High Serum Levels of Vascular Endothelial Growth Factor-A and Transforming Growth Factor-β1 Before Neoadjuvant Chemoradiotherapy Predict Poor Outcomes in Patients with Esophageal Squamous Cell Carcinoma Receiving Combined Modality Therapy

Background and Purpose

This study was aimed at using proximity ligation assay (PLA) followed by enzyme-linked immunosorbent assay (ELISA) to identify serum biomarkers that predict treatment response and survival for patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy.

Methods

Seventy-nine patients with ESCC receiving CCRT of taxane-based/5-fluorouracil-based chemotherapy and 40 Gy followed by surgery were enrolled. Serum samples were collected before and <1 month after CCRT. Fifteen biomarkers were analyzed using PLA. Biomarkers significantly correlating with pathological response/survival were verified by ELISA. Associations of the serum level of biomarkers and clinical factors with pathological response, disease-free survival (DFS), and overall survival (OS) were evaluated by analysis of variance and log-rank tests.

Results

Thirty patients had complete response (38 %), 37 had microscopic residual disease (47 %), and 12 had macroscopic residual disease (15 %). With a median follow-up of 52.8 months, the median DFS was 43 months. Among the 15 biomarkers screened by PLA, vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-β1 were significantly associated with pathological response and/or DFS. These biomarkers were further analyzed by ELISA to confirm initial biomarker findings by PLA. After ELISA of these two markers, only VEGF-A levels were significantly correlated with pathological response. On multivariate analysis, patients with combined high pre-CCRT VEGF-A and TGF-β1 levels (greater than or equal to the median), independent of pathological response, had significantly worse DFS (11 months vs. median not reached; p = 0.007) and OS (16 vs. 46 months; p = 0.07).

Conclusions

Pre-CCRT serum VEGF-A and TGF-β1 levels may be used to predict pathological response and survivals for ESCC patients receiving combined-modality therapy.     

Endoscopic Tumor Length Is an Independent Prognostic Factor in Esophageal Squamous Cell Carcinoma

Purpose

To investigate the impact of endoscopic esophageal tumor length on survival for patients with resected esophageal squamous cell carcinoma (ESCC).

Methods

We retrospectively reviewed the clinicopathologic characteristics of 244 ESCC patients who underwent curative resection as the primary treatment at Taipei Veterans General Hospital between January 2000 and November 2010. The endoscopic tumor length was defined as a uniform measurement before completion of the esophagectomy. The impact of endoscopic tumor length on a patient??s overall survival (OS) and disease-free survival (DFS) were assessed. A Cox regression model was used to identify prognostic factors.

Results

The 1-, 3-, and 5-year OS rates were 81.2, 48.2, and 39.6%, respectively, with a median survival time of 18.0?months. The 1-, 3-, and 5-year DFS rates were 66.2, 34.7, and 32.4%, respectively, with a median DFS of 15.0?months. Endoscopic tumor length correlated with pathologic tumor length [Pearson correction (r)?=?0.621; P?4?cm to identify patients with decreased long-term survival. In multivariate survival analysis, endoscopic tumor length (more or less than 4?cm) remained an independent prognostic factor for both OS (P?=?0.006) and DFS (P?=?0.002).

Conclusions

Endoscopic tumor length could have a significant impact on both the OS and DFS of patients with resected ESCC and may provide additional prognostic value to the current tumor, node, and metastasis staging system before patients receive any cancer-specific treatment.     

Surgical Cytoreduction and Survival in Appendiceal Cancer Peritoneal Carcinomatosis: An Evaluation of 46 Consecutive Patients

Background

Surgical cytoreduction and intraperitoneal chemotherapy is increasingly accepted as an effective treatment modality for mucinous appendiceal neoplasm. For the majority of patients with low-grade histology, outcomes have been encouraging. The survival of patients with neoplasms of malignant character is protracted and this study was designed to evaluate the effectiveness of this surgical strategy on outcomes.

Methods

Forty-six consecutive patients with mucinous and nonmucinous appendiceal cancer with peritoneal dissemination were studied. Clinicopathological and treatment related factors were obtained from a prospective database. The study’s end points of disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.

