Surgical strategy and outcome in patients with bilateral proliferative diabetic retinopathy.

OBJECTIVES: To investigate the current surgery strategies for bilateral proliferative diabetic retinopathy (PDR), as well as the surgical outcomes of patients with bilateral PDR who underwent pars plana vitrectomy (PPV). MATERIALS: Patients undergoing bilateral vitrectomy for PDR from January 2019 to December 2020 at The Eye Hospital of Wenzhou Medical University were enrolled. Clinical data were collected from the electronic medical records. Factors associated with the time interval between the surgeries on two eyes and postoperative visual outcomes were analyzed. RESULTS: In total, 152 patients with bilateral PDR who underwent bilateral PPV were included in this analysis. Mean age was 53.7 ± 11.4 years. Compared with second-surgery eyes, 60.5% of first-surgery eyes had worse preoperative best-corrected visual acuity (BCVA). The overall PPV time (median, quartile range) between first and second surgeries eye was 1.40 (0.70, 3.15) months. Multivariate analysis showed that the preoperative BCVA of the second-surgery eye had a significant effect on the inter-surgery time interval (P = 0.048). First-surgery eyes had greater vision improvement than second-surgery eyes (Difference of the logarithm of the minimum angle of resolution [LogMAR] BCVA: - 1.00 [- 1.48, - 0.12] versus 0.00 [- 1.30, 0.00], respectively, P < 0.001), especially when eyes with poorer BCVA underwent PPV first (- 1.15 [- 1.87, - 0.54] versus 0.00 [- 0.70, 0.00], respectively, P < 0.001). CONCLUSIONS: Visual acuity is a significant factor that influences surgical strategies, including both surgery order and interval, for patients with bilateral PDR. The eyes operated upon first show more vision improvement due to prompt surgery.

Comparison of operation time, efficacy and safety between through-the-scope stent and over-the-while stent in malignant central airway obstruction: a multi-center randomized control trial.

Background: Self-expandable metallic (SEM) airway stents are an important approach to treating malignant central airway obstruction (CAO). Standard over-the-while (OTW) stent needs the guidance of a guide-wire. It should be implanted under flouroscopy or the guidance of bronchoscope visualization. In this study, we evaluated the operation time and safety between OTW stent and a novel through-the-scope (TTS) SEM airway stent. Methods: In this multi-center, randomized, parallel-group superiority study, malignant CAO patients were enrolled randomly assigned (2:1) to the TTS stent implantation group (TTS group) or the standard OTW stent group (OTW group) in six sites across China. The entire process of all surgical procedures was recorded by video. Primary endpoint was the operation time of the airway stent implantation and secondary endpoint was the success rate of the stent implantation as well as its efficacy and safety. Results: From May 15, 2017, to December 30, 2018, 148 patients were enrolled from the six sites. We analyzed 134 patients (including 91 patients from the TTS group and 43 patients from the OTW group) according to the per-protocol set. There were no significant differences in the ages, genders, underlying diseases, and stenosis sites between the two groups. The operation time in the TTS group was significantly shorter than that in the OTW group (104±68 vs. 252±111 seconds, P<0.001). Compared to the OTW group, the efficacy of stent implantation (97.80% vs. 90.70%, P=0.093) and rate of first-time successful stent implantation (78.02% vs. 74.42%, P=0.668) were higher in the TTS group, but did not reach statistically significance. The rates of granulation (28.57% vs. 41.86%, P=0.128) and restenosis (15.38% vs. 30.23%, P=0.064) in the TTS group were slightly lower as compared with the OTW group without achieving statistical significance. Conclusions: The TTS stent implantation procedure time was significantly shorter than that of the OTW airway stent with similar efficacy and complications, which might reduce the risk and flexibility of stent implantation. Trial Registration: Chinese Clinical Trial Registry ChiCTR-IOR-17011431.

Pars plana vitrectomy relieves the depression in patients with symptomatic vitreous floaters.

AIM: To investigate the depressive state among the patients with symptomatic vitreous floaters (SVF), as well as its change after SVF removal via vitrectomy surgery. METHODS: Twenty-eight eyes of 28 patients who underwent 27-gauge pars plana vitrectomy (PPV) for SVF were included. Thirty-nine eyes of 39 age- and gender-matched healthy volunteers without SVF were also recruited as a healthy control. Center for Epidemiologic Studies Depression (CES-D) was used to assess volunteers and patients' depression (before and 1wk after PPV). RESULTS: The CES-D score was 18.3±8.6 for patients, and was 12.4±6.0 for healthy control (P=0.003). Patients were significantly more likely to be in a depressive state (53.6%, defined as CES-D score ≥16) than the healthy control (20.5%, P=0.005). For patients with SVF, the CES-D score was negatively correlated with their age (r s=-0.42, P=0.025). After PPV, both the CES-D score (11.9±5.4 vs 18.3±8.6, P<0.001) and proportion of depressive state (18.5% vs 53.6%, P=0.005) were significantly decreased. CONCLUSION: This study suggests that symptoms of vitreous floaters have an apparently negative impact on patients' psychological state. The PPV can effectively relieve the depressive state for patients with SVF.

Low-dose apatinib monotherapy in advanced chemotherapy-refractory small cell lung cancer: a case series and literature review.

The therapeutic regimen for small cell lung cancer (SCLC) has changed little in the past several decades. Apatinib is a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib has demonstrated efficacy against advanced gastric cancer and breast cancer, and recent studies have also reported its successful use in non-SCLC; however, its efficacy in SCLC remains unclear. In this study, we used apatinib as salvage therapy for chemotherapy-refractory SCLC. Five male patients with advanced SCLC were administered oral apatinib (250 mg/day) as 2nd- to 4th-line treatment. One patient showed a partial response to apatinib, one showed stable disease, and three patients showed progressive disease. The progression-free survival durations in the patients with stable disease and partial response were 1.5 and 3 months, respectively. Only three patients showed adverse effects, including mild hypertension, vomiting, and hand-foot syndrome, respectively, all of which were manageable. Apatinib might thus be a salvage option in patients with advanced SCLC after chemotherapy.

A Pilot Study of a Novel through-the-Scope Self-Expandable Metallic Airway Stents Delivery System in Malignant Central Airway Obstruction.

Objective: Self-expandable metallic (SEM) airway stents are an important approach to malignant central airway obstruction (CAO). SEM airway stent insertions are usually performed under fluoroscopic guidance over a guide wire placed through a flexible bronchoscope often resulting in a longer procedure time and exposure to radiation. In this pilot study, we designed a novel delivery system of the through-the-scope (TTS) SEM airway stent insertion and observed its feasibility. Methods: From Jan 2015 to Sept 2016, 25 consecutive patients with inoperable malignant CAO were enrolled requiring airway stent implantation. All patients were followed up to death or at least 6 months. Results: 36 TTS stents were inserted into 25 patients using a flexible bronchoscope under general anesthesia or local anesthesia. All stents were successfully deployed directly through the working channel (2.8 mm diameter) of the flexible bronchoscope in 91.7% (33/36) of the subjects. The mMRC score and stenosis grade improved significantly after stent implantation. The common stent-related complications were secretion retention (25%, 9/36), development of granulation tissue (13.9%, 5/36), tumor in-growth (13.9%, 5/36), and hemoptysis (8.3%, 3/36). The 6-month overall survival (OS) was 44% (11/25). Conclusion: The novel TTS stent release system was an effective and safe approach in malignant central airway obstruction.

Low dosage of apatinib monotherapy as rescue treatment in advanced lung squamous cell carcinoma.

PURPOSE: Platinum-based doublet chemotherapy and radiotherapy are the standard treatment option in advanced squamous cell carcinoma patients. However, few agents could be selected for subsequent post-second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase, apatinib had been proved in advanced gastric cancer. Here, we showed its efficacy and safety in lung squamous cell carcinoma. METHODS: In this retrospective study, 13 advanced lung squamous cell carcinoma patients were enrolled. They received doublet chemotherapy or docetaxel as the first-line treatment. After disease progressed, all patients were administrated apatinib monotherapy (250-425 mg/day) for second-line or fourth-line therapy. RESULTS: After apatinib monotherapy, two patients achieved partial response, four patients achieved stable disease, and seven patients achieved progression disease. The medium PFS was 3.1 months. The median OS had not yet been reached. The objective remission rate was 15.4% (2/13). The total disease control rate was 46.2% (6/13). The main advert effects were vomiting and hypertension. CONCLUSION: Apatinib might be an option as rescue treatment in advanced lung squamous cell carcinoma.

Endobronchial ultrasound-guided transbronchial needle aspiration can improve the diagnostic accuracy of positron emission tomography/computed tomography in hilar and/or mediastinal lymphadenopathy.

CONTEXT: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and positron emission tomography/computed tomography (PET/CT) are the two most extensively used methods for the diagnosis and staging of lung cancer. AIMS: The present study was designed to compare the diagnostic performance of EBUS-TBNA with that of PET/CT in patients with hilar and/or mediastinal lymphadenopathy. SETTINGS AND DESIGN: We compared the accuracy of EBUS-TBNA with that of PET/CT in the diagnosis of hilar and/or mediastinal lymphadenopathy and evaluated the diagnostic utility of EBUS-TBNA in patients with PET/CT false-positive and false-negative findings. METHODS: This study retrospectively analyzed 85 patients with hilar and/or mediastinal lymphadenopathy who underwent EBUS-TBNA and PET/CT between January 2014 and December 2017. The accuracy of EBUS-TBNA histopathology and cytopathology was evaluated and compared with PET/CT scan findings. RESULTS: The diagnostic accuracy of EBUS-TBNA combined with PET/CT was significantly higher than that of the single diagnostic method (P < 0.001). Among PET/CT-negative lymph nodes, 4 of 9 (44.4%) malignant lymph nodes were identified by EBUS-TBNA. Among PET/CT-positive lymph nodes, 43 of 47 (91.5%) benign lymph nodes were diagnosed by EBUS-TBNA. CONCLUSIONS: EBUS-TBNA combined with PET/CT could effectively reduce false-positive and false-negative rates in the diagnosis of hilar and mediastinal lymphadenopathy, which might provide accurate staging, determine optimum therapeutic strategy and improve survival in patients with lung cancer.

The association of neuron-derived orphan receptor 1 with pulmonary vascular remodeling in COPD patients.

INTRODUCTION: Chronic hypoxia-induced pulmonary vascular remodeling is a feature of chronic obstructive pulmonary disease (COPD). Our previous reports indicate that neuron-derived orphan receptor 1 (NOR1) promoted pulmonary smooth muscle cell proliferation in vitro. But it remains unclear whether NOR1 participated into hypoxia-induced pulmonary vascular remodeling in COPD patients. PATIENTS AND METHODS: For this study, we collected peripheral lung tissues of 26 male COPD patients with or without hypoxemia. We detected the pulmonary vascular remodeling in all the peripheral lung tissues. Primary human pulmonary arterial smooth muscle cells were also cultured in vitro and stimulated with hypoxia or normoxia. Cell proliferation and protein levels were detected. RESULTS: COPD patients with hypoxemia showed significantly enlarged pulmonary vessels wall thickness and increased protein levels of HIF-1α, smooth muscle actin, cyclin D1, and NOR1 when compared with those in normoxic patients. Moreover, hypoxia induced human pulmonary arterial smooth muscle cell proliferation and NOR1 overexpression in vitro. The plasmid-based NOR1 gene overexpression markedly promoted DNA synthesis and proliferation in hypoxia or normoxic cells. Human NOR1 gene-specific siRNA intensively suppressed DNA synthesis and proliferation. Transfection of NOR1 overexpression plasmid raised cyclin D1 protein levels, which could be significant inhibited by NOR1-specific siRNA or a CDK4/6 inhibitor PD0332991. CONCLUSION: We concluded that NOR1 upregulation is associated with hypoxia-induced pulmonary vascular remodeling in COPD via promoting human pulmonary arterial smooth muscle cell proliferation.

Effective assessment of low times MET amplification in pleural effusion after epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance: Cases report.

RATIONALE: The mechanism of the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance included T790M mutation, cellular-mesenchymal to epithelial transition factor (MET) or EGFR amplification, PIK3CA mutation, and transformation to small cell lung cancer. MET amplification accounted for only about 5% of the resistance cases. PATIENTS CONCERNS: Few report detected MET amplification in pleural effusion. Here, we reported 2 lung adenocarcinoma cases with MET amplification in pleural effusion rapidly responded to crizotinib after EGFR-TKIs acquired resistance. DIAGNOSES: Biopsy via bronchoscopy, next-generation sequencing (NGS) in pleural effusion. INTERVENTIONS: EGFR-TKIs (Icotinib), MET inhibitor crizotinib. OUTCOMES: After a progression-free survival of 9 months and 23months, respectively, both cases progressed accompanying with pleural effusion. Results of NGS in pleural effusion showed MET amplification (2-3 times) in both cases. The 2 patients were treated with a MET inhibitor crizotinib and rapidly responded. CONCLUSION: MET amplification in pleural effusion could predict a perfect response to crizotinib after EGFR-TKIs acquired resistance, even only a low times gene amplification.

Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

Apatinib in the treatment of advanced lung adenocarcinoma with KRAS mutation.

Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment.

Diagnosis of a rare primary pulmonary synovial sarcoma with endobronchial ultrasound-guided transbronchial needle aspiration.

Primary pulmonary synovial sarcoma (PPSS) is a rare disease. Diagnosis is made postoperatively following resection of the tumor. We describe the case of a 39-year-old non-smoking woman whose chest imaging revealed a heterogeneous mass (5.4 cm × 4.6 cm), with soft tissue density in the right upper lobe and pleural effusion in the right hemithorax. The tumor was enhanced on a computed tomography scan, in which enlargement of the mediastinal lymph nodes compressing the adjacent superior vena cava was observed. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was then performed, which demonstrated PPSS, subsequently confirmed by immunohistochemistry and the detection of a SYT-SSX fusion gene. We believe that a diagnostic approach of EBUS-TBNA for lung sarcoma would provide helpful information to clinicians.

Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions: Six cases reports and review of literature.

BACKGROUND: Patients with isolated mediastinal or hilar lymphadenopathy, or peribronchial lesions, are common presentation to clinicians. Due to the difficulty in tissue sampling, the pathological diagnosis is not so easy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an established, highly effective, minimally invasive technique for sampling. The current study was conducted to investigate the value of EBUS-TBNA in patients of solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions. METHODS: Six patients with different pathological results diagnosed via EBUS-TBNA were retrospectively analyzed in this study. RESULTS: All 6 patients of solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions underwent conventional flexible bronchoscopy before EBUS-TBNA, but only EBUS-TBNA was helpful for the finally definite diagnosis. No complication was observed. CONCLUSION: EBUS-TBNA is a safe and highly effective diagnostic procedure for both benign and malignant diseases, especially for patients with solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions.

Primary tracheal papilloma disguised as asthma: A case report.

INTRODUCTION: Tracheal papilloma presenting as asthma is a rare occurrence. CASE STUDY: We report a case of a 32-year-old male patient who presented with features of asthma. Flexible bronchoscopy demonstrated a large growth arising from the lower end of the trachea. Successful treatment using snare loop and argon plasma coagulation (APC) of the polyploidal growth was performed via flexible bronchoscope. RESULTS: The patient had immediate relief of airway obstruction and histopathological examination of the neoplasm demonstrated features of papilloma. CONCLUSION: Primary tracheal papilloma is mimicker of asthma, CT scan should be considered in patients with persistent chronic cough, or stridor. Endoscopic papillectomy is a safe and effective treatment and should be considered as first-line therapy for tracheal papilloma.

(18)F-FDG PET-CT: a powerful tool for the diagnosis and treatment of relapsing polychondritis.

OBJECTIVE: This study aimed to evaluate fluorine-18 fludeoxyglucose positron emission tomography-CT ((18)F-FDG PET-CT) for the diagnosis, targeted biopsy and therapy of relapsing polychondritis (RP). METHODS: The literature pertaining to the use of (18)F-FDG PET-CT in patients with RP was retrieved from the Cochrane Library, PubMed, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI) and Wanfang databases until July 2015. Clinical characteristics, auxiliary examination results, chest CT findings, tracheoscopy and biopsy findings, high metabolic activity lesions, maximum standardized uptake values, (18)F-FDG PET-CT-guided biopsy site, pathologic results of biopsy samples and alteration in high (18)F-FDG-uptake lesions after treatment were retrospectively analysed. RESULTS: 18 publications with 26 cases were enrolled. The five most common symptoms of patients with RP diagnosed with (18)F-FDG PET-CT were cough, fever, chest tightness, sore throat and arthralgia. Of the 26 patients, 23 patients had multiple and symmetric cartilage lesions with high metabolic activity, revealed by (18)F-FDG PET-CT. The disease mainly affected organs such as the bronchus, trachea, throat, costicartilage and auricle. The maximum standardized uptake values ranged from 1.93 to 13.03 (mean, 4.94). (18)F-FDG PET-CT revealed that patients with RP with tracheal and bronchial involvement had a close correlation with cough (χ(2) = 6.80, p = 0.006). (18)F-FDG PET-CT showed a significantly higher positive biopsy rate compared with bronchoscopy (χ(2) = 12.91, p < 0.001) for targeted lesions with high metabolic activity. Post-treatment re-examinations with (18)F-FDG PET-CT showed obvious subsidence or complete disappearance of high (18)F-FDG-uptake lesions in 13 cases, showing highly consistent symptom improvements. CONCLUSION: (18)F-FDG PET-CT is likely to become a valuable imaging tool in the diagnosis and treatment of RP. ADVANCES IN KNOWLEDGE: The presence of symmetrically distributed high FDG-uptake lesions may be a criterion for the diagnosis of RP. (18)F-FDG PET-CT is useful for targeting biopsy sites, which remarkably increase the positive biopsy rate. Therefore, (18)F-FDG PET-CT may be of great value in the diagnosis and treatment of RP.

Endobronchial ultrasound elastography: a new method in endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: TBNA through the flexible bronchoscope is a 37-year-old technology that utilizes a TBNA needle to puncture the bronchial wall and obtain specimens of peribronchial and mediastinal lesions through the flexible bronchoscope for the diagnosis of benign and malignant diseases in the mediastinum and lung. METHODS: Since 2002, the Olympus Company developed the first generation ultrasound equipment for use in the airway, initially utilizing an ultrasound probe introduced through the working channel followed by incoroporation of a fixed linear ultrasound array at the distal tip of the bronchoscope. This new bronchoscope equipped with a convex type ultrasound probe on the tip was subsequently introduced into clinical practice. The convex probe (CP)-EBUS allows real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal and hilar lymph nodes. EBUS-TBNA is a minimally invasive procedure performed under local anesthesia that has been shown to have a high sensitivity and diagnostic yield for lymph node staging of lung cancer. RESULTS: In 10 years of EBUS development, the Olympus Company developed the second generation EBUS bronchoscope (BF-UC260FW) with the ultrasound image processor (EU-M1), and in 2013 introduced a new ultrasound image processor (EU-M2) into clinical practice. FUJI company has also developed a curvilinear array endobronchial ultrasound bronchoscope (EB-530 US) that makes it easier for the operator to master the operation of the ultrasonic bronchoscope. Also, the new thin convex probe endobronchial ultrasound bronchoscope (TCP-EBUS) is able to visualize one to three bifurcations distal to the current CP-EBUS. CONCLUSIONS: The emergence of EBUS-TBNA has also been accompanied by innovation in EBUS instruments. EBUS elastography is, then, a new technique for describing the compliance of structures during EBUS, which may be of use in the determination of metastasis to the mediastinal and hilar lymph nodes. This article describes these new EBUS techniques and reviews the relevant literature.

FDG PET-CT combined with TBNA for the diagnosis of atypical relapsing polychondritis: report of 2 cases and a literature review.

OBJECTIVE: To explore the value of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) combined with transbronchial needle aspiration (TBNA) in diagnosing atypical relapsing polychondritis (RP). METHODS: Data from two patients with atypical RP, which had been diagnosed in our hospital using FDG PET-CT combined with TBNA, were retrospectively analyzed. A review of the relevant literature was also performed. RESULTS: Consistent with the previously reported 20 cases of RP that had been diagnosed using FDG PET-CT, the two patients in the present study showed the involvement of multiple organs, including the nose, throat, trachea, bronchi, costicartilage and joint cartilages, and increased FDG uptake was found in these areas. The mean value of SUVmax was 5.14. PET-CT revealed that 86.4% of the patients with RP had airway involvement. TBNA technique was used for biopsy of the hypermetabolic lesions, and pathologic examinations confirmed the diagnosis of RP. The time to diagnosis in these two patients and the 20 cases reported previously was about 6.9 months, significantly shorter than the average diagnosis time (20 months). CONCLUSIONS: FDG PET-CT has several advantages for diagnosing RP, especially atypical RP. TBNA is a minimally invasive and safe technique for obtaining airway cartilage. Combining PET-CT with TBNA may play an important role in shortening the time to diagnosis in patients with RP involvement of airway.