Correlation Between Connexin 26 Expression and Poor Prognosis of Esophageal Squamous Cell Carcinoma

Background  Failure of gap junction formation affects the development of various types of cancer. We aimed to clarify the clinicopathologic outcome and prognostic significance of connexin (Cx) 26 in human esophageal squamous cell carcinoma (ESCC). Methods  Immunohistochemical staining for Cx26 was performed on surgical specimens obtained from 123 patients with ESCC. Results  There was no positive staining for Cx26-specific expression in normal esophageal squamous cells. Primary ESCC with Cx26-positive expression was detected in the cytoplasm of cancer cell nests in 60 cases. Cx26 expression was correlated with N (lymph node metastasis, P = 0.014) and the number of metastatic lymph nodes (P = 0.047). The 5-year survival rates of ESCC patients with Cx26-positive expression were significantly lower than those with Cx26-negative expression (positive, 39.7%; negative, 65.7%; P = 0.007). By multivariate analysis, tumor–node–metastasis (TNM) clinical classification (T, P < 0.001; N, P = 0.002; M, P = 0.046) and Cx26 (P = 0.024) were independent prognosis predictors of ESCC. Conclusions  These results suggest that abnormal expression of Cx26 participates in the progress of ESCC.     

The Immunological Impact of Neoadjuvant Chemotherapy on the Tumor Microenvironment of Esophageal Squamous Cell Carcinoma

Background  

Esophageal cancer is an aggressive cancer with poor prognosis. However, little is known about the immune response in the tumor microenvironment after neoadjuvant chemotherapy.     

Correlation Between gp96 Expression and the Surgical Outcome in Patients With Esophageal Squamous Cell Carcinoma

Background

Heat-shock protein gp96 plays an important role in antitumor immunoreactions. Gp96 has a close relationship with antitumor immunity. This study evaluated the correlation between gp96 expression and the prognosis in esophageal squamous cell carcinoma.

Methods

Seventy-eight patients with primarily resected esophageal squamous cell carcinoma were enrolled onto this study, and gp96 expression was evaluated by immunohistochemical staining. The association of clinicopathological factors and patients’ survival was calculated by univariate (log rank test) and multivariate (Cox proportional hazard regression method) analyses.

Results

Fifty-seven (73%) of 78 cases were gp96 positive, and 21 were negative (27%). The survival of patients with gp96-negative disease was significantly shorter (5-year survival, 22.9 months) than with gp96-positive disease (45.8 months; P = 0.049), and the multivariate analysis showed that gp96 negativity is an independent risk factor for poor survival (hazard ratio, 2.577; P = 0.040). Gp96-negative cases had more metastatic lymph nodes than did negative cases, especially in T1 cases (4.8 in gp96-negative cases vs. 0.84 in gp96-positive cases; P = 0.064)

Conclusions

The downregulation of gp96 expression is closely correlated with poor survival in esophageal squamous cell carcinoma.     

Salvage Lymphadenectomy of the Right Recurrent Nerve Node with Tracheal Involvement After Definitive Chemoradiation Therapy for Esophageal Squamous Cell Carcinoma: Report of Two Cases

Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma.     

Surgery or Surveillance for Esophageal Squamous Cell Carcinoma With Clinical Complete Response After Neoadjuvant Chemoradiotherapy

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Hemoglobin Level Influences Tumor Response and Survival After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Background

Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy confers a survival benefit on patients with esophageal cancer. However, nCRT might be less meaningful for poor responders. Thus, being able to predict responses would help ensure the selection of optimal therapy.

Methods

We reviewed data from 123 patients with esophageal squamous cell carcinoma (ESCC) who underwent nCRT that comprised concurrent radiation (40 Gy) and chemotherapy followed by esophagectomy. We assessed associations between clinical and blood data obtained before starting nCRT and the pathologic response.

Results

We compared good (Japan Esophageal Society response evaluation criteria grades 3/2; n = 89, 72.4 %) and poor (grades 1/0; n = 34, 27.6 %) responders. Performance status (p = 0.02), hemoglobin level (p = 0.005), and platelet counts (p = 0.03) were statistically significant pretherapeutic factors for a response to nCRT. Multivariable analysis subsequently selected the hemoglobin level (odds ratio 1.52; 95 % confidence interval 1.08–2.15; p = 0.02) as the sole independent predictor. Receiver operating characteristic curves showed that the optimal cutoff for pretherapeutic hemoglobin was 13 g/dl for predicting a response. We found that 48.8 and 17.1 % of patients with hemoglobin level ≤13 and >13 g/dl, respectively, were poor responders (p = 0.0002), with 5-year overall survival rates of 40.9 and 58.9 %, respectively (p = 0.048).

