Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous cancer cells in vitro and in vivo.

The effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, have not been studied in esophageal squamous cell cancer (ESCC). Cell viability assay; flow cytometry for cell cycle and annexin V apoptosis assays; assays for cell migration, invasion, and adhesion to extracellular matrix (ECM); and immunoblotting and immunofluorescence staining were performed in three ESCC cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used to study the effects of SAHA in vivo. SAHA effectively inhibited growth of ESCC cells with half-inhibitory concentrations (IC50 ) ranging from 2.6 to 6.5 µmol/L. SAHA restored acetylation of histone 3 lysine 9 (H3K9Ac) and histone 4 lysine 12 (H4K12Ac) with an induction of G1 or G2 cell cycle arrest and apoptosis. Expression of cell cycle checkpoint regulatory proteins including cyclin-dependent kinases (CDKs) and cyclins was decreased, whereas expression of cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells with an induction of E-cadherin expression. SAHA significantly inhibited growth of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while decreasing expression of CDK4 and cyclin D1 within the murine tumors. In conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its potential as an epigenetic therapeutic agent for ESCC.

Thymoma associated with myasthenia gravis and Sjögren syndrome / Timoma asociado con miastenia grave y síndrome de Sjögren

Thymoma is the most common neoplasm of the anterior mediastinum but thymoma with Sjögren syndrome (SS) is rare. Sjögren syndrome is a systemic autoimmune inflammatory disorder. It is characterized by lymphocytemediated destruction of exocrine glands, which leads to absent glandular secretion. Here, we present the case of a 63yearold man with thymoma and concurrent myasthenia gravis and SS, who achieved remission after thymectomy.

El timoma es la neoplasia más frecuente del mediastino anterior, pero un timoma acompañado del síndrome de Sjögren (SS) constituye una ocurrencia rara. El síndrome de Sjögren es un trastorno inflamatorio autoinmune sistémico. Se caracteriza por la destrucción - mediada por linfocitos - de las glándulas exocrinas, lo cual conduce a la ausencia de secreción glandular. Aquí presentamos el caso de un hombre de 63 años de edad con timoma, y miastenia gravis y SS concurrentes, que logró la remisión después de una timectomía.

Thymoma associated with myasthenia gravis and Sjögren syndrome.

Thymoma is the most common neoplasm of the anterior mediastinum but thymoma with Sjögren syndrome (SS) is rare. Sjögren syndrome is a systemic autoimmune inflammatory disorder. It is characterized by lymphocyte-mediated destruction of exocrine glands, which leads to absent glandular secretion. Here, we present the case of a 63-year-old man with thymoma and concurrent myasthenia gravis and SS, who achieved remission after thymectomy.

Positron emission tomography in bronchioloalveolar carcinoma of the lung.

OBJECTIVES: This study assessed the maximum standard uptake value of positron emission tomography-computed tomography in patients of pulmonary adenocarcinoma with bronchioloalveolar carcinoma features and whether SUVmax correlates with pathological status, lymph node metastasis, and prognosis. METHODS: We retrospectively reviewed 674 patients diagnosed with non-small-cell lung cancer between January 2002 and June 2009. Patients with clinical stage I-II disease underwent a preoperative PET-CT scan followed by anatomic resection. We reviewed the clinical features of 209 patients with an average follow-up of 87 months. RESULTS: We analyzed clinical variables for 40 patients with BAC features and 169 patients without BAC features. Age, sex, location, and number of dissected lymph nodes, carcinoembryonic antigen level, and lymphovascular invasion had no difference between the two groups. Compared with non-BAC patients, patients with BAC features had a lower SUVmax (2.51 ± 2.02 vs 4.98 ± 4.03, p < 0.001), lower ratio of SUVmax (1.10 ± 0.34 vs 1.22 ± 0.27, p = 0.014), better tumor differentiation (p < 0.001), and smaller tumor size (2.30 ± 1.41 vs 2.97 ± 1.71, p < 0.03). The negative prediction rate was 87.08% for N2 and 80.80% for N1 disease. All patients in the BAC group were alive after the operation. The five-year survival rate of patients without BAC features was 71.2%. CONCLUSIONS: Preoperative SUVmax of PET-CT was more accurate at predicting negative N2 than N1 disease. BAC is associated with markedly better prognosis compared with invasive adenocarcinoma and may be cured with surgical resection Aggressive surgical resection is recommended even for patients with false-negative N2 disease.

