Involvement of increased p53 expression in the decrease of mitochondrial DNA copy number and increase of SUVmax of FDG-PET scan in esophageal squamous cell carcinoma.

We appraised Warburg effect through analysis of mitochondrial DNA (mtDNA) copy number and maximum standard uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan and their alterations in esophageal squamous cell carcinoma (ESCC). Later T-status and longer longitudinal tumor length were associated with lower mtDNAESCC copy number (p < .05) but higher SUVmax-ESCC (p < .05), respectively. Lower mtDNAESCC copy number correlated with higher SUVmax-ESCC, reciprocally (p < .05). ESCCs expressing mutant p53 protein had lower mtDNAESCC copy number (p = .056) but higher SUVmax-ESCC (p = .046). We conclude that mutant p53 protein may be involved in the Warburg effect of ESCC.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy.

BACKGROUND: The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. METHODS: Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3-5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. RESULTS: Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3-5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all's P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3-5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all's P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. CONCLUSIONS: Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion.

The prognostic value of metastatic lymph node number and ratio in oesophageal squamous cell carcinoma patients with or without neoadjuvant chemoradiation.

OBJECTIVES: We aim to evaluate the prognostic value of metastatic lymph node number (MLN) and ratio (MLR) in oesophageal squamous cell carcinoma (OSCC) patients with or without neoadjuvant chemoradiation. METHODS: Two thousand one hundred and fifty-one OSCC patients receiving oesophagectomy with (n = 850) or without (n = 1301) neoadjuvant chemoradiation were included. The MLN was categorized into 0 (N0), 1-2 (N1), 3-6 (N2) and more than 7 (N3); the MLR was categorized into 0, 0-0.2 and >0.2. The prognostic value was evaluated with survival analysis using the Cox proportional hazards regression model and the Kaplan-Meier method. RESULTS: In patients without neoadjuvant chemoradiation, the 3-year overall survival rates were 54.8, 34.4, 21.8 and 6.5% with MLN = 0, 1-2, 3-6 and more than 7, respectively (P < 0.001). The 3-year overall survival rates were 54.7, 31.2 and 14.2% with MLR = 0, 0-0.2 and more than 0.2, respectively (P < 0.001). In patients with neoadjuvant chemoradiation, the 3-year overall survival rates were 49.0, 28.4, 12.5 and 0.0% with MLN = 0, 1-2, 3-6 and more than 7, respectively (P < 0.001). However, the survival curves of MLN = 3-6 and MLN ≥7 overlapped on the Kaplan-Meier plots. In contrast, MLR demonstrated good ability to show the survival differences on the Kaplan-Meier plots. The 3-year overall survival rates were 48.9, 27.3 and 0.0% with MLR = 0, 0-0.2 and more than 0.2, respectively (P < 0.001). CONCLUSIONS: Both MLN and MLR were significant prognostic factors in OSCC patients regardless of neoadjuvant chemoradiation. But in patients with neoadjuvant chemoradiation, the survival rates were similar between ypN2 and ypN3 patients, suggesting that there was no necessity of separating patients into ypN2 and ypN3 stages.

Comparison of the short-term postoperative results of prone positioning and lateral decubitus positioning during thoracoscopic esophagectomy.

INTRODUCTION: The conventional approach during thoracoscopic esophagectomy was performed in the left lateral decubitus position (LLDP). Recently, thoracoscopic esophagectomy in the prone position (PP) has attracted the attention of surgeons. AIM: To report institutional experience with thoracoscopic esophagectomy in PP and compare it with the conventional LLDP approach. MATERIAL AND METHODS: We reviewed 59 consecutive patients who had presented with esophageal cancer undergoing three-stage thoracoscopic/laparoscopic esophagectomy (TLE) from May 2011 to Dec 2013. The TLE was sequentially performed on enrolled patients in LLDP from May 2011 to Oct 2012 and in PP from Nov 2012 to Dec 2013. Immediate postoperative outcomes were collected and compared to determine differences between the 2 groups. RESULTS: Thirty-eight patients had their operations in LLDP and 21 in PP. No differences in blood loss, respiratory condition during surgery, or postoperative pain scores were observed between the 2 groups. The PP had a shorter thoracic stage duration (3.4 vs. 3.9 h; p = 0.03) and shorter intensive care unit (ICU) stay (1.0 vs. 1.5 days; p = 0.03) but yielded a similar number of lymph nodes. Incidence of complications was similar between the 2 groups, except significantly lower incidence of pneumonia in PP (0% vs. 21.1%; p = 0.04) and higher incidence of hoarseness in PP (52.4% vs. 23.7%; p = 0.03). The symptoms resolved within 3 months in all patients except in the 2 patients with vocal cord palsy. CONCLUSIONS: It is feasible and safe to perform thoracoscopic esophagectomy by adopting the prone position. Thoracoscopic esophagectomy in the prone position is potentially associated with fewer major complications and shorter ICU stay.