Conclusions

Pretherapeutic hemoglobin levels can influence responses and survival after nCRT for ESCC. Thus, hemoglobin levels can serve as a useful marker for tailoring optimal therapies for individual patients with advanced ESCC.     

鳞状细胞癌抗原在食管癌临床的应用

采用微粒酶免疫荧光法测定了４０例食管癌和７例术后复发病人的血清鳞状细胞癌（ＳＣＣ）抗原含量，取２０例正常人，１５例食管良性病人和１５例腺癌病人作对照。结果表明，食管癌和术后复发病人的血清ＳＣＣ抗原含量显著高于正常人、良性病人和腺癌病人（Ｐ值分别＜０．００１、０．０１和０．０５），ＳＣＣ抗原与临床病期、细胞的分化程度有关。这提示血清ＳＣＣ抗原是食管癌理想的肿瘤标志物，对食管癌的诊断、预示术后复发和判断食管癌的恶性程度都有重要的临床价值。     

Histological Regression of Squamous Esophageal Carcinoma Assessed by Percentage of Residual Viable Cells after Neoadjuvant Chemoradiation is an Important Prognostic Factor

Background  

Whether the TNM staging system is applicable after neoadjuvant chemoradiation in esophageal cancer is controversial. The aim of this study was to evaluate the prognostic value of histopathological regression of the primary tumor in postchemoradiated patients.     

The Usefulness of Neoadjuvant Chemoradiation Therapy for Locally Advanced Esophageal Cancer with Multiple Lymph-Node Metastases

Background

The prognosis of patients with esophageal squamous-cell cancer (ESCC) and multiple lymph-node metastases is quite poor. We examined whether neoadjuvant chemoradiation therapy (CRT) has a beneficial effect in such patients.

Methods

A total of 50 consecutive patients with T3–4 tumors and without organ metastases were prospectively enrolled. Of those patients, 20, who had four or more nodal metastases, underwent neoadjuvant CRT (CRT group), and the remaining 30 patients, who had three or fewer nodal metastases, underwent surgery alone (surgery group). CRT consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The groups’ clinical outcomes were compared.

Results

Surgery was performed in 48 patients: all enrolled patients except for 2 who had organ metastasis after CRT. In the CRT group, the number of patients with pathological complete response was observed in 8 patients (44 %), mean nodal metastases number was changed from 8.2 to 2.6 and 9 patients had pN0. The 3-year survival rate was 76 % in the CRT group (4 patients relapsed) and 68 % in the surgery group (8 patients relapsed), which is not a statistically significant difference (P = 0.61).

Conclusions

Neoadjuvant CRT is beneficial for locally advanced ESCC with four or more lymph-node metastases.     

Outcome of Histologically Node-negative Esophageal Squamous Cell Carcinoma

The outcome of node-negative esophageal carcinoma and the prognostic significance of lymph node micrometastasis remain unknown. The aim of this retrospective study was to clarify these two points. A series of 98 patients who underwent curative operation for histologically node-negative (pN0 in TNM classification) esophageal carcinoma were enrolled in the study. We reviewed the cause of death of these patients. The survival curves were calculated and compared after stratifications according to clinicopathologic parameters. Lymph node micrometastasis in the patients with recurrences was examined using immunohistochemical staining of cytokeratin. Their ages ranged from 45 to 83 years (mean 64.3 years). There were 83 men and 15 women. Altogether, 54 patients were still alive, and 44 had died. A total of 9 patients died from recurrence of their esophageal carcinoma, 33 died from other causes (pneumonia 11, extraesophageal carcinoma 7, and so on), and 2 died from unknown causes. Eight patients had locoregional recurrences, and two patients had distant recurrences. The overall survival rate for the 98 patients was 58.2%. The survival for patients with pT2 or pT3 tumors was significantly worse than for those with pTis or pT1 tumors (p = 0.02, log-rank test). Other clinicopathologic factors did not affect the prognosis. Immunohistochemical study found no lymph node micrometastasis in 365 lymph nodes resected from the patients with recurrences. Only the depth of tumor invasion affected the outcome of patients with node-negative esophageal carcinoma. Altogether, 75% of patients died of other causes without recurrence, with the two main causes of death being pulmonary complications and extraesophageal carcinoma in these patients. Lymph node micrometastasis was not associated with recurrence in this series.     

