Jiun Yi Hsia

Outpatient thoracoscopic limited sympathectomy for hyperhidrosis palmaris

Thoracoscopic sympathectomy is considered the most effective treatment for hyperhidrosis palmaris. We have treated 1,043 cases of this disease by this method. We have developed an outpatient technique of thoracoscopic sympathectomy using electrocautery. This procedure has been used in 47 patients with hyperhidrosis palmaris. The early results have been favorable. We describe this fast, safe, economic, and effective method for the treatment of hyperhidrosis palmaris.

Prediction of prognosis by the extent of lymph node involvement in squamous cell carcinoma of the thoracic esophagus

OBJECTIVES Current criteria of the N-category in the TNM staging system for carcinoma of the esophagus needs further subgrouping due to its simplicity in mixing together patients with different prognosis. METHOD A retrospective cohort study of 186 patients (176 men and ten women; mean age, 59.9 years) with squamous cell carcinoma (SCC) of the thoracic esophagus who underwent esophagectomy followed by two-field lymphadenectomy and cervical lymph node sampling between 1992 and 1999 was conducted. A proposed N-category which involved dividing the nodal status into N0 (no nodal involvement), N1 (< or =4 nodes or < or =20% nodal involvement), and N2 (>4 nodes, or >20%, or non-regional nodal involvement) subgroups was used for survival analysis. RESULTS The overall 5-year cumulative survival rate was 27%. Lymph node metastases were identified in 101 (54.3%) patients. Cumulative survival rates were 46% at 4 years in the N0 group and 21% at 4 years in the N1 group, whereas no patients in N2 group survived longer than 3 years (P<0.01). A multivariable analysis revealed that independent prognostic factors included the depth of tumor invasion (P<0.01), nodal involvement (P<0.01), and organ metastasis (P<0.01). CONCLUSION In addition to the location of nodes, the extent of nodal involvement in SCC of the thoracic esophagus also plays an important role in prognosis prediction.

R331W Missense Mutation of Oncogene YAP1 Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability

PURPOSE Adenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential. PATIENTS AND METHODS Whole-genome sequencing was performed for a family with an unusually high density of lung adenocarcinoma with available DNA from the affected mother, four affected daughters, and one nonaffected son. Candidate risk alleles were confirmed by matrix-assisted laser desorption ionization time of flight mass spectroscopy. Validation was conducted in an external cohort of 1,135 participants without cancer and 1,312 patients with lung adenocarcinoma. Family follow-ups were performed by genotyping the relatives of the original proband and the relatives of the identified risk-allele carriers. Low-dose computed tomography scans of the chest were evaluated for lung abnormalities. RESULTS YAP1 R331W missense mutation from the original family was identified and validated in the external controls and the cohort with lung adenocarcinoma. The YAP1 mutant-allele carrier frequency was 1.1% in patients with lung adenocarcinoma compared with 0.18% in controls (P = .0095), yielding an odds ratio (adjusted for age, sex, and smoking status) of 5.9. Among the relatives, YAP1-mutant carriers have overwhelmingly higher frequencies of developing lung adenocarcinoma or ground-glass opacity lung lesions than those who do not carry the mutation (10:0 v 1:7; P < .001). YAP1 mutation was shown to increase the colony formation ability and invasion potential of lung cancer cells. CONCLUSION These results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management.

Clustered Genomic Alterations in Chromosome 7p Dictate Outcomes and Targeted Treatment Responses of Lung Adenocarcinoma With EGFR-Activating Mutations

PURPOSE Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been proven more effective for patients with lung adenocarcinoma with EGFR-activating mutation rather than wild type, the former group still includes approximately 30% nonresponders. The molecular basis of this substantial response heterogeneity is unknown. Our purpose was to seek molecular aberrations contributing to disease progression at the genome-wide level and identify the prognostic signature unique to patients with EGFR-activating mutation. PATIENTS AND METHODS We first investigated the molecular differences between tumors with EGFR-activating mutation and wild-type tumors by conducting high-density array comparative genomic hybridization on a collection of 138 adenocarcinoma tissues. We then used an independent group of 114 patients to validate the clinical relevance of copy-number alterations (CNAs) in predicting overall and disease-free survival. Finally, focusing on 23 patients with EGFR mutation receiving EGFR-TKI treatment, we investigated the association between CNAs and response to EGFR-TKIs. RESULTS We identified chromosome regions with differential CNAs between tumors with EGFR-activating mutation and wild-type tumors and found the aberration sites to cluster highly on chromosome 7p. A cluster of six representative chromosome 7p genes predicted overall and disease-free survival for patients with EGFR-activating mutation but not for those with wild type. Importantly, simultaneous presence of more genes with increased CNAs in this cluster correlated with less favorable response to EGFR-TKIs in patients with EGFR-activating mutation. CONCLUSION Our results shed light on why responses to EGFR-TKIs are heterogeneous among patients with EGFR-activating mutation. They may lead to better patient management in this population.

Epidermal Growth Factor Receptor Mutation Status in Stage I Lung Adenocarcinoma with Different Image Patterns

Purpose: Early lung adenocarcinoma may present with ground-glass opacity (GGO) component in computed tomography (CT) scan. Epidermal growth factor receptor (EGFR) mutation had been reported in patients with lung cancer with GGO patterns. Nevertheless, the correlation between clinical characteristics, CT image patterns, and EGFR mutation status was indeterminate. Methods: Patients with stage I lung adenocarcinoma with tumor lesions less than 3 cm were included and classified into pure GGO, part-solid, and solid patterns by CT scan images. All patients had EGFR mutation test from frozen tumors. Available paraffin-embedded archival tissues were microdissected into three different locations similar to CT images with central and peripheral parts of tumor, and adjacent normal part for EGFR mutation tests. Results: Totally, 162 patients were analyzed, 90 women and 72 men, and 128 nonsmokers. The patients included 35 (21.6%) pure GGO, 41 (25.3%) part-solid, and 86 (53.1%) solid lesions. The EGFR mutation rate was 64.2% (n = 104). Analysis of the correlation between CT image patterns and EGFR mutation, the less GGO ratio had more typical mutation, especially L858R (p = 0.037). In 45 microdissected tumors, the central and peripheral parts had the same EGFR mutation status. In adjacent normal parts, 5 of 32 (15.6%) EGFR mutant patients had identical mutation but none in nonmutant patients. Conclusions: In stage I lung adenocarcinoma, typical mutation, especially L858R was detected more frequent in invasive solid pattern and significantly less in pure GGO pattern. EGFR mutation is an early event in the pathogenesis of lung adenocarcinoma and may facilitate the tumor into aggressive behavior.

Adenosquamous carcinoma of the lung. Surgical results compared with squamous cell and adenocarcinoma

The outcome of surgery for adenosquamous carcinoma of the lung in 39 patients treated in 1982-1996 was compared with results in squamous cell carcinoma and adenocarcinoma. Adenosquamous carcinoma comprised only 4.2% of all 914 resected primary lung cancers. The cumulative 5-year postoperative survival rate was 22.6% for the adenosquamous tumours. Comparison of survival curves with those for squamous cell carcinoma and adenocarcinoma indicated non-significant differences. The incidence of lymph-node metastasis was significantly higher in the patients with adenosquamous carcinoma than in the other patient groups.

Identification of Five Driver Gene Mutations in Patients with Treatment-Naïve Lung Adenocarcinoma in Taiwan

Background It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations. Methods This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2). Results From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age. Conclusion This was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials.

Outpatient thoracoscopic sympathicotomy for axillary osmidrosis

OBJECTIVE We evaluate the clinical results of thoracoscopic T3-4 sympathicotomy for axillary osmidrosis. METHODS From July 1995 to June 2001, 262 patients (208 females, 54 males) with axillary osmidrosis have been treated by thoracoscopic T3-4 sympathicotomy. All patients were followed up for a minimum of 10 months (average 42 months). The patients were evaluated by telephone or mail questionnaires. The results were categorized as excellent, good, fair, or poor. RESULTS There were no surgical mortalities and major complications in this series. The surgical outcomes were excellent in 144 (55%) patients, good in 39 (15%) patients, fair in 55 (21%) patients, and poor in 24 (9%) patients. Compensatory sweating developed in 171 (65%) patients. Dry hands developed in 40 (15%) patients. CONCLUSIONS Thoracoscopic T3-4 sympathicotomy is a safe, fast, cosmetic, and effective method in treating axillary osmidrosis.

EGFR L858R Mutation and Polymorphisms of Genes Related to Estrogen Biosynthesis and Metabolism in Never-Smoking Female Lung Adenocarcinoma Patients

Purpose: To assess whether polymorphisms of genes related to estrogen biosynthesis and metabolism are associated with EGFR mutations. Experimental Design: We studied 617 patients with lung adenocarcinoma, including 302 never-smoking women. On the basis of multiple candidate genes approach, the effects of polymorphisms of CYP17, CYP19A1, ERα, and COMT in association with the occurrence of EGFR mutations were evaluated using logistic regression analysis. Results: In female never-smokers, significant associations with EGFR L858R mutation were found for the tetranucleotide (TTTA)n repeats in CYP19A1 (odds ratio, 2.6; 95%CI, 1.2–5.7 for 1 or 2 alleles with (TTTA)n repeats >7 compared with both alleles with (TTTA)n repeats ≤7), and the rs2234693 in ERα (OR, 2.1; 95% CI, 1.1–4.0 for C/T and C/C genotypes compared with T/T genotype). The C/C genotype (vs. T/T genotype) of ERα was significantly associated with EGFR L858R mutation (OR, 3.0; 95% CI, 1.1–8.1), in-frame deletion (OR, 2.9; 95% CI, 1.1–7.6) and other mutations (OR, 4.3; 95% CI, 1.3–14.0). The genotype of COMT rs4680 was significantly associated with EGFR L858R mutation in female and male never-smokers showing ORs (95% CI) of 1.8 (1.0–3.2) and 3.6 (1.1–11.3), respectively, for genotypes G/A and G/G compared with genotype A/A. The number of risk alleles of CYP17, CYP19A1, ERα, and COMT was associated with an increasing OR of EGFR L858R mutation in female never-smokers (P = 0.0002 for trend). Conclusions: The L858R mutation of EGFR is associated with polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients. Clin Cancer Res; 17(8); 2149–58. ©2011 AACR.

Surgical feasibility of ipsilateral multifocal non-small cell lung cancer in different lobes: excellent survival in node-negative subgroup.

OBJECTIVE The management of ipsilateral multifocal non-small cell lung cancer (NSCLC) in different lobes is still controversial. We analyzed our surgical results and the prognostic factors with the findings of other studies and evaluated the surgical feasibility. METHODS Between January 1, 1983 and December 31, 2001, 1408 patients underwent operation for primary NSCLC, including 20 patients who received complete resections for multifocal NSCLC of the same histological type in ipsilateral different lobes. RESULTS The 1-, 2- and 5-year survival rate of the 20 patients were 60.0, 39.3 and 28.1%, respectively. There were no statistically significant differences in T-status, gender, pathological type, and stage. An excellent 5-year survival rate of 66.7% (median, 101 months) in the group without node involvement was found (N0 vs. N1+2, P=0.0872). CONCLUSION Our data suggest that surgical resection is mandatory in patients with ipsilateral multifocal NSCLC when there is no evidence of node metastasis.