[The effectiveness and safety of the anti gastroesophageal reflux system in the treatment of gastroesophageal reflux disease: a single center study of 23 cases].

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged (M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) (κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) (κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Metformin inhibits self-renewal of colorectal cancer stem cells by inhibiting mitochondrial oxidative phosphorylation].

OBJECTIVE: To investigate the mechanism of metformin for inhibiting self-renewal of colorectal cancer stem cells (CSCs). METHODS: CSCs were sorted from Wnt reporter- transfected colorectal cancer patient-derived organoids (PDOs) by fluorescence-activated cell sorting (FACS) and treated with metformin. The changes in self-renewal of the cells were assessed using sphere formation, colony formation and limiting dilution assays. The mRNA expressions of genes related with stemness and differentiation and Wnt target genes was detected by qRT-PCR. Wnt activity was assessed using flow cytometry in the CSCs. Seahorse analysis was used to evaluate cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) after metformin treatment. Mitochondrial membrane potential levels were detected with TMRE staining, and reactive oxygen species (ROS) levels were detected using MitoSOX staining. Galactose (10 mmol/L), metformin (10 µmol/L), NAC (5 mmol/L), and galactose+metformin were used to modulate ROS levels in the CSCs, and sphere-formation assay and flow cytometry were used to assess the changes in self- renewal capacity and Wnt activity. The effect of lentiviral transfection of yeast NADH dehydrogenase NDI1 on TMRE staining, MitoSOX staining and Wnt activity in the CSCs were analyzed with flow cytometry. RESULTS: Metformin significantly decreased the capacities of CSCs to form spheres, colonies and xenografts and reduced Wnt activity in the cells (P < 0.01). The mRNA levels of stemness-related genes and Wnt target genes decreased significantly while those of differentiation-related genes increased in metformin-treated CSCs (P < 0.05), which also showed significantly decreased OCR, TMRE and ROS levels with enhanced ECAR (P < 0.001). Galactose significantly increased sphereforming capacity, ROS levels and Wnt activity of the cells, and these effects were significantly inhibited by metformin (P < 0.05). Transfection of the CSCs with NDI1 significantly attenuated the inhibitory effects of metformin on proportion of CSCs and Wnt signaling pathway activity. CONCLUSION: Metformin reduces mitochondrial oxidative phosphorylation and ROS levels by inhibiting mitochondrial complex Ⅰ, thereby suppressing Wnt signaling pathway to reduce selfrenewal ability of colorectal CSCs.

[Research progress on the histological scoring system for nonalcoholic fatty liver disease].

Non-alcoholic fatty liver disease (NAFLD) has replaced chronic hepatitis B as the most common chronic liver disease in China and has now been renamed metabolic dysfunction-associated fatty liver disease (MAFLD). The Brunt, the American NASH Clinical Research Network (NASH-CRN), the European Steatosis, Activity, and Fibrosis/Fatty Liver Inhibition of Progression (SAF/FLIP), and the Pediatric NAFLD are currently the four semi-quantitative grading systems for histological evaluation. This paper reviews these four scoring systems for the clinical selection of appropriate systems for diagnosis and prognosis assessment. This article is a review, and in order to coordinate the evaluation criteria of various scoring systems, the old name "NAFLD" is used.

[Activation of cannabinoid receptor 2 alleviates acute lung injury in rats with lipopolysaccharide-induced sepsis].

