Publications

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    ABSTRACT: To investigate the prognostic significance of lymphovascular invasion (LVI) in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT).
    Annals of Surgical Oncology 07/2014; · 4.12 Impact Factor
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    ABSTRACT: Backgrounds: In this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).
    World Journal of Surgical Oncology 05/2014; 12(1):170. · 1.09 Impact Factor
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    ABSTRACT: Transthoracic thoracoscopic lobectomy is the preferred method of surgical treatment for early lung cancer. Current methods require a transthoracic approach and are associated with chronic postoperative pain in up to 25 % of patients. Single-port transumbilical uniport surgery may offer advantages over multiport surgery with less postoperative pain and better cosmetic results. The aim of this study was to evaluate the feasibility of a transumbilical anatomic lobectomy of the lung (TUAL) in a canine model.
    Surgical Endoscopy 05/2014; · 3.43 Impact Factor
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    ABSTRACT: The optimal tip position for an intravenous port and the angle between the locking nut and the catheter are still debatable. This study evaluates the use of chest X-ray plain films for screening patients with potential intravenous port complications. We reviewed, retrospectively, 1505 patients who had an intravenous port implanted between January 1 and December 31, 2006 at Chang Gung Memorial Hospital, and were followed up until June 30, 2010. Of the 1119 patients with an intravenous port implanted via the superior vena cava (SVC), 279 underwent re-interventions for complications. There were four different types of single lumen port, and entry vessels on the right side were utilized as the predominant entry sites through the vessel cut-down method for catheter cannulation. The anatomic catheter tip was confirmed on the postero-anterior view of plain chest X-ray films. We used the Picture Arching and Communicating System (PACS) (GE, Fairfield, CT, USA) to record the angle and distance in degrees and centimeters, respectively. The tracheal carina was seen easily on the chest X-ray plain film and the location of the catheter tip and the angle between the locking nut and the catheter were identified. The location of the catheter tip was significantly related to migration (p < 0.0001). The cut-off value of the receiver operating characteristic (ROC) curve for location and migration was 0.68 cm below the carina. The area under the curve (AUC) was 0.8385 and had favorable predictive power. The ideal position of an intravenous port to avoid migration is 0.68 cm below the carina. For surgeons, a quantified reference may minimize technical errors. Patients with shallow tip location should be followed up regularly and aggressive intervention initiated for any intravenous port malfunction.
    Surgery Today 04/2014; · 0.96 Impact Factor
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    ABSTRACT: We studied whether the bronchoscopic findings could be help to predict outcome after chemoradiotherapy (CRT) in patients with airway invasion by esophageal cancer. Between 2000 and 2010, we retrospectively investigated esophageal cancer patients with T4 disease due to airway invasion who had received CRT as first line treatment. Airway invasion is defined as infiltration of the tracheobronchial wall or protruded intraluminal growth on bronchoscopy. The total radiation dose of CRT was 60 Gy and divided into two cycles. Bronchoscopic findings were evaluated together with other clinical parameters and correlated with overall survival (OS). There were 68 patients with a mean age of 54.5 years. After the first cycle of CRT, bronchoscopic examination showed complete regression of endobronchial lesion in 16 patients. OS was 26% at 1 year and 5% at 3 years with the median survival time (MST) of 7 months. Multivariate analysis revealed vocal cord palsy (unfavorable, OR [95% CI]:2 [1.07-3.84], P = 0.03), carina involvement (unfavorable, OR [95% CI]:2.6 [1.12-6], P = 0.025) and intraluminal tumor growth (unfavorable, OR [95% CI]:1.9 [1.1-3.3], P = 0.023) as independent factors for survival. The MST after CRT was 12.1, 6.1, 5.7 months in patients with 0, 1, 2 factors, respectively (P < 0.001). Bronchoscopic finding determined outcome after CRT in esophageal cancer patients with airway invasion J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 02/2014; · 2.64 Impact Factor
  • Journal of thoracic disease. 01/2014; 6(1):61-63.