Should the pectus bar be removed before pregnancy? Two case reports.

The Nuss procedure is a minimally invasive repair for pectus excavatum in children and adults. However, it is unclear whether or not the stainless steel bar should be removed before pregnancy. We report on two adult females who had undergone a Nuss repair for pectus excavatum and successfully delivered prior to removal of the pectus bar.

Prognostic value of 18-FDG uptake in early stage NSCLC.

BACKGROUND: We assessed whether the standard uptake of 18-fluorodeoxyglucose (18-FDG) in non-small cell lung cancers (NSCLC) differed between stage I and non-stage I tumors. METHODS: We reviewed 163 patients with NSCLC who underwent surgical lymph node dissection after tumor resection in 2002-2003. Patients with clinical stage I NSCLC who were investigated with preoperative positron emission tomography integrated computed tomography (PET-CT) scans using 18-FDG uptake were included; those with N2 disease were excluded. We reviewed 55 patients with a mean follow-up of 68 months. RESULTS: We analyzed 36 patients with stage I (Group 1) and 19 patients with non-stage I NSCLC (Group 2; 8 stage II, 7 stage III and 4 stage IV). There were no statistical differences in sex, age, tumor size, histological type, location or tumor differentiation between the groups. Group 1 had lower maximum standard 18-FDG uptake values (SUVmax) than Group 2 (4.9 +/- 2.7 vs. 8.1 +/- 3.8; P = 0.001). Using multiple logistic regression, patients with higher preoperative SUVmax and serum carcinoembryonic antigen (CEA) levels showed advanced tumor stages postoperatively (SUVmax > 4.7, odds ratio 7.65; CEA > 3.5 ng/mL, odds ratio 8.39). High 18-FDG uptake was significantly associated with reduced median survival (62.69 months for SUVmax < 4.7 and 40.89 months for SUVmax > 4.7). CONCLUSIONS: High preoperative 18-FDG uptake of tumors was significantly associated with reduced overall patient survival. The SUVmax of the tumor and serum CEA levels demonstrated aggressive tumors and could be helpful preoperatively when considering patients for induction therapy or resection.

Cortactin, fascin, and survivin expression associated with clinicopathological parameters in esophageal squamous cell carcinoma.

Cortactin, fascin, and survivin have been documented in several human cancers and play important roles in tumor progression. We collected 57 surgical specimens, including esophageal squamous cell carcinomas (SqCC; 7 well-differentiated, 15 moderately differentiated, and 24 poorly differentiated), 3 dysplasias, and 8 normal esophageal tissues. Tissue microarrays were constructed and the immunostaining scores for cortactin, fascin, and survivin were assessed. In 46 SqCC specimens, we examined the relationship between the expression of three biomarkers and tumor differentiation or clinical parameters. Higher immunostaining scores for cortactin, fascin, and survivin correlated positively with tumor differentiation of esophageal SqCC. Univariate survival analysis showed significantly worse prognosis in patients with high scores of cortactin (>or=290), fascin (>or=245), and survivin (score >or= 175), poor differentiation, T4 stage, positive for lymph node metastasis, and positive for distant metastasis. In multivariate survival analysis, high scores of survivin (>or=175) and poor differentiation were independent risk factors for worse prognosis. Our results demonstrated that higher expression of survivin may be related to tumor progression and it is an independent risk factor for poor survival time of esophageal SqCC. Survivin may be a good biomarker to be applied in clinic to predict the prognosis of esophageal SqCC.