Results

The median DFS and OS after cytoreduction were 20.5 and 56.4 months respectively. Five-year overall survival rate was 45%. Five independent factors associated with DFS and OS were identified through a multivariate analysis: age (DFS p = 0.001, OS p = 0.002), completeness of cytoreduction (DFS p = 0.001, OS p = 0.003), previous chemotherapy treatment (DFS p = 0.021), CA 199 levels (DFS p = 0.013), and tumor grade (OS p = 0.005).

Conclusions

Cytoreductive surgery and intraperitoneal chemotherapy may achieve long-term survival in appendiceal malignancies with peritoneal dissemination for which the predictors of outcomes identified through this study may tailor the disease management to commit patients early toward this successful surgical strategy.     

Clinical benefits of thoracoscopic esophagectomy in the prone position for esophageal cancer

Purposes

The clinical benefits of thoracoscopic radical esophagectomy in the prone position compared to conventional open esophagectomy have not been fully documented.

Methods

Forty-six patients with esophageal cancer who underwent MIE in the prone position (MIE-P group) were enrolled, and 46 case-matched controls that underwent open esophagectomy (OE group) were identified using propensity score methods to achieve a valid comparison of outcomes between MIE and open esophagectomy.

Results

The duration of systemic inflammatory response syndrome was shorter in the MIE-P group than in OE group (P = 0.005). The time to first walking was earlier in the MIE-P group (P < 0.001). Although the vital capacity ratio (%VC) declined after the operation in both groups, the change ratio of the %VC was 85.3 % in the MIE-P group and 69.6 % in the OE group (P < 0.001). No mortality occurred in either group. The postoperative morbidity rate was lower in the MIE-P group (13 %) than in the OE group (30.4 %) (P = 0.020). Two patients (4.3 %) in the OE group and one patient in the MIE-P group (2.2 %) had pneumonia.

Conclusions

MIE in the prone position was associated with less impairment of the pulmonary function, earlier recovery of activity and lower subsequent morbidity compared to open esophagectomy. Further investigation of the long-term outcomes is, therefore, needed.     

Lymph Node Harvest in Esophageal Cancer After Neoadjuvant Chemoradiotherapy

Background

This study was designed to determine the effects of lymph node (LN) harvest on survival in esophageal cancer after neoadjuvant chemoradiation (nCRT).

Methods

An analysis of surgically resected esophageal cancer patients after nCRT was performed to determine an association between the number of LNs resected and survival. Overall survival (OS) and disease-free survival (DFS) curves were calculated according to the Kaplan–Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model.

Results

We identified 358 patients with a mean follow-up of 27.3 months. The number of LN removed was not impacted by the type of surgical procedure. The number of LNs removed (<10 vs. ≥10, <12 vs. ≥12, and <15 vs. ≥15) did not impact OS or DFS. We found a significant difference in OS and DFS by pathologic response. The median and 5-year OS for patients with complete, partial, and no response was 65.6 months and 52.7 %, 29.7 months and 30.4 %, and 17.7 months and 25.4 % (p = 0.0002). However, the number of LN harvested did not impact OS and DFS when patients were stratified by pathologic response. MVA also revealed that the number of lymph nodes removed was not prognostic for OS or DFS. Higher age, higher stage, and less than a complete response were associated with a decreased OS. Higher stage and less than a complete response were prognostic for worse DFS.

Conclusions

The number of LNs harvested during esophagectomy does not impact survival after nCRT. Stage and pathologic response continue to be the strongest prognostic factors for survival in esophageal cancer after nCRT.     

Value of Preoperative Inflammation-Based Prognostic Scores in Predicting Overall Survival and Disease-Free Survival in Patients with Gastric Cancer

Background

This study was designed to identify which are the best preoperative inflammation-based prognostic scores in terms of overall survival (OS) and disease-free survival (DFS) in patients with gastric cancer.

Methods

Between January 2004 and January 2013, 102 consecutive patients underwent resection for gastric cancer at S. Andrea Hospital, "La Sapienza", University of Rome. Their records were retrospectively reviewed.