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    ABSTRACT: There is growing evidence that cancer-associated fibroblasts (CAFs) interact with tumor cells and play important roles in tumor progression and invasion. Podoplanin is a type-1 transmembrane glycoprotein expressed in a variety of normal human tissues, including lymphatic endothelium. Tumor cell expression of podoplanin correlates with nodal metastasis and poor prognosis in squamous cell carcinoma (SCC) of oral cavity and esophagus. Recently, podoplanin-positive CAFs have been shown to exert adverse or beneficial prognostic effect on different cancer types. However, the significance of podoplanin-positive CAFs in esophageal SCC has not been investigated. This is the first study to investigate podoplanin expression in CAFs and tumor cells by immunohistochemistry in 59 cases of surgically resected esophageal SCC. We found significant association of podoplanin expression between CAFs and tumor cells (P = 0.031). Although the abundance of podoplanin-positive CAFs per se had no prognostic effect, concordant podoplanin expression in CAFs and tumor cells (both high or both low) was strongly associated with short survival (P = 0.00088). Multivariate analysis showed that concordant podoplanin expression was the strongest independent adverse prognostic factor (hazard ratio: 3.62; 95% confidence interval: 1.69-7.77; P = 0.00094). Our data suggest that interaction between podoplanin-positive CAFs and tumor cells is important in tumor biology of esophageal SCC.
    International journal of clinical and experimental pathology. 01/2014; 7(8):4847-56.
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    ABSTRACT: Although esophagectomy traditionally is recommended to perform within 8 weeks after neoadjuvant chemoradiotherapy (nCRT), data from neoadjuvantly treated rectal cancer patients demonstrate that delayed surgery (>8 weeks) can maximize the effect of CRT. Despite these promising data, investigators are concerned that delayed surgery may lead to tumor repopulation. We report the impact of delayed surgery in patients with esophageal cancer who were treated with nCRT. We retrospectively studied 276 esophageal cancer patients treated with nCRT and surgery between 2002 and 2008. We compared perioperative complication, rate of pathological complete response (pCR), distribution of tumor regression grade (TRG), and overall survival (OS) in patients who underwent surgery within 8 weeks (group A) and after 8 weeks (group B) after nCRT. There were 138 patients in each group with similar pre/post-nCRT characteristics. Delayed surgery did not result in lower surgical risk or higher pCR rate. Survival outcome also did not improve following a longer surgery interval (5-year OS: group A vs. group B, 29 vs. 23 %; P = 0.3). On the contrary, a subgroup analysis showed that delayed surgery might be hazardous, especially in patients who demonstrate a good response after nCRT. The amount of residual cancer, as measured by TRG, increased significantly after a longer surgical interval (P = 0.024). Survival also decreased after a longer surgical interval (5-year OS ≤8 vs. >8 weeks, 50 vs. 35 %; P = 0.038). After nCRT, esophagectomy should be performed within 8 weeks, especially in patients with good response.
    Annals of Surgical Oncology 08/2013; · 4.12 Impact Factor
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    ABSTRACT: Abstract Background: Chronic wound discomfort and intercostal neuralgia are well-known postoperative complications of video-assisted thoracoscopic surgery (VATS). To explore the possibility of a surgical platform that would cause less postoperative discomfort and avoid these complications, this study evaluated the feasibility of transumbilical lung wedge resection in a canine model. Materials and Methods: Twelve dogs (4 in the nonsurvival group and 8 in the survival group) were used in this study. Transumbilical thoracoscopy was performed using a homemade metallic tube via umbilical and diaphragmatic incisions with the animal in a supine position. After thoracic exploration, wedge resection was performed on the lung using an endoscopic stapling device placed through the transumbilical and transdiaphragmatic incisions under direct bronchoscopic guidance. The animals were sacrificed 30 minutes after the procedure (nonsurvival group) or 14 days postsurgery (survival group) for necropsy and histological evaluations. Results: Eleven preplanned lung wedge resections were completed in a median time of 101 minutes (range, 65-175 minutes) with one exception due to inadequate stapling in the early phase of the experiment. There was one death directly related to postoperative massive airleaks and sepsis in the survival group. The other 7 animals had an uneventful postoperative period. Necropsies at 2 weeks after surgery confirmed successful lung resections and revealed no evidence of vital organ injury. Two animals exhibited complete healing of the diaphragmatic incision. Liver herniation was identified in 1 of 5 animals with partial wound healing. Conclusions: This preliminary animal study demonstrates that large lung wedge resection can be performed with mechanical staplers via a single transumbilical incision. Future studies will investigate the cardiopulmonary and immunologic effects of transumbilical VATS compared with conventional VATS.
    Journal of Laparoendoscopic & Advanced Surgical Techniques 07/2013; · 1.07 Impact Factor
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    ABSTRACT: PURPOSE: This study evaluated the use of intravenous ports and provides a guide related to clinical decision making. METHODS: This study retrospectively reviewed 1505 patients who had received intravenous ports at Chang Gung Memorial Hospital in 2006. The relationships between the complications and entry routes were assessed. The intervention-free periods were also determined and compared. The patients were followed up until June 2010. RESULTS: Of the 1543 procedures performed, 412 were reinterventions to treat complications, most of which corresponded to fewer than 0.1 episodes per 1000 catheter-days; these were not associated with any particular entry route. There was a higher catheter fracture rate when the right subclavian vein was chosen as the entry vessel (p < 0.05). The intervention-free period ranged from 207 to 533 days. CONCLUSION: The subclavian vein is not recommended for the use of intravenous ports. There is not only a higher risk of iatrogenic pneumothorax or hemothorax using this entry route but also a higher fracture rate, which may be caused by pinch-off syndrome. The greater saphenous vein should only be considered when the patient has superior vena cava syndrome. However, a higher incidence of infection and a lower device survival rate should be expected with this location.
    Surgery Today 05/2013; · 0.96 Impact Factor
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    ABSTRACT: BACKGROUND: Two randomized trials have shown that in patients with good response to neoadjuvant chemoradiotherapy (nCRT), a nonoperative approach (additional CRT) had equal survival to scheduled esophagectomy. However, controversy exists because of the high locoregional recurrence (LR) following a nonoperative approach. Endoscopic complete response (e-CR) determined by endoscopic finding is a good criterion for predicting local control after definitive CRT. We evaluated whether e-CR could also be used to select patients for nonoperative treatment after nCRT. METHODS: We retrospectively analyzed esophageal squamous cell carcinoma (SCC) patients with e-CR after nCRT between 1999 and 2006. Patients were divided into two groups by the type of treatment given after e-CR (group A, scheduled esophagectomy; group B, no scheduled surgery and continued CRT). RESULTS: There were 71 and 79 patients in groups A and B, respectively with similar pre/post-nCRT characteristics. Despite similarity in survival and recurrence between groups, the recurrence site differed significantly. LR occurred more frequently in group B, whereas systemic recurrence was the predominant failure pattern in group A (P < .001). With use of multivariate analysis on group B, we determined that pretreatment depth of tumor invasion ≥T3 [odds ratio (OR), 11.19; 95 % CI, 1.4-89; unfavorable, P = .023] and tumor length ≥6 cm (OR, 3.069; 95 % CI, 1.17-8.1; unfavorable, P = .023) were predictors for LR. Patients with initial clinical T2 and <6 cm tumor had comparable LR (5 %) to the surgery group; these patients were candidates for nonoperative treatment after nCRT. CONCLUSION: In esophageal SCC patients who achieved e-CR after nCRT, pretreatment tumor depth and length were good indicators to select candidates for nonoperative treatment.
    Annals of Surgical Oncology 04/2013; · 4.12 Impact Factor
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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; · 1.54 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; · 3.43 Impact Factor
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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. · 3.73 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; · 2.02 Impact Factor
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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. · 4.12 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. · 2.64 Impact Factor

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