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Yi-Cheng Wu,
Yen-Chu,
Chi-Ju Yeh,
Ming-Ju Hsieh,
Tzu-Ping Chen,
Ying-Kai Chao,
Ching-Yang Wu,
Hsu-Chia Yuan,
Po-Jen Ko,
Yun-Hen Liu, Hui-Ping Liu
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ABSTRACT: Background. To date there are no practical platforms for performing natural orifice transluminal endoscopic surgery in the thoracic cavity. This study evaluates the feasibility of transumbilical thoracosopy for lung biopsy and pericardial window creation. Methods. Eleven dogs (6 in the nonsurvival group and 5 in the survival group) were used for this study. A homemade metallic tube was advanced into the abdominal cavity via a 12-mm umbilical incision. The metallic tube was advanced into the thoracic cavity through a subxyphoid diaphragmatic incision under video guidance. Access to the thoracic cavity was achieved by a flexible bronchoscope via the metallic tube. Surgical lung biopsy and pericardial window creation were performed using an electrocautery loop and needle knife. The animals were euthanized 20 minutes after the surgery was complete (nonsurvival group) or 14 days postsurgery (survival group) for necropsy evaluation. Results. Eight pericardial window creations and 21 of 22 preplanned lung biopsies were completed in a median time of 72.18 minutes (range 50-105 minutes). One dog in the nonsurvival group died after tension pneumothorax due to postprocedure massive air leaks. In the survival group, the postoperative period was uneventful in all 5 dogs. Autopsies revealed no signs of vital organ injury and complete healing of the diaphragmatic incision occurred in all animals. Conclusions. The study demonstrated that transumbilical thoracoscopic surgical lung biopsy and pericardial window creation is feasible. The safety and efficacy of the transumbilical approach need to be verified by a more detailed survival study.
Surgical Innovation 04/2013; · 2.13 Impact Factor
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ABSTRACT: PURPOSE: Transoral endoscopic surgery has been shown to be feasible and safe in both humans and animal models. The purpose of this study was to evaluate the safety and efficacy of transoral and conventional thoracoscopy for thoracic exploration, surgical lung biopsy, and pericardial window creation. METHODS: The animals (n = 20) were randomly assigned to the transoral endoscopic approach group (n = 10) or conventional thoracoscopic approach group (n = 10). Transoral thoracoscopy was performed with a flexible bronchoscope via an incision over the vestibulum oris. In conventional thoracoscopy, access to the thoracic cavity was obtained through a thoracic incision. Surgical outcomes (body weight, operating time, operative complications, and time to resumption of normal diet), physiologic parameters (respiratory rate, body temperature), inflammatory parameters [white blood cell (WBC) counts and C-reactive protein (CRP)], and pulmonary parameters (arterial blood gases) were compared for both procedures. RESULTS: The surgical lung biopsy and pericardial window creation were successfully performed in all animals except one animal in the transoral group. There was no significant difference in operating times between the groups. The increase in WBC in the transoral thoracoscopy group was significantly smaller on postoperative day 1 than in the conventional thoracoscopy group (p = 0.0029). The transoral group had an earlier return to preoperative body temperature (p = 0.041) and respiratory rate (p = 0.045) on day 7. With respect to pulmonary parameters, there was no significant difference in blood pH, pCO(2), or PaCO(2) between the transoral and transthoracic groups. All animals survived without complications 14 days after surgery. CONCLUSIONS: This study demonstrated that the transoral approach was comparable to conventional thoracoscopic surgery for lung biopsy and pericardial window creation in terms of safety and efficacy.
Surgical Endoscopy 01/2013; · 4.01 Impact Factor
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Yen Chu,
Chien-Ying Liu,
Yi-Cheng Wu,
Ming-Ju Hsieh,
Tzu-Ping Chen,
Ying-Kai Chao,
Ching-Yang Wu,
Hsu-Chia Yuan,
Po-Jen Ko,
Yun-Hen Liu, Hui-Ping Liu
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ABSTRACT: Natural orifice transluminal endoscopy has been developed for abdominal surgical procedures. The aim of this study was to compare the surgical outcome between a novel transoral approach and a standard transthoracic approach for the thoracic cavity in a canine model.