Clinical experience of Nuss procedure for pectus excavatum in adult female patients.

BACKGROUND: Pectus excavatum (PE) repair by Nuss procedure is well established in pediatrics, but studies of adult female patients are rare. We analyzed the efficacy of the Nuss procedure in adult, female PE patients. METHODS: We retrospectively reviewed adult patients who underwent Nuss repair of PE from April 2005 to November 2007. Precise morphologic characterization of the pectus allowed an appropriate shaping of the bars to achieve a symmetric repair. RESULTS: Out of 126 consecutive adult patients who underwent the Nuss procedure at our institution, 15 women with a mean age of 24.6 +/- 4.01 years were enrolled in the study. Their preoperative Haller index had a mean of 5.72 +/- 2.38. Seven patients (46.67 %) underwent repair with the insertion of double pectus bars. Complications included transient bilateral pneumothorax (n = 1) and right-sided pleural effusion (n = 1). One patient received a subsequent breast augmentation, which yielded a better thoracic contour. CONCLUSIONS: The Nuss procedure offers a high satisfaction rate and an acceptable complication rate for PE repair in adult female patients. A subsequent surgery for breast augmentation can be considered after the Nuss repair has stabilized.

Surgical treatment of gastrointestinal stromal tumor in the esophagus: report of three cases.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the alimentary tract. The term GIST was introduced in 2004 and understanding of the tumor's cellular origin, classification, diagnostic markers, and prognostic parameters has evolved dramatically over the last two decades. Hirota et al. proposed that GISTs originate from interstitial cells of Cajal - regulators of gut peristalsis that normally express CD 117 - which is the product of the c-kit proto-oncogene that encodes a tyrosine kinase receptor that regulates cellular proliferation in GISTs. In the esophagus, squamous cell carcinoma and adenocarcinoma are common malignant tumors and leiomyoma is the most frequent mesenchymal neoplasm. Esophageal GISTs, however, have been reported less frequently. METHODS: We report three cases of esophageal GISTs in patients who underwent surgical intervention in our institution. The patients suffered from dysphagia, without specific findings on initial physical examination. Submucosal tumors were suspected after the patients underwent barium swallow and endoscopic studies. In addition, positron emission tomography was used to study a submucosal tumor in one patient. RESULTS: The pathological diagnosis was confirmed in all cases by microscopic examination with hematoxylin and eosin stain and positive immunoreaction for c-kit. Two of them were low risk and the third one was high risk in character, according to the consensus approach and depending on the size and mitotic index of the tumor. CONCLUSION: The patients had uneventful postoperative recoveries and were followed up regularly at 3-month intervals.

Esophageal bronchogenic cyst: a rare entity.

BACKGROUND/AIMS: Bronchogenic cysts are congenital lesions of foregut origin, usually found in intrapulmonary or mediastinal locations. However, an esophageal bronchogenic cyst is an uncommon occurrence. The definitive diagnosis is based on histological findings after extirpation of the cyst. Surgical excision of bronchogenic cysts is considered appropriate because of the high complication rates of subsequent infection, rupture, hemorrhage, and malignant degeneration if left untreated. RESULTS: A 42-year-old man presented with a two-year history of progressive dysphagia. An esophageal bronchogenic cyst was evidenced by esophagography, Computed tomography, magnetic resonance imaging, and endoscopic ultrasound, followed by confirmation with surgical exploration. CONCLUSION: Esophageal bronchogenic cysts should be included in the differential diagnosis of a mediastinal tumor, especially when the tumor is within or near the tracheobronchial tube, even though it is a rare condition.

Factors related to primary bilateral spontaneous pneumothorax.

