association of body fat distribution and metabolic syndrome with the occurrence of colorectal adenoma: A case-control study.

OBJECTIVE: Visceral fat is thought to play different roles in the carcinogenesis of the colon with peripheral fat. Our aim was to evaluate the association of body fat distribution measured by bioelectrical impedance analysis (BIA) with the incidence of colorectal adenoma (CRA). METHODS: A total of 410 asymptomatic participants who underwent a screening colonoscopy from July 2017 to December 2019 in our center were recruited, including 230 with adenomas and 180 without detected adenomas. The participants' body fat was measured by BIA, including their body fat mass (BFM), body fat percentage (BFP), and waist-to-hip ratio. Parameters of metabolic syndrome (MetS), including waist circumference, blood pressure, fasting blood glucose (FBG), blood level of triglyceride, cholesterol, and high-density lipoprotein were measured as well. RESULTS: According to univariate analysis, age, male sex, body mass index, waist circumference, BFM, waist-to-hip ratio, blood pressure, and FBG were higher in the adenoma group than in the adenoma-free group (P < 0.05). On multivariate logistical analysis (adjusted for age, sex, smoking, drinking, and family history of CRC), a high waist-to-hip ratio was associated with a high incidence of CRA (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.09-3.09, P = 0.02). Only a large waist circumference in components of MetS was independently associated with the incidence of CRA (OR 1.90, 95% CI 1.17-3.08, P = 0.01) in the multivariate analysis. CONCLUSION: Body fat distribution is associated with CRA, central obesity is a core risk factor for CRA in MetS. Chinese Clinical Trial Registration number: ChiCTR-RRC-17010862.

Antibiotic is a safe and feasible option for uncomplicated appendicitis in pregnancy - A retrospective cohort study.

INTRODUCTION: Acute appendicitis is the commonest surgical emergency during pregnancy. The aim of this study is to evaluate the outcomes between antibiotic therapy and appendectomy in the management of uncomplicated appendicitis during gestation. METHODS: From January 2015 to April 2019, there were 2174 emergency appendicitis diagnosed in the University of Hong Kong-Shenzhen Hospital. Among them, 54 pregnant women were diagnosed with acute uncomplicated appendicitis and the clinical records were reviewed. Clinical demographics and outcomes including gestational age at delivery, mode of delivery, birth weight, APGAR score at 1 minute, fetal loss and overall length of stay were compared between the operation group and the antibiotic treatment group. RESULTS: The baseline characteristics showed no statistically significant difference between the two groups (P > .05). In the appendectomy group (n = 20), one patient had wound infection while none of the patients in the antibiotic therapy group (n = 34) experienced any complication. In the antibiotic treatment group, appendicitis recurred in one patient during pregnancy and in two patients after deliveries, which were all treated with appendectomy. The mean hospital stay of the antibiotic treatment group was shorter than that of the appendectomy group, but there was no significant difference (4.94 ± 2.6 days vs 6.25 ± 3.5 days, P = .540). There was no difference in gestational age at delivery, mode of delivery, birth weight and APGAR scores between the two groups (P > .05). CONCLUSIONS: For acute uncomplicated appendicitis during pregnancy, antibiotics treatment is a safe and feasible option.

Real-world Scenario: CROSS Regimen as Preoperative Therapy for Oesophageal Squamous Cell Carcinoma.

BACKGROUND: Preoperative chemoradiation (CROSS regimen) has been widely adopted worldwide. The survival advantage imparted is especially impressive for oesophageal squamous cell carcinoma (OSCC). This study aimed at investigating the efficacy of the CROSS regimen in real-world scenario. METHODS: This is a retrospective study of all patients with OSCC intended for preoperative treatment using the CROSS regimen during 2012-2017. Patients were divided into two groups: those within the selection criteria in the CROSS trial and those beyond criteria, namely age > 75 years old, tumour length > 8 cm or clinical M1 stage of lymph node involvement (AJCC 6th edition). Clinical outcome and survival data were compared. RESULTS: Eighty-eight patients were included. There were 46 patients in the "CROSS eligible" group and 42 in the "CROSS ineligible" group. By intention-to-treat, the estimated median survival was 24.2 months vs. 12.7 months, respectively (p = 0.047). The results were much inferior compared to that published in the original CROSS trial. Univariable and multivariable analyses showed tumour length and resectability as independent variables affecting survival. DISCUSSION: In a real-world scenario, the clinical outcome remains suboptimal and the excellent results in the trial setting were not reproducible in this Asian cohort. Patient selection is one key element accountable for the difference. The efficacy of the CROSS regimen may not be adequate for patients with more advanced disease. The optimal multimodal therapy for this group of patients remains undefined.

Combined endo-laparoscopic surgery for difficult benign colorectal polyps.

