Abdominal Lymph Node Metastasis in Patients with Mid Thoracic Esophageal Squamous Cell Carcinoma

Background  There are few reports about abdominal lymph node metastasis of mid thoracic esophageal carcinoma. This study was designed to explore the pattern of abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma and to evaluate the prognostic factors. Methods  The complete data of 368 patients with mid thoracic esophageal squamous cell carcinoma, who underwent modified Ivor-Lewis esophagectomy with two-field lymphadenectomy from January 1998 to January 2003, were reviewed. Survival rate was calculated by Kaplan-Meier method. Cox regression analysis was performed to identify risk prognostic factors. Results  Abdominal lymph node metastasis occurred in 58 (15.8%) patients: 34.5% (20/58) of them were stage T1 and T2. Skipping abdominal node metastasis was recognized in 13.8% (8/58) patients: all were stage T1 and T2. The overall 5-year survival rate of patients with abdominal lymph node metastasis (10.3%) was lower than that of those with thoracic node metastasis (18.3%). The prognosis of patients with distant abdominal lymph node metastasis was poor, and no one could survive more than 5 years. Cox regression analysis showed that five or more positive nodes and distant abdominal node metastasis were independent risk factors of patients with abdominal lymph node metastasis. Conclusions  Abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma occurred frequently, and the surgery favorable for extensive abdominal lymph node dissection should be selected. The prognosis of patients with abdominal lymph node metastasis was poor, especially those with more positive nodes and distant abdominal node metastasis.     

18F-FAMT-PET Is Useful for the Diagnosis of Lymph Node Metastasis in Operable Esophageal Squamous Cell Carcinoma

Background

The role and potential usefulness of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. ¹⁸F-FAMT (L-[3-¹⁸F]-α-methyltyrosine) is an amino acid tracer for PET. This study investigated whether PET/CT with ¹⁸F-FAMT provides additional information for preoperative diagnostic workup of esophageal squamous cell carcinoma compared with that obtained by ¹⁸F-FDG (fluorodeoxyglucose) PET or CT.

Methods

PET/CT studies with ¹⁸F-FAMT and ¹⁸F-FDG were performed as a part of the preoperative workup in 21 patients with histologically confirmed esophageal squamous cell carcinoma.

Results

For the detection of primary esophageal cancer, ¹⁸F-FAMT-PET exhibited a sensitivity of 76.2%, whereas the sensitivity for ¹⁸F-FDG-PET was 90.5% (P = 0.214). ¹⁸F-FAMT uptake in primary tumors showed significant correlation with depth of invasion (P = 0.005), lymph node metastasis (P = 0.045), stage (P = 0.031), and lymphatic invasion (P = 0.029). In the evaluation of individual lymph node groups, ¹⁸F-FAMT-PET exhibited 18.2% sensitivity, 100% specificity, 71.9% accuracy, 100% positive predictive value, and 70.0% negative predictive value, compared with 24.2%, 93.7%, 69.8%, 66.6%, and 70.2%, respectively, for ¹⁸F FDG-PET. CT exhibited 39.4% sensitivity, 85.7% specificity, 69.8% accuracy, 59.1% positive predictive value, and 73.0% negative predictive value. The specificity of ¹⁸F-FAMT-PET is significantly higher than that of ¹⁸F-FDG-PET (P = 0.042) and CT (P = 0.002). ¹⁸F-FAMT-PET did not have any false-positive findings compared to those with ¹⁸F-FDG-PET.

Conclusions

Our findings suggest that the addition of ¹⁸F-FAMT-PET to ¹⁸F-FDG-PET and CT would permit more precise staging of esophageal cancer.     

Lymph Node Station-Based Nodal Staging System for Esophageal Squamous Cell Carcinoma: A Large-Scale Multicenter Study

Annals of Surgical Oncology - The American Joint Committee on Cancer (AJCC) nodal staging for esophageal squamous cell carcinoma (ESCC) has been defined by the number of metastatic lymph nodes (N...     

Lymph Node Metastasis Density and Growth Pattern as Independent Prognostic Factors in Advanced Esophageal Squamous Cell Carcinoma

BACKGROUND: Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC. METHODS: The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital. RESULTS: Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease. CONCLUSIONS: From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer.     

Impact of Examined Lymph Node Count for Esophageal Squamous Cell Carcinoma in Patients who Underwent Right Transthoracic Esophagectomy

Annals of Surgical Oncology - The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who...     

Metastatic Lymph Node CHIP Expression is a Potential Prognostic Marker for Resected Esophageal Squamous Cell Carcinoma Patients

Background

C-terminal Hsp-interacting protein (CHIP) is an HSP70 and HSP90 interacting co-chaperone and an E3 ubiquitin ligase. Previous studies have reported the role of CHIP in cancer progression by targeting protein degradation. However, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) has not been elucidated. We investigated the correlation of CHIP expression and clinical outcome in a group of T3N1-3M0 surgically resected ESCCs.

