Mong-Wei Lin

Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes.

BACKGROUND Programmed cell death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable targets for specific immunotherapy. This study investigated the expression of PD-L1 in surgically resected stage I adenocarcinomas and correlated this with known major driver mutations and clinical outcomes. MATERIALS AND METHODS One hundred and sixty-three patients with surgically resected stage I adenocarcinomas were explored. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in ⩾ 5% of tumour cells were scored as positive for PD-L1 overexpression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing and anaplastic lymphoma kinase (ALK) by immunohistochemistry. The correlations of PD-L1 expression with major driver mutations and clinicopathologic parameters were analysed. RESULTS The overall frequency of PD-L1 overexpression was 39.9% (65/163). PD-L1 had higher positive results in tumours with higher grade differentiation and vascular invasion and PD-L1 expression was not associated with the expressions of EGFR, KRAS, BRAF and ALK. Multivariate analysis revealed that abnormal carcinoembryonic antigen (CEA) and higher grade of differentiation were risk factors for poor relapse-free survival (RFS) and PD-L1 expression correlated with better RFS. Advanced pathologic stage was the independent risk for poor overall survival (OS). CONCLUSIONS The PD-L1 expression can be used as a prognostic indicator predictive of RFS in patients with surgically resected stage I lung adenocarcinomas. There may be a possibility for immunotherapy targeting the PD-L1 pathway in patients with lung adenocarcinoma in the future.

Clinical and biological characteristics of acute promyelocytic leukemia in Taiwan : a high relapse rate in patients with high initial and peak white blood cell counts during all-trans retinoic acid treatment

Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML–RARα fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.

Thymectomy for non-thymomatous myasthenia gravis: a comparison of surgical methods and analysis of prognostic factors.

OBJECTIVE While thymectomy is an accepted treatment for myasthenia gravis (MG), video-assisted thoracoscopic surgery (VATS) thymectomy has recently become a popular surgical treatment, especially for non-thymomatous MG (NTMG). This study aims to compare the results of VATS thymectomy and trans-sternal thymectomy, and identify prognostic factors in NTMG patients after thymectomy. METHODS A 10-year retrospective review (January 1995 to December 2004) of 60 consecutive thymectomies (22 trans-sternal thymectomies and 38 VATS thymectomies) of NTMG patients performed in a university teaching hospital was undertaken. RESULTS There were 43 female patients and 17 male patients with a median MG-onset age of 25 years (range: 5-78 years). Median follow-up time was 44 months. VATS thymectomy patients had a shorter hospital stay than the trans-sternal thymectomy patients (5.6 days vs 8.1 days, p=0.008). There was no other statistically significant difference between the two operative methods in NTMG patients, including intensive care unit (ICU) stay, ventilator support time, operative time, postoperative status, complete stable remission (CSR) rate, morbidity and mortality. Three prognostic factors associated with better remission rate were hyperthyroidism (p=0.003), age <40 years (p=0.022) and the presence of thymic hyperplasia (p=0.041). Other factors, including gender, disease duration, preoperative MG severity, acetylcholine receptor antibody, perioperative therapy and operative methods (32% vs 36%, p=0.91, 95% confidence interval (CI)=0.27-3.21) were not statistically relevant to better remission rate. CONCLUSIONS VATS thymectomy is more advantageous for NTMG patients because of shorter hospital stay, less tissue injury, better cosmetic result and equivalent CSR rate. NTMG patients aged <40 years with hyperthyroidism and a histologic diagnosis of lymphofollicular hyperplasia have better chances of remission after thymectomy.

Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma

BACKGROUND Programmed cell death-ligand 1 (PD-L1) is expressed in a subgroup of lung cancer that may benefit from immunotherapy. The interaction between PD-L1 expression and tumour infiltrating lymphocytes (TIL) remains poorly understood. This study investigated the expression of PD-L1 in surgically resected stage I pulmonary squamous cell carcinoma (SqCC) and correlated it with TILs in tumour microenvironments, common driver mutations, and clinical outcomes. MATERIALS AND METHODS One hundred and five patients with surgically resected stage I squamous cell carcinoma were examined. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in ≥ 5% of tumour cells were scored as positive for PD-L1 expression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing, while anaplastic lymphoma kinase (ALK), phosphoinositide 3-kinase catalytic alpha (PI3KCA), and fibroblast growth factor receptor 1 (FGFR1) were analysed by immunohistochemistry. The correlations of PD-L1 expression with each subtype of TIL, driver mutations, clinicopathologic parameters, and clinical outcomes were analysed. RESULTS There was positive PD-L1 expression in 56.2% (59/105) of patients. PD-L1 expression was not associated with the common clinicopathologic features and mutations of EGFR, KRAS, BRAF, ALK, PI3KCA, and FGFR1. As regards TILs composition, tumour PD-L1 expression was significantly associated with increased tumour epithelial CD8+ T cells and stromal CD4+ T cells. Otherwise, PD-L1 (+) tumour cells were negatively correlated with PD-L1 (+) immune cells within tumour stroma. By multivariate analysis, tumour PD-L1 expression and increased CD4+ T cell infiltrations in the tumour stroma were independent predictors of better overall survival and had a trend of better disease-free survival. CONCLUSIONS PD-L1 expression is associated with a favourable immune microenvironment in stage I pulmonary SqCC and correlates with better clinical outcome.

Thoracoscopic pleurodesis for primary spontaneous pneumothorax with high recurrence risk: a prospective randomized trial.

Objective:To compare the efficacy and safety between apical pleurectomy and pleural abrasion with minocycline in primary spontaneous pneumothorax (PSP) with high recurrence risk. Background:The optimal thoracoscopic pleurodesis procedure for PSP with high recurrence risk remains controversial. Methods:Between January 2006 and May 2009, a total of 369 patients with spontaneous pneumothorax were treated by video-assisted thoracoscopic surgery. After stapled bullectomy, 160 patients with no identifiable bleb or multiple blebs (≥3) were randomly chosen to undergo apical pleurectomy (pleurectomy group, 80 patients) or pleural abrasion with minocycline (abrasion/minocycline group, 80 patients). Results:Patients in the pleurectomy group had a longer operation duration (mean, 81.4 minutes vs 55.8 minutes, P < 0.001), a greater amount of operation bleeding (mean, 29.4 mL vs 13.2 mL, P = 0.025), and a greater amount of postoperative chest drainage (mean, 287.4 mL vs 195.8 mL, P = 0.040). Patients in the abrasion/minocycline group had a higher intensity of chest pain and required more frequent meperidine injections. Hemothorax occurred in 3 pleurectomy patients (3.8%). The short-term results showed that the 2 groups had comparable durations of postoperative chest drainage, durations of postoperative hospital stay, and complication rates. After a mean follow-up of 26.1 months, recurrent ipsilateral pneumothorax occurred in 3 patients (3.8%) in the pleurectomy group and 3 patients (3.8%) in the abrasion/minocycline group. Postoperative long-term residual chest pain and pulmonary function were comparable in both groups. Conclusions:Pleural abrasion with minocycline pleurodesis is as effective as apical pleurectomy and either technique is appropriate for treating PSP patients with high recurrence risk. This trial was registered at http://www.clinicaltrials.gov (ID: NCT00270751).

Intracardiac extension of lung cancer via the pulmonary vein

A 69-year-old male heavy smoker had intermittent haemoptysis for 1 month. He did not have exertional dyspnoea, palpitations or chest pain. Chest radiography showed a mass over the right lower lung (RLL). A CT scan of the chest revealed a dumbbell-shaped tumour with an irregular mass in the RLL field, with a tubular part extending along the right inferior …

PD-L1 is highly expressed in lung lymphoepithelioma-like carcinoma: A potential rationale for immunotherapy.

OBJECTIVES Programmed cell death-ligand 1 (PD-L1) and driver mutations are found in non-small cell lung cancers (NSCLCs) and may be suitable targets for specific therapies, but their roles in lymphoepithelioma-like carcinoma (LELC) of the lung are unclear. MATERIALS AND METHODS Sixty-six patients with pulmonary LELCs were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Tumors with moderate-to-strong membrane staining in ≥5% of tumor cells were positive for PD-L1 overexpression. The presence of driver mutations in the genes for epidermal growth factor receptor (EGFR), KRAS, and BRAF were examined by direct sequencing. Anaplastic lymphoma kinase (ALK) and ROS1 levels were determined by immunohistochemistry. Correlations of PD-L1 expression and driver mutations with clinicopathologic parameters were analyzed. RESULTS The overall frequency of PD-L1 overexpression and EGFR mutation was 75.8% and 12.1%, respectively. No KRAS, BRAF, ALK or ROS1 aberrations could be detected. PD-L1 expression was not associated with driver mutations. Multivariate analysis revealed that smoking and advanced stage were independent risk factors for poor overall survival, whereas PD-L1 positivity was not significantly associated with patient outcome. CONCLUSION There are high PD-L1 expression and infrequent driver mutations in LELCs compared with conventional NSCLCs. The high expression of PD-L1 in EBV and inflammation associated LELC may provide a rationale for immunotherapy in this subtype of lung cancer.

Clinicopathologic characteristics and prognostic significance of EGFR and p53 mutations in surgically resected lung adenocarcinomas ≤2 cm in maximal dimension

Small lung adenocarcinomas are detected more frequently than in the past. However, the clinicopathologic characteristics and prognostic significance of EGFR/p53 mutations in these tumors remains unclear.

Image-guided thoracoscopic surgery with dye localization in a hybrid operating room

BACKGROUND The rate of detection of small pulmonary nodules (SPNs) has increased. Thoracoscopic resection following image-guided localization had been a reliable alternative in their treatment. We present our experience with image-guided dye localization using robotic C-arm computed tomography (CT) followed by immediate video-assisted thoracoscopic surgery (VATS) for SPNs in a hybrid operating room (OR). METHODS From July 2015 to July 2016, 25 consecutive patients with SPNs smaller than 2 cm underwent robotic C-arm CT-guided blue dye tattooing followed by immediate VATS in a hybrid OR. Their medical records were retrospectively reviewed to evaluate the feasibility and safety of this novel procedure. RESULTS Robotic C-arm CT-guided dye localization was successfully performed in 23 patients (92%). Wound extension was required for nodule identification in the remaining two patients. The median size of the nodules was 1.0 cm (range, 0.6-2.0 cm). The median needle localization time and surgery time were 46 and 109 min, respectively. All 25 patients had successful resection of their lesions. The pathological diagnoses were primary lung adenocarcinoma in 18 (72%), benign tumors in 5 (20%), and metastatic lesions in 2 (8%). There was no operative mortality. The median length of the postoperative stay was 3 days (range, 2-8 days). Complications were noted in two patients (8%). One patient had a penetrating injury of the diaphragm during needle localization. The other had pneumonia postoperatively. Both patients were managed conservatively. CONCLUSIONS Our experience showed that robotic C-arm CT-guided dye localization followed by immediate thoracoscopic surgery in a hybrid OR is safe and feasible. It may become an effective and attractive alternative in managing SPNs.

Non-functional paraganglioma of the posterior mediastinum.

Mediastinal paraganglioma is a rare and slow growing neurogenic tumor. Here, we describe a 49-year-old woman with a non-functional posterior mediastinal paraganglioma. Video-assisted thoracoscopic surgery for tumor excision failed due to massive bleeding. The tumor was excised successfully by lateral thoracotomy with bipolar electrocautery 1 week after the first operation. Mediastinal paraganglioma remains a surgical challenge due to its hypervascular character and firm adhesion to adjacent mediastinal structure. Since the non-functional posterior mediastinal paraganglioma is often diagnosed after operation, it should be regarded as a differential diagnosis of mediastinal mass, especially if surgeons experience unexpected massive bleeding during operation.