Prevention of colorectal cancer (CRC) depends largely on the detection and removal of colorectal polyps. Despite the advances in endoscopic techniques, there are still a subgroup of polyps that cannot be treated purely by endoscopic approach, which comprise of about 10-15% of all the polyps. These so-called "difficult colorectal polyps" are polyps with large size, morphology, at difficult location, scarring or due to recurrence, which have historically been managed by surgical segmental resection. In treating benign difficult colorectal polyps, we have to balance the operative risks and morbidities associated with surgical segmental resection. Therefore, combined endoscopic and laparoscopic surgery (CELS) has been developed to remove this subgroup of difficult benign polyps. We review the currently use of CELS for difficult benign colorectal polyps which includes laparoscopy-assisted endoscopic polypectomy (LACP), full-thickness laparo-endoscopic excision (FLEX) and colonoscopy-assisted laparoscopic wedge resection (CAL-WR).

Impact of Extracapsular Extension of Lymph Node in Adenocarcinoma of the Stomach.

BACKGROUND: Extracapsular extension (ECE) of lymph node may have important prognostic impact for patients with adenocarcinoma of the stomach, but it generally is ignored in staging systems and prognostic models. This study aimed to examine the impact that ECE of lymph node has on prognosis for patients with adenocarcinoma of the stomach. METHODS: The study analyzed 321 consecutive patients with gastric cancer who underwent radical gastrectomy between January 2008 and December 2015. None of these patients had distant metastases. Lymph node metastases were found in 187 patients. The ECE grade was evaluated according to the previously described system used in head and neck cancers. Deposits of cancer cells in sub-serosal fat without a recognizable lymph node were classified as ECE grade 4. Survival outcomes were compared using Kaplan-Meier and Cox regression analyses. A nomogram was constructed using identified significant prognostic factors. The predictive accuracy and model performance were measured by the concordance index (C-index). RESULTS: Patients with ECE(+) showed significantly worse 3-year overall survival (OS) and disease-free survival (DFS) than those without ECE. In the sensitivity analysis, ECE had independent prognostic value for both 3-year OS and 3-year DFS, whereas ECE grading showed little impact on mortality trend or disease progression trend. The ECE-based nomogram showed a significantly higher C-index than the pathological tumor and node staging (pTN) staging system. CONCLUSIONS: The adverse prognostic impact of ECE was validated. Sub-serosal tumor deposits without recognizable lymph node tissue are recommended for inclusion in the ECE definition. A nomogram involving ECE could provide better individual prediction of survival for patients with lymph node-positive gastric cancer.

Preventable Deaths in Multiple Trauma Patients: The Importance of Auditing and Continuous Quality Improvement.

BACKGROUND: Management errors during pre-hospital care, triage process and resuscitation have been widely reported as the major source of preventable and potentially preventable deaths in multiple trauma patients. Common tools for defining whether it is a preventable, potentially preventable or non-preventable death include the Advanced Trauma Life Support (ATLS®) clinical guideline, the Injury Severity Score (ISS) and the Trauma and Injury Severity Score (TRISS). Therefore, these surrogated scores were utilized in reviewing the study's trauma services. METHODS: Trauma data were prospectively collected and retrospectively reviewed from January 1, 2018, to December 31, 2018. All cases of trauma death were discussed and audited by the Hospital Trauma Committee on a regular basis. Standardized form was used to document the patient's management flow and details in every case during the meeting, and the final verdict (whether death was preventable or not) was agreed and signed by every member of the team. The reasons for the death of the patients were further classified into severe injuries, inappropriate/delayed examination, inappropriate/delayed treatment, wrong decision, insufficient supervision/guidance or lack of appropriate guidance. RESULTS: A total of 1913 trauma patients were admitted during the study period, 82 of whom were identified as major trauma (either ISS > 15 or trauma team was activated). Among the 82 patients with major trauma, eight were trauma-related deaths, one of which was considered a preventable death and the other 7 were considered unpreventable. The decision from the hospital's performance improvement and patient safety program indicates that for every trauma patient, basic life support principles must be followed in the course of primary investigations for bedside trauma series X-ray (chest and pelvis) and FAST scan in the resuscitation room by a person who meets the criteria for trauma team activation recommended by ATLS®. CONCLUSION: Mechanisms to rectify errors in the management of multiple trauma patients are essential for improving the quality of trauma care. Regular auditing in the trauma service is one of the most important parts of performance improvement and patient safety program, and it should be well established by every major trauma center in Mainland China. It can enhance the trauma management processes, decision-making skills and practical skills, thereby continuously improving quality and reducing mortality of this group of patients.

Mesh-preservation approach to treatment of mesh infection after large incisional ventral hernia repair-how I do it.

Mesh infection after large incisional ventral hernia repair is a clinical dilemma in abdominal wall hernia surgery. It is believed foreign material should be removed but it causes secondary trauma to the abdominal wall tissue and might be associated with a higher risk of complications. Currently, there is no consensus on mesh-preservation treatment in cases of mesh infection after hernia repair in general. Herein we present the case of a 27-year-old male who recovered well from mesh infection after large incisional ventral hernia repair by mesh-preservation approach. The path to success is choice of material of prosthetic mesh; surgical approach of hernia repair, sufficient wound irrigation and drainage, and acquiring sterility of the mesh surface by wound care techniques such as local iodophor packing and vacuum sealing drainage. Clinical cohorts are needed to verify the feasibility of mesh-preservation treatment of mesh infection after large incisional hernia repair.

