Po-Kuei Hsu

The Metastatic Lymph Node Number and Ratio Are Independent Prognostic Factors in Esophageal Cancer

ObjectiveThe current American Joint Committee on Cancer staging system for esophageal cancer is based on lymph node location, irrespective of the number of involved and examined lymph nodes.MethodsWe enrolled 488 patients receiving primary curative resection without neoadjuvant therapy for esophageal cancer between 1995 and 2006. The importance of total resected lymph node number (TLN) and metastatic lymph node number (MLN) and ratio (MLR) on patient survival was investigated.ResultsThe overall 3-year survival rate was 35.4%. The 3-year survival rate was equivalent among patients in N1 (23.3%), M1a (22.0%), and nonregional lymph node metastasis-related M1b (18.5%, p = 0.321). No survival difference was noted between patients with TLN < 15 or ≥15 (p = 0.249). Both MLN and MLR significantly predicted patient survival. The 3-year survival rate was 52.3%, 29.2%, and 8.0% for patients with MLN = 0, 1–3, and ≥4, respectively (p < 0.001). For patients with MLR = 0–0.2 or >0.2, the 3-year survival rate was 28.7% and 9.8%, respectively (p < 0.001). However, survival rate differences were more evident when TLN was more than 15.ConclusionsWe recommend designating both regional and nonregional lymph nodes as N nodes. MLN and MLR, but not TLN, are prognostic factors in esophageal cancer.

Tumor Length as a Prognostic Factor in Esophageal Squamous Cell Carcinoma

BACKGROUND Tumor size is an important prognostic factor in many cancers, but its role in esophageal cancer remained undetermined. The aim of this study is to investigate the impact of tumor length on survival for patients with resected esophageal squamous cell carcinoma. METHODS A total 582 esophageal squamous cell carcinoma patients underwent surgical resection as the primary treatment was enrolled into this retrospective review. The longitudinal tumor length was defined as a uniformly measurement from the surgeons in the operating room immediately after completion of the esophagectomy. The impact of tumor length on patients overall survival was assessed and compared with the factors among the current tumor-nodes-metastasis (TNM) staging system published in 2009. RESULTS The overall 1-, 3-, and 5-year survival rates were 70.4%, 37.8%, and 30.0%, respectively, with a median for 22 months. The length adversely affected the overall survival, and the 5-year survival rate was 77.3%, 48.1%, 38.5%, and 23.3 % for tumor lengths of 1 cm, 2 cm, 3 cm, and more than 3 cm, respectively (p < 0.001). In multivariate survival analysis, tumor length (more or less than 3 cm) remained an independent prognostic factor (p = 0.020) as did the other current TNM factors. For subgroup analysis, the predictive value of tumor length was significant in patients with T1 or T2 disease (p < 0.001), T3 or T4 disease (p = 0.029), and patients with N0 disease (p < 0.001), but not for patients with N1, N2, or N3 disease. CONCLUSIONS Tumor length, which represents longitudinal spreading of the cancerous cells, could impact the overall survival of patients with resected esophageal squamous cell carcinoma, especially among those with nodal-negative disease. It may provide additional prognostic information to the current TNM staging system.

Positron Emission Tomography–Computed Tomography in Predicting Locoregional Invasion in Esophageal Squamous Cell Carcinoma