Results

After a median follow up of 40.8 months (8–107 months), patients’ 1-, 3-, and 5-year OS rates were 88, 72, and 59 %, respectively. After R0 resection, the 1-, 3-, and 5-year DFS rates were 93, 74, and 56 %, respectively. A multivariate analysis of the significant variables showed that only the modified Glasgow prognostic scores (p < 0.001) and PI (p < 0.001) were independently associated with OS. Regarding DFS, multivariate analysis of the significant variables showed that the modified Glasgow prognostic score (p = 0.002) and prognostic index (p < 0.001) were independently associated with DFS.

Conclusions

The results of this study show that modified Glasgow prognostic score and prognostic index are independent predictors of OS and DFS in patients with gastric cancer.     

Postoperative Pneumonia is Associated with Long-Term Oncologic Outcomes of Definitive Chemoradiotherapy Followed by Salvage Esophagectomy for Esophageal Cancer

Background or Purpose

As we previously indicated, postoperative pneumonia has a negative impact on the overall survival after planned esophagectomy. However, the impact of postoperative pneumonia after salvage esophagectomy on long-term oncologic outcomes still remains unclear. This study aimed to indicate the association between postoperative pneumonia and long-term outcomes of definitive chemoradiotherapy followed by salvage esophagectomy. Furthermore, we determined a prediction model for overall survival (OS) and disease-free survival (DFS) using a survival classification and regression tree (CART).

Methods

Ninety-three patients who underwent CRT followed by esophagectomy for thoracic esophageal cancer were identified for this study. Forty-nine patients and 44 patients were included in the salvage and neoadjuvant groups, respectively. We investigated the association between postoperative pneumonia and long-term oncologic outcomes following salvage esophagectomy.

Results

Patients from the salvage group tended to have a lower OS compared to neoadjuvant group (median survival: salvage, 24 months vs neoadjuvant, 43 months, p?=?0.117). Multivariate analyses revealed that postoperative pneumonia adversely affected both OS (p?<?0.001) and DFS (p?=?0.044) after salvage esophagectomy. We generated the prediction model for OS and DFS in the salvage group using survival CART. Postoperative pneumonia was the most important parameter for predicting the OS.

Discussion

The present study demonstrates the long-term outcomes and risk factors for mortality of salvage esophagectomy. To improve OS after salvage surgery, the development of a means of decreasing pulmonary complications is needed.

     

Thoracoscopic esophagectomy while in a prone position for esophageal cancer: a preceding anterior approach method

Background

In 2009, the rate of thoracoscopic esophagectomy for esophageal cancer was about 20 % in Japan. This low rate may be due to the difficulty in maintaining a good surgical field and the meticulous procedures that are required. The purpose of this study was to establish and evaluate a new procedure for performing a thoracoscopic esophagectomy while the patient is in a prone position using a preceding anterior approach to make the esophagectomy easier to perform.

Methods

We have performed thoracoscopic esophagectomy using our new procedure in 60 patients with esophageal cancer. Each patient was placed in a prone position and five trocars were inserted; only the left lung was ventilated and a pneumothorax was maintained. The esophagus was mobilized from the anterior structure during the first step and from the posterior structure during the second step. The lymph nodes around the esophagus were also dissected anteriorly and posteriorly. The patients were sequentially divided into two groups and their clinical outcomes were evaluated.

Results

The mean operative time for the thoracoscopic procedure for the latter 30 cases (203 min) was shorter than that for the former 30 cases (260 min) (P = 0.001). Among the 52 cases without pleural adhesion, the mean blood loss in the latter 26 cases (18 mL) was also less than that in the former 26 cases (40 mL) (P = 0.027). There were no conversions to a thoracotomy and no operative deaths in this series. Postoperative complications related to the thoracoscopic procedure occurred in 8 cases (27 %) in the former group and in 4 cases (13 %) in the latter group.

Conclusions

Thoracoscopic esophagectomy with the patient in the prone position using a preceding anterior approach is a safe and feasible procedure. As experience performing the procedure increases, the performance of the procedure stabilizes. This method seems to make the esophagectomy easier to perform.     