Melanosis coli: Harmless pigmentation? A case-control retrospective study of 657 cases.

BACKGROUNDS AND AIMS: The association of melanosis coli with the development of colorectal polyps remains uncertain. METHODS: From a total of 18263 patients who had received colonoscopy in our hospital, 219 with melanosis coli cases and 438 controls matched by age and sex (at 1:2 ratio) were included in this study. The association of incidence, number, location, and pathology of colorectal neoplasm with grades and distribution of melanosis coli were analyzed. RESULTS: Melanosis coli was associated with significantly more colorectal polyps than control, a higher incidence of numerous colorectal polyps (number ≥ 20) (7.3% vs 0.5%; p < 0.001), and higher number of small colorectal polyps (diameter ≤ 5 mm; p < 0.01). Patients with melanosis coli had higher incidences of low-grade adenomas (31.1% vs 23.3%, p < 0.05) and non-adenoma polyps (20.1% vs 12.8%, p < 0.05) than the controls. On multivariate analysis, melanosis coli was independently associated with increased detecting rates of low grade adenoma (OR = 1.54; 95%: 1.06-2.23; p < .05), non-adenoma polyp (OR = 1.72; 95%: 1.11-2.70; p < .05) and numerous polyps (OR = 16.2, 95%: 3.66-71.6; p < .05). There was no significant difference in the incidence of high-grade adenomas or adenocarcinomas in the two population groups, but the numbers of these lesions were insufficient to permit firm conclusions. No significant differences in incidence, number, and pathology of colorectal polyps between individuals with melanosis coli of three different grades of severity were found. Melanosis located predominantly in the right colon had an interestingly lower incidence of colonic polyps in right colon than did melanosis located predominantly in the left colon or total colon (8.9% vs. 26.3%, 24.0%, p < 0.05). Patients with melanosis coli had significantly more nonspecific distal ileal ulcers than did controls (8.0% vs 0%, p < 0.001). CONCLUSION: Melanosis coli is associated with a higher incidence and number of colonic non-adenoma polyps and low-grade adenomas, and higher incidence of distal ileal ulcers. Melanosis coli may not be a harmless pigmentation, but a sign of chronic injury of colonic and intestinal mucosa.

An Exploratory Analysis of the Geographical Distribution of Trauma Incidents in Shenzhen, China.

BACKGROUND: The city of Shenzhen, China, is planning to establish a trauma system. At present, there are few data on the geographical distribution of incidents, which is key to deciding on the location of trauma centres. The aim of this study was to perform a geographical analysis in order to inform the development of a trauma system in Shenzhen. METHODS: Retrospective analysis of trauma incidents attended by Shenzhen Emergency Medical Services (EMS) in 2014. Data were obtained from Shenzhen EMS. Incident distribution was explored using dot and kernel density estimate maps. Clustering was determined using the nearest neighbour index. The type of healthcare facilities which patients were taken to was compared against patients' needs, as assessed using the Field Triage Decision Scheme. RESULTS: There were 49,082 recorded incidents. A total of 3513 were classed as major trauma. Mapping demonstrates that incidents predominantly occurred in the western part of Shenzhen, with identifiable clusters. Nearest neighbour index was 0.048. Of patients deemed to have suffered major trauma, 8.5% were taken to a teaching hospital, 13.6% to a regional hospital, 42.6% to a community hospital, and 35.3% to a private hospital. The proportions of Step 1 or 2 negative patients were almost identical. CONCLUSION: The majority of trauma patients, including trauma patients who are at greater likelihood of severe injury, are taken to regional and community hospitals. There are areas with identifiable concentrations of volume, which should be considered for the siting of high-level trauma centres, although further modelling is required to make firm recommendations.

Surgical smoke.

Surgical smoke is the gaseous by-product formed during surgical procedures. Most surgeons, operating theatre staff and administrators are unaware of its potential health risks. Surgical smoke is produced by various surgical instruments including those used in electrocautery, lasers, ultrasonic scalpels, high speed drills, burrs and saws. The potential risks include carbon monoxide toxicity to the patient undergoing a laparoscopic operation, pulmonary fibrosis induced by non-viable particles, and transmission of infectious diseases like human papilloma virus. Cytotoxicity and mutagenicity are other concerns. Minimisation of the production of surgical smoke and modification of any evacuation systems are possible solutions. In general, a surgical mask can provide more than 90% protection to exposure to surgical smoke; however, in most circumstances it cannot provide air-tight protection to the user. An at least N95 grade or equivalent respirator offers the best protection against surgical smoke, but whether such protection is necessary is currently unknown.