Clinical and Pathologic Evaluation of the Effectiveness of Neoadjuvant Chemoradiation Therapy in Advanced Esophageal Cancer Patients

Background  Chemoradiation therapy (CRT) has the strongest antitumor effect against local tumors of esophageal cancer; however, no standard strategy has yet been established to achieve a clinical complete response (CR) after CRT. The aim of this study was to clarify when a decision can be made to perform further treatment for a clinical CR. Methods  We evaluated 78 patients that underwent an esophagectomy after neoadjuvant CRT in our department between 1998 and 2007. The study investigated the clinical and pathologic results of neoadjuvant CRT. Results  Of the 78 cases, 19 (24.3%) were a pathologic CR (Grade 3). Pathologic CR could be estimated in only 3 of 8 clinical CR cases (37.5%). On the other hand, 12 (20.7%) of the 58 clinical partial response (PR) cases achieved pathologic CR. Likewise, 4 cases (36.4%) achieved pathologic CR among the clinical no change/progressive disease (NC/PD) patients. Conclusions  The clinical evaluation for CRT does not reflect the pathologic effectiveness and, even if clinical CR was achieved, viable cancer cells were still present at the primary site in the majority of the population.     

Open Versus Thoracoscopic Esophagectomy in Patients with Esophageal Squamous Cell Carcinoma

Background

The impact of minimally invasive esophagectomy on patient prognosis, particularly disease-free survival (DFS), has not been well addressed. We compared the clinical outcomes of open and thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma (ESCC).

Methods

Sixty-three and 66 patients, nonrandomized, underwent open and thoracoscopic esophagectomies for ESCC between 2008 and 2011 were included. The clinicopathological data were reviewed retrospectively. Perioperative outcome, overall survival (OS), DFS, and the recurrence sites after open and thoracoscopic esophagectomy were compared.

Results

The open and thoracoscopic groups were comparable with regard to the total number of harvested lymph nodes and the percentage patients undergoing R0 resection. Fewer patients in the thoracoscopic group had pneumonia and wound complications. Intensive care unit (ICU) stay also was shorter in the thoracoscopic group. The recurrence pattern was similar in the two groups. In the open and thoracoscopic groups, the 3-year OS rates were 47.6 and 70.9 % (p = 0.031), respectively, and the 3-year DFS rates were 35 and 62.4 % (p = 0.007), respectively. However, the trends in better OS and DFS in the thoracoscopic group were not significant after stratification according to pathologic stage.

Conclusions

The perioperative benefit of thoracoscopic esophagectomy included fewer postoperative complications and shorter ICU stays. Mid-term OS and DFS associated with thoracoscopic techniques are at least equivalent to those associated with open procedures.     

Selective Lymphadenectomy for Salvage Esophagectomy in Patients with Esophageal Squamous Cell Carcinoma

Annals of Surgical Oncology - Extensive lymph node dissection increases the risk of postoperative complications, especially in salvage surgery, after definitive chemoradiotherapy (≥ 50 Gy) in...     

Using Pretreatment Tumor Depth and Length to Select Esophageal Squamous Cell Carcinoma Patients for Nonoperative Treatment After Neoadjuvant Chemoradiotherapy

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.     

食管鳞状上皮细胞癌细胞凋亡表达及其临床意义

目的探讨食管鳞状上皮细胞癌（食管鳞癌）中细胞凋亡的表达及其临床意义。方法应用末端脱氧核苷酸转移酶介导的ｄＵＴＰ缺口末端标记（ＴＵＮＥＬ）法，研究人食管鳞癌细胞凋亡的表达水平。结果３８例手术切除的食管鳞癌组织平均细胞凋亡指数ＡｐｏＬＩ为１２．１０±５．１３‰。角化型ＡｐｏＬＩ高于非角化型（Ｐ＜０．０１）；肿瘤分化越好，细胞凋亡越多，低度、中度、高度分化ＡｐｏＬＩ有差异（Ｐ＜０．０５）；不同性别、年龄、肿瘤部位、长度、深度，其ＡｐｏＬＩ并无差异；以１０‰为界将ＡｐｏＬＩ分组绘制Ｋａｐｌａｎ－Ｍｅｉｅｒ生存曲线，ＡｐｏＬＩ≥１０‰组术后生存率高。结论细胞凋亡与原发食管鳞癌临床病理特征密切相关，并可用于食管鳞癌预后判断。     

Correlation Between Tumor Budding and Post-Resection Prognosis in Patients with Invasive Squamous Cell Carcinoma of the Thoracic Esophagus

Background  

Tumor budding is defined as an isolated single cancer cell or a cluster of cancer cells composed of fewer than five cells at the invasive front of a tumor. The aim of the present study was to identify correlations between tumor budding and clinicopathological factors and their impact on postoperative prognosis in invasive squamous cell carcinoma of the thoracic esophagus.     

Significance of Lymph Node Capsular Invasion in Esophageal Squamous Cell Carcinoma

Background

Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC.

Methods

We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC.

Results

LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1?C3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases.

Conclusions

LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.