Surgery Is an Essential Component of Multimodality Therapy for Patients with Locally Advanced Esophageal Adenocarcinoma

Background

Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality-eligible patients treated with definitive CXRT vs. CXRT followed by esophagectomy.

Methods

We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival.

Results

Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR?=?2.041, 95% CI?=?1.235–3.373) and surgical resection (HR?=?0.504, 95% CI?=?0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50 and 54 % risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 vs. 20.3 months, p?=?0.012) and DFS (21.5 vs. 11.4 months, p?=?0.007) were significantly improved with the addition of surgery compared to definitive CXRT.

Conclusions

Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease.     

Prognostic Impact of Body Mass Index in Patients with Squamous Cell Carcinoma of the Esophagus

Purpose

To clarify the prognostic impact of body mass index (BMI) in patients with esophageal squamous cell carcinoma (ESCC).

Methods

Two hundred forty-three patients who underwent esophagectomy for ESCC from April 2005 through December 2010 were eligible. Prognoses of the patients were compared between groups stratified according to BMI. We also analyzed the survival difference using propensity score matching to adjust differences in staging and treatment.

Results

Low, normal, and high BMI groups had 35, 177, and 31 patients, respectively. The low BMI group included more advanced cases than did the normal BMI group, while tumor stage was equivalent in the normal and high BMI groups. Disease-free survival of the low and high BMI groups was significantly worse than that of the normal BMI group (P < 0.0001 between the low and normal BMI groups; P = 0.0076 between the normal and high BMI groups). Disease-free survival of the high BMI group was significantly worse than that of the normal BMI group in the propensity score-matched cohort (P = 0.0020). Multivariate analysis in this cohort demonstrated that high BMI was an independent prognostic factor (hazard ratio 2.949, 95 % confidence interval, 1.132–7.683).

Conclusions

High BMI was an independent prognostic factor after curative esophagectomy for ESCC. Although further analysis is required to clarify the influence of overweight on the biological features of ESCC, glucose metabolism may be a therapeutic target for ESCC.     

Should Stage T2 Esophageal Squamous Cell Carcinoma Be Subclassified?

Background

In patients with esophageal squamous cell carcinoma (ESCC), pathologic examination allows T2 tumors to be further subclassified according to whether the circular or longitudinal muscle layers are invaded. Therefore, we aimed to investigate whether subclassifying the T2 stages can aid in determining the prognosis for patients with ESCC.

Methods

The clinical and pathologic characteristics of 85 ESCC patients with T2 tumors who underwent thoracoscopic esophagectomy between 2008 and 2013 were retrospectively analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. The Kaplan–Meier method was used to compare survival differences with respect to each prognostic factor.

Results

Thirty-nine patients had tumors invading the circular muscle layer and were designated as having T2a disease. The remaining 46 patients had T2b disease, with tumors invading the longitudinal muscle layer. The overall 1-, 3-, and 5-year survival rates were 96.1, 53.8, and 36.4 %, respectively, with a median survival of 39.0 months. Univariate analysis indicated that sex, smoking history, grade, location, and tumor length did not significantly influence on survival. Only T stage (P = 0.017) and N stage (P = 0.003) were associated with survival. The results of multivariate Cox proportional hazard regression analysis showed that T stage (P = 0.045) and N stage (P = 0.003) were independent prognostic factors.

Conclusions

N stage and subclassified T stage are independent prognostic factors in patients with T2 tumors. Therefore, we concluded that T2 tumors can be subclassified further into T2a and T2b stages, and patients with different T2 stages may have different prognoses.     

STMN-1 Gene: A Predictor of Survival in Stage IIA Esophageal Squamous Cell Carcinoma After Ivor-Lewis Esophagectomy?

Background

Prognosis of esophageal squamous cell carcinoma (ESCC) is stage-specific; however, some patients with the same stage have different survival outcomes. Clinically, it is significant to explore the biological marker to predict patient’s outcome. We investigated the association between the stathmin1 gene (STMN-1) expression and the prognosis of patients who underwent Ivor-Lewis esophagectomy.