Twenty-eight dogs were assigned to transoral (n = 14) or standard thoracoscopy (n = 14). Each group underwent thoracic exploration, pre-determined surgical lung biopsy, and pericardial window creation. Blood draws were obtained before surgery and at postoperative days 1, 3, 7, and 14. Operative time, complications, laboratory parameters, hemodynamic parameters, and inflammatory parameters were compared between the two procedures. The animals were monitored for two weeks and necropsy were performed for surgical outcome evaluation.
The thoracic procedures were successfully performed in all of the dogs, with the exception of one animal in the transoral group. There were no serious acute or delayed complications related to surgery. There was no difference between the two surgical groups for each of the hemodynamic parameters that were evaluated. Regarding the immunological impact of the surgeries, transoral thoracoscopy was associated with significant elevations in interleukin 6 and c-reactive protein levels on postoperative days 1 and 3, respectively, when compared with the standard thoracoscopy. All dogs recovered well, without signs of mediastinitis or thoracic infection. Necropsy revealed absence of infection, no injury to vital organs, and confirmed the success of the novel procedure.
This study suggests that both techniques were comparable with respect to procedure success rate, hemodynamic impact, and inflammatory changes. Furthermore, there was no difference in the incidence of postoperative discomfort between groups.
PLoS ONE 01/2013; 8(1):e50338. · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: Transumbilical laparoscopy allows the patient to undergo various surgical procedures associated with abdominal disease. The aim of this study was to evaluate the feasibility and safety of transumbilical thoracic exploration and surgical lung biopsy in a canine survival model. METHODS: We performed the procedure in 12 dogs weighting 7.1-9.1 kg. The thoracic cavity was accessed using a metal tube inserted via umbilical and diaphragmatic incisions. After transumbilical thoracoscopy, we resected the predetermined lung lobe with an electrocautery loop. We carried out daily clinical examinations, including determination of respiratory rate and rectal temperature. Laboratory parameters (white blood cell count) and inflammatory parameters, including serum interleukin-6 and C-reactive protein, were measured before surgery and at postoperative days 1, 3, 7, and 14. We performed necropsies 2 wk after surgery. RESULTS: We successfully performed corrected surgical lung biopsies for the predetermined lung lobe in all animals, with a median time of 43.5 min (range, 32-65 min). We observed two perioperative complications: One dog had minor postoperative air leakage and one had hemodynamic collapse because of inadequate ventilation. These animals recovered well without signs of perioperative infection. Necropsies at 2 wk after surgery showed no evidence of mediastinitis or peritonitis. CONCLUSIONS: Exposure of the thoracic cavity and surgical lung biopsy via a transumbilical incision is feasible in this canine model of survival. This procedure may have potential advantages over currently used transthoracic thoracoscopy techniques.
Journal of Surgical Research 12/2012; · 2.25 Impact Factor
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ABSTRACT: Recently the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene with transforming activity was identified in non-small cell lung cancer (NSCLC). In addition, NSCLC patients with the EML4-ALK fusion gene had a dramatic response and longer progression free survival after ALK inhibitor treatment than those without this fusion gene. However, the incidence and clinical and molecular characteristics of the EML4-ALK fusion gene in NSCLC patients of Taiwan are still unclear.
Sixty-four fresh frozen tumor specimens were obtained from the tissue bank of Chang Gung Memorial Hospital for RNA extraction and EML4-ALK fusion gene detection. Paraffin sections of lung tumors from all of these patients were available and were analyzed for ALK protein expression by immunohistochemical (IHC) study. The results were correlated with clinical and molecular biomarkers.
Three of the 64 tumors (4.7%) had the EML4-ALK fusion gene. Two were adenocarcinomas, and one was adenosquamous carcinoma. Twenty patients with non-squamous cell carcinomas had epidermal growth factor receptor (EGFR) mutations, so the EML4-ALK fusion gene was found in 14.3% of EGFR wild type non-squamous cell carcinomas. Two tumors were variant 3 (3a+3b with 3b predominant) and had strong staining (3+) for ALK by IHC stains. One tumor was variant 1 and had moderate staining (2+) for ALK. None of the ALK wild type tumors had strong staining for ALK. When compared with other clinical and molecular features, only the IHC stain for ALK was significantly correlated with the EML4-ALK fusion gene (p = 0.0002).
ALK overexpression detected by IHC study could be a promising detection method for the EML4-ALK fusion gene and is worth further confirmation with more samples.
Chang Gung medical journal 07/2012; 35(4):309-17.
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ABSTRACT: Extensive lymph node dissection (LND) is beneficial in primarily resected esophageal cancer patients. Such benefit was believed to be seen in neoadjuvant chemoradiotherapy (CRT)-treated patients, but evidence was inconsistent. We hypothesized that CRT might offset the benefit of LND in certain subgroup of patients, especially in major responders.
The clinical pathological data and survival of esophageal squamous cell carcinoma patients who received curative resection after CRT between 1996 and 2007 were analyzed. On the basis of the mean LND number of the cohort, patients were divided into two groups: group 1, lower LND, and group 2, higher LND.
The cohort comprised 303 patients (295 men and 8 women) with a mean age of 55.4 years. There were 179 patients in group 1 and 124 patients in group 2. One hundred one patients had pathological complete response (pCR). There were more pCR in group 1 (38 vs. 26.6 %, P = 0.039) and more lymph node positive cases in group 2 (16 vs. 27.4 %, P = 0.018). Extent of LND had no survival difference in the entire cohort (overall survival 32 vs. 38 %, P = 0.31). With the stratification analysis according to tumor response, inadequate LND exhibited negative impact in patients who did not experience pCR (P = 0.027). Without adequate LND, the survival of ypTxN0 was equally poor as ypN-positive cases (overall survival 15 vs. 16 %, P = 0.791). In the pCR group, the extent of LND had an impact on survival.
The effect of LND was influenced by tumor response after CRT. There is a strong survival benefit for extensive LND after CRT in esophageal squamous cell carcinoma, especially in non-pCR patients.
Annals of Surgical Oncology 05/2012; 19(11):3500-5. · 4.17 Impact Factor
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ABSTRACT: Higher extent of lymph node dissection (LND) is beneficial in primarily resected esophageal cancer patients by providing accurate staging and better tumor control. Achieving pathological complete response (pCR) after chemoradiotherapy (CRT) also represents better outcome. We studied the controversial question whether higher LND could further improve survival after pCR.
Between 1996 and 2007, Esophageal squamous cell carcinoma (ESCC) patients with pCR after CRT were included. Based on the median number of dissected lymph node, patients were divided into two groups (Group 1: Lower LND; Group 2: Higher LND). We compared the demographic features, perioperative outcomes, recurrence, and survival between groups.
The cohort comprised 101 patients (100 males and one female) with a mean age of 58 years. There were 56 and 45 patients in Group 1 and 2, respectively. Clinical features and perioperative outcome were similar between groups. During a mean follow-up of 78.8 months, 32 (33.7%) patients died of the disease and 35.8% of patients developed recurrence. There was no difference in locoregional (11.3% vs. 9.5%, P=0.78) or distant recurrence (22.6% vs. 33.3%, P=0.18) between the two groups. Patients with lowest LND also had similar outcomes as those with the highest LND. The 5-year disease specific survival rate was 65 and 64% in Group 1 and 2, respectively.
In ESCC patients, the number of negative lymph nodes had no prognostic impact after pCR.
Journal of Surgical Oncology 05/2012; 106(4):436-40. · 2.10 Impact Factor
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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.
Surgical Endoscopy 05/2012; 26(10):2988-92. · 4.01 Impact Factor
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ABSTRACT: The correlation between high tumor podoplanin (PP) immunoreactivity and poor outcome in patients with non-chemoradiotherapy(CRT) pretreated upper aerodigestive tract squamous cell carcinoma (SCC) has been reported recently. Little is known about the implication of PP expression after CRT. Therefore, we conducted this study.
We evaluated the PP immunoreactivity in ypT3N0 esophageal SCC patients by using immunohistochemistry. The impact of PP expression intensity in tumors on patient survival was judged in combination with clinical and pathological descriptors.
Our study included 109 males and 4 females (mean age, 57.6 years; range, 38-79 years). PP immunoreactivity was expressed in tumors in 95% of patients and 38% of patients had high PP expression. High PP expression tumors had positive association with lymphovascular invasion (LVI). Multivariate analyses revealed tumor PP immunoreactivity and circumferential resection margin (CRM) status as independent prognostic factors. Patients with positive CRM and high PP expression had shortest survival followed by those with either positive CRM or high PP expression, and then by patients with neither positive CRM nor high PP expression (5-year disease-specific survival: 5%, 20%, 40%, P < 0.001).
Tumor PP immunoreactivity in conjunction with CRM status are useful markers to identify aggressive post-CRT treated ypT3N0 stage esophageal SCC.
Journal of Surgical Oncology 02/2012; 105(2):183-8. · 2.10 Impact Factor
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ABSTRACT: Objectives The benefits of video-assisted thoracoscopic surgery (VATS) for performing pulmonary metastasectomy are considered controversial. This case-matched study aimed to compare long-term outcomes after surgical resection of pulmonary metastases from colorectal cancer using different approaches (VATS vs. thoracotomy). Methods Between 1997 and 2008, 143 patients with colorectal cancer who had received their first pulmonary metastasectomy were selected. Fifty-three patients underwent a surgical procedure that utilized a thoracotomy approach (Group 1), and 90 patients underwent a surgical procedure that used a VATS-based approach (Group 2). After being matched for tumor number, diameter (measured by computed tomography), and surgical procedure (wedge resection or lobectomy), 35 pairs of patients were finally enrolled. Study endpoints included tumor recurrence and survival.Results There was no hospital mortality in both groups. Within the mean follow-up period of 50 months, 47.1% patients developed a recurrence (52% at the pulmonary level and 48% at systemic level), and 52.9% of the patients were alive at the time of analysis. There was no difference between Groups 1 and 2 in terms of overall recurrences (54 vs. 40%, p = 0.23), all pulmonary recurrences (25.7 vs. 22.9%, p = 0.78), and same side lung recurrences (14.3 vs. 20%, p = 0.75). The 5-year overall survival (OS) after lung resection was 43 and 51% in Groups 1 and 2, respectively (p = 0.21). Conclusions Our case-matched study showed that survival outcome of pulmonary metastasectomy using VATS is not inferior to that of open thoracotomy in selected cases.
The Thoracic and Cardiovascular Surgeon 01/2012; 60(6):398-404. · 0.88 Impact Factor
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ABSTRACT: Recently, two studies revealed that MET amplification was associated with secondary epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients. But it remains uncertain whether MET amplification could be related to primary TKI resistance in NSCLC because of limited data.
MET gene dosage of the tumor tissues from 208 NSCLC patients was investigated by real time quantitative polymerase chain reaction and compared with molecular and clinical features, including EGFR mutations, KRAS mutations, EGFR gene copy numbers, and patient survivals. Three copies were used as the cutoff. Among them, 25 patients were also evaluable for EGFR TKI responsiveness.
The proportion of high MET gene dosage was 10.58% (22/208) with higher incidence in squamous cell carcinoma (11.86%) and smokers (16.18%), although the differences with adenocarcinoma and nonsmokers were nonsignificant. Coexisting EGFR mutations were identified, and the incidence (8.54%) was similar to wild type (12.0%). High MET gene dosage was significantly associated with higher tumor stage (stage I + II versus stage III + IV; p = 0.0254) and prior chemotherapy for stage III + IV adenocarcinoma patients (35.71% versus 7.41%; p = 0.0145) but not correlated with primary TKI resistance. Among the 155 surgically resectable patients (stage I to IIIA), high MET gene dosage was significantly associated with shorter median survival (21.0 months versus 47.1 months; p = 0.042) by univariate analysis.
High MET gene dosage was not related to primary TKI resistance and the incidence was increased after chemotherapy, suggesting high MET gene dosage may also be related to chemotherapy resistance.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2011; 6(12):2027-35. · 4.55 Impact Factor
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ABSTRACT: Percutaneous cryotherapy has become a minimally invasive treatment option for unresectable lung malignancies. We report the experience and outcomes with percutaneous computed tomography (CT)-guided cryotherapy of primary lung malignancies, as well as recurrence and metastases, in patients ineligible for surgery.
The procedure was performed after administration of local anesthesia on 23 tumors in 19 patients (10 male and 9 female patients; mean age, 58.7 years). None of the patients were surgical candidates and underwent CT-guided percutaneous cryotherapy for treatment of the malignant mass in the lung. Visualization of low-attenuation ice ball formation was performed using CT scanning after each cycle of freezing and thawing therapy. Subsequent CT scans were scheduled at 3-month intervals post-procedure to assess tumor control.
No lethal complication, major bleeding or bronchial damage was observed in any of the 23-cryotherapy sessions performed. Three patients developed pneumothorax and one patient required chest tube insertion. Thirteen tumors (56.5%) regressed, including two complete responses, five tumors (21.7%) were stationary and the remaining five tumors (21.7%) were found to be progressing at the 3-month follow-ups. No recurrence was found in the 11 regressed tumors for 6 months, and there was also no recunence in the two tumors that completely responded up to 12 months later with a satisfactory procedure.
Percutaneous cryotherapy for primary lung cancer, recurrence and metastatic lung tumors is feasible and safe for local control.
Journal of the Formosan Medical Association 07/2011; 110(7):460-6. · 1.13 Impact Factor
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ABSTRACT: As an advanced status of cancer stem cells (CSCs), metastatic CSCs (mCSCs) have been proposed to be the essential seeds that initiate tumor metastasis. However, the biology of mCSCs is poorly understood. In this study, we used a lymph node (LN) metastatic CEA-producing carcinoma cell line, UP-LN1, characterized by the persistent appearance of adherent (A) and floating (F) cells in culture, to determine the distribution of CSCs and mechanisms for the induction of mCSCs. F and A cells displayed distinct phenotypes, CD44(high)/CD24(low) and CD44(low)/CD24(high), respectively. The CSC-rich nature of F cells was typified by stronger expression of multiple drug resistance genes and a 7.8-fold higher frequency of tumor-initiating cells in NOD/SCID mice when compared with A cells. F cells showed a greater depression in HLA class I expression and an extreme resistance to NK/LAK-mediated cytolysis. Moreover, the NK/LAK-resistant F cells were highly susceptible to IFN-γ-mediated induction of surface CXCR4, with concomitant downregulation of cytoplasmic CXCL12 expression, whereas these two parameters remained essentially unchanged in NK/LAK-sensitive A cells. Following the induction of surface CXCR4, enhanced migratory/invasive potential of F cells was demonstrated by in vitro assays. Confocal immunofluorescence microscopy showed the two distinct phenotypes of F and A cells could be correspondingly identified in monodispersed and compact tumor cell areas within the patient's LN tumor lesion. In response to IFN-γ or activated NK/LAK cells, the CXCR4(+) mCSCs could be only induced from the CSCs, which were harbored in the highly tumorigenic CD44(high)/CD24(low) F subset. Our results revealed the complexity and heterogeneity of the CSC of this cell line/tumor and the differential immunomodulatory roles of F and A cells. A better understanding of the interactions among different classes of CSCs and their niches may assist us in eradicating the CSCs/mCSCs through targeted immunotherapy, chemotherapy, or both.
Laboratory Investigation 06/2011; 91(10):1502-13. · 3.64 Impact Factor
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Po-Jen Ko,
Yen Chu,
Yi-Cheng Wu,
Chieng-Ying Liu,
Ming-Ju Hsieh,
Tzu-Ping Chen,
Yin-Kai Chao,
Ching-Yang Wu,
Hsu-Chia Yuan,
Yun-Hen Liu, Hui-Ping Liu
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ABSTRACT: The thoracic cavity approach for natural orifice transluminal endoscopic surgery (NOTES) is technically challenging. The aim of this study was to evaluate the feasibility of a transoral endoscopic technique for a surgical lung biopsy and pericardial window creation
Under general anesthesia, a 12 mm incision was made over the vestibulum oris region. Under video guidance, a homemade metallic tube was introduced through the incision, extending along the pre-tracheal space to the substernal space with blunt dissection technique, and used as the entrance into the thoracic cavity. A surgical lung biopsy and a pericardial window creation were performed in 12 canines, using the transoral NOTES technique.
The transoral endoscopic surgical lung biopsy and pericardial window creation were successfully completed in 11 of the 12 canines. Intraoperative bleeding and death from an injury to the pulmonary hilum developed in one animal during the electrosurgical excision of lung tissue.
Transoral surgical lung biopsy and pericardial window creation in canine models is technically feasible and can be used as a novel experimental platform for studies of NOTES for intra-thoracic surgery.
Journal of Surgical Research 04/2011; 175(2):207-14. · 2.25 Impact Factor
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ABSTRACT: Close circumferential resection margin (CRM) is an established predictor for locoregional recurrence (LR) in rectal cancer but remains controversial in esophageal malignancy. As yet, little is known about the significance of CRM after chemoradiotherapy (CRT), especially in squamous cell carcinoma (SCC). This study investigated the relationship between CRM distance and recurrence after neoadjuvant CRT in esophageal SCC patients.
Between 1997 and 2005, esophageal SCC patients who underwent surgery after neoadjuvant CRT and with pathology stage T3N0M0 and T3N1M0 (metastatic lymph nodes <2) were selected. CRM distance was reassessed and divided into three groups (group 1: CRM >1 mm, group 2: uninvolved CRM but <1 mm, group 3: CRM involved).
The cohort comprised 145 male and 6 female patients with mean age of 57 years. There were 74, 51, and 26 patients in group 1, 2, and 3, respectively. With median follow-up period of 50 months, LR developed in 30.5% of patients. Both group 2 and group 3 had significantly higher LR than group 1 (37 and 42% vs. 21%, P < 0.05). Meanwhile, mean time from operation to recurrence was also significantly shorter in group 2 and group 3 than in group 1 (267 and 269 days versus 402 days, P < 0.05). Five-year disease-specific survival (DSS) was highest in group 1 (40%). Despite the similarity in LR, 5-year DSS significantly differed between group 2 and group 3 (22 vs. 7%, P < 0.05). The higher rate of distant recurrence (DR) and concomitant LR + DR in group 3 accounted for the survival difference.
In ypT3 esophageal SCC patients, CRM distance provides useful information for risk stratification in cancer recurrence and survival.
Annals of Surgical Oncology 02/2011; 18(2):529-34. · 4.17 Impact Factor
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Jiz-Yuh Wang,
Chi-Ling Yeh,
Hsiao-Chin Chou,
Chi-Hwa Yang,
Yu-Ning Fu,
Ya-Ting Chen,
Hui-Wen Cheng,
Chi-Ying F Huang, Hui-Ping Liu,
Shiu-Feng Huang,
Yi-Rong Chen
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ABSTRACT: Vaccinia H1-related phosphatase (VHR) is classified as a dual specificity phosphatase. Unlike typical dual specificity phosphatases, VHR lacks the MAPK-binding domain and shows poor activity against MAPKs. We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. Decreasing VHR expression by RNA interference caused higher EGFR phosphorylation at Tyr-992. In addition to EGFR, VHR also directly dephosphorylated ErbB2. Consistent with these results, suppression of VHR augmented the foci formation ability of H1299 non-small cell lung cancer (NSCLC) cells, whereas overexpression of VHR suppressed cell growth in both two- and three-dimensional cultures. Expression of VHR also suppressed tumor formation in a mouse xenograft model. Furthermore, VHR expression was significantly lower in NSCLC tissues in comparison to that in normal lung tissues. Collectively, this study shows that down-regulation of VHR expression enhances the signaling of ErbB receptors and may be involved in NSCLC pathogenesis.
Journal of Biological Chemistry 01/2011; 286(12):10177-84. · 4.77 Impact Factor
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ABSTRACT: The present study aimed to evaluate the performance of transtracheal thoracic exploration and pericardial window creation in a canine survival model.
Transthoracic exploration was performed in 14 dogs. Under general anesthesia, after an incision in the right lateral wall of the middle-lower portion of the trachea was made, a 9-mm metal tube was advanced into the thoracic cavity. For thoracic cavity exploration and pericardial window creation, a flexible bronchoscope was introduced through the metal tube into the thoracic cavity. After thoracoscopy, a Dumon stent (Novatech, Grasse, France) was used to cover the tracheal incision site and facilitate healing. Animals were evaluated by endoscopy 1 and 2 weeks later. Animals were humanely killed, and necropsy was performed 2 weeks after the transtracheal natural orifice transluminal endoscopic surgery.
Fourteen dogs underwent transtracheal thoracic exploration lasting for an average of 110 minutes (range, 80-150), with 3 perioperative deaths. At 2 weeks after pericardial window creation, endoscopy revealed normal healing of the tracheal incision sites in all 11 surviving animals. Necropsy on the 11 animals at 2 weeks showed 9 adhesions around the pericardial window and 5 adhesions around the tracheal incision region. No mediastinitis or abscesses could be identified.
Transtracheal thoracic exploration is technically feasible. Increasing surgical experience together with improvement in endoscopic techniques will further facilitate the development of natural orifice transluminal endoscopic surgery for thoracic diseases.
The Journal of thoracic and cardiovascular surgery 01/2011; 141(5):1223-30. · 3.41 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the performance of a novel transtracheal endoscopic technique for thoracic evaluation and intervention in a large animal model.
In 12 animals (6 pigs and 6 dogs) under general anesthesia, a tracheal incision was made on the right lateral wall of the lower trachea and used as an entrance for thoracic evaluation and intervention. Postoperative follow-up included endoscopy at 1 and 2 weeks after surgery and necropsy at 2 weeks after surgery.
Transtracheal opening and thoracic exploration were achieved in all animals. Four animals (3 pigs and 1 dog) died as a result of complications from the procedure. At the follow-up endoscopy, healing at the tracheal opening region was noted in seven animals.
The transtracheal approach to the thoracic cavity is technically feasible in both porcine and canine models (4/12 animals died). The canine model is perhaps more suitable than the porcine model for the study of the transtracheal approach to the thoracic cavity.
Surgical Endoscopy 10/2010; 25(5):1652-8. · 4.01 Impact Factor
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Shih Sheng Jiang,
Wen-Tsen Fang,
Ya-Hsiue Hou,
Shiu-Feng Huang,
B Linju Yen,
Junn-Liang Chang,
Shih-Miao Li, Hui-Ping Liu,
Ying-Lan Liu,
Chih-Ting Huang,
Yu-Wei Li,
Te-Hsuan Jang,
Shih-Hsuan Chan,
Su Jing Yang,
Chao A Hsiung,
Cheng-Wen Wu,
Lu-Hai Wang,
I-Shou Chang
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ABSTRACT: SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell growth.
Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms.
SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and downregulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity.
Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4.
Clinical Cancer Research 09/2010; 16(17):4363-73. · 7.74 Impact Factor
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ABSTRACT: Non-regional lymph node metastasis in intrathoracic esophageal cancer is classified as M1 lesion with poor prognosis following surgery alone. We studied the controversial question of whether chemoradiotherapy (CRT) improves survival of these patients.
A cohort of patients with clinically overt nodal M1 disease, which could be encompassed by a tolerable radiation therapy port, was selected from the database of the Chang Gung Memorial Hospital.
From 1994 to 2005, 54 nodal stage IV intrathoracic esophageal squamous cell carcinoma (SCC) patients received neoadjuvant CRT. Significant response occurred in 24 patients. Scheduled esophagectomy was performed in 26 patients. The 3-year overall survival (OS) and disease-free survival (DFS) for the whole group were 27% (median: 14.2 months) and 22% (median: 14.7 months), respectively. Multivariate analysis identified pretherapy lymph nodes classified as M1a and R0 resection after CRT as independent favorable prognosticators. Median survival reached 36.9 months in the pretherapy M1a subgroup as opposed to 12.5 months in the M1b subgroup (3-year-DFS: 40% vs. 10%, P = 0.0117). Scheduled surgery after CRT benefits only after R0 resection (3-year-DFS: 36%, median survival: 45 months). The group with incomplete resection had a high surgical risk and dismal survival compared to the non-surgery group (3-year-DFS: 0% vs. 9%, 9.5 vs. 10.5 months).
Pretherapy M1a disease had a significantly better survival than nodal M1b disease after CRT in SCC. Aggressive surgical treatment after CRT is reserved for cases when complete resection is anticipated.
Journal of Surgical Oncology 08/2010; 102(2):158-62. · 2.10 Impact Factor