BACKGROUND In order to clarify the role of positron emission tomography-computed tomography (PET/CT) in thoracic esophageal squamous cell carcinoma we investigated its value in predicting locoregional invasion. METHODS Forty-five patients receiving curative esophagectomy and lymph node dissection were included. The relationship between PET/CT findings and pathology results were studied. Correlation between nodal uptake and the modified lymph node staging, which is based on number of involved nodes (N0 = no nodes; N1 = 1 to 3 nodes; N2 = more than 3 nodes), was evaluated. RESULTS The mean maximal standardized uptake value (SUV(max)) was 5.09 +/- 4.00 in T1, 14.17 +/- 2.46 in T2, 13.32 +/- 3.96 in T3, and 10.37 +/- 1.94 in T4 primary tumor. The SUV(max) was significantly lower in stage T1 tumors than in stage T2 and T3 tumors. For regional nodal involvement, PET/CT findings significantly correlated with pathology results. However, the sensitivity, specificity, and accuracy of PET/CT were only 57.1%, 83.3%, and 71.1%, respectively, and even lower for detecting nonregional lymph node metastasis. When stratified by the modified staging system, the mean SUV(max) was 0.64 +/- 1.60 in N0, 1.43 +/- 2.08 in N1, and 4.67 +/- 4.32 in N2 regional lymph node metastases, and was significantly higher in patients with N2 metastasis than in patients with N0 and N1 metastases. CONCLUSIONS Locoregional invasion in esophageal cancer can be predicted by PET/CT. The SUV(max) of the primary tumor helped identify T1 tumor, and the SUV(max) of the regional lymph nodes correlated with the severity of nodal involvement.

Bile Acid Aspiration in Suspected Ventilator-Associated Pneumonia

AIMS The aims of this study were to measure the levels of bile acids in patients with suspected ventilator-associated pneumonia (VAP) and provide a possible pathway for neutrophilic inflammation to explain its proinflammatory effect on the airway. METHODS Bile acid levels were measured by spectrophotometric enzymatic assay, and liquid chromatography mass spectrometry was used to quantify the major bile acids. Alveolar cells were grown on modified air-liquid interface culture inserts, and bile acids were then employed to stimulate the cells. Reverse transcriptase polymerase chain reaction and Western blots were used to determine the involved gene expression and protein levels. RESULTS The mean (+/- SE) concentration of total bile acids in tracheal aspirates was 6.2 +/- 2.1 and 1.1 +/- 0.4 mumol/L/g sputum, respectively, for patients with and without VAP (p < 0.05). The interleukin (IL)-8 level was significantly higher in the VAP group (p < 0.05). The major bile acid, chenodeoxycholic acid, stimulated alveolar epithelial cells to increase IL-8 production at both the messenger RNA and protein level through p38 and c-Jun N-terminal kinase (JNK) activation. The selective p38 and JNK inhibitors, as well as dexamethasone, successfully inhibited IL-8 production. CONCLUSION These data suggest that early intervention to prevent bile acid aspiration may reduce the intensity of neutrophilic inflammation in intubated and mechanically ventilated patients in the ICU.

Single-incision versus multiple-incision thoracoscopic lobectomy and segmentectomy: a propensity-matched analysis.

OBJECTIVE To compare the perioperative outcomes of single-incision and multiple-incision thoracoscopic lobectomy and segmentectomy. BACKGROUND Reports of single-incision thoracoscopic lobectomy and segmentectomy for lung cancer are limited, and a comparison between single-incision and multiple-incision thoracoscopic lobectomy or segmentectomy for lung cancer has not been previously reported. METHODS From January 2005 to June 2013, a total of 233 patients with lung cancer underwent thoracoscopic lobectomy or segmentectomy via a single-incision or multiple-incision technique. A propensity-matched analysis, incorporating preoperative variables, was used to compare the short-term outcomes between single-incision and multiple-incision thoracoscopic lobectomy and segmentectomy. RESULTS Overall, 50 patients underwent single-incision thoracoscopic pulmonary resections, including 35 lobectomies and 15 segmentectomies, and 183 patients underwent multiple-incision thoracoscopic lobectomy or segmentectomy between January 2005 and December 2011. Propensity matching produced 46 patients in each group. The length of hospital stay and the complication rate were not significantly different between the 2 groups. Single-incision thoracoscopic lobectomy and segmentectomy were associated with shorter operative time (P = 0.029), more numbers of lymph nodes (P = 0.032), and less intraoperative blood loss (P = 0.017) than with the multiple-incision approach. No in-hospital mortality occurred in either group. CONCLUSIONS Single-incision thoracoscopic lobectomy and segmentectomy are feasible, and perioperative outcomes are comparable with those of the multiple-incision approach.