Methods

A total of 162 patients who suffered from midthoracic stage IIA ESCC and completely resected with Ivor-Lewis esophagectomy were studied for STMN-1 expression by qRT-PCR in fresh-frozen tissue and validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples. STMN-1 level was evaluated as a prognostic factor in ESCC. SPSS 21.0 software was used to analyze the relationship between STMN-1 expression and clinicopathological characteristics and survival probability.

Results

The overall 3- and 5-year survival was 72.20 and 42.00 % respectively. Ninety-four patients (58.02 %) experienced disease recurrence with a disease-free interval of 21.50 ± 1.20 months. qRT-PCR result showed that STMN-1 mRNA level in patients who were alive at the end of follow-up was lower compared with patients who died during the follow-up period (p < 0.05). Immunohistochemical results showed that 94 patients had STMN-1 protein overexpression (58.02 %), patient with STMN-1 overexpression had worse survival compared with patients who had low STMN-1 expression (p = 0.00). Cox regression analysis revealed that STMN-1 protein expression and T classification are independent prognostic factors.

Conclusions

Even localized ESCC are potential to relapse with poor prognosis. This study demonstrates that STMN-1 level is an independent prognostic factor after Ivor-Lewis esophagectomy. In addition, assessment of STMN-1 level could improve stratification of stage IIA ESCC patients.     

DNA Methylation Profiling Identifies EYA4 Gene as a Prognostic Molecular Marker in Hepatocellular Carcinoma

Background

DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values.

Materials and Methods

DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene.

Results

Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050).

Conclusions

EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.     

Extent of Lymphadenectomy Does Not Predict Survival in Patients Treated with Primary Esophagectomy

Background

The number of lymph nodes resected and its impact on survival for patients with esophageal cancer remains undefined. Current guidelines recommend extended lymphadenectomy in patients not receiving neoadjuvant therapy. We reviewed our single institutional experience with nodal harvest for esophageal cancer in a non-neoadjuvant therapy setting.

Methods

Patients who underwent esophagectomy as primary therapy were indentified from a prospectively maintained database consisting of 704 patients who underwent esophagectomy. Patients were stratified by number of lymph nodes (LN) resected: >5, 10, 12, 15, or 20. Survival, clinical, and pathologic parameters were analyzed with Kaplan–Meier curves, chi-square, or Fisher’s exact tests where appropriate.

Results

We identified 246 patients who underwent esophagectomy as initial treatment. The mean age was 65?±10 years. The majority of patients were male (87 %). Ivor–Lewis esophagectomy was performed for 71 %, minimally invasive esophagectomy for 15 %, transhiatal esophagectomy for 12 %, and three-field esophagectomy for 2 %. At 60 months follow-up, there was no statistically significant difference in overall survival (OS) or disease-free survival (DFS) between patients with < vs. >5 LN resected (p?=?0.74 and p?=?0.67, respectively) or in the < vs. >10 (p?=?0.33, p?=?0.11), 12 (p?=?0.82, p?=?0.90), 15 (p?=?0.45, p?=?0.79), or 20 (p?=?0.72, p?=?0.86) resected LN groups. Patients were then subdivided into node-positive and node-negative cohorts and stratified by nodal harvest. In the subgroups of patients with node-negative and node-positive disease, OS and DFS also did not significantly differ between groups with respect to number of nodes resected (p?>?0.05). A total of 49 (20 %) patients developed recurrent disease; however, recurrence was not statistically associated with number of LN resected (p?>?0.05).

Conclusion

We found no impact of extent of lymphadenectomy on overall or disease-free survival in patients treated with esophagectomy without neoadjuvant therapy. In addition, the number of nodes resected at esophagectomy did not affect recurrence rates. Current recommendations for increased nodal resection during esophagectomy in patients not receiving neoadjuvant therapy may not improve patient outcomes, and this phenomenon warrants further investigation.     

Does Postoperative Complication Have a Negative Impact on Long-Term Outcomes Following Hepatic Resection for Colorectal Liver Metastasis?: A Meta-Analysis

Background

The negative impact of postoperative complications (POCs) on long-term outcomes is well documented for several cancer surgeries, but conclusive evidence has yet to be provided on the influence of POCs on long-term oncological outcomes after hepatic resection for colorectal liver metastasis (CRLM).