OBJECTIVE: To investigate the protective effect of cannabinoid receptor 2 (CB2) activation against acute lung injury in rats with lipopolysaccharide (LPS)-induced sepsis and explore the underlying mechanism. METHODS: Forty-eight SD rats were randomly assigned into control group, model group, CB2 agonist group and P38 MAPK inhibitor group (n=12). In the latter 3 groups, the rats received intraperitoneal injection of LPS to induce sepsis, and the control rats were given saline injection. In CB2 agonist group, JWH133 (3 mg/kg) was injected intraperitoneally 30 min before LPS injection; in P38 MAPK inhibitor group, the rats received intraperitoneal injection of SB203580 (5 mg/kg) 30 min prior to JWH133 injection. The changes in lung histopathology, water content, fluid clearance rate, inflammatory factors, pulmonary expressions of CB2 and tight junctionrelated genes, and phosphorylation of P38 MAPK in the lung tissues were examined. RESULTS: The rat models of sepsis showed severe damage of alveolar structures with significantly decreased fluid clearance rate, lowered pulmonary expressions of CB2, occludin and ZO-1 mRNA and proteins, increased water content in the lung tissue, and increased phosphorylation level of P38 MAPK and TNF-α and IL-1ß levels in lung lavage fluid (all P < 0.05). Treatment with JWH133 improved alveolar pathology in the septic rats, but there was still inflammatory infiltration; lung tissue water content, phosphorylation of P38 MAPK, and TNF-α and IL-1ß levels in lung lavage fluid were all significantly decreased, and the fluid clearance rate, pulmonary expressions of CB2, occludin and ZO-1 were significantly increased (all P < 0.05). Additional treatment with SB203580 resulted in further improvements of alveolar pathologies, lowered phosphorylation levels of P38 MAPK in the lung tissue and TNF-α and IL-1ß levels in lung lavage fluid, and increased the protein expressions of occludin and ZO-1 (P < 0.05) without causing significant changes in mRNA and protein expression of CB2 (P > 0.05). CONCLUSION: In rats with LPS-induced sepsis, activation of CB2 can inhibit the p38 MAPK signaling pathway, reduce the release of inflammatory factors in the lung tissues, promote tight junction protein expressions, and thus offer protection against acute lung injury.

Effects of honeycomb extract on the growth performance, carcass traits, immunity, antioxidant function and intestinal microorganisms of yellow bantam broilers.

Although many studies have already described the physiological effects of bee products, such as honey, propolis, pollen, and royal jelly, on livestock farming, the health benefits of the honeycomb are still not fully understood. The problem of drug residues and bacterial resistance caused by the abuse of antibiotics is becoming increasingly serious. For this reason, a safe, green substitute has to be sought. We conducted a comparative study of honeycomb extract (HE) and an antibiotic on growth performance, carcass traits, immunity, antioxidant function and intestinal microorganisms of yellow bantam broilers. A total of four hundred eighty 21-day-old female yellow bantam broilers were randomly divided into 5 groups of 6 replicates of 16 birds each. The 5 groups were as follows, with birds receiving a basal diet supplemented with 150 ppm (mg/kg) of chlortetracycline (CTE), a basal diet without HE (control group), and a basal diet with 0.1%, 0.15%, or 0.2% HE for 60 days. The results showed that HE addition significantly increased average daily feed intake (ADFI), average daily gain (ADG), decrease feed gain ratio (F/G) from 21 to 80 and 51 to 80 days of age compared to the control group, with all 3 HE addition groups having statistically identical values to the antibiotic group. HE implementation dramatically increased spleen index, serum immunoglobulin A (IgA), immunoglobulin M (IgM,), glutathione peroxide (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and total cecum bacteria and Lactobacillus compared to the control group, numerically at the same level as, or even better than, the antibiotic group. HE and CTE both markly reduced serum malondialdehyde (MDA) concentration compared to the control group, with higher concentrations of HE reducing the effect more dramatically than antibiotics. Both HE and CTE significantly raised dressed yield compared to the control group. In summary, HE, as a potential antibiotic alternative, improved growth performance, carcass traits, immune function, serum antioxidant capacity and intestinal microorganisms in yellow bantam broilers. According to the cubic regression analyses, the recommended supplemental dose of HE was calculated to be 0.15 to 0.17% for female yellow bantam broilers between 21 and 80 d of age.

[Clinical study on the relationship between the exosomes in bronchoalveolar lavage fluid and plasma and the severity of lung injury and outcome in early acute respiratory distress syndrome patients].