Reduced membranous β-catenin protein expression is associated with metastasis and poor prognosis in squamous cell carcinoma of the esophagus

OBJECTIVES The aim of this study was to evaluate, by immunohistochemical analysis, the protein expression of beta-catenin and p53 in resected esophageal squamous cell carcinoma specimens. The clinical relevance and prognostic significance of the expression of these proteins were also analyzed. METHODS Immunohistochemistry was performed on paraffin-embedded tissue specimens from 68 resected esophageal squamous cell carcinoma tumor specimens to detect the expression of beta-catenin and p53. The correlation between the results of immunoexpression and the clinicopathologic parameters and patient survival was processed statistically. RESULTS Reduced membranous beta-catenin expression was noted in 43 (63.2%) of 68 tumor specimens. Increased expression of p53 was observed in 43 (63.2%) of 68 specimens. Reduced membranous beta-catenin protein expression was associated with the presence of distant metastasis (P = .006). Patients with reduced membranous beta-catenin expression had a worse prognosis than patients with normal membranous beta-catenin expression (P = .005). Patients with combined increased p53 and reduced membranous beta-catenin protein expression had the worst prognosis (P = .012). In a multivariate survival analysis, reduced membranous beta-catenin expression and nodal involvement were independent prognostic factors (P = .004 and .019, respectively). CONCLUSIONS Immunohistochemical analysis revealed that reduced membranous beta-catenin protein expression was associated with the presence of distant metastasis and a poor prognosis in patients with esophageal squamous cell carcinoma. Combined increased p53 and reduced membranous beta-catenin protein expression indicated a very poor prognosis in patients with esophageal squamous cell carcinoma. Further investigation is needed to understand the roles of beta-catenin and p53 in the tumorigenesis and metastasis of esophageal squamous cell carcinoma.

Survival benefits of postoperative chemoradiation for lymph node-positive esophageal squamous cell carcinoma.

BACKGROUND Little is known about the efficacy of chemoradiation therapy after surgery for patients with esophageal squamous cell carcinoma. This retrospective study aimed to determine whether postoperative chemoradiation improves survival compared with surgery alone. METHODS Of 290 patients with esophageal squamous cell carcinoma, 104 received postoperative chemoradiation therapy (CRT group) and 186 underwent surgery alone (S group). Propensity score matching analysis was used to identify 56 well-balanced pairs of patients to compare outcomes. RESULTS For N0 patients, overall survival (OS) and disease-free survival (DFS) were similar in both groups. For N+ patients, the median OS (31.0 versus 16.0 months) and the 3-year OS rate (45.8% versus 14.1%) were significantly higher in the CRT group than in the S group (p<0.001). Similarly, the median DFS (16.0 versus 9.0 months) and the 3-year DFS rate (24.1% versus 11.5%) were significantly higher in the CRT group than in the S group (p=0.002). In propensity-matched patients, a survival benefit was observed for N+ patients receiving postoperative chemoradiation (CRT versus S group: median OS 29.0 versus 16.0 months, 3-year OS rate 48.6% versus 16.8%; p=0.003). Disease-free survival (median DFS 11.0 versus 8.0 months, 3-year DFS rate 21.3% versus 12.5%) tended to be better in the CRT group than in the S group (p=0.057). CONCLUSIONS Postoperative chemoradiation therapy provided a survival benefit for patients with lymph node-positive esophageal squamous cell carcinoma.