Methods

Studies published through February 2012 evaluating the oncological impact of POCs after hepatectomy for CRLM were identified by an electronic literature search. Finally, 4 studies were identified and included in the meta-analysis. The main outcome measures were 5-year disease-free survival (DFS) and overall survival (OS). A meta-analysis was performed using the DerSimonian-Laird random-effects models to compute odds ratio (OR) along with 95 % confidence intervals (95 % CI).

Results

The outcomes of 2,280 patients were studied. Meta-analysis of 5-year DFS data extracted from three studies demonstrated a significant reduction in 5-year DFS after POCs, with an OR of 1.98 (95 % CI = 1.33–2.96; P = .0008). Meta-analysis of 5-year OS data extracted from four studies demonstrated a significant reduction in 5-year OS after POCs, with an OR of 1.68 (95 % CI = 1.25–2.27; P = .0006). No differences between study heterogeneity were observed in either the DFS or the OS analyses.

Conclusions

This study provides persuasive evidence that POCs following hepatic resection for CRLM have significant adverse oncological outcomes. These findings emphasize the need for meticulous surgical technique and careful perioperative management to minimize POCs.     

Factors Influencing the Long-Term Survival in Patients with Esophageal Cancer Who Underwent Esophagectomy After Chemoradiotherapy

Background

Salvage esophagectomy is potentially the only treatment available that can offer a chance of long-term survival when definitive chemoradiotherapy (CRT) fails to achieve local control for patients with esophageal squamous cell carcinoma (ESCC). However, salvage esophagectomy is a highly invasive procedure with various postoperative complications compared to planned esophagectomy after neoadjuvant chemoradiotherapy (CRT). We hypothesize that severe postoperative complications may affect not only surgical mortality but also tumor recurrence and long-term survival for patients with salvage esophagectomy after definitive CRT.

Methods

For the present study we reviewed the surgical procedures, postoperative complications, and the prognosis of 65 consecutive patients with thoracic ESCC who underwent the esophagectomy after neoadjuvant (neoadjuvant group: n = 40) or definitive (salvage group: n = 25) CRT.

Results

Most patients underwent right-transthoracic extended esophagectomy and reconstruction using gastric conduit by way of subcutaneous route with left cervical anastomosis. The incidence of postoperative pneumonia was found to be higher in the salvage group than in the neoadjuvant group. In both groups, the survival of patients with R0 resection was significantly better than those with R1/R2 resection. Moreover, in the salvage group, the postoperative survival rate of patients with pneumonia or bacteremia/sepsis was significantly lower than that for patients who did not suffer the same complications. In the neoadjuvant group, R0 resection was selected to be the only independent prognostic factor in univariate and multivariate analysis. In contrast, in the salvage group, R0 resection and bacteremia/sepsis remained significant and were independent of the other factors in multivariate analysis.

Conclusions

This study reveals that postoperative morbidity affects not only the perioperative mortality but also the long-term survival of patients with ESCC who undergo salvage esophagectomy after definitive CRT.     

REG1A Expression Status Suggests Chemosensitivity Among Advanced Thoracic Esophageal Squamous Cell Carcinoma Patients Treated with Esophagectomy Followed by Adjuvant Chemotherapy

Background

Regenerating gene 1A (REG1A) plays an important role in tissue regeneration and in cell proliferation in the mucous membrane of the gastrointestinal tract. We previously reported that the positive expression status of REG1A was predictive of chemoradiosensitivity in patients treated with preoperative chemoradiotherapy before esophagectomy or with definitive chemoradiotherapy. To further confirm the utility of REG1A as a chemosensitivity marker, we carried out an additional retrospective clinical study aimed at determining whether REG1A is a reliable chemosensitivity marker in patients treated with esophagectomy followed by adjuvant chemotherapy.

Method

A total of 177 patients with T2–4 thoracic esophageal squamous cell carcinoma received curative surgery without preoperative treatment at Akita University Hospital between 2001 and 2011. A tissue microarray was constructed, and REG1A expression status was analyzed immunohistochemically. We then statistically analyzed the relationships between REG1A expression status and 5-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS).

