Ming-Shian Lu

Chang Gung University, Hsin-chu-hsien, Taiwan, Taiwan

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Publications (45)132 Total impact

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    ABSTRACT: The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival.As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.
    Preview · Article · Jan 2016 · Oncotarget
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    ABSTRACT: Purpose: The use of video-assisted thoracoscopic surgery (VATS) in patients with thymoma remains controversial. We sought to evaluate the perioperative and oncological outcomes after VATS resection for stage I and II thymoma and to compare the outcomes with those obtained after median sternotomy (MST). Methods: Between 1991 and 2007, a total of 140 patients with stage I and II thymoma underwent surgery at the Chang Gung Memorial Hospital. Of them, 58 underwent MST, 61 VATS, and 21 thoracotomy. Using a propensity score based on four variables (myasthenia gravis, tumor size on CT images, age, and Masaoka stage), 48 VATS-treated patients were matched to 48 patients who received MST. Outcomes compared included perioperative complications, length of stay, tumor recurrence, and survival. Results: No operative deaths occurred in this study. VATS was associated with fewer intraoperative blood loss, and more patients in the VATS group were extubated in the operating room after surgery compared with the MST group (37.5 vs. 12.5 %, respectively, P = 0.005). The mean length of stay was shorter in the VATS group than in the MST group (5.8 vs. 7 days, respectively; P = 0.008). After a median follow-up of 53 months, five patients developed recurrent tumors (four pleural and one pericardial). No statistically significant differences were found in the 5-year survival rates between the two study groups. Conclusions: VATS appears feasible for patients with stage I and II thymoma and is associated with better perioperative outcomes than MST. The oncological outcomes are also similar.
    No preview · Article · Sep 2014 · Annals of Surgical Oncology
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    ABSTRACT: The aim of this study was to assess the significance of myeloid-derived suppressor cells (MDSCs) and their association with IL-6 in esophageal squamous cell carcinoma (SCC). We examined the percentage of CD11b+CD14+HLA-DR- myeloid cells and the levels of IL-6 in the peripheral blood of 50 patients with esophageal SCC and 12 healthy controls. Moreover, we evaluated the relationship between MDSC recruitment, IL-6 levels, and tumor progression by adding 4-nitroquinoline 1-oxide (4-NQO) to the drinking water of mice to induce esophageal tumors. Here we demonstrated that circulating CD11b+CD14+HLA-DR- cells were significantly increased in esophageal SCC patients compared with healthy people, and this was associated with the clinical stage, treatment response and circulating IL-6 levels. In a 4-NQO-induced esophageal tumor animal model, MDSC recruitment was associated with invasive esophageal tumors and with increased IL-6 levels. IL-6 stimulated reactive oxygen species, arginase 1 and p-STAT3 in MDSCs. Blockade of IL-6 prevented induction of MDSCs and the incidence of 4-NQO- induced invasive tumors. In conclusion, the levels of MDSCs and IL-6 predicted the prognosis of patients with esophageal SCC. Moreover, we suggest inhibition of IL-6 as a potential strategy for the treatment of esophageal SCC.
    Full-text · Article · Aug 2014 · Oncotarget
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    ABSTRACT: Background: Mycotic aortic aneurysm (MAA) is an infrequent but devastating form of vascular disease. Methods: We conducted a retrospective cohort study at a major medical center to identify independent risk factors for MAA and to provide opinions about treating it. The study population consisted of 43 patients who had had 44 MAAs over a period of 15 y. Results: All of the patients had positive blood cultures, radiologic findings typical of MAA, and clinical signs of infection (leukocytosis, fever, and elevated C-reactive protein). The mean age of the patients was 63.8±10.6 y and the mean period of their follow up was 35.7±39.3 mo. Twenty-nine patients with MAAs underwent traditional open surgery, 11 others received endovascular stent grafts, and four MAAs were managed conservatively. The most frequent causative pathogens were Salmonella (36/44 patients [81.8%]), in whom organisms of Salmonella serogroup C (consisting mainly of S. choleraesuis) were identified in 14 patients, organisms of Salmonella serogroup D were identified in 13 patients, and species without serogroup information were identified in nine patients. The overall mortality in the study population was 43.2% (with an aneurysm-related mortality of 18.2%, surgically related mortality of 13.6%, and in-hospital mortality of 22.7%). Conclusions: Shock is a risk factor for operative mortality. Misdiagnosis and treatment of MAA as low back pain, co-existing connective-tissue disease such as systemic lupus erythematosus and rheumatoid arthritis, and Salmonella serogroup C-associated bacteremia are risk factors for aneurysm-related death. Endovascular repair should be considered as an alternative option to the open repair of MAA.
    Full-text · Article · May 2014 · Surgical Infections
  • Chung-Hang Wong · Ming-Shian Lu · Li-Wen Lee · Yao-Kuang Huang

    No preview · Article · Aug 2013 · European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery
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    ABSTRACT: The identification of potential tumor markers can improve therapeutic planning and patient management. The objective of this study was to highlight the role of DNA methyltransferase 3b (DNMT3b) in esophageal squamous cell carcinoma (SCC). One hundred seventy-three esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of DNMT3b with clinical outcome. Furthermore, a human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments to investigate changes in tumor behavior and treatment response after the manipulation of DNMT3b expression. The incidence of nuclear DNMT3b immunoreactivity in esophageal cancer specimens was significantly higher than in nonmalignant epithelium, and this incidence was linked positively to developing distant metastasis (56% in localized disease vs 80% in distant metastasis; P = .002). Furthermore, increased expression of DNMT3b was linked significantly to lower treatment response rates (P = .002) and reduced survival rates (P = .000). Inhibition of DNMT3b expression resulted in slower cellular proliferation, increased cell death, a less invasive capacity, and less epithelial-mesenchymal-transition changes. Moreover, DNMT3b silencing vectors sensitized esophageal cancer cells to irradiation and cisplatin treatment. The current results also indicated that constitutional activation of signal transducer and activator of transcription 3 (STAT3) signaling associated with inhibited expression of suppressor of cytokine signaling 3 (SOCS3) may be the mechanism underlying more aggressive tumor growth in DNMT3b-positive esophageal cancer. DNMT3b was linked significantly to a poor prognosis for patients with esophageal cancer. Moreover, the current results indicated that targeting this enzyme may be a promising strategy for treating esophageal cancer, as evidenced by inhibited aggressive tumor behavior and treatment resistance.
    Full-text · Article · Aug 2012 · Cancer
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    ABSTRACT: The success of natural orifice transluminal endoscopic surgery (NOTES) depends on an adequate exploration of surgical regions. Currently, limited data are available regarding the optimal position for the NOTES approach for thoracic surgery. This study therefore aimed to evaluate the effectiveness of transoral thoracic exploration in a canine model placed in a lateral decubitus position. A total of 14 dogs were used in this study. Transoral thoracoscopy was performed using a custom-made metal tube via an incision over the vestibular incision with the animal in a supine position. After thoracic exploration, the animal was placed in a lateral decubitus position. The thoracic intervention (surgical lung biopsy, pericardial window creation, and dorsal sympathectomy) was performed by passing a flexible bronchoscope through the lumen of a metal tube. The mean operative time for this procedure was 70 min (range 45-100 min). For 12 dogs, all procedures were completed without major complications. However, for one dog, the exploration of the thoracic cavity was incorrect (the right lower lobe had been misinterpreted as the left lower lobe). Another dog had minor bleeding because of an intercostal artery injury that occurred during sympathectomy. The posterior aspect of the thoracic cavity can be exposed via a transoral approach with the animal in a lateral decubitus position. This approach may be considered as an adjuvant to the supine approach, in which exploration of the posterior thoracic cavity is restricted.
    Full-text · Article · May 2012 · Surgical Endoscopy
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    ABSTRACT: The feasibility of using a transoral approach to the thoracic cavity has not yet been measured in humans or animals. The present study aimed to evaluate the feasibility of transoral surgical lung biopsy (TOLB) in 10 canines. Through an incision over the vestibulum oris, a homemade metal tube was introduced into the thoracic cavity under endoscopic guidance and used as a working channel of surgical lung biopsy. TOLB was performed on the predetermined lung lobe by using an electrocautery loop and endoscopic grasper. Successful surgical lung biopsy was achieved in 8 of 10 animals in a mean time of 132 minutes (range 130-190 minutes). There were no major intraoperative or postoperative complications, and all animals survived for 2 weeks after surgery. Autopsy showed no evidence of vital structure injury, mediastinitis, or empyema. TOLB was demonstrated to be safe and feasible in a canine model.
    Full-text · Article · Oct 2011 · Surgical Innovation
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    ABSTRACT: Interleukin (IL)-1 beta has been reported to be a marker of shorter survival in gastric and colorectal adenocarcinoma. In the present study, we examined the potential role and prognostic value of IL-1 beta in esophageal squamous cell carcinoma (SCC). Human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments, in which biological changes after experimental manipulation of IL-1 beta signaling were explored, including tumor growth, invasion capacity, and the sensitivity to treatment. Moreover, 147 esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of IL-1 beta with clinical outcome. Our data revealed that IL-1 beta was significantly overexpressed both at mRNA and protein levels in cancer specimens compared to nonmalignant tissues. When IL-1 beta signaling was blocked, tumor growth, invasion ability, and treatment resistance were attenuated. Activation of NF-kappa B, increase of E2-EPF ubiquitin carrier protein and subsequent epithelial-mesenchymal transition might be the underlying mechanisms of the more aggressive tumor growth in IL-1 beta-positive esophageal cancer. The immunochemistry findings indicate that positivity staining of IL-1 beta correlated significantly with higher clinical stage, lower response rate to concurrent chemoradiotherapy (CCRT), and higher recurrence rate after curative treatment. Moreover, IL-1 beta was a significant predictor of survival in patients undergoing surgical intervention or definite CCRT. In conclusion, IL-1 beta is significantly linked to poor prognosis for patients with esophageal cancer and may be a promising molecular target for therapeutic intervention for esophageal SCC.
    No preview · Article · Sep 2011 · Journal of Molecular Medicine
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    Chiung-Lun Kao · Ming-Shian Lu · Jen-Ping Chang

    Full-text · Article · Aug 2011 · Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital
  • Wei-Hsun Yang · Ming-Shian Lu · Yu-Kai Cheng · Ting-Chung Wang
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    ABSTRACT: Pial arteriovenous fistula (AVF) is a rare vascular lesion, with less than 120 reported cases in the English literatures (Hoh et al., Neurosurgery 2001;49(6):1351). The angio-architecture, clinical course and therapeutic options are all different from arteriovenous malformation (AVM), dural AVM or other intracranial vascular lesions. A review of literatures to analyse the clinical course of pial AVF was carried out. The presence of varix dictates the clinical course and presentation. Paediatric type had high percentage of varix, and mass effect as clinical presentation while the adult type usually manifest by haemorrhage. Disconnection of direct shunting, either by endovascular or surgically, is sufficient to achieve successful treatment; therefore, total resection of the lesion is unnecessary.
    No preview · Article · Apr 2011 · British Journal of Neurosurgery
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    ABSTRACT: In trauma patients with chest injuries, traumatic pericardial effusion is an important scenario to consider because of its close linkage to cardiac injury. Even with advances in imaging, diagnosis remains a challenge and use of which surgical approach is controversial. This study reviews the treatment algorithm, surgical outcomes, and predictors of mortality for traumatic pericardial effusion. Information on demographics, mechanisms of trauma, injury scores, diagnostic tools, surgical procedures, associated injuries, and hospital events were collected retrospectively from a tertiary trauma center. Between June 2003 and December 2009, 31 patients (23 males and 8 females) with a median age of 31 (range 16-77), who had undergone surgical drainage of pericardial effusion were enrolled in the study. Blunt trauma accounted for 27 (87.1%) insults, and penetrating injury accounted for 4 (12.9%). Patients were diagnosed by Focused Assessment with Sonography for Trauma (FAST) (8 patients), computerized tomography (7 patients), echocardiography (9 patients), and incidentally during surgery (7 patients). Notably, sixteen (51.7%) patients required surgical repair for traumatic cardiac ruptures, including 6 (19.6%) with pericardial defects who presented initially with hemothorax. The surgical approaches were subxiphoid in 8 patients (25.8%), thoracotomy in 7 (22.6%), and sternotomy in 19 (61.2%), including 3 conversions from thoracotomy. The survival to discharge rate was 77.4% (24/31). Concomitant cardiac repair, associated pericardial defects, and initial surgical approach did not affect survival, but the need for massive transfusion, cardiopulmonary cerebral resuscitation (CPCR), trauma score, and incidental discovery at surgery all had a significant impact on the outcome. Precise diagnoses of traumatic pericardial effusions are still challenging and easily omitted even with FAST, repeat cardiac echo and CT. The number of patients with traumatic pericardial effusion requiring surgical repair is high. Standardized therapeutic protocol, different surgical approaches have not impact on survival. Correct identification, prompt drainage, and preparedness for concomitant cardiac repair seem to be the key to better outcomes.
    No preview · Article · Dec 2010 · Resuscitation
  • Ming-Shian Lu · Yen-Yao Li · Yao-Kuang Huang · Chiung-Lung Kao

    No preview · Article · Jun 2010 · The Journal of trauma
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    ABSTRACT: Spinal epidural abscess (SEA) is a rare and devastating clinical entity. Definitive diagnosis is usually delayed because most patients present initially with minor or variable symptoms resulting in poor outcome. The clinical outcome of SEA has been associated with various prognostic factors; however, reports on factors relating to motor function improvement after surgical treatment are limited. The aim of this study is to elucidate which clinical factors may affect motor function recovery after surgical treatment of SEA. The clinical features of patients with SEA undergoing surgical drainage and antibiotics treatment were reviewed, and their outcomes were identified and analyzed. The most common presenting symptoms were neck or back pain, motor deficits, and urinary incontinence. The most common underlying medical condition was diabetes mellitus. Leukocytosis (P = .036; odds ratio [OR] = 0.754; confidence interval [CI] = 0.579-0.982), elevated C-reactive protein level (P = .017; OR 0.96; CI = 0.965-0.994), poor glycemic control (P = .012; OR = 23.33; CI = 1.992-273.29), and duration of motor deficit at the time of operation (P = .005; OR = 40.50; CI = 3.093-530.293) were found to have a strong influence on motor function improvement after surgical treatment. Infection control and the prevention of further neurological deterioration in time are paramount in the treatment of SEA for optimal recovery. Patients with rapid neurological deterioration or higher white blood cell count or C-reactive protein level on presentation warrant aggressive surgical intervention; even in those who are completely paralyzed, an improvement in muscle power may still be possible.
    No preview · Article · May 2010 · Neurosurgery

  • No preview · Article · Dec 2009 · Surgery
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    ABSTRACT: To analyze the risk factors for central port failure in cancer patients administered chemotherapy, using univariate and multivariate analyses. A total of 1348 totally implantable venous access devices (TIVADs) were implanted into 1280 cancer patients in this cohort study. A Cox proportional hazard model was applied to analyze risk factors for failure of TIVADs. Log-rank test was used to compare actuarial survival rates. Infection, thrombosis, and surgical complication rates (chi(2) test or Fisher's exact test) were compared in relation to the risk factors. Increasing age, male gender and open-ended catheter use were significant risk factors reducing survival of TIVADs as determined by univariate and multivariate analyses. Hematogenous malignancy decreased the survival time of TIVADs; this reduction was not statistically significant by univariate analysis [hazard ratio (HR) = 1.336, 95% CI: 0.966-1.849, P = 0.080)]. However, it became a significant risk factor by multivariate analysis (HR = 1.499, 95% CI: 1.079-2.083, P = 0.016) when correlated with variables of age, sex and catheter type. Close-ended (Groshong) catheters had a lower thrombosis rate than open-ended catheters (2.5% vs 5%, P = 0.015). Hematogenous malignancy had higher infection rates than solid malignancy (10.5% vs 2.5%, P < 0.001). Increasing age, male gender, open-ended catheters and hematogenous malignancy were risk factors for TIVAD failure. Close-ended catheters had lower thrombosis rates and hematogenous malignancy had higher infection rates.
    Full-text · Article · Oct 2009 · World Journal of Gastroenterology

  • No preview · Article · Aug 2009 · The Journal of trauma
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    ABSTRACT: Cardiac rupture following blunt thoracic trauma is rarely encountered by clinicians, since it commonly causes death at the scene. With advances in traumatology, blunt cardiac rupture had been increasingly disclosed in various ways. This study reviews our experience of patients with suspected blunt traumatic cardiac rupture and proposes treatment protocols for the same. This is a 5-year retrospective study of trauma patients confirmed with blunt traumatic cardiac rupture admitted to a university-affiliated tertiary trauma referral centre. The following information was collected from the patients: age, sex, mechanism of injury, initial effective diagnostic tool used for diagnosing blunt cardiac rupture, location and size of the cardiac injury, associated injury and injury severity score (ISS), reversed trauma score (RTS), survival probability of trauma and injury severity scoring (TRISS), vital signs and biochemical lab data on arrival at the trauma centre, time elapsed from injury to diagnosis and surgery, surgical details, hospital course and final outcome. The study comprised 8 men and 3 women with a median age of 39 years (range: 24-73 years) and the median follow-up was 5.5 months (range: 1-35 months). The ISS, RTS, and TRISS scores of the patients were 32.18+/-5.7 (range: 25-43), 6.267+/-1.684 (range: 2.628-7.841), and 72.4+/-25.6% (range: 28.6-95.5%), respectively. Cardiac injuries were first detected using focused assessment with sonography for trauma (FAST) in 4 (36.3%) patients, using transthoracic echocardiography in 3 (27.3%) patients, chest CT in 1 (9%) patient, and intra-operatively in 3 (27.3%) patients. The sites of cardiac injury comprised the superior vena cava/right atrium junction (n=4), right atrial auricle (n=1), right ventricle (n=4), left ventricular contusion (n=1), and diffuse endomyocardial dissection over the right and left ventricles (n=1). Notably, 2 had pericardial lacerations presenting as a massive haemothorax, which initially masked the cardiac rupture. The in-hospital mortality was 27.3% (3/11) with 1 intra-operative death, 1 multiple organ failure, and 1 death while waiting for cardiac transplantation. Another patient with morbid neurological defects died on the thirty-third postoperative day; the overall survival was 63.6% (7/11). Compared with the surviving patients, the fatalities had higher RTS and TRISS scores, serum creatinine levels, had received greater blood transfusions, and had a worse preoperative conscious state. We proposed a protocol combining various diagnostic tools, including FAST, CT, transthoracic echocardiography, and TEE, to manage suspected blunt traumatic cardiac rupture. Pericardial defects can mask the cardiac lesion and complicate definite cardiac repair. Comorbid trauma, particularly neurological injury, may have an impact on the survival of such patients, despite timely repair of the cardiac lesions.
    No preview · Article · Jul 2009 · Injury
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    ABSTRACT: Extracorporeal life support (ECLS) has been applied successfully to patients with acute cardiopulmonary failure. However, ECLS remains controversial for traumatized patients who are prone to bleeding. From March 2004 to October 2007, nine patients with post-traumatic respiratory distress refractory to ventilator support were treated with ECLS. Mean patient age was 35.1+/-9.7 (range, 18-47) years, average injury severity score (ISS) was 44.56+/-4.93 (range, 35-50), and Sequential Organ Failure Assessment score (SOFA) score was 12.1+/-3.67 (range, 7-16). Before ECLS, all patients had received thoracic interventions, including four lung resections, with a mean PaO(2) of 49.04+/-9.82 (range, 31-64) mmHg and PaCO(2) of 66.4+/-15.72 (range, 45-86) mmHg. Seven patients were supported in standard veno-venous mode, and the other two were initially supported in veno-arterial mode due to hemodynamic instability. Median interval from trauma to ECLS was 33 (range, 4-384) h, and median duration of ECLS was 145 (range, 69-456) h. Six (66.7%) patients received additional surgeries during ECLS. One died of sepsis from occult colon rupture and the other of acute liver failure, 6 and 13 days respectively after trauma. Seven (77.8%) patients were weaned and discharged. Using ECLS to resuscitate traumatic respiratory distress proved to be safe and effective when conventional therapies had been exhausted. Early deployment of ECLS to preserve systemic organ perfusion, aggressive treatment of coexisting injuries and tailored anticoagulation protocols are crucial to a successful outcome.
    No preview · Article · May 2009 · Resuscitation

  • No preview · Article · Mar 2009 · The Journal of thoracic and cardiovascular surgery

Publication Stats

324 Citations
132.00 Total Impact Points


  • 2005-2014
    • Chang Gung University
      • College of Medicine
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2002-2014
    • Chang Gung Memorial Hospital
      • Division of Thoracic and Cardiovascular Surgery
      T’ai-pei, Taipei, Taiwan