Radical Lymph Node Dissection in Primary Esophagectomy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Subtotal esophagectomy with radical lymph node dissection (RLND) remains an effective therapeutic strategy for localized esophageal squamous cell carcinoma (ESCC). However, controversy exists regarding the extent to which RLND should be performed. We reappraised the prognostic impact and accurate nodal staging of RLND in ESCC. METHODS: The data from 101 ESCC patients (mean age, 57.5 years; 93 men) who underwent primary subtotal esophagectomy were retrospectively collected. Candidate variables, including the number of total dissected lymph nodes (TDLN [subgrouped into TDLN less than 13, TDLN 13 to 40, and TDLN more than 40]), were evaluated to determine their prognostic impacts and hazard ratio (HR). RESULTS: Fewer TDLN (p < 0.001; HR 9.011, 2.449, and 1.000 for TDLN less than 13, TDLN 13 to 40, and TDLN more than 40, respectively), tumor length exceeding 3.5 cm (p < 0.001; HR 3.321), resection margin invasion (p < 0.001; HR 14.493), and positive nodal status (p = 0.002; HR 2.730) were independent predictors of a poor prognosis. Considering the 54 node-negative patients, more TDLN correlated with improved survival (p = 0.001). Risk analysis demonstrated that one fewer TDLN could contribute to an increased HR of 1.047 (p = 0.014). However, RLND involving more TDLN appeared to lose the prognostic impact for the 47 node-positive patients (p = 0.072). Furthermore, the number of positive dissected lymph nodes remained at approximately 4 if the number of TDLN exceeded 20. CONCLUSIONS: For N-negative or N-positive ESCC patients undergoing primary surgical resection, the number of TDLN influenced their prognosis or nodal staging accuracy, respectively. At least 20 TDLN were necessary for N-positive patients.

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.

Hospital type- and volume-outcome relationships in esophageal cancer patients receiving non-surgical treatments.

AIM: To study the "hospital type-outcome" and "volume-outcome" relationships in patients with esophageal cancer who receive non-surgical treatments. METHODS: A total of 6106 patients with esophageal cancer diagnosed between 2008 and 2011 were identified from a national population-based cancer registry in Taiwan. The hospital types were defined as medical center and non-medical center. The threshold for high-volume hospitals was based on a median volume of 225 cases between 2008 and 2011 (annual volume, >56 cases) or an upper quartile (>75%) volume of 377 cases (annual volume>94 cases). Cox regression analyses were used to determine the effects of hospital type and volume outcome on patient survival. RESULTS: A total of 3955 non-surgically treated patients were included in the survival analysis. In the unadjusted analysis, the significant prognostic factors included cT, cN, cM stage, hospital type and hospital volume (annual volume, >94 vs ≤94). The 1- and 3-year overall survival rates in the non-medical centers (36.2% and 13.2%, respectively) were significantly higher than those in the medical centers (33.5% and 11.3%, respectively; P=0.027). The 1- and 3-year overall survival rates in hospitals with an annual volume of ≤94 (35.3% and 12.6%, respectively) were significantly higher than those with an annual volume of >94 (31.1% and 9.4%, respectively; P=0.001). However, in the multivariate analysis, the hospital type was not statistically significant. Only cT, cN, and cM stages and hospital volume (annual volume>94 vs ≤94) were independent prognostic factors. CONCLUSION: Whether the treatment occurs in medical centers is not a significant prognostic factor. High-volume hospitals were not associated with better survival rates compared with low-volume hospitals.

Impact of hospital volume on long-term survival after resection for oesophageal cancer: a population-based study in Taiwan†.