Results

In the adjuvant group (n = 105), REG1A-positive patients showed significantly better prognoses than REG1A-negative patients. (5-year OS, p = .0022; DSS, p = .0004; and DFS, p = .0040). However, there were no significant differences between REG1A-positive and REG1A-negative patients in the surgery group (n = 72). Univariate and multivariate analyses showed REG1A expression status to be a significant prognostic factor affecting 5-year DSS, comparable to lymph node metastatic status.

Conclusion

The present study suggests REG1A expression status has the potential to be a highly reliable and clinically useful chemosensitivity marker in patients treated with advanced thoracic esophageal squamous cell carcinoma. REG1A expression status will provide a good indication of treatment strategy and enable more individualized treatment for patients.     

Efficacy and safety of artificial pneumothorax under two-lung ventilation in thoracoscopic esophagectomy for esophageal cancer in the prone position

Background

Thoracoscopic esophagectomy for esophageal cancer performed using two-lung ventilation in the prone position has many advantages, such as convenient anesthesia induction and maintenance, and good oxygenation. We examined the safety of surgery and anesthetic management by following chronological changes in intraoperative respiration and hemodynamics.

Methods

We focused on the most recent and consecutive 14 cases of thoracoscopic esophagectomy for esophageal cancer in the prone position performed from November 2010 until recently. We measured the following items by use of FloTrac system : cardiac index (CI), central venous pressure (CVP), mean arterial pressure, partial pressure of oxygen in arterial blood (PaO₂), partial pressure of carbon dioxide in arterial blood (PaCO₂), peak airway pressure (APmax), and tidal volume.

Results

No major changes were observed in CI, systolic blood pressure, and TV after the start of pneumothorax (statically not significant). Conversely, CVP increased immediately after pneumothorax (p < 0.05) and decreased almost to its original level thereafter. The mean APmax value was 18–20 cm H₂O [mean increase, 4.2 cm H₂O; (p < 0.05)]. The mean P/F ratio and mean PaCO₂ were 244.4 and 48.3 mmHg, respectively, during artificial pneumothorax.

Conclusion

No excessive increases in airway pressure or clear circulatory depressions were observed because of artificial pneumothorax under two-lung ventilation in thoracoscopic esophagectomy for esophageal cancer in the prone position. These results suggest that artificial pneumothorax under two-lung ventilation is beneficial for maintaining stable hemodynamics and oxygenation in thoracoscopic esophagectomy in prone position.     

T1 Squamous Cell Carcinoma of the Esophagus: Long-Term Outcomes and Prognostic Factors After Esophagectomy

Background

Mucosal (T1a) and submucosal (T1b) squamous cell carcinoma of the esophagus (ESCC) have often been analyzed together and are staged as the same category in the UICC/TNM staging system. The difference in surgical outcomes between T1a and T1b ESCC therefore remains unclear. The purpose of this study was to examine the differences in surgical outcomes between T1a and T1b ESCC, and to investigate the prognostic factors in T1 ESCC.

Methods

A prospectively maintained database identified 145 previously untreated patients with pT1 ESCC who underwent radical transthoracic (n = 134) or transhiatal esophagectomy (n = 11). Median follow-up was 108 months.

Results

Of the 145 patients, 35 (24 %) had pT1a cancer and 110 (76 %) had pT1b cancer. Lymph node metastasis was present in 45 patients (31 %): 3 patients with pT1a cancer and 42 patients with pT1b cancer (P = 0.0003). The 5-year survival rate for the whole group was 77 %. The 5-year survival rate of the T1a patients was 94 % compared with 72 % for the T1b patients (P = 0.0282). In multivariate analysis, only the depth of tumor invasion (pT1a vs. pT1b) was an independent prognostic factor (hazard ratio 2.358; 95 % confidence interval 1.009–5.513; P = 0.0477).

Conclusions

After esophagectomy, the prognosis of patients with pT1b ESCC is significantly worse than that of patients with pT1a ESCC. Infiltration into the submucosa is the only independent prognostic factor affecting survival. These findings suggested that T1a and T1b ESCC could be staged separately in the next version of UICC/TNM staging system.