OBJECTIVES: We studied the risk factors associated with primary bilateral spontaneous pneumothorax. METHODS: From January 2001 to December 2002, 102 patients with primary spontaneous pneumothorax were reviewed and divided into two groups. Group A patients had primary spontaneous bilateral pneumothorax (PSBP; simultaneous or nonsimultaneous). Group B included patients with a primary spontaneous pneumothorax (PSP). We compared age, smoking habits, body weight, height, body mass index (BMI), and radiological findings between groups. RESULTS: Twenty-four patients developed PSBP (24 %). The male-to-female ratio was 22 : 2 in group A and 73 : 5 in group B ( P = 0.106). Eleven group A patients (46 %) and 34 group B patients (44 %) were smokers ( P = 0.037). The mean BMI was 18.39 +/- 2.45 kg/m (2) in group A and 19.70 +/- 2.00 kg/m (2) in group B ( P = 0.009). High-resolution computed tomography revealed bilateral lung blebs or bullae in 63 % of group A patients and in 53 % of group B patients ( P = 0.724). CONCLUSION: PSBP was significantly more frequent in patients with a lower BMI and among smokers. These patients require extended hospitalization and vigilant treatment.

Expression of EMMPRIN and matriptase in esophageal squamous cell carcinoma: correlation with clinicopathological parameters.

Extracellular matrix metalloproteinase inducer (EMMPRIN) and the type II transmembrane serine protease, matriptase, are expressed in several human cancers and play an important role in tumor progression. The aim of the present study was to investigate the immuno-staining patterns of EMMPRIN and matriptase in patients with esophageal squamous cell carcinomas (SCC) and correlate the percentage tumor staining with tumor differentiation and clinical parameters. EMMPRIN and matriptase immunoreactivity was seen on the cell membrane and in the cytoplasm of tumor cells in all 41 cases of esophageal SCC evaluated. The percentage tumor staining of EMMPRIN was 48 +/- 3% for well differentiated, 73 +/- 3% for moderately differentiated, and 92 +/- 3% for poorly differentiated esophageal SCC. Higher percentage tumor staining with EMMPRIN correlated significantly with poorly differentiated esophageal SCC (P < 0.05). The percentage tumor staining with matriptase correlated significantly with tumor differentiation (52 +/- 3% for well differentiated, 85 +/- 2% for moderately differentiated, and 88 +/- 3% for poorly differentiated esophageal SCC). Additionally, higher percentage tumor staining with matriptase was significantly correlated with the advanced N and M stages (P < 0.05). Our results demonstrate that EMMPRIN and matriptase are over-expressed in esophageal SCC and are correlated with advanced clinicopathological stages. Pharmacological agents targeting EMMPRIN and matriptase expressions may be beneficial in the treatment of esophageal SCC.

Malignant pleural effusion treatment outcomes: pleurodesis via video-assisted thoracic surgery (VATS) versus tube thoracostomy.

STUDY OBJECTIVES: Video-assisted thoracic surgery (VATS) has been widely used in the diagnosis and management of various thoracic diseases. The objective of this retrospective study was to compare the effectiveness of patients undergoing pleurodesis through VATS versus tube thoracostomy for malignant pleural effusion (MPE). Study design was a retrospective review of patients treated in medical centers and hospitals in Taiwan. PATIENTS: One hundred and forty-eight patients with MPE resistant to systemic therapy resulting from various types of carcinomas were retrospectively reviewed. VATS pleurodesis was carried out in 82 and tube thoracostomy with pleurodesis in 66 patients. RESULTS: There were no intraoperative deaths and 4 (2.7 %) in-hospital deaths. One hundred and eighteen (79.7 %) patients were available for follow-up. There were no statistically significant differences in the preoperative characteristics of the two treatment groups, except that the amount of effusion and the percentage of patients with dyspnea were both higher in the VATS treatment group. The duration of chest tube drainage was significantly longer ( P < 0.01) in the tube thoracostomy treatment group (9.1 +/- 3.3 vs. 6.2 +/- 2.3 days). There were no significant differences between the treatment groups with regard to the incidence of surgical complications and perioperative mortality. Median survival was similar in both treatment groups; however, the VATS treatment group had a significantly longer median recurrence-free survival than the tube thoracostomy treatment group. CONCLUSIONS: VATS treatment for MPE appears to be superior to tube thoracostomy for diagnostic accuracy and effectiveness in preventing effusion recurrence; however, the role of these treatments for MPE is palliative, and does not significantly prolong survival time.