The Prognostic Value of the Number of Negative Lymph Nodes in Esophageal Cancer Patients After Transthoracic Resection

BACKGROUND Although the number of positive lymph nodes (LN), the total number of resected LN, and the proportion of positive LN have been reported to be associated with survival in patients with esophageal cancer, little is known about the prognostic impact of the number of negative LN. METHODS A retrospective review of 754 patients receiving transthoracic esophagectomy for cancer between January 1995 and September 2011 was performed. The prognostic impact of the number of negative LN was analyzed. Log rank testing was used to compare survival curves, and Cox regression analysis was performed to identify significant prognostic factors. RESULTS A total of 707 patients were included. The mean follow-up time was 28.4±30.9 months. The 5-year overall survival for the entire cohort was 30.1%. Patients with a high number of negative LN (≥19) had better overall survival than patients with a low number of negative LN (5-year survival rate 33.4% versus 26.4%, p=0.005). Stratified analysis showed that the impact of the number of negative LN was significant in patients with T3/4 (p=0.027) and node-positive (p=0.002) esophageal cancers but not in patients with less advanced tumors. Multivariate Cox regression analysis demonstrated that the number of negative LN (in addition to age, sex, T stage, N stage, tumor length, and surgical approach) was an independent prognostic factor. CONCLUSIONS A higher number of negative LN is associated with better overall survival of esophageal cancer patients after resection. The correlation of a high number of negative LN (≥19) with survival was more prominent in patients with advanced (T3/4 stage, node-positive) tumors.

Multiinstitutional Analysis of Single-Port Video-Assisted Thoracoscopic Anatomical Resection for Primary Lung Cancer

BACKGROUND Multiinstitutional analysis of single-port video-assisted thoracic surgery (VATS) for anatomic pulmonary resection is rare. This study aimed to address the technical feasibility and applicability of single-port video-assisted anatomical resection for primary lung cancer. METHODS A total of 121 patients with primary lung cancer undergoing single-port video-assisted anatomical resection between 2011 and 2014 in 4 hospitals were included. The clinicopathologic variables and perioperative outcomes were collected and analyzed retrospectively. RESULTS Single-port VATS segmentectomies and lobectomies were performed in 24 (19.8%) and 97 (80.2%) patients, respectively. One hundred seven of 121 (88.4%) patients had adenocarcinoma and 93 of 121 (76.9%) had pathologic stage I lung cancer. The average operative time and estimated blood loss was 198.8 ± 65.4 minutes and 99.1 ± 147.6 mL, respectively. The conversion and complication rates were 2.5% (3 of 121 cases) and 14.0% (17 of 121 cases), respectively. There was no surgical mortality, and the average length of hospital stay was 6.6 ± 2.6 days. The mean resected lymph node was 22.6 ± 12.0. We also identified patient age of 60 years or more, male sex, and tumor size greater than 3 cm as unfavorable perioperative outcome predictors after single-port video-assisted anatomical pulmonary resection. CONCLUSIONS This first multiinstitutional single-port VATS study demonstrated that anatomical resection for primary lung cancer can be safely and effectively completed through a single-port VATS approach in hospitals experienced in VATS techniques.

Preoperative positron emission tomography/computed tomography predicts advanced lymph node metastasis in esophageal squamous cell carcinoma patients.

BackgroundWe aimed to study whether positron emission tomography/computed tomography (PET/CT) findings are associated with lymph node staging, as outlined by the 7th edition American Joint Committee on Cancer (AJCC) TNM staging system in patients with esophageal squamous cell carcinoma (ESCC).MethodsA series of 76 ESCC patients undergoing esophagectomy were included in this study. The relation between PET/CT findings [maximum standardized uptake value (SUVmax)] and pathologic lymph node status (N stage) was studied.ResultsThe SUVmax of extra-tumor uptake, but not that of the main tumor, was significantly associated with the N classification. N2/N3 disease was observed in 61.1% of patients with an SUVmax for extra-tumor uptake of >4.9, whereas only 17.2% of patients with an SUVmax of extra-tumor uptake of <4.9 were classified as N2/N3 The number of PET abnormalities (NPAs) was also significantly associated with the N classification. Patients with three or more NPAs had a 65% chance of being classified as N2/N3, whereas patients with one or two NPAs had less than a 20% chance of being classified as N2/N3.ConclusionsThe SUVmax of extra-tumor uptake and the NPAs were significantly associated with the N classification outlined by the 7th edition of the AJCC TNM staging system. PET/CT does help identify patients with advanced lymph node metastasis (N2/N3 stage) instead of simply indicating nodal involvement.