Objective: To investigate the relationship between the levels of exosomes in bronchoalveolar lavage fluid (BALF) and plasma and the severity of lung injury and its outcome in patients with acute respiratory distress syndrome (ARDS). Methods: Patients who were admitted to the Department of Critical Care Medicine, Zhongda Hospital Affiliated to Southeast University and received invasive mechanical ventilation were selected from August 2020 to April 2021, and they were divided into ARDS group and non-ARDS group. Finally, 33 ARDS patients were included, including 18 males and 15 females, aged (65.5±15.5) years; 10 non-ARDS patients, 8 males and 2 females, aged (57.2±15.3) years. The BALF and plasma of the two groups of patients were collected within 24 hours after enrollment, and the total exosomes of the samples were collected by ultracentrifugation. Nanoparticle tracking analysis (NTA) was used to detect and compare the differences in exosome content between the two groups. Correlation of content with the severity and prognosis of lung injury in ARDS patients. Results: There was no significant difference in gender and age between ARDS group and non-ARDS group (both P>0.05). The exosome in plasma of ARDS group was significantly higher than that of non-ARDS group [(25.3±1.2)/ml vs (24.2±1.6)/ml, P=0.031], while the exosomes in BALF of ARDS group was also higher than that of non-ARDS group [(26.5±1.6)/ml vs (24.6±1.1)/ml, P=0.001]. The exosomes in BALF of patients with ARDS caused by intrapulmonary causes was higher than that in ARDS group caused by extrapulmonary causes [(26.9±1.5)/ml vs (25.2±0.9)/ml, P=0.01], and the infection caused by bacterial shows that the highest exosome level in BALF. The exosomes in the BALF of the mild ARDS group was significantly lower than that of the severe ARDS group [(25.7±1.3)/ml vs (27.2±1.5)/ml, P=0.038]; the exosomes in BALF of ARDS patients was negatively correlated with P/F ratio (r=-0.38, P=0.03); and it was positively correlated with Murray lung injury score (r=0.47, P=0.01). However, the static compliance levels, length of hospital stay, duration of mechanical ventilation, and 28-day outcome were not associated with the exosomes in BALF. Conclusion: Compared with non-ARDS patients, ARDS patients have significantly higher levels of exosomes in BALF and plasma, there is a certain correlation between exosomes derived from BALF and the severity of lung injury in ARDS.

[Status of vaccination and related influencing factors in patients with chronic obstructive pulmonary disease: a real-world cross-sectional study].

Objective: To investigate the influenza and pneumonia vaccination rates in patients with chronic obstructive pulmonary disease (COPD), and analyze the factors affecting vaccination. Methods: Totally 4 016 COPD patients at the initial visit were included in the Respiratory Department of Xiangya Second Hospital of Central South University from December, 2016 to December, 2019. Each patient's vaccination status after the visit for 1 year was reviewed, and finally 3 177 patients were included in the analysis. Relevant factors affecting vaccination were analyzed with logistic regression. Results: The overall vaccination rates of COPD patients with influenza vaccine, pneumonia vaccine and influenza combined pneumonia vaccine were 2.3% (72/3 177), 1.1% (34/3 177) and 1.1% (34/3 177), respectively. The influenza vaccination rate of urban patients (3.3%, 41/1 252) was higher than that of rural patients (1.6%, 31/1 925,P=0.002). The rates of influenza vaccine, pneumonia vaccine and influenza combined pneumonia vaccine in ex-smokers with COPD were 3.3% (33/993), 2.1% (21/993), 2.1% (21/993), respectively and 1.7% (25/1 467), 0.7% (11/1 467), 0.7% (11/1 467), in current smokers with COPD, respectively (P=0.034, P=0.015, P=0.015, respectively). The influenza vaccination rate was higher in patients with COPD assessment test (CAT) scored less than 10 (4%, 27/673) than patients with CAT scored more than 10 (1.8%, 45/2 504,P=0.002). In a multifactor analysis, patients who lived in country side, were current smokers, and had more symptoms were less likely to be vaccinated, with an aOR 1.73(95%CI 1.02-2.93), 2.10(95%CI 1.18-3.76), 2.06(95%CI 1.24-3.43), respectively. 81.2% of COPD patients did not receive the vaccine because they did not know the vaccine. Conclusions: Vaccination rates for influenza vaccine, pneumonia vaccine and both of them in COPD patients were low and the patients lacked knowledge of vaccine. The residence, smoking status and symptoms were related to the vaccination of COPD patients, and these should be taken into account in the vaccination health education.

Acceleration of Brain Susceptibility-Weighted Imaging with Compressed Sensitivity Encoding: A Prospective Multicenter Study.

BACKGROUND AND PURPOSE: While three-dimensional susceptibility-weighted imaging has been widely suggested for intracranial vessel imaging, hemorrhage detection, and other neuro-diseases, its relatively long scan time has necessitated the clinical verification of recent progresses of fast imaging techniques. Our aim was to evaluate the effectiveness of brain SWI accelerated by compressed sensitivity encoding to identify the optimal acceleration factors for clinical practice. MATERIALS AND METHODS: Ninety-nine subjects, prospectively enrolled from 5 centers, underwent 8 brain SWI sequences: 5 different folds of compressed sensitivity encoding acceleration (CS2, CS4, CS6, CS8, and CS10), 2 different folds of sensitivity encoding acceleration (SF2 and SF4), and 1 without acceleration. Images were assessed quantitatively on both the SNR of the red nucleus and its contrast ratio to the CSF and, subjectively, with scoring on overall image quality; visibility of the substantia nigra-red nucleus, basilar artery, and internal cerebral vein; and diagnostic confidence of the cerebral microbleeds and other intracranial diseases. RESULTS: Compressed sensitivity encoding showed a promising ability to reduce the acquisition time (from 202 to 41 seconds) of SWI while increasing the acceleration factor from 2 to 10, though at the cost of decreasing the SNR, contrast ratio, and the scores of visual assessments. The visibility of the substantia nigra-red nucleus and internal cerebral vein became unacceptable in CS6 to CS10. The basilar artery was well-distinguished, and diseases including cerebral microbleeds, cavernous angiomas, intracranial gliomas, venous malformations, and subacute hemorrhage were well-diagnosed in all compressed sensitivity encoding sequences. CONCLUSIONS: Compressed sensitivity encoding factor 4 is recommended in routine practice. Compressed sensitivity encoding factor 10 is potentially a fast surrogate for distinguishing the basilar artery and detecting susceptibility-related abnormalities (eg, cerebral microbleeds, cavernous angiomas, gliomas, and venous malformation) at the sacrifice of visualization of the substantia nigra-red nucleus and internal cerebral vein.

Efficacy of Kanglaite against radiotherapy-induced mucositis in head and neck cancer, a phase II trial.

PURPOSE: To explore the potential protective effect of Kanglaite injection against radiotherapy-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: This was an open-label, single-arm, and phase II trial. The primary endpoint was the incidence of grade 3-4 radiation-induced mucositis. The secondary endpoints were hematological toxicity, non-hematological toxicity, nutritional status, and quality of life. All patients received 20g Kanglaite daily concurrently with radiotherapy. RESULTS: The data of 46 patients were available for analysis. The incidence rates of grade 3 mucositis, pain, dysphagia, and neutropenia were 10.9%, 2.2%, 10.9%, and 6.5%, respectively, while the incidence of grade 4 acute toxicities was zero. The rate of opioid use was 2.2%. Radiotherapy dose reduction was 2.2% and no irradiation field was modified. The nutritional supports were oro-enteral nutritional supplements (13.0%), TPN (10.9%), and feeding tubes (0%) during radiotherapy. After radiotherapy, 52.2% of patients lost weight, and the weight loss was <10%. The mean pain score in the QLQ-H&N35 and QLQ-C30 was <50. Patients had nearly normal physical, emotional, and cognitive functions. CONCLUSIONS: A low incidence of grade 3-4 radiation-induced mucositis and no severe acute toxic events, with favorable nutritional status and quality of life, were observed in cancer patients after Kanglaite injection. Our findings highlight the need for a prospective, multicenter, and randomized study to investigate the effect of Kanglaite injection on the reduction of radiation-induced mucositis in patients with head and neck cancer.

Consensus for HER2 alterations testing in non-small-cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Its alterations, including mutation, amplification and overexpression, could result in oncogenic potential and have been detected in many cancers such as non-small-cell lung cancer (NSCLC). Such alterations are, in general, considered markers of poor prognosis. Anti-HER2 antibody-drug conjugates, e.g. trastuzumab deruxtecan (T-DXd, DS-8201) and disitamab vedotin (RC48), were recently approved for HER2-positive breast and gastric cancers. Meanwhile, several HER2-targeted drugs, such as T-DXd, neratinib, afatinib, poziotinib and pyrotinib, have been evaluated in patients with advanced NSCLC, with several of them demonstrating clinical benefit. Therefore, identifying HER2 alterations is pivotal for NSCLC patients to benefit from these targeted therapies. Recent guidelines on HER2 testing were developed for breast and gastric cancer, however, and have not been fully established for NSCLC. The expert group here reached a consensus on HER2 alteration testing in NSCLC with the focus on clinicopathologic characteristics, therapies, detection methods and diagnostic criteria for HER2-altered NSCLC patients. We hope this consensus could improve the clinical management of NSCLC patients with HER2 alterations.

[Free rectus abdominis myocutaneous flap for the reconstruction of major and complex defects in the craniofacial regions after ablation of advanced sinonasal carcinomas].

Objective: To explore the method and plausibility of using free rectus abdominis flap (FRAF) to reconstruct the major and complex defects in the craniofacial regions after ablation of advanced sinonasal carcinoma. Methods: From 2007 to 2018 at No. 980 Hospital of Joint Logistic Supportive Force of People's Liberation Army of China, 13 patients with advanced carcinoma of nasal cavity and paranasal sinuses, including 11 males and 2 females, aged from 33 to 67 years, were treated with FRAF to repair the invasion of skull base, face and orbit. Based on adequate and meticulous preoperative evaluations on patients and tumors, complete resection of tumor bulks was performed. According to the sites, characters and extents of the defects, FRAF was introduced in different ways into reconstruction of major and complex defects in the craniofacial regions after resection of advanced sinonasal carcinomas, restoring the structure and contour of the craniofacial region. Results: Complete resection of tumors was achieved in all cases. For repairing the major and complex defects resulted from tumor ablation, FRAF graft was conducted in 13 patients with advanced sinonasal carcinomas. The recipient vessels were facial artery and vein in 9 cases, superficial temporal artery and vein in 4 cases. Vascular bridging with the external jugular vein was carried out in 2 cases who underwent submandibular neck dissections, in which facial artery and vein were used as recipient vessels. Free fibular flap was used along with FRAF in a case undergone bilateral maxillectomy. Pedicled galea capitis and periosteal flap were applied simultaneously in 3 cases with dura defects at the skullbase resulted from tumor resection. All flaps used in 13 cases survived uneventfully without major complications, with successful repair of defects, reconstruction of structures and restoration of contour of craniofacial regions. Conclusion: With adequate evaluation of resectability of tumors as well as nature and extent of defects after tumor removal, FRAF transplantation is an ideal method and strategy of choice for reconstructing the major and complex defects in craniofacial regions resulted from tumor ablation of advanced sinonasal carcinomas.

[Epithelioid hemangioendothelioma with TFE3 translocation in soft tissue:a clinicopathological study].

Objective: To investigate the clinicopathological and molecular features, diagnosis and differential diagnosis of TFE3-rearranged epithelioid hemangioendothelioma (EHE). Methods Two cases of TFE3-rearranged EHE arising from soft tissues, diagnosed by the Pathology Department of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 were observed. EnVision method was used for immunophenotyping, fluorescence in situ hybridization (FISH) was used to test TFE3 gene rearrangements and WWTR1-CAMTA1 fusion gene,and next-generation sequencing (NGS) was used to delineate the fusion transcripts. Results: Details of these two cases were as follows: case 1, male, 51 years old, with tumor in the right temporal region; case 2, female, 42 years old, with tumor in the right neck. The tumors showed progressive painless enlargement. Grossly, the tumor of case 1 was multinodular with unclear boundary and grayish red cut surface, while the tumor of case 2, originating from a vein, appeared as a firm, tan mass within vessel wall. Microscopically, both tumors showed moderate cellularity and were consisted of plump, epithelioid, or histiocytoid cells with eosinophilic cytoplasm and mild-to-moderate nuclear pleomorphism. Most of the tumor cells were arranged in solid or alveolar growth patterns, while some tumor cells showed intraluminal papillary growth pattern in case 1 and anastomosing vascular channels and extramedullary hematopoiesis in case 2. Immunohistochemically, the tumor cells showed diffuse positivity for CD31, CD34, ERG, and TFE3. FISH revealed TFE3 break-apart signals in two cases, but WWTR1-CAMTA1 gene fusion was not detected. NGS identified YAP1 (exon1)-TFE3 (exon6) fusion gene in case 2. Clinical follow-up information was available in both cases for a follow-up period of 15 and 59 months respectively. Patient 1 had a relapse 22 months after surgery, and was currently alive with the tumor. Patient 2 remained disease-free. Conclusions: TFE3-rearranged EHE is a rare molecular subtype of EHE, with accompanying characteristic morphologic features. However the morphologic spectrum remains under-recognized, and more experience is needed. Immunohistochemical and molecular examinations are helpful for the diagnosis and differential diagnosis of the disease.