Spontaneous massive haemothorax caused by rupture of an intercostal vein.

Spontaneous massive haemothorax is rare. We describe a healthy 44 year old woman who experience sudden onset chest pain while sleeping. Chest radiograph revealed massive right pleural effusion. Progressive dyspnoea, cold sweating, and tachycardia developed later. A tube thoracostomy was performed immediately and massive haemothorax was noted. An emergency thoracotomy was performed because of unstable vital signs. Disruption of the right third intercostal vein with continuous bleeding was observed, and suture ligation of the vein was performed. The total blood loss was about 4000 ml. The patient recovered uneventfully, and her condition at follow up visits to the outpatient department was satisfactory.

APACHE II score and primary liver cancer history had risk of hospital mortality in patients with pyogenic liver abscess.

BACKGROUND: The Acute Physiology and Chronic Health Evaluation II classification system has been extensively used for predicting the patient mortality in various diseases. However, its utilisation on the pyogenic liver abscess has not yet been well studied. AIMS: The purpose of this study was to validate this system on this high death rate disease. PATIENTS: A retrospective study was conducted to assess 314 patients with pyogenic liver abscesses admitted to tertiary medical centre in past 12 years. METHODS: The outcome measurement was the in-hospital mortality. A multiple logistic regression model was used to assess the association between mortality and Acute Physiology and Chronic Health Evaluation II score while controlling for the potential confounding factors. RESULTS: The overall in-hospital mortality was 8.3%. The mean Acute Physiology and Chronic Health Evaluation II score of the expired patients was higher (P<0.0001). The mortality rate increased rapidly when Acute Physiology and Chronic Health Evaluation II score >or=15. After controlling for the potential confounding factors, patient with high admission Acute Physiology and Chronic Health Evaluation II score >or=15 had a higher chance of in-hospital mortality (P<0.01). In addition, the primary liver cancer history is also a risk factor (P=0.03). CONCLUSIONS: The Acute Physiology and Chronic Health Evaluation II score and the primary liver cancer history predict the in-hospital mortality of the pyogenic liver abscess patient.

Prediction of the risk of hepatic failure in patients with portal vein invasion hepatoma after hepatic resection.

AIM: Hepatic failure can develop after curative hepatectomy in patients with a hepatocellular carcinoma (HCC) invading the portal vein, because of cirrhosis and excessive tissue loss. This study aimed to identify the risk factors for hepatic failure in such patients. METHOD: Forty patients with an HCC invading the portal vein underwent curative hepatectomy from January 1995 to June 2003. Eight patients developed hepatic failure and died within 3 months. Possible risk factors for this were analysed using univariate and multivariate regression. These included the liver function index, surgical blood loss, tumour pattern, portal hypertension, estimated residual liver volume measured by computed tomography (ERLV(CT)) and estimated residual liver volume using the indocyanine green (ICG) retention rate at 15 min (ERLV(ICG15)). RESULTS: The ERLV(CT) smaller than the ERLV(ICG15) and presence of portal hypertension were independent risk factors for post-hepatectomy hepatic failure. CONCLUSION: Having portal vein invasion HCC with portal hypertension or an ERLV(CT) less than an ERLV(ICG15) are significant predictors of post-hepatectomy hepatic failure. These factors are important considerations for patients with portal vein invasion HCC who could undergo curative hepatic resection.

Solitary fibrous tumors of the pleura: clinical, radiological, surgical and pathological evaluation.