Methods

Tissue microarrays constructed of 234 surgically resected T3N1-3M0 ESCC primary tumors (PTs) and 163 paired metastatic lymph nodes (MLNs), and sections of 56 cancer-adjacent normal epithelial blocks were used for CHIP evaluation by immunohistochemistry. The clinical and prognostic significance of CHIP expression was analyzed statistically.

Results

The expression level of CHIP in ESCC MLNs was significantly higher than that in PTs (P < 0.001). Patients with low MLNs’ CHIP expression demonstrated better overall survival than those with high CHIP expression (median, 44 vs. 17.9 months; P = 0.010). Multivariate analysis showed that the MLNs’ CHIP expression level was an independent prognostic factor in ESCC (relative risk, 2.157; P = 0.028).

Conclusions

High expression of CHIP in MLNs suggests poor prognosis for patients with resected T3N1-3M0 ESCC. The result suggests that considering the protein expression of metastatic tumors is important for prognostic prediction.     

Preoperative Positron Emission Tomography/Computed Tomography Predicts Advanced Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma Patients

Background  

We 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).     

The Positive Lymph Node Ratio Predicts Long-Term Survival in Patients with Operable Thoracic Esophageal Squamous Cell Carcinoma in China

Background

Controversy exists concerning the optimal cutoff points for the positive lymph node ratio (PLNR) to predict overall survival. We aim to propose reasonable PLNR categories for the discrimination of the survival difference between groups.

Methods

We used data from two centers to establish a training (n = 1006) and a validation (n = 783) cohort. All of the patients underwent curative surgical treatment. Martingale residuals from a Cox proportional hazards regression model were used to determine the optimal cutoff points for PLNR to predict overall survival. The survival rate was calculated using the Kaplan–Meier method, and a log-rank test was used to assess the survival differences between groups. The results obtained from the training cohort were tested with the validation cohort at each step.

Results

We classified the patients into four revised nodal categories: R-pN0 (PLNR = 0), R-pN1 (0< PLNR ≤0.1), R-pN2 (0.1< PLNR ≤0.3), and R-pN3 (PLNR >0.3). Subgroup analysis for the pT2 and pT3 cases showed that the survival differences could be well discriminated between groups based on PLNR in both the training cohort and validation cohort. When we modified the current staging system using revised nodal categories (based on PLNR) instead of the AJCC nodal categories, the survival rate could also be easily distinguished between patients in different stages in both cohorts of patients.

Conclusions

The survival rate of ESCC can be discriminated between four groups: PLNR = 0, 0< PLNR ≤0.1, 0.1< PLNR ≤0.3, and PLNR >0.3. Further studies are required to confirm these results.     

胸段食管癌锁骨上淋巴结清扫的临床价值

目的分析食管癌锁骨上淋巴结清扫的临床价值。方法将1997年3月至2004年9月厦门大学附属中山医院收治的无明显锁骨上淋巴结转移食管癌患者197例分为两组,对照组:非锁骨上淋巴结清扫,96例,男62例、女34例,年龄40～69(55.2±3.1)岁;采用区域(胸内淋巴引流区和胃左贲门旁)淋巴结清扫。观察组:锁骨上淋巴结清扫,101例,男68例、女33例,年龄41～68(53.8±4.5)岁;采用三野淋巴结清扫(胸内淋巴引流区、胃左贲门旁及双侧锁骨上淋巴结清扫)。随访两组患者的生存率、淋巴结转移率、吻合口复发率和锁骨上淋巴结远期转移率。结果全组5年生存率为39.59%(78/197),对照组和观察组的5年生存率差异无统计学意义[37.50%(36/96)vs.41.58%(42/101),P>0.05];胸上段食管癌观察组5年生存率显著高于对照组[38.10%(8/21)vs.29.17%(7/24),P<0.05];对照组与观察组胸内淋巴结转移率(14.58%vs.12.87%)、腹腔淋巴结转移率(6.25%vs.7.92%)和吻合口复发率(5.20%vs.5.94%)差异均无统计学意义(P>0.05);锁骨上淋巴结远期转移率观察组显著低于对照组(2.97%vs.8.33%,P<0.05)。结论胸上段食管癌锁骨上淋巴结清扫可以提高其术后的生存率,降低锁骨上淋巴结的远期复发转移率。     

Clinicopathological Significance of BMP7 Expression in Esophageal Squamous Cell Carcinoma

Background

Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor-?? (TGF-??) superfamily of growth factors. Recent studