Major hemorrhage and subsequent cardiac tamponade during mediastinoscopy.
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Publications and source records attributed to Han-Shui Hsu.
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BACKGROUND: There is neither a nation-wide nor a large-scale, multi-institutional lung cancer database available for stage-by-stage survival analysis in Taiwan at present. METHODS: Using the data element provided by the International Association for the Study of Lung Cancer, the Taiwan Lung Cancer Society initiated a project to include native lung cancer patients into a global database. A total of 1112 Taiwan lung cancer patients treated in 7 medical centers were enrolled. RESULTS: In small cell lung cancer, patients with ipsilateral pleural effusion had a survival between those with locoregional disease alone and those with distant metastasis; however, the difference was not statistically significant (P = 0.204). In non-small cell lung cancer, tumor size had significant survival influence for patients as a whole (P < 0.001) but it did not support the further division of stage IA according to tumor size (P = 0.122). The survival was compatible in stage IIIB and IV patients and therefore, the survival impact of pleural effusion cannot be determined. In patients with pIIIA-N2 disease, those who had station 8 nodal metastasis had inferior survival (P = 0.020) and station 5 superior survival (P = 0.010). In patients with distant metastasis, bone, liver, or distant lymph node metastasis predicted an inferior survival (all P values < 0.05). CONCLUSIONS: The present study provides for comparison in this area a stage-by-stage reference for the survival of lung cancer patients. Some factors other than current TNM descriptors need to be further investigated in constructing the next version of the staging system.
Overexpression of DNA methyltransferases DNMT1, DNMT3a and DNMT3b has been reported in various cancers. However, physical binding of DNA methyltransferase (DNMT) to the hypermethylated promoter of tumor suppressor genes (TSGs) has never been demonstrated in tumor tissues. In addition, alteration of DNMT at the protein level has never been reported in the same series of cancer patients. By immunohistochemical analysis, we demonstrated that DNMT1, DNMT3a and DNMT3b proteins were highly expressed in a coordinate manner in lung tumors, particularly in smokers (P=0.037, by the Fisher exact test). Patients with DNMT1 overexpression had a trend of poorer prognosis than those without such overexpression, and this prognostic significance was apparent in squamous carcinoma (SQ) patients (P=0.041, by the log-rank test). Both DNMT1 and DNMT3b overexpressions correlated with hypermethylation in the TSG promoters, especially among smoking SQ patients (P=0.012). To further explore the molecular mechanisms between altered TSGs promoter methylation and overexpression of DNMTs protein, we performed a tissue chromatin-immunoprecipitation polymerase chain reaction assay for lung tumors and showed that the methylated FHIT, p16(INK4a) and RARbeta promoters were bound by both DNMT protein and methyl-CpG-binding protein 2. These data suggest that overexpression and strong binding of various DNMTs may result in promoter hypermethylation of multiple TSGs and ultimately lead to lung tumorigenesis and poor prognosis.
BACKGROUND: Malignant lymphoma presenting as a solitary chest wall mass is not frequently seen. Only a few case reports have been found in the English literature. The treatment for primary chest wall lymphoma remains unclear. METHODS: From 1991 to 2004, of 157 patients with initial presentation of isolated chest wall mass, non-Hodgkin's lymphoma was diagnosed in 7 of them. Patients with tumors arising from axillary lymph nodes or mediastinal lymphadenopathy with chest wall extension were excluded in the study. The clinical manifestation, management, and outcome of these patients were reviewed. RESULTS: There were 1 female and 6 male patients with a mean age of 66.5 years. The mean largest diameter of the mass was 10.3 cm. Four of these 7 patients had the chest wall lymphoma as the only site of disease. The other 3 patients had other organ involvement including lung, bone, or liver. The pathologic diagnoses were malignant lymphoma in 2 patients and diffuse large B-cell lymphoma in 5 patients. Three patients with chest wall lymphoma as the only site of disease had tumor excision followed by adjuvant chemotherapy. No recurrence or metastasis was noted for these 3 patients. The mean follow-up period was 102 months. The other patient with chest wall lymphoma as the only site of disease, who had chemotherapy as the initial treatment, remained free of disease for 6 months after treatment. The other 3 patients with other organ involvement who were managed with chemotherapy with or without radiotherapy died of disease after a mean survival of 20 months. CONCLUSIONS: Malignant lymphoma presenting as a large chest wall mass is not common. Although the primary treatment of choice for lymphoma with or without chest wall involvement is chemotherapy, surgery followed by adjuvant chemotherapy can provide satisfactory outcome for some patients in whom the chest wall lymphoma was the only site of disease.
BACKGROUND: Promoter methylation inactivates expression of some important tumor suppressor genes and may be associated with histone modification. The fragile histidine triad (FHIT) gene is considered a tumor suppressor gene in different human epithelial cancers. We investigated whether FHIT methylation is associated with aberrant expression of Fhit protein and acetylated histone, and whether aberrant expression of Fhit protein and acetylated histone are related to prognosis after resection for esophageal squamous cell cancer. METHODS: We analyzed FHIT methylation using methylation-specific polymerase chain reaction and Fhit protein and acetylated histone H4 using immunohistochemistry in 60 resected tumor specimens. Concordance analysis was performed between FHIT methylation and expression of Fhit as well as H4. RESULTS: The FHIT methylation was observed in 33(55%) specimens, and the aberrant expression of Fhit and acetylated H4 was found in 42 (70%) and 40 (67%) specimens, respectively. Expression of aberrant Fhit correlated positively with tumor staging (p < 0.017) and nodal involvement (p = 0.004). Aberrant expression of acetylated H4 correlated positively with tumor staging (p < 0.001), nodal involvement (p < 0.001), and metastasis (p = 0.004). Concordance rates of 75% and 81.7% were present between promoter methylation of FHIT and expression of Fhit (p = 0.035) and acetylated H4 (p = 0.02). CONCLUSIONS: Aberrant expression of Fhit and acetylated histone H4 are frequently associated with the presence of esophageal squamous cell carcinoma, and they are potential prognostic predictors for patients after resection of the tumor.
BACKGROUND: The aim of this study was to retrospectively assess the results of en bloc chest wall plus lung resection for patients with non-small cell lung cancer (NSCLC) invading the chest wall. METHODS: From January 1986 to December 2000, of 1,820 patients having surgery for NSCLC, 42 (2.3%) patients with neoplasms involving the chest wall underwent en bloc chest wall and lung resection. Patient demographics, preoperative symptoms, operative procedures, tumor cell type and size, removed nodal status, and pathologic stage were summarized. The 5-year survival rates of the groups were compared. RESULTS: Postoperative staging revealed 28 were T3N0M0, 4 were T3N1M0, and 10 were T3N2M0. The in-hospital mortality rate was 11.9% (5/42). The mean age was 79.0 +/- 2.8 years in the patients who died of complications, which was significantly older than the mean age of 67.9 +/- 8.1 years in the patients who survived the surgery (p = 0.005). The overall 5-year survival was 28.4%. The 5-year survival was significantly longer in the patients with negative (N0) nodal metastasis than in those with N1 and/or N2 nodal metastasis (39.6% versus 7.1%, p = 0.01). Eleven patients had tumor involvement of the parietal pleura. Thirty-one patients had tumor involvement of the soft tissue and/or bone. There was no significant difference of 5-year survival rate between the patients with involvement of the parietal pleura only and the patients with involvement of the parietal pleura and the soft tissue and/or bone (10.9% versus 33.5%, p = 0.94). CONCLUSION: En bloc resection for bronchogenic carcinoma invading the chest wall provides a favorable prognosis in cases without nodal metastasis. Significant postoperative mortality is associated with old age (> 80 years). The 5-year survival rate is not significantly different between the patients with involvement of the parietal pleura only and the patients with involvement of the parietal pleura and the soft tissue and/or bone.
BACKGROUND: Primary chest wall tumor is rare but it encompasses tumors of various origins. We analyzed our experience with primary chest wall tumors with emphasis on its demographic presentation and management. METHODS: From 1991 to 2004, 62 patients with the diagnosis of primary chest wall tumors were enrolled. Lipoma, chest wall metastasis, direct invasion from nearby malignancy, infection, and inflammation of chest wall were excluded. The clinical features, management, and the outcome of these patients were retrospectively reviewed. RESULTS: There were 37 males and 25 females. Malignant and benign tumors were equally distributed. Chondrosarcoma and lymphoma were the 2 most common types of malignant chest wall tumors. The most common clinical symptoms were palpable mass (54.8%) and pain (40.3%). Nine of 31 patients (29.0%) with benign chest wall tumors were free of symptoms whereas patients with malignant chest wall tumors were all symptomatic (p = 0.002). A definite diagnosis was obtained in 21 of 26 patients (80.7%) who received nonexcision biopsy. All patients with primary chest wall tumors, except 6 who had medical treatment only, underwent surgical resection. Patients with malignant chest wall tumors were older than those with benign tumors (p < 0.001). The mean largest diameter of tumors was also larger in malignant tumors than in benign tumors (p = 0.04). CONCLUSION: Patients with primary malignant chest wall neoplasm were older than those with benign tumors. The mean size of malignant tumors was larger than that of benign tumors. Adequate surgical resection remains the treatment of choice for patients with primary chest wall tumors. Nonexcision biopsy should be reserved for patients with a past history of malignancy, suspicion of hematologic disease, and with high operative risk. For patients with isolated chest wall lymphoma, surgical resection followed by chemotherapy can be considered to obtain a better outcome.
Lung cancer is the leading cause of cancer deaths worldwide. This study was designed to select multiple DNA markers, which have high sensitivity and specificity to serve as biomarkers for diagnosis of lung cancer. We examined the promoter hypermethylation of three tumor suppressor genes by methylation-specific PCR (MSP), and the instability of eight microsatellite markers by loss of heterozygosity (LOH) and microsatellite instability (MSI) analyses in lung tumor tissues and matched sputum specimens from 79 lung cancer patients. On the basis of the results of sensitivity, specificity, and concordance from each marker analyzed, we selected seven biomarkers, which are LOH of D9S286, D9S942, GATA49D12, and D13S170, MSI of D9S942, and methylation of p16(INK4a) and RARbeta, from the sputum analyses. These selected etiologically associated biomarkers can potentially be used as supplemental diagnostic biomarkers for early lung cancer detection.
PURPOSE AND EXPERIMENTAL DESIGN: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non-small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme-based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. RESULTS: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). CONCLUSION: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.
EGFR mutations have been shown to correlate with the clinical responsiveness to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). The detection of EGFR mutations in non-small cell lung cancer (NSCLC) is important from the perspective of targeted anticancer therapy. We report the first case showing that the status of EGFR mutations can be successfully determined in malignant pleural effusion of NSCLC using polymerase chain reaction (PCR) technique, and correlated to the clinical responsiveness to gefitinib, an EGFR-TKI. This case demonstrated the importance of molecular cytology in the era of targeted therapy.
Lipomas of the gastrointestinal tract are rare, and those of the esophagus are extremely rare. Indeed, fewer than 20 resected cases of esophageal lipoma have been reported in the literature. In the current case, a 71-year-old man presented with a 4-month history of a slight swallowing disturbance in the upper chest. Upper gastrointestinal endoscopy revealed a submucosal space-occupying mass, with normal mucosa, in the upper third of the thoracic esophagus; the mass was yellowish in color, soft in consistency, and about 3.5 x 3.0 cm in diameter. The patient underwent video-assisted thoracoscopic enucleation of the submucosal esophageal tumor, which pathologically, was proved to be a lipoma.
PURPOSE AND EXPERIMENTAL DESIGN: The molecular mechanisms by which the p14ARF gene is altered in non-small cell lung cancer (NSCLC) are complex and unclear. Using genetic and epigenetic analyses, we examined various molecular alterations including the loss of protein and mRNA expression, and 5'CpG hypermethylation, allelic imbalance, and mutation of the p14ARF gene in a series of 102 NSCLC samples, in parallel with clinicopathological and prognostic analyses. To clarify the biological significance of p14ARF alterations, its relationship with p16INK4a and p53 alterations was also examined. RESULTS: We found that 34% of NSCLC patients had aberrant P14ARF protein expression, which was more frequent in adenocarcinomas (AD; 44%) than in squamous cell carcinomas (22%; P = 0.024). A high concordance was observed between alterations in protein and mRNA expression and 5'CpG hypermethylation (P </= 0.001). The p14ARF hypermethylation inversely correlated with P53 overexpression (P = 0.001). This mutually exclusive relationship for alteration between p14ARF and p53 was also supported by a worse prognosis of AD patients with positive P14ARF expression (P = 0.01) and of AD patients with P53 overexpression (P = 0.006). Our data also indicated that hemizygous/homozygous deletion and mutation in the p14ARF gene occurred at 26%, 9%, and 0%, respectively, of microdissected NSCLCs. CONCLUSIONS: Our data suggest that p14ARF 5'CpG hypermethylation is the predominant mechanism involved in the aberrant expression of the p14ARF gene. In addition, p14ARF 5'CpG hypermethylation occurs inversely to P53 overexpression.
Among patients with adenocarcinoma of the gastric cardia, we noted that patients with higher preoperative serum albumin levels appeared to survive longer than patients with lower levels. Thus, we evaluated serum albumin as a prognostic factor for patient survival. From 1987 to 1997, 314 patients with adenocarcinoma of the gastric cardia underwent curative resection. Patient serum albumin levels were evaluated on the second day after admission, before any nutritional support. Patients were divided into two groups: those with normal serum albumin levels (>3.5 g/dl) and those with abnormal serum albumin levels. The perioperative mortality and morbidity were 5.7% (18 of 314) and 22.3% (70 of 314), respectively. The surgical resectability rate was significantly better among patients with normal serum albumin levels (P < 0.001). The 5-year overall survival rate of patients with normal serum albumin levels was also better than those with abnormally low serum albumin levels (38.4% versus 19.1%, P=0.0003). In each cancer stage, the 5-year survival rate of patients with normal serum albumin levels was better than that among those with hypoalbuminemia. By multivariate analysis, serum albumin level and the pathologic T, N statuses were independent factors correlated with prognosis. Preoperative serum albumin level correlated highly with resectability and survival. Patients with abnormal serum albumin levels had worse survival than did those with normal serum albumin levels. We recommend that postoperative adjuvant therapy be given to all patients with hypoalbuminemia preoperatively.
BACKGROUND: Pulmonary hamartoma is the most common type of benign lung tumors. We retrospectively reviewed the clinicopathological features of 61 patients with pulmonary hamartomas undergoing surgical resection in our institution. METHODS: From 1971 to 2002, 61 patients with 62 pulmonary hamartomas underwent surgical resection in the Division of Thoracic Surgery, Taipei Veterans General Hospital. 45 were men and 16 were women (approximately in 3:1 ratio). Their mean age was 56.9 years (range 20 to 77 years). The medical records of these patients were reviewed. The information collected using a standardized data-collection form consisted of the age at presentation, gender, initial manifestations or symptoms, history of tobacco consumption, location of hamartoma, size of the lesions, state of calcification in the hamartoma, the results of preoperative bronchoscopic examination, operative procedures and pathological report of intra-operative frozen section. All available histological slides were reviewed by the same pathologist to reconfirm the diagnosis of pulmonary hamartoma. RESULTS: Of the 61 patients with pulmonary hamartoma, 41 patients were clinically asymptomatic, 16 patients had new onset of respiratory symptoms and 4 patients had chronic cough. One patient had synchronous 2 separate lesions. The hamartomas were equally distributed in the pulmonary lobes with the mean transverse diameter of 1.8 cm measured in operation (range 0.2 to 5.0). No tumor recurrence developed after resection in our series. The mean follow-up was 8.9 years. CONCLUSIONS: The vast majority of pulmonary hamartomas represent as solitary pulmonary nodule. Definite diagnosis and the treatment can be achieved by surgical resection with minimal morbidity. No tumor recurrence was encountered in the follow-up period.
BACKGROUND: Surgery is the treatment of choice for thymic epithelial tumors (TET), but the resectability is about 60-70%. For those with locally advanced unresectable TETs (LAU-TETs), some controversies about the prognostic factors and treatment modalities existed. The aims of this study are to elucidate the roles of various therapeutic options and to determine the survival and prognostic factors of LAU-TETs. METHODS: Twenty-seven patients diagnosed with LAU-TETs underwent treatment in Taipei Veterans General Hospital between 1979 and 1997. Multiple treatment modalities, including surgical intervention, irradiation and chemotherapy, were advocated for these patients. The clinicopathological factors and the effects of the treatment modalities were evaluated retrospectively. RESULTS: Twenty seven cases of LAU-TETs, included 18 thymomas (12 at stage III and 6 at stage IVa) and 9 thymic carcinomas (4 at stage III and 5 at stage IVa), were enrolled for study. The overall 5-year and 10-year survival rates were 54.6% and 35.1%, respectively. Patients receiving debulking surgery and those with irradiation dosage higher than 4400 cGy had significantly better survivals (P = 0.021 and P = 0.016, respectively). CONCLUSIONS: Aggressive debulking surgery and sufficient irradiation dosage provide better survivals for patients with LAU-TETs, especially for those with thymoma.
Gastrointestinal mesenchymal tumors are a group of tumors originated from the mesenchymal stem cells of the gastrointestinal tract, consisting of gastrointestinal stromal tumors (GIST), leiomyomas or leiomyosarcomas or schwannomas. Gastric schwannoma is a very rare gastrointestinal mesenchymal tumor, which represents only 0.2% of all gastric tumors and 4% of all benign gastric neoplasms. We report a 24-year-old girl who suffered from an episode of upper gastrointestinal bleeding. The endoscopic examination showed a round submucosal tumor with a central ulceration and bleeding over the high body of the stomach. Surgical resection of the tumor was performed. The pathological examination revealed a picture of spindle cell tumor that was strongly positive for S-100 protein stain, and non-reactive for CD34, CD117, actin, HHF-35, desmin, melan-A and HMB-45, consistent with gastric schwannoma. The literature is reviewed.
BACKGROUND: Hepatocellular carcinoma (HCC) is seldom resectable due to advanced status. Even though hepatectomy is feasible, a large proportional of patients may still develops extrahepatic recurrence. Pulmonary metastasis is the most common site of extrahepatic spread. Few articles have discussed the benefit of resection for lung metastasis after curative hepatectomy. We evaluated the general information and the result of lung resection for patients having lung metastasis after curative resection of HCC. METHODS: Six patients who underwent pulmonary metastasectomy for HCC at Taipei Veterans General Hospital between August 1995 and May 2004 were enrolled in the study. All of them had received the hepatectomy for primary HCC. The demographic information of patients, the site and number of extrahepatic recurrence, the method of surgical intervention and the outcome after surgery were retrospectively reviewed. RESULTS: There were 4 men and 2 women with the mean age of 47.3 years. All of them were HBV carriers. Five patients had multiple pulmonary metastases removed by wedge resection. Two patients had bilateral lung metastases upon diagnosis of extrahepatic recurrence. The mean duration of follow-up after hepatic resection was 75.0 +/- 25.1 months (32 to 104 months). The mean survival after pulmonary resection was 47.2 +/- 34.3months (1 to 94 months). Four patients are still alive and free of the disease. One patient is alive but with the disease. One patient who refused further aggressive treatment after resection of lung metastasis died of the disease 40 months after lung resection, 77 months after hepatic resection. CONCLUSIONS: Lung resection for the pulmonary metastasis of HCC can result in a favorable long-term survival when there is no other intrahepatic or extraphepatic recurrence of HCC. For patients with multiple lung metastases in different lobes or different lungs, aggressive surgical resection is recommended if complete resection can be achieved.
BACKGROUND: The reoperative procedures for achalasia vary. Repeat esophagomyotomy with or without antireflux procedure and esophageal resection of varying extent with reconstruction using stomach, jejunum, or colon have been reported. In this series, we have retrospectively reviewed our experience and reported the results with limited distal esophagectomy and short-colon interposition in the treatment of patients with recurrent symptoms of achalasia after prior failed esophagomyotomy. METHODS: Nine consecutive patients (5 men, 4 women; 27 to 74 years of age; mean, 52 years) with recurrent symptoms of achalasia and at least one failed prior esophagomyotomy underwent gastric cardiectomy, distal esophagectomy, and replacement with an at least 30-cm short-colon interposition through a left thoracoabdominal approach. Morbidity of the procedure and the length of hospital stay were recorded. The symptomatic evaluation, ability to have a meal, and overall patient satisfaction after the operations were assessed. RESULTS: Follow-up results were available in 8 patients. One patient had intestinal strangulation with graft failure 3 days after operation. Takedown of the graft and end-to-side esophagogastrostomy were successful. There was no mortality. Outcome assessment was completed at a median of 6 years (range, 1 to 12 years). Overall patient satisfaction was good in 6 patients, and fair and worse in 1 patient each. Most of the patients could have regular meals. Two patients had intermittent abdominal fullness after meals. Six of these 8 patients would have the operation again. CONCLUSIONS: Limited distal esophagectomy with short-colon interposition through a left thoracoabdominal approach is a safe and feasible alternative to near total esophagectomy in patients with achalasia who have prior failed esophagomyotomy. Improved alimentary function was observed in most of the patients after operation, which resulted in a better quality of life.