AIMS: To report a clinicopathological series of cases of solitary fibrous tumor of the pleura from Taiwan. METHODS: Clinical data was collected from a review of medical records and telephone interviewing for follow-up. RESULTS: Eight patients, three men and five women aging from 34 to 71 years, underwent tumor resection and were followed in a period from 7 months to 13.5 years. Six patients underwent standard thoracotomy and two had VATS for tumor excision. Tumors were pathologically benign in seven patients and malignant in one. Patients were all alive with no evidence of tumor recurrence at the time of this report. CONCLUSIONS: One should always consider SFTPs as potentially malignant tumors. Complete resection remains the mainstay of cure. Standard thoracotomy should always be considered when a high suspicion of malignancy is raised, whereas VATS may be a preferred approach for smaller tumors.

Minithoracotomy with simultaneous video-assisted thoracoscopic surgery vs. video-assisted thoracoscopic surgery for spontaneous hemopneumothorax.

BACKGROUND: Spontaneous hemopneumothorax, a life-threatening and rare disorder and complication of primary spontaneous pneumothorax, is regarded as a surgical emergency. We have prospectively investigated the differences in safety and utility between minithoracotomy with simultaneous video-assisted thoracoscopic surgery (MT + VATS) and the video-assisted thoracoscopic surgery approach (VATS) in the treatment of spontaneous hemopneumothorax. METHODS: From Jan 1998 to May 2002, 248 patients with primary spontaneous pneumothorax were treated in our hospital. Among these patients, 12 (4.8 %) spontaneous hemopneumothorax occurred, all in the first episode of spontaneous pneumothorax. After tube thoracostomy, the amount of blood drainage ranged from 500 to 1,500 ml. 8 patients were treated by MT + VATS and 4 by VATS. RESULTS: During surgery, the sources of hemorrhage were all from the torn aberrant vessels between the apical blebs and the parietal pleura. The duration of main surgical procedure (including removal of blood clot in pleural cavity, control of bleeding and blebectomy) was significantly shorter in MT + VATS than in VATS (p < 0.01, Mann-Whitney U). There were no differences between these two groups in postoperative chest tube drainage duration, average postoperative pain score or hospital stay. No relapses occurred in the succeeding 6 months to 4 years. CONCLUSIONS: Spontaneous hemopneumothorax is usually treated as an urgent surgical condition. MT + VATS is an easy accessible and safe procedure that could be applied as an initial treatment method in the patient with spontaneous hemopneumothorax, especially in the treatment of the patients with active hemorrhage and massive blood clot in the thorax.

Tracheoinnominate artery fistula: successful surgical management of one case.

Fistula formation between the trachea and the innominate artery following tracheostomy is a rare, but life-threatening complication. Because of its clinical presentation with acute, massive, intractable bleeding, the mortality is nearly 100% without operation. To the best of our knowledge, the autologous pericardium flap for coverage of the tracheal defect has not been discussed in the English-language literature. We successfully treated one case of tracheoinnominate artery fistula following tracheostomy by using autologous pericardium flap.

Pulmonary hypertension alters soluble guanylate cyclase activity and expression in pulmonary arteries isolated from fetal lambs.

The nitric oxide (NO)-guanosine 3',5'-cyclic monophosphate (cGMP) signaling pathway plays an important role in the pulmonary vascular transition at birth. We studied pulmonary arteries and veins isolated from normal late-gestation fetal lambs and from fetal lambs with persistent pulmonary hypertension (PPHN) following prenatal ligation of the ductus arteriosus. We additionally used double immunolabeling and immunoblot analysis to determine relative vascular contents of endothelial nitric oxide synthase (NOS-III) and soluble guanylate cyclase (sGC). Cyclic GMP content and sGC activity were significantly lower in arteries from hypertensive lambs than controls. A rank order for contents of both soluble guanylate cyclase and NOS-III was observed by both immunolabeling and immunoblotting: Control vein = Hypertensive vein > Control artery > Hypertensive artery. Our data demonstrate that the relative expression of sGC correlates well with the relative expression of NOS-III, and indicate the potential importance of soluble guanylate cyclase in the regulation of the perinatal pulmonary circulation. These data may help us understand vascular mechanisms producing PPHN, as well as patterns of response to exogenous NO.