OBJECTIVES: Previous studies have shown that patients who undergo oesophageal cancer surgery in high-volume hospitals have lower postoperative mortality rates. However, the impact of hospital volume on long-term survival is controversial. METHODS: We identified 2151 patients who were diagnosed with oesophageal cancer between 2008 and 2011 from a national population-based cancer registry in Taiwan. High-volume hospitals were defined as those performing more than 86 oesophagectomies during that period (22 cases/year). Patients were stratified by whether they received preoperative chemoradiation. Cox regression analyses were used to determine the survival impact of hospital volume. RESULTS: The 3-year overall survival rates after oesophagectomies were 44.9% in high-volume hospitals, compared with 40.2% in low-volume hospitals (P = 0.002). For patients who received preoperative chemoradiation (n = 850), the 1- and 3-year overall survival rates were 74.7 and 36.8%, respectively, in high-volume hospitals, compared with 73.5 and 42.6%, respectively, in low-volume hospitals (P = 0.333). For patients who did not receive preoperative chemoradiation (n = 1301), the 1- and 3-year overall survival rates were 78.1 and 50.0%, respectively, in high-volume hospitals, compared with 67.9 and 38.8%, respectively, in low-volume hospitals (P < 0.001). Multivariate analysis showed that hospital volume, resection margin, cT, pT and pN stages are significant independent prognostic factors. CONCLUSIONS: Overall survival rate of patients who undergo oesophagectomies without preoperative chemoradiation at high-volume hospitals is significantly higher than at low-volume hospitals. However, there was no significant correlation between hospital volume and long-term outcome in patients who received preoperative chemoradiation.

Single-port video-assisted thoracoscopic surgery for lung cancer.

In 2004, novel results using pulmonary wedge resection executed through single-port video-assisted thoracoscopic surgery (VATS) was first described. Since that time, single-port VATS has been advocated for the treatment of a spectrum of thoracic diseases, especially lung cancer. Lung cancer remains one of the top three cancer-related deaths in Taiwan, and surgical resection remains the "gold standard" for early-stage lung cancer. Anatomical resections (including pneumonectomy, lobectomy, and segmentectomy) remain the primary types of lung cancer surgery, regardless of whether conventional open thoracotomy, or 4/3/2-ports VATS are used. In the past three years, several pioneers have reported their early experiences with single-port VATS lobectomy, segmentectomy, and pneumonectomy for lung cancer. Our goal was to appraise their findings and review the role of single-port VATS in the treatment of lung cancer. In addition, the current concept of mini-invasive surgery involves not only smaller resections (requiring only a few incisions), but also sub-lobar resection as segmentectomy. Therefore, our review will also address these issues.

The prognostic value of circumferential resection margin in esophageal squamous cell carcinoma after concurrent chemoradiation therapy and surgery.

BACKGROUND: Despite the significant advances in surgical techniques and multimodality treatments for esophageal cancer, the overall survival remains unsatisfactory. During the past years, efforts were made to determine the prognostic factors that would help in identifying patients suitable for surgery or guiding adjuvant therapy. Positive circumferential resection margins (CRMs) in esophageal cancer have been previously linked with poor prognosis, but their impact on survival remains controversial in patients treated by a multimodality protocol. The aim of our study was to examine the significance of tumor involvement of CRM in patients with esophageal squamous cell carcinoma after concurrent chemoradiation therapy followed by esophagectomy. METHODS: Between 2000 and 2010, 94 esophageal squamous cell carcinoma patients who received preoperative concurrent chemoradiation therapy followed by surgery were enrolled in our study. We focused on the CRM, which was defined microscopically as clear (negative) or involved (positive). Univariate and multivariate survival analyses were performed with overall survival as the endpoint. RESULTS: Our cohort was predominantly male (94.7%) with a median age of 57 years. All of them received concurrent chemoradiation therapy followed by esophagectomy. Overall, 17 patients (18.1%) had positive CRM. Kaplan-Meier survival analysis demonstrated that the 5-year overall survival of patients with clear and involved CRM is 60.1% and 11.8%, respectively (log rank p < 0.001). Multivariate analysis with the Cox proportional hazard model demonstrated that CRM involvement is a significant prognostic factor for overall survival (p < 0.001). CONCLUSION: In patients with esophageal squamous cell carcinoma who underwent trimodality treatment, CRM involvement is a significant risk factor predicting survival. Additional effort is required to achieve a clear CRM in esophageal cancer treatment.