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BACKGROUND AND AIM Thoracotomy is the foremost choice of giant esophageal lipomatous tumors in previous studies, but it is highly traumatic and possibly diminishes the quality of patients' lives. To minimize such impacts, a minimally invasive method without loss of curability is desirable for giant lipomatous tumors of the esophagus. With recent progress in endoscopic techniques and devices, endoscopic submucosal dissection (ESD) has been successfully used to remove esophageal or gastric submucosal tumors. In our study, we aimed to evaluate the clinical impact of ESD for giant esophageal lipomatous tumors. METHODS Design, single-center, retrospective study; setting, academic medical center; patients, six patients with six giant lipomatous tumors of the esophagus between February 2013 and December 2020; interventions, ESD; and main outcome measurements, procedure duration, en bloc resection rate, complications, local recurrence, and distant metastases. RESULTS Endoscopic en bloc resections of esophageal lipomatous tumors were successfully performed in all patients, with a mean duration of 56.5 ± 26.0 min. All en bloc resection lesions showed both lateral and deep tumor-free margins. The average maximum diameter of the esophageal lipomatous tumors was 171.7 ± 66.2 mm. No complications such as bleeding and perforations happened during hospitalization with 4.0 ± 1.6 days. Besides, local recurrence and distant metastasis have not occurred during the follow-up period. CONCLUSIONS Endoscopic submucosal dissection is a safe and effective way to dissect giant lipomatous tumors of the esophagus thoroughly.

OBJECTIVE To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG). METHODS This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial. RESULTS At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P 0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P

Spinal cord injury (SCI) is a traumatic disease that can cause severe nervous system dysfunction. SCI often causes spinal cord mitochondrial dysfunction and produces glucose metabolism disorders, which affect neuronal survival. Zinc is an essential trace element in the human body and plays multiple roles in the nervous system. This experiment is intended to evaluate whether zinc can regulate the spinal cord and neuronal glucose metabolism and promote motor functional recovery after SCI. Then we explore its molecular mechanism. We evaluated the function of zinc from the aspects of glucose uptake and the protection of the mitochondria in vivo and in vitro. The results showed that zinc elevated the expression level of GLUT4 and promoted glucose uptake. Zinc enhanced the expression of proteins such as PGC-1α and NRF2, reduced oxidative stress, and promoted mitochondrial production. In addition, zinc decreased neuronal apoptosis and promoted the recovery of motor function in SCI mice. After administration of AMPK inhibitor, the therapeutic effect of zinc was reversed. Therefore, we concluded that zinc regulated the glucose metabolism of the spinal cord and neurons and promoted functional recovery after SCI through the AMPK pathway, which is expected to become a potential treatment strategy for SCI.

Background Liquid biopsy through the detection of circulating tumor DNA (ctDNA) has potential advantages in cancer monitoring and prediction. However, most previous studies in this area were performed with a few hotspot genes, single time point detection, or insufficient sequencing depth.Methods In this study, we performed targeted next-generation sequencing (NGS) with a customized panel in metastatic breast cancer (MBC) patients. Fifty-four plasma samples were taken before chemotherapy and after the third course of treatment for detection and analysis. Paired lymphocytes were also included to eliminate clonal hematopoiesis (CH)-related alternatives.Results A total of 1182 nonsynonymous mutations on 419 genes were identified. More ctDNA mutations were detected in patients with tumors> 3cm (P = 0.035) and HER2(−) patients (P = 0.029). For a single gene, the distribution of ctDNA mutations was also correlated with clinical characteristics. Multivariate regression analysis revealed that HER2 status was significantly associated with mutation burden (OR 0.02, 95% CI 0–0.62, P = 0.025). The profiles of ctDNA mutations exhibited marked discrepancies between two time points, and baseline ctDNA was more sensitive and specific than that after chemotherapy. Finally, elevated ctDNA mutation level was positively correlated with poor survival (P Conclusion Mutations in ctDNA could serve as a potential biomarker for the evaluation and prediction, and guide the clinical management of MBC patients with chemotherapy.

BACKGROUND AND AIM Gastrointestinal submucosal tumors (SMTs) can be removed by submucosal tunneling endoscopic resection (STER). However, limited studies have evaluated STER for the removal of multiple upper gastrointestinal SMTs. The aim of this study was to evaluate the feasibility and outcomes of STER in the treatment of multiple upper gastrointestinal SMTs. METHODS From January 2011 to April 2020, the cases of patients with multiple upper gastrointestinal SMTs undergoing STER were retrospectively analyzed. Variables of clinicopathological characteristics, major adverse events (mAEs), and follow up were collected and analyzed. RESULTS Submucosal tunneling endoscopic resection was performed in 54 patients (48 male and 6 female patients) with 120 SMTs. Forty-four patients had two tumors, eight patients had three tumors, and two patients had four tumors. The median size of each patient was 1.8 cm (range 0.7 to 3.5 cm). Forty-five patients had tumors removed by one tunnel, and nine patients by two tunnels. The median procedure time was 50 min (range 14 to 120 min), and the mAE rate was 16.7% (9/54). No significant differences were found between patients with two tumors and those with > 2 tumors in terms of tunnel length, hospital stay, procedure time, and mAEs (all P > 0.05). In addition, patients with two tunnels had procedure time, hospital stay, and mAE rates comparable with those with one tunnel (all P > 0.05). No local recurrence or distant metastasis occurred during a median follow up of 64 months. CONCLUSIONS Submucosal tunneling endoscopic resection is a safe and effective technique for the resection of multiple upper gastrointestinal SMTs.

BACKGROUND Pulmonary alveolar proteinosis (PAP) is a pulmonary syndrome wherein large volumes of phospholipid and protein-rich surfactants accumulate within the alveoli. PAP forms include primary (auto-immune PAP), secondary, and congenital. Nocardiosis is a form of suppurative disease induced upon infection with bacteria of the Nocardia genus. Clinically, cases of PAP complicated with Nocardia infections are rare, regardless of form. Unfortunately, as such, they are easily overlooked or misdiagnosed. We describe, here, the case of a patient suffering from simultaneous primary PAP and nocardiosis. CASE SUMMARY A 45-year-old Chinese man, without history of relevant disease, was admitted to our hospital on August 8, 2018 to address complaints of activity-related respiratory exertion and cough lasting over 6 mo. Lung computed tomography (CT) revealed diffuse bilateral lung infiltration with local consolidation in the middle right lung lobe. Subsequent transbronchial lung biopsy and CT-guided lung biopsy led to a diagnosis of primary PAP (granulocyte-macrophage colony-stimulating factor antibody-positive) complicated with nocardiosis (periodic acid-Schiff-positive). After a 6 mo course of anti-infective treatment (sul-famethoxazole), the lesion was completely absorbed, such that only fibrous foci remained, and the patient exhibited significant symptom improvement. Follow-up also showed improvement in pulmonary function and the CT imaging findings of PAP. No whole-lung lavage has been conducted to date. This case highlights that active anti-nocardia treatment may effectively improve the symptoms and alleviate PAP in patients with PAP and nocardia, possibly reducing the need for whole-lung lavage. CONCLUSION When evaluating patients presenting with PAP and pulmonary infections, the potential for nocardiosis should be considered.

Vascular rings (VRs) are defined as congenital abnormalities of the aortic arch and its branches. VR can form a ring that may compress the esophagus and trachea, which likely result in feeding difficulties and respiratory distress. Physicians performing fetal echocardiography are knowledgeable about VRS and can provide this information to pediatric cardiothoracic surgeons. However, VRs are rare and can be missed. The three vessels and trachea (3VT) view used to diagnose VRs has been reported in the literature multiple times but in a small series. We diagnosed three cases of VRs using high-definition (HD) flow render mode and spatiotemporal image correlation (STIC). The composition of the VRs and vessel connections were shown more intuitively. This article reports our experience of the following related cases. In addition, postnatal imaging features of VRs were also evaluated.

The surgery for esophageal cancer arising after prior gastrectomy is technically difficult with high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic treatment for superficial SCC with high curative resection rate. But few studies are concerned about ESD under these circumstances. The aim of this study was to elucidate the short- and long-term outcomes of ESD for superficial esophageal squamous cell cancer (SCC) in patients with prior gastrectomy. From January 2009 to January 2019, 37 patients with prior gastrectomy who underwent ESD for superficial esophageal SCC were retrospectively enrolled at the Zhongshan Hospital, Fudan University in Shanghai, China. Rates of en bloc resection, complete resection, curative resection, incidence of postoperative bleeding, perforation and postoperative stricture were evaluated as short-term outcomes. Overall survival, and local recurrence-free survival were evaluated as long-term outcomes. The rate of en bloc resection, complete resection and curative resection were 94.6%, 86.5% and 78.4%, respectively. No perforation was observed. 1 (2.7%) patient experienced postoperative bleeding. During the median observation of 43 months, 3 (8.6%) patients experienced esophageal stricture, successfully managed by balloon dilation. 3(8.6%) patients had local recurrence after ESD with 5-year local recurrence-free survival rate of 91.4%. During the observation period, 4 patients died of other reasons. The 1, 3, 5-year overall survival rates were 97.1%, 97.1% and 91.4%. The short-term outcomes indicate ESD is technically difficult with lower resection completeness in patients after gastrectomy, while the long-term outcomes are rather favorable.

Background To evaluate the orbital involvement epidemiology in facial fractures, the clinical distribution and effects of orbital involvement in these patients, the frequency and nature of treatment procedures performed for these involvements, and the immediate- and intermediate-term effects of these treatment procedures. Methods Two hundred patients with hard tissue maxillofacial injuries were included in this study. Clinical examination was performed in-depth. Images were taken to determine and confirm clinical observations and to finalize treatment modality. Orbital involvement in patients was noted as present or absent. The clinical effects and features in postoperative imaging studies were noted until 3 months after trauma in each patient. Results Out of 200 patients, about one-third patients (58;29%) had orbital involvement and out of which 49 were males. Regarding clinical-radiological signs in orbit involved fractures, the incidences were variable, that is, periorbital ecchymosis (77.6%), periorbital edema (74.1%), subconjunctival hemorrhage (67.2%), palpable step/crepitus in orbital rim (62.1%), infraorbital nerve paresthesia (46.6%), restricted globe movement (5.2%), orbital rim discontinuity/step (72.4%), maxillary sinuses (51.7%), orbital wall/floor/roof rupture (55.2%), and infraorbital foramen involvement (36.2%). Palpable step/crepitus in orbital rim was recovered remarkably earlier in patients of open reduction internal fixation (ORIF) group, and features of restricted globe movements, orbital rim discontinuity/step, orbital wall/floor/roof rupture, and infraorbital foramen involvement in patients were recovered immediately after open reduction and internal fixation treatment. Conclusion Early repair of the maxillofacial injuries with orbital involvement has better functional and esthetic outcome.

Residual bacteria and microleakage in a complicated root canal can often result in reinfection of the periapical tissues. To promote the antibacterial and sealing effects of a root canal filling, core-shell structured CaO/ZnO nanospheres were synthesized using a precipitation method based on a traditional root canal sealer, zinc oxide-eugenol(ZOE). The obtained CaO/ZnO particles had a size of 80–90 nm and a core-shell structure. The film thickness, flow rate, pH, and calcium ion release of the core-shell structured CaO/ZnO nanospheres-eugenol paste were tested. The pH and calcium ion release results showed a slight increase in the prepared nanospheres, with a flow rate of 24.22 mm and a formed film thickness of 30 µm, which are basically consistent with ISO 6876:2001 standards(regarding dental root canal sealing materials). Cytotoxicity tests showed that the cytocompatibility of the CaO/ZnO nanospheres-eugenol paste was much higher than that of the ZOE or iRoot SP groups(P

Aim To evaluate the patterns of macular ganglion cell-inner plexiform layer (GCIPL) loss in normal tension glaucoma (NTG) and primary open angle glaucoma (POAG) in a detailed, disease severity-matched way; and to assess the diagnostic capabilities of GCIPL thickness parameters in discriminating NTG or POAG from normal subjects. Methods A total of 157 eyes of 157 subjects, including 57 normal eyes, 51 eyes with POAG and 49 eyes with NTG were enrolled and strictly matched in age, refraction, and disease severity between POAG and NTG groups. The average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL thickness, and the average, superior, temporal, inferior, and nasal retinal nerve fiber layer (RNFL) thickness were obtained by Cirrus optical coherence tomography (OCT). The diagnostic capabilities of OCT parameters were assessed by area under receiver operating characteristic (AUROC) curves. Results Among all the OCT thickness parameters, no statistical significant difference between NTG group and POAG group was found (all P>0.05). In discriminating NTG or POAG from normal subjects, the average and inferior RNFL thickness, and the minimum GCIPL thickness had better diagnostic capabilities. There was no significant difference in AUROC curve between the best GCIPL thickness parameter (minimum GCIPL) and the best RNFL thickness parameter in discriminating NTG (inferior RNFL; P=0.076) and indiscriminating POAG (average RNFL; P=0.913) from normal eyes. Conclusion Localized GCIPL loss, especially in the inferior and inferotemporal sectors, is more common in NTG than in POAG. Among all the GCIPL thickness parameters, the minimum GCIPL thickness has the best diagnostic performance in differentiating NTG or POAG from normal subjects, which is comparable to that of the average and inferior RNFL thickness.

Background It is very difficult to predict the early response to NAC only on the basis of change in tumor size. ADC value derived from DWI promises to be a valuable parameter for evaluating the early response to treatment. This study aims to establish the optimal time window of predicting the early response to neoadjuvant chemotherapy (NAC) for different subtypes of locally advanced breast carcinoma using diffusion-weighted imaging (DWI). Methods We conducted an institutional review board-approved prospective clinical study of 142 patients with locally advanced breast carcinoma. All patients underwent conventional MR and DW examinations prior to treatment and after first, second, third, fourth, sixth and eighth cycle of NAC. The response to NAC was classified into a pathologic complete response (pCR) and a non-pCR group. DWI parameters were compared between two groups, and the optimal time window for predicting tumor response was established for each chemotherapy regimen. Results For all the genomic subtypes, there were significant differences in baseline ADC value between pCR and non-pCR group (p

BackgroundAutologous cell therapies with an engineered T-cell receptor targeting MAGE-A4 have shown responses in patients with synovial sarcoma1 with additional responses in myxoid/round cell liposarcoma (MRCLS), head and neck, lung, esophagogastric junction, and melanoma cancers.2 3 Low-dose radiation may control tumor growth locally and modulate stroma of solid tumors,4 potentially facilitating T-cell infiltration into tumors and antitumor activity.MethodsSub-study designed to assess safety, tolerability, and efficacy in up to 10 patients with low-dose radiation in combination with lymphodepleting chemotherapy, followed by afami-cel (an autologous TCR cell T-cell therapy targeting MAGE-A4). Eligible patients are HLA-A*02^+ with MAGE-A4 expressing tumors including urothelial, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, and MRCLS cancers. Patients receive afami-cel by infusion following low-dose radiation and lymphodepleting chemotherapy. Radiation was 4.2–7 Gy per lesion or isocenter (maximum of 5). Lymphodepleting regimen was IV fludarabine 30 mg/m^2/day for 4 days (−7 to −4) and cyclophosphamide 600 mg/m^2/day for 3 days (−7 to −5). Afami-cel doses ranged from 1.2 x 10^9 to 10 x 10^9 transduced cells. Pts receive afami-cel infusion on Day 1.ResultsAs of Dec 27, 2020, a total of 8 patients, including 4 patients (1 male) with melanoma (2), HNSCC (1), or ovarian (1) cancers received low-dose radiation and afami-cel. Most frequently reported AEs (4/4 pts) were leukopenia/decreased white blood cell count, lymphopenia/decreased lymphocyte count, and neutropenia/decreased neutrophil count; all of which were related to the lymphodepletion regimen. The most commonly (>1 patient) reported AEs considered related to T-cell infusion were cytokine release syndrome (2/4 pts) and fatigue (2/4 pts). Two patients had a total of 5 SAEs: adrenal insufficiency, hyperglycemia, neurotoxicity, pneumonia aspiration, and pneumothorax. The only SAE considered to be related to treatment was Grade 3 neurotoxicity. Best overall responses per RECIST 1.1: 1 partial response (melanoma, −42% in target lesions), 2 stable diseases (ovarian cancer, −23%; HNSCC, no change), and 1 patient did not have post-baseline scans yet. Translational analyses showed peripheral persistence and serum cytokine response profiles consistent with that of afami-cel monotherapy, whilst a relatively greater T cell infiltration in tumor biopsies was evident.ConclusionsAfami-cel with low-dose radiation has had an acceptable safety profile. Most AEs were consistent with those typically experienced by cancer patients undergoing lymphodepletion cytotoxic chemotherapy and cellular therapy. Infused T-cells were observed in tumor biopsies at high frequency, and one patient exhibited a clinical partial response.Trial RegistrationNCT03132922ReferencesVan Tine BA, et al. CTOS 2020.Hong DS, et al. ASCO 2020.Hong DS, et al. SITC 2020.De Selm C, et al. Mol Ther 2018;26(11):2542–2552.

The spectrum of endoscopic resection methods, including full thickness techniques, has enabled removal of most smaller gastric submucosal tumours (SMTs). We developed an extended transmural endoscopic dissection technique for lesions with predominately extraluminal growth arising from the muscularis propria. It consists of transmural intraperitoneal access with the endoscope besides the lesion followed by subserosal dissection from the outside. The technique was successful in two patients with smaller (2–3 cm) gastric stromal tumours; lesions were resected completely and short-term follow-up was normal. Further studies are warranted to confirm the safety and feasibility of this this new approach. With the popularisation of endoscopy and the development of endoscopic ultrasonography (EUS), the detection rate of gastrointestinal (GI) SMT has increased significantly.1 Complete surgical resection is still recognised as the primary and the most important way to treat gastric SMT and to get clear pathological diagnosis.2 Minimally invasive endoscopic therapy received increasing recognition due to its advantages of less invasiveness, fewer complications, quicker recovery and lower costs compared with open surgery or laparoscopic surgery. Gastric SMTs derived from mucosal and submucosal layers could be resected by endoscopic mucosal resection and endoscopic submucosal dissection, while those originated from deep layers of the gastric wall can be resected using endoscopic full-thickness resection (EFTR), which intentionally perforates the gastric wall to achieve complete resection.3 With an increasing emphasis on protecting the intact of mucosa, endoscopic mucosa-sparing lateral dissection was developed to reduce the postoperative complications.4 Inspired by the submucosal tunnelling endoscopic resection (STER)5 technique, in which maintenance of mucosal integrity and the longitudinal submucosal tunnel lead to rapid healing and decreased risk of pleural infection, STER for extraluminal tumours was reported for resection of SMTs with a predominant extraluminal growth pattern or extra-GI tumours.6 However, for most SMTs with a predominately extraluminal …

BackgroundNon-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited.Patients and methodsWe retrospectively included metastatic NSCLC patients harboring HER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed.ResultsWe included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16–36%), the median PFS was 3.3 months (95% CI, 2.2–4.4), and the median OS was 13.9 months (95% CI, 11.4–16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2–5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3–14.8; P = 0.009) than patients with other mutations. For HER2-amplified patients, the ORR was 33% (95% CI, 14–61%), the median PFS was 3.3 months (95% CI, 2.6–4.0), and the median OS was 13.4 months (95% CI, 0–27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations.ConclusionsOur results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.

The approach to paraoesophageal structures and lesions via the oesophagus was initiated by the introduction of peroral endoscopic myotomy (POEM), followed by peroral endoscopic removal of tumours within the muscular layer. We now report a case which suggests that the next step, that is, to remove paraoesophageal tumours not related to the oesophageal wall, would also be possible. This is the case of a 66-year-old male patient with a 4.0×2.0×1.5 cm benign schwannoma from the recurrent laryngeal nerve bulging into the proximal oesophagus, which we removed via a POEM tunnel. The postoperative course was uneventful. Further controlled studies have to show which lesions may be suitable for this expanded approach and also confirm the safety and feasibility of this technique which can be regarded as much less invasive than operative minimal invasive alternatives. Due to the complicated anatomy of the mediastinum, mediastinal masses represent a heterogeneous group of tumours.1 2 Characteristic location of the mass establishes a useful differential diagnosis that aids in planning the diagnostic evaluation. Video-assisted thoracoscopic surgery and conventional open surgery are the currently available treatments for these patients with benign lesions in whom removal is considered to be indicated, also for clarification of the diagnosis.3–5 Traditional surgical approach can be associated with substantial trauma, slower recovery, higher complication rate and decreased postoperative quality of life. To overcome these disadvantages, we report on a novel technique, transoesophageal endoscopic surgery, for treating mediastinal tumours. This technique takes advantage of the submucosal tunnelling technique popularised by natural orifice translumenal endoscopic surgery (NOTES). NOTES stimulated with the development of POEM and submucosal tunnelling endoscopic resection (STER), the submucosal or ‘third space’ endoscopy combining minimal invasive surgery and endoscopy. Here we present a rare case of schwannoma originated from the recurrent laryngeal nerve, which we removed via transoesophageal endoscopic surgery …

Objective: To estimate and comparably analyze the life-time death probability (LDP) caused by malignant tumors in different regions in 2004 and 2014. Methods: LDP was calculated by a probability additive formula and based on an abridged life table. Data on age-specific mortality was obtained from the National Cause-of- Death Surveillance Dataset in 2014 using surveillance sites in China and data on age-specific mortality was collected from the third retrospective investigation of death cause in China in 2004. Results: LDP caused by malignant tumors, lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal, and anal cancer were 19.2%, 5.6%, 2.8%, 2.8%, 1.7%, 1.3%, respectively. In addition, we calculated LDP caused by malignant tumors in three different regions of China. LDP caused by malignant tumors were 21.2%, 6.1%, 3.1%, 2.8%, 2.0%, and 1.5% in the eastern region, were 18.3%, 5.5%, 2.7%, 3.0%, 1.5%, and 1.1% in the central region, and were 16.7%, 4.6%, 2.3%, 2.8%, 1.6%, and 1.2% in the western region, respectively. Additionally, LDP caused by malignant tumors in 2004 and 2015 were compared. We found that LDPs caused by malignant tumors, lung cancer, and colorectal cancer have increased in the past decade, while LDPs caused by gastric cancer, liver cancer, and esophageal cancer have experienced a decreasing trend. Conclusions: Malignant tumors were still the main cause of death in one’s life time, giving rise to LDP. LDP caused by malignant tumours has two divisions. First, traditional upper digestive system cancers related to long-term chronic infection, such as esophageal cancer, gastric cancer, and liver cancer, which has shown a significant downward trend. Second, lung and colorectal cancers related to the environmental factors and lifestyle, which are on the rise.

BACKGROUND AND AIM Salivary characteristics are altered in gastrointestinal diseases and related to oral taste disorder. However, specific salivary biochemical characteristics and their relationships with oral taste disturbances in chronic non-atrophy gastritis (CNAG) remain uncertain. METHODS Seventy patients with CNAG and 70 subjects in healthy control group (HCG) were enrolled in our study. The levels of salivary flow rate (SFR), pH, salivary α-amylase (sAA) activity, total protein density (TPD), chloride concentration, and calcium concentration were determined before and after citric acid stimulation and compared between CNAG with and without oral taste disturbances. RESULTS Average body mass index (BMI) of CNAG (17.75 ± 2.08) was lower than that of HCG (21.96 ± 1.72, P

Background: Percutaneous coronary intervention (PCI) is an effective revascularization strategy in patients with coronary heart disease (CHD). However, recent studies had indicated that postPCI patients usually suffer from a low-quality life. Cardiac rehabilitation (CR) has been recommended by numerous guidelines in the clinic for these patients. And Baduanjin exercise can significantly benefit patients with CHD. Regrettably, the effect of Baduanjin exercise on postPCI patients is still not clear. Therefore, this systematic review and meta-analysis protocol is planned to explore the effect of Baduanjin exercise in patients with CHD who have undergone PCI. Methods: PubMed, Excerpta Medica Database, Cochrane Library, Web of Science, Wanfang Database, SINOMED, China Science and Technology Journal Database, and China National Knowledge Infrastructure will be searched for appropriate articles from respective inceptions until December 1th, 2020. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Disagreements will be resolved first by discussion and then by consulting a third author for arbitration. The primary outcome will include left ventricular ejection fraction. And the change in the scores on the Seattle Angina Questionnaire, SF-36 health survey scale, Zung Self-rating Anxiety scale and self-rating depression scale will be used as the secondary outcomes. RevMan 5.3 will be used for meta-analysis. Results: This systematic review and meta-analysis will explore whether Baduanjin exercise is an effective intervention in postPCI patients. Conclusion: This systematic review and meta-analysis will provide convincing evidence of Baduanjin exercise that specifically focuses on CR of Baduanjin exercise on CHD after PCI. Registration number: INPLASY202130065.

BACKGROUND AND AIM Traditionally, surgery is the only choice for esophageal foreign bodies (FBs) penetrating into the mediastinum or cervical para-esophageal space. Recent progress in endoscopic techniques and devices has made it possible to perform endoscopic procedures in the mediastinum. Here, we describe a novel method to remove the entirely embedded esophagus-penetrating FBs through an endoscopic approach. METHODS Patients who underwent endoscopic removal of entirely embedded esophagus-penetrating FBs were prospectively enrolled between December 2018 and June 2020. All procedures were performed by using five major steps: localization of the FB; mucosal incision; wound debridement, myotomy, and FB exposure; FB extraction; and closure of the esophageal wound. RESULTS A total of five cases of entirely embedded esophagus-penetrating FBs were evaluated, two in children and three in adults. All FBs were successfully removed and extracted using a therapeutic endoscope and a hook knife or a hybrid knife and a grasping forceps as accessories. The average procedure time was 19.0 ± 12.4 min (range 10-40 min). The major surgical procedure was avoided in all patients. The average length of hospital stay was 3.8 ± 2.5 days (range 2-8 days). There were no severe short-term adverse events after all procedures. During the 1 month and 3 months follow-up, no patient developed long-term adverse events including stenosis of the esophagus and fistula formation. CONCLUSIONS Endoscopic approach was a safe and effective way to remove entirely embedded esophagus-penetrating FBs.

Hepatocellular carcinoma (HCC) is the most common digestive system cancer. In the current study, we investigated the biological effects of Ras-related protein Rap-2a (RAP2A), a GTPase protein, in HCC tissues and cells. We found that RAP2A was upregulated in HCC tissues and cells. RAP2A knockdown could effectively inhibit the proliferation of HCC cells and weaken its apoptosis resistance. In terms of its action mechanism, RAP2A may be involved in activating the mTOR signaling pathway. Therefore, we believe that RAP2A is abnormally highly expressed in HCC tissues and promotes tumor cell proliferation and apoptosis resistance by activating the mTOR signaling pathway, and it may serve as a potential target for HCC treatment.

Background The ongoing SURPASS trial (NCT04044859) evaluates safety and efficacy of next-generation ADP-A2M4CD8 SPEAR T-cells co-expressing the CD8α co-receptor with the engineered MAGE-A4c1032T cell receptor (TCR). Methods First-in-human trial in HLA-A*02 positive patients (pts) with advanced cancers expressing MAGE-A4 antigen by immunohistochemistry. Eligible pts undergo apheresis, T-cells are isolated, transduced with a Lentiviral vector containing the MAGE-A4c1032 TCR and CD8α co receptor, and expanded. Expansion, transduction level, cellular composition and function of the manufactured product (MP) are assessed in vitro. Prior to infusion, pts receive lymphodepletion with fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 600 mg/m2/day for 3 days. Results As of 16 July 2020, 5 pts (1 with MRCLS, 2 with esophagogastric junction [EGJ] cancers, 1 with ovarian cancer, and 1 with head and neck cancer) were treated with ADP-A2M4 CD8 (range ~1 to 5.7 billion transduced cells). No DLTs or SAEs have been reported. To date, 1 pt with EGJ cancer had a partial response (PR per RECIST) and has had progression-free survival >6 months. One pt with head and neck cancer also had a PR. All other pts have had best overall response of stable disease.MP expanded by an average of 15.3 fold during manufacturing (range 5.9 to 25.6-fold). On average, 43% of T-cells in the MP expressed the TCR (range 23 to 63%). The fraction of CD4+ cells in the final MP varied (range 45 to 84%). Co-expression of the MAGE-A4 TCR and CD8α in CD4+ T-cells in the patient MP enabled CD4+ T-cells to kill tumor target cells directly in vitro. MAGE-A4 expression in tumor biopsies varied (H-score range 55 to 300). Transduced T-cells were detected in peripheral blood of all pts. IFN-gamma increased transiently in the serum of 1 pt who responded. Conclusions ADP-A2M4CD8 SPEAR T-cells have shown an acceptable safety profile and pts with EGJ cancer and head and neck cancer have demonstrated evidence of antitumor activity. Translational data and early clinical results indicate that co-expression of the CD8α co-receptor on CD4+ SPEAR T-cells may increase the potency of the product by conferring additional killing activity to the helper T-cell subset. This dose escalation trial is ongoing and updated clinical and translational data will be presented. Trial Registration NCT04044859 Ethics Approval The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines and was approved by local authorities. An independent ethics committee or institutional review board approved the clinical protocol at each participating center. All the patients provided written informed consent before study entry.

Endoscopic submucosal dissection (ESD) is a prominent minimally invasive operative technique for treating early gastrointestinal tumors but can result in postoperative bleeding. We conducted a randomized controlled trial to determine whether increasing blood pressure under hemostasis during gastric ESD to identify potential bleeding spots reduces the risk of post-ESD bleeding. In this randomized, controlled, single-blinded clinical trial, 309 patients with early gastric cancer who were admitted to a hospital to undergo ESD were recruited from March 2017 to February 2018 and were randomized into intervention and control groups. In the control group, patients underwent normal ESD. In the intervention group, we increased patients’ blood pressure to 150 mmHg for 5 min using a norepinephrine pump (0.05 μg/kg/min initial dose) after the specimen was extracted during the ESD operation to identify and coagulate potential bleeding spots with hot biopsy forceps. Our primary outcome was the incidence of postoperative bleeding over 60-day follow-up. The incidence of post-ESD bleeding was lower in the intervention group (1.3%, 2/151) than in the control group (10.1%, 16/158, p = 0.01). Deeper tumor invasion was associated with a higher risk of post-ESD bleeding (5.3% in mucosal/submucosal layer 1 group vs. 12.5% in submucosal layer 2/muscularis propria group, p

Background Cumulative mortality rate and cumulative mortality risk are two commonly used indicators to measure the impact and severity of diseases. However, they are calculated during a defined life span and assume the subject does not die from other causes. This study aims to use a new indicator, lifetime death probability (LDP), to estimate the lifetime death probabilities for the top five leading causes of death in China and explore the regional differences and trends over time. Methods LDPs were calculated using a probability additive formula and abridged life tables. Results In 2014, LDPs for heart disease, cerebrovascular disease, malignancy, respiratory disease, and injury and poisoning were 24.4, 23.7, 19.2, 15.5, and 5.3%, respectively. The LDPs for heart disease and malignancy increased by 7.3 and 0.5%, respectively, compared to those from 2004 to 2005. In contrast, the LDPs for cerebrovascular and respiratory disease decreased by 1.0 and 3.9%, respectively, compared to those in 2004–2005. Across the eastern, central and western regions, malignancy had the highest LDP in the eastern region, cerebrovascular and heart diseases in the central region, and respiratory diseases, and injury and poisoning in the western region. Conclusions LDP is an effective indicator for comparing health outcomes and can be applied for future disease surveillance. Heart disease and malignancy were the two most common causes of death in China, but with regional differences. There is a need to implement targeted measures to prevent chronic diseases in different regions.

BACKGROUND Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-s1 (P

Achalasia is characterized by impaired swallowing due to lower esophageal sphincter (LES) dysfunction and an increased risk of esophageal carcinoma. Aflatoxin is a known carcinogen. Esophageal retention is relieved by per oral endoscopic myotomy (POEM), which lowers the esophageal cancer risk. The present study determined whether aflatoxin is involved in the pathogenesis of achalasia or esophageal cancer. A total of 75 patients with achalasia were prospectively enrolled from a tertiary center. Aflatoxin levels in their esophageal contents were measured using ELISA, and esophageal mucosal specimens were immunohistochemically evaluated for Ki67 and p53 expression prior to and 3 months after POEM. The effect of aflatoxin on esophageal contractility was assessed using murine specimens. Aflatoxin was detected in 67 patients before POEM and only 2 patients after POEM. The number of Ki67- and p53-immunopositive cells in the esophageal mucosa significantly decreased after POEM: [Ki67: 27.8% (95% confidence interval (CI), 25.98–29.70) vs. 20.7% (95% CI, 19.78–24.03), P=0.04 and p53: 2.14% (95% CI, 1.85–2.41) vs. 1.45% (95% CI, 1.22–1.68), P=0.03]. In vitro experiments revealed that 500 ng/ml aflatoxin significantly increased the amplitude (P0.05). Aflatoxin was found in most patients with achalasia and was eliminated following POEM. Reduced Ki67 and p53 expression after POEM indicated a decreased risk of carcinogenesis. Aflatoxin accumulation increased LES contractility via cholinergic signaling. Therefore, aflatoxin may maintain achalasia symptoms and increase esophageal cancer risk.

Whether GDF11 is a systemic factor from young animals’circulation that mediates the rejuvenation process in old animals during heterochronic parabiosis has been debated. We carried out transcriptomic analyses of young versus old monkey and human blood samples demonstrating negative correlations between GDF11 expression and old age, which is further confirmed by quantitative RT-PCR of GDF11 mRNA from more than 400 young and old human blood samples. Reduced GDF11 expression is also correlated with age-dependent cognitive decline. Tail vein injection of recombinant mature GDF11 into aged mice led to increased numbers of cerebral blood vessels and cerebral blood flow, enhanced neurogenesis and spatial learning. Objective and systemic transcriptomic analyses of GDF11-treated brains revealed and subsequently confirmed through biological assays, that rGDF11 regulated angiogenesis, neurogenesis, cell cycle, energy metabolism, clearance of senescent cells, as well as increased telomere length and GDF11 gene expression in neural stem cells via the Smad2/3-PI3K-AKT-mTOR pathway.

Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. Clinical Trials.gov identifier: NCT02804100.

Background and Aims The management of subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors can be challenging and traditionally requires a surgical resection that is not only invasive but may carry a significant risk of morbidity and mortality. We aimed to assess the feasibility, safety, and efficacy of a novel endoscopic technique termed submucosal tunnel endoscopic resection for extraluminal tumors (STER-ET). Methods We prospectively enrolled patients who underwent STER-ET for GI subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors located at the level of cardia or the proximal part of the lesser curvature of the stomach seen on cross-sectional imaging between January 2016 and March 2017. Results Eight patients underwent STER-ET. The mean (± standard deviation) tumor size was 2.8 ± 0.6 cm and 2.3 ± 0.8 cm in longest and shortest dimension, respectively. The average procedure time was 67 ± 4.4 minutes. The rates of curative en bloc resection and en bloc retrieval was 100% and 87.5%, respectively. On final histology, 6 tumors were GI stromal tumors, 1 was a schwannoma, and 1 was a foregut cyst. Five patients had capnoperitoneum during the procedure and required abdominal decompression. One patient had a small mucosotomy successfully treated with a hemostatic clip. There were no major adverse events or deaths. The median length of hospital stay was 3 days. There was no residual tumor on surveillance imaging after a mean follow-up period of 10.0 ± 2.1 months. Conclusions STER-ET is a novel technique that appears to be safe and effective in achieving a curative resection for GI subepithelial tumors with a predominantly extraluminal growth pattern or extraluminal tumors in a selected group of patients. However, larger studies are required to validate our finding.

Background In this study, we developed and validated a nomogram to predict lymph node metastasis before surgery in patients with intrahepatic cholangiocarcinoma (ICC). Methods Using the data from January 2006 to January 2015, we enrolled a total of 218 eligible patients with clinicopathologically confirmed ICC as a primary cohort to develop the nomogram. After various variables before surgery were analyzed by multivariable logistic regression, we combined the preoperative carbohydrate antigen 19-9, primary site of tumor, lymphonodus size on computed tomography imaging, tumor growth pattern, and (if applicable) histologic grade to make two different predictive nomograms. Then, the results were validated in 62 consecutive ICC patients from February 2015 to December 2016. We also compared the performance of the different nomograms via calibration, discrimination, and clinical use. Results The nomogram displayed fine discrimination (the concordance index, 0.761) and fine calibration in the primary cohort. When applied to the validation cohort, the nomogram also showed fine discrimination (concordance index, 0.794) and fine calibration. After adding the histologic grade to the nomogram, the integrated discrimination for predictive performance improved significantly. Finally, the clinical usefulness of predictive nomogram was proven via the decision curve analysis. Conclusions The proposed nomograms can be selectively used to achieve more accurate lymph node metastasis predictions before surgery in patients with ICC, and this information can help with clinical management.

Background: A randomised phase 2 trial of trimodality with or without induction chemotherapy (IC) in oesophageal cancer (EC) patients showed no advantage in overall survival (OS) or pathologic complete response rate. To identify subsets that might benefit from IC, a secondary analysis was done. Methods: The trial had accrued 126 patients (NCT 00525915). Recursive partitioning and proportional hazards regression with interactions were performed. Results: The median follow-up of surviving patients was 6.7 years and the median OS duration was 3.8 years (95% confidence interval (CI), 2.6-5.8 years). OS was associated with tumour length (P=0.03), cT (P=0.02), cN (P=0.04), clinical stage (P=0.01), and tumour grade (P

Background and Aims This article systemically describes the landscape of peroral endoscopic myotomy (POEM)-related adverse events (AEs) and compares the different grading systems; and establishes and validates a combined risk factor model and a simplified risk-scoring system to predict POEM-related major AEs. Methods A total of 3135 patients with achalasia treated with POEM were included and the AEs were systemically described and graded. A predictive model and risk-scoring system was developed using logistic regression and then internally validated using bootstrapping approaches. Results A total of 258 out of 3135 patients, accounting for 8.23% of the total patients, presented with 297 AEs. According to Clavien-Dindo grading, 175 (67.83%), 23 (8.91%), 56 (21.71%), 4 (1.55%), and 0 (0.00%) patients were graded as grade I–V, respectively. By American Society of Gastrointestinal Endoscopy lexicon, 175 (67.83%) patients were classified with mild AE, 66 (25.58%) were classified with moderate AE, and 17 (6.59%) were classified with severe AE, respectively. Sixty-eight (2.17%) patients were classified with major AE. Air insufflation, selective myotomy, mucosal injury, and long operation time were selected into the predictive model with an area under the curve of 0.795. They were assigned with scores of 18, 5, 3, and 5 in the risk-scoring system, respectively. By applying the risk scoring system, patients with higher scores had higher rates of major AEs. The model showed little evidence for overfitting and was well-calibrated. Conclusions Based on a systematic landscape analysis, POEM is a safe procedure with low rates of severe AEs. Our prediction model and risk-scoring system demonstrated good performance in predicting major AEs.

Outcomes of patients with advanced gastric or gastroesophageal junction adenocarcinoma (GEAC) remain poor despite recent advances. The standard of care in the management of this disease had not changed much over the past decade. In the first line, a platinum containing doublet/triplet is used, while in

Background: Predictive biomarkers or signature(s) for oesophageal cancer (OC) patients undergoing preoperative therapy could help administration of effective therapy, avoidance of ineffective ones, and establishment new strategies. Since the hedgehog pathway is often upregulated in OC, we examined its transcriptional factor, Gli-1, which confers therapy resistance, we wanted to assess Gli-1 as a predictive biomarker for chemoradiation response and validate it. Methods: Untreated OC tissues from patients who underwent chemoradiation and surgery were assessed for nuclear Gli-1 by immunohistochemistry and labelling indices (LIs) were correlated with pathologic complete response (pathCR) or

// Elena Elimova 1, 8 , Rebecca S. Slack 2 , Hsiang-Chun Chen 2 , Venkatram Planjery 1 , Hironori Shiozaki 1 , Yusuke Shimodaira 1 , Nick Charalampakis 1 , Quan Lin 1 , Kazuto Harada 1 , Roopma Wadhwa 1 , Jeannelyn S. Estrella 3 , Dilsa Mizrak Kaya 1 , Tara Sagebiel 4 , Jeffrey H. Lee 5 , Brian Weston 5 , Manoop Bhutani 5 , Mariela Blum Murphy 1 , Aurelio Matamoros 4 , Bruce Minsky 6 , Prajnan Das 6 , Paul F. Mansfield 7 , Brian D. Badgwell 7 and Jaffer A. Ajani 1 1 Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 2 Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 3 Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 4 Department of Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 5 Department of Gastroenterology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 6 Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 7 Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 8 Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada Correspondence to: Jaffer A. Ajani, email: jajani@mdanderson.org Keywords: localized gastric adenocarcinoma, cancer surveillance, cost-effectiveness analysis, imaging studies, esophagogastroduodenoscopy Received: December 02, 2016 Accepted: June 02, 2017 Published: July 13, 2017 ABSTRACT Purpose: After therapy of localized gastric adenocarcinoma (GAC) patients, the costs of surveillance, relapse patterns, and possibility of salvage are unknown. Materials and Methods: We identified 246 patients, who after having a negative peritoneal staging, received therapy (any therapy which included surgery) and were surveyed (every 3–6 months in the first 3 years, then yearly; ~10 CTs and ~7 endoscopies per patient). We used the 2016 Medicare dollars reimbursed as the “costs” for surveillance. Results: Common features were: Caucasians (57%), men (60%), poorly differentiated histology (76%), preoperative chemotherapy (74%), preoperative chemoradiation (59%), and had surgery (100%). At a median follow-up of 3.7 years (range, 0.1 to 18.3), the median overall survival (OS) was 9.2 years (95% CI, 6.0 to 11.2). Tumor grade ( p = 0.02), p/yp stage ( p < 0.001), % residual GAC ( p = 0.05), the R status ( p = 0.01), total gastrectomy ( p = 0.001), and relapse type ( p = 0.02) were associated with OS. Relapse occurred in 79 (32%) patients (only 8% were local-regional) and 90% occurred within 36 months of surgery. P/yp stage ( p < 0.001) and total gastrectomy ( p = 0.01) were independent prognosticators for OS in the multivariate analysis. Only 1 relapsed patient had successful salvage therapy. The estimated reimbursement for imaging studies and endoscopies was $1,761,221.91 (marked underestimation of actual costs). Conclusions: The median OS of localized GAC patients was excellent with infrequent local-regional relapses. Rigorous surveillance had a low yield and high “costs”. Our data suggest that less frequent surveillance intervals and limiting expensive investigations to symptomatic patients may be warranted.

Hypoxic‑ischemia stress causes severe brain injury, leading to death and disability worldwide. Although it has been reported that endoplasmic reticulum (ER) stress is an essential step in the progression of hypoxia or ischemia‑induced brain injury, the underlying molecular mechanisms are and have not yet been fully elucidated. Accumulating evidence has indicated that both nitric oxide (NO) and hydrogen sulfide (H2S) play an important role in the development of cerebral ischemic injury. In the present study, we aimed to investigate the effect of the association between NO signaling and the cystathionine β‑synthase (CBS)/H2S system on ER stress in a cell model of cerebral hypoxia‑ischemia injury. We found that oxygen‑glucose deprivation (OGD) markedly increased the NO level and neuronal NO synthase (nNOS) activity. 3‑Bromo‑7‑nitroindazole (3‑Br‑7‑NI), a relatively selective nNOS inhibitor, abolished the OGD‑induced inhibition of cell viability and the increased expression of ER stress‑related proteins, including glucose‑regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and cleaved caspase‑12 in PC12 cells, indicating the contribution of excessive nNOS/NO signaling to OGD‑induced ER stress. Furthermore, we found that OGD increased the phosphorylated AMP‑activated protein kinase (p‑AMPK)/AMPK ratio, and the AMPK activator, 5‑aminoimidazole‑4‑carboxamide‑1‑β‑D‑ribofuranoside (AICAR), attenuated the effects on OGD‑induced ER stress, suggesting that OGD‑induced NO overproduction results in AMPK activation in PC12 cells. We also found that OGD induced the downregulation of the CBS/H2S system, as indicated by the decreased H2S level in the culture supernatant and CBS activity in PC12 cells. In addition, we found that treatment with NaHS (a H2S donor) or S‑adenosyl‑L‑methionine (SAM, a CBS agonist) mitigated OGD‑induced ER stress, as well as the NO level, nNOS activity and AMPK phosphorylation in PC12 cells. On the whole, these results suggest that the inhibition of the CBS/H2S system, which facilitated excessive nNOS/NO/AMPK activation, contributes to OGD‑induced ER stress.

Endoscopic full-thickness resection (EFTR) is a minimally invasive method for en bloc resection of gastrointestinal (GI) lesions originating from the muscularis propria layer. Successful closure of the wall defect is a critical step.The aim of this study was to evaluate the feasibility and efficacy of a novel and simplified endoscopic grasp-and-loop (GAL) closure method using an endo-loop assisted with grasping forceps for defect closure.From January 2015 to March 2016, 13 patients with submucosal tumors (SMTs) originating from the muscularis propria (MP) layer underwent EFTR and were enrolled in this study. After successful tumor resection, an endo-loop was anchored onto the circumferential margin of the gastric defect with grasping forceps assistance and tightened gently. Patient characteristics, tumor size, en bloc resection, and postoperative complications were evaluated.Of the 13 lesions in the stomach, two were located in the greater curvature of the mid-upper body, 11 were located in the fundus. The endoscopic GAL closure method was successfully performed after EFTR in all the 13 patients without laparoscopic assistance. The mean procedure time was 43.5 min (range 20-80 min), while the GAL closure procedure took a mean of 9.4 min (range 3-18 min). The mean resected lesion size was 1.5 cm (range 0.5-3.5 cm). Pathological diagnoses of these lesions were 11 gastrointestinal stromal tumors (GISTs) and two leiomyomas. No major adverse events occurred during or after the procedure. All the patients were discharged after a mean time of 2.4 days (range 1-4 days). No residual lesion or tumor recurrence was found during the follow-up period (median, 5 months; range, 1-15 months).The endoscopic GAL closure method is feasible, effective, and safe for closing the gastric defect after EFTR in patients.

The hypertrophic scar is a medical difficulty of humans, which has caused great pain to patients. Here, we investigated the inhibitory effect of miR-29b on scar formation. The scalded model was established in mice and miR-29b mimics or a negative control was subcutaneously injected into the injury skin. Then various molecular biological experiments were performed to assess the effect of miR-29b on scar formation. According to our present study, first, the results demonstrated that miR-29b was down-regulated in thermal injury tissue and miR-29b treatment could promote wound healing, inhibit scar formation, and alleviate histopathological morphologic alteration in scald tissues. Additionally, miR-29b treatment suppressed collagen deposition and fibrotic gene expression in scar tissues. Finally, we found that miR-29b treatment inhibited the TGF-β1/Smad/CTGF signaling pathway. Taken together, our data suggest that miR-29b treatment has an inhibitory effect against scar formation via inhibition of the TGF-β1/Smad/CTGF signaling pathway and may provide a potential molecular basis for future treatments for hypertrophic scars.

Scarring is the inevitable consequence of wound repair, which may cause significant physical and mental pain to patients when excessive. Bone morphogenetic protein-7 (BMP-7) has been proved to inhibit TGF-β-induced fibrosis in various tissues including dermal papilla cells. However, the effect of BMP-7 on hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, has not been determined. To overcome this problem, the present study established a mouse model of thermal injury to investigate the inhibitory effects of BMP-7 on scar formation. The histological analysis of scar tissues was performed by H&E and Masson's trichrome staining. Western blot assay was used to determine the level changes of related proteins and TUNEL assay was performed to assess the apoptosis of scar tissues. The results demonstrated that BMP-7 promoted wound healing and inhibited scar formation when compared with untreated mice. Collagen deposition and the expression of fibrotic proteins were suppressed in the scar tissues of mice treated with BMP-7. In addition, BMP-7 induced fibroblast apoptosis in scar tissues. Furthermore, activation of the BMP-7/Smad1/5/8 signaling pathway may have been involved in the inhibitory effects of BMP-7 on scar formation. In conclusion, the results of the present study indicate that BMP-7 may inhibit excessive scar formation via activation of the BMP-7/Smad1/5/8 signaling pathway. The results present a potential alternative therapeutic strategy for the treatment of hypertrophic scarring.

Background BRAF mutations occur in 2–4% non-small cell lung cancer (NSCLC) patients and can be categorized into three functional classes based on signaling mechanism and kinase activity: RAS-independent kinase-activating V600 monomers (class 1), RAS-independent kinase-activating dimers (class 2) and RAS-dependent kinase-inactivating heterodimers (class 3). The association between functional classes and clinical features in Chinese NSCLC patients remains unexplored. Our multi-center study aimed to survey the BRAF mutation rate and analyze the associated clinical features in this population. Methods Capture-based sequencing data of either plasma or tissue samples obtained from 8405 Chinese stage I–IV NSCLC patients were retrospectively analyzed. Results BRAF mutations were detected in 238 patients, revealing an overall mutation rate of 2.8%. Among them, 32%, 21% and 13% had BRAF mutant class 1, 2 and 3 respectively. The remaining 34% had other BRAF mutations. V600 (32%) and G469 (13%) were the two most predominant BRAF mutations. Patients with class 2 and 3 mutations were more likely to have concurrent KRAS mutations (P = 0.001). Collectively, BRAF mutations, including non-class 1–3 mutations, were more likely to occur in males (P

Background: Unexplained common bile duct (CBD) dilatation may be caused by many etiologies, such as periampullary tumors, a pancreatic neoplasm, choledocholithiasis or an inflammatory stenosis. The aim of this study is to evaluate the diagnostic yield of endoscopic ultrasonography (EUS) in patients with unexplained CBD dilatation, in combination with tumor markers, liver chemistry, symptoms, surgical history and whether there is dilatation of the pancreatic duct (PD). Methods: From January 2016 to July 2017, 115 patients were referred for EUS in our center for CBD dilatation of an unknown etiology. A treatment plan is made based on the EUS result combined with the other clinical information. The final diagnosis is determined by surgical histology or follow-up of at least 3 months. Results: The sensitivity, specificity and accuracy of EUS for patients with choledocholithiasis were 100.0% (10/10), 100.0% (105/105) and 100.0% (115/115), respectively. The sensitivity, specificity and accuracy of EUS for patients with periampullary tumor were 86.5% (32/37), 89.7% (70/78) and 88.7% (102/115), respectively. The sensitivity, specificity and accuracy of EUS for patients with inflammatory stenosis were 88.2% (60/68), 89.4% (42/47) and 88.7% (102/115), respectively. The overall accuracy of EUS for diagnosing an undetermined etiology for CBD dilatation was 88.7% (102/115) and was higher than the accuracy of ultrasound (US) (64.1%), computed tomography (CT) (66.2%), magnetic resonance imaging (MRI) (67.0%) or PET-CT (66.0%). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS combined with tumor markers for patients with malignant dilatation of CBD were 91.9% (34/37), 97.4% (76/78), 94.4% (34/36), 96.2% (76/79) and 95.7% (110/115), respectively. PD dilation (P=0.026) and weight loss (P=0.035) had significant predictive values of malignancy. Conclusions: EUS is an effective diagnostic tool for determining the etiology of a CBD dilatation, and offers meaningful information for guiding a treatment plan. EUS used in conjunction with tumor markers has high yield in differentiating benign and malignant CBD dilatation. More attention should be paid to patients with PD dilation or weight loss to prevent misdiagnosis of malignant CBD dilation.

Adenoid cystic carcinoma (ACC) is an uncommon salivary gland malignancy with a poor long-term prognosis. Clinical reports show the high rates of local recurrences and distant metastases. This study aimed to investigate the expression of MIF, Beclin1, and light-chain 3 (LC3) in salivary adenoid cystic carcinoma (SACC). Tissue specimens were obtained from 48 salivary glands adenoid cystic carcinoma (SACC) patients and 15 oral squamous cell carcinoma (OSCC) patients. Immunohistochemical staining was performed to estimate the level of LC3, Beclin1, and MIF. All SACC patients were followed up. The Kaplan–Meier method was used to compare the prognosis of patients after treatment. The 3-year, 5 year-, and 10 year-survival rates of the SACC patients were 83.9%, 69.9%, and 46.6%, respectively. MIF, LC3, and Beclin1 in SACC were all obviously over-expressed. MIF showed an increased tendency in cases with advanced TNM stages, and at the same time, there was an inversely proportional relationship between MIF and LC3, Beclin1. The long-term survival of SACC patients is poor. MIF might be a risk factor for SACC patients, whereas, LC3 and Beclin1 might be an effective strategy for treatment of SACC.

Peroral endoscopic myotomy (POEM) is a safe and effective approach for achalasia. However, the safety, feasibility, perioperative and long-term efficacy in treating geriatric patients has not been well evaluated. Data of 2367 patients diagnosed with achalasia and treated with POEM in the Endoscopy Center, Zhongshan Hospital, Fudan University from August 2010 to December 2017 were retrospectively reviewed. Last follow-up was in December 2018. Propensity score matching based on baseline characteristics was used to adjust for confounding. With a caliper of 0.01 in propensity scoring, 139 patients aged ≥ 65 years were matched at a 1:2 ratio with 275 patients aged

Peroral endoscopic myotomy (POEM) has shown excellent results for the treatment of achalasia in adults, but studies for children are limited. The study was aimed to analyze outcomes of peroral endoscopic myotomy (POEM) in children and compared with those in adults in a large multi-center study.Records of consecutive patients with achalasia who underwent POEM at three tertiary centers were reviewed. A total of 130 children were included in this study. The primary outcomes of perioperative outcomes and clinical follow-up data were analyzed.One child (0.8%) experienced technical failure. Five children (3.8%) had major adverse events, including one with pneumothorax requiring drainage, two with delayed mucosa barrier failure, one with readmission, and one with vital-sign instability. Both post-POEM Eckardt score and median LES pressure were significantly lower than their pre-POEM reference values in children (0.7 vs 7.4; 7.0 vs 27.1 mmHg; both P 0.001). During a median follow-up time of 40 months, clinical reflux rate was 27.0% and clinical failure rates at 1, 3, and 5 years were 1.8%, 3.5%, and 4.4% for children. The technical failure, major adverse events, and postoperative clinical reflux were comparable between children and adults (all P 0.05). Kaplan-Meier analysis showed that the risk of clinical failure was lower in children than adults (log-rank test, hazard ratio = 0.37, 95% confidence interval 0.15-0.91, P = 0.023).POEM can be safely performed in children with achalasia, and produce a better clinical response during long-term follow-up compared with that in adults.

We aimed to establish a predictive model and develop a simple risk-scoring system (Zhongshan POEM Score) to help clinicians to characterize high-risk patients for clinical failure after peroral endoscopic myotomy (POEM).A total of 1538 patients with achalasia treated with POEM with available follow-up data were included in this study and were randomly classified to the training cohort (n = 769) or internal validation cohort (n = 769). A risk-scoring system was developed using multivariate Cox regression analysis in the training cohort. The system was then internally validated by survival analysis in the validation cohort.During a median follow-up time of 42 months, 109 patients had clinical failure. In the training stage, 3 risk factors for clinical failure were weighted with point values: previous treatment (2 points), intraprocedural mucosal injury (2 points for type I and 6 points for type II), and clinical reflux (3 points). The patients were categorized into low-risk and high-risk groups. In the validation stage, Kaplan-Meier curves differed significantly between the 2 groups. Patients in the high-risk group had a significantly higher risk of clinical failure than those in the low-risk group (hazard ratio, 3.99; 95% confidence interval, 2.31-6.91; P .001). Satisfactory discrimination and calibration were shown.This risk-scoring system demonstrated good performance in predicting clinical failure in patients who underwent POEM.

Rationale: Gastric duplication cyst is an anomaly that primarily occurs to children. Apart from the conventional use of surgical resection, few cases using endoscopic treatment have been reported. Patient concerns: A 5-month-old female infant was hospitalized with the chief complaint of gastric cyst. No significant abnormalities were identified by physical examination. Interventions: Endoscopic submucosal dissection (ESD) was performed successfully for the infant and the duration was less than 20 minutes. The patient showed no postoperative complications. Outcomes: At 4 months during the follow-up, upper endoscopy revealed a small scar at the previous site of the lesion and no recurrence. Lessons: According to the results of PUBMED review, she was the youngest with gastric duplication cyst removed with ESD. The less invasive ESD should be considered an effective therapeutic option to remove gastric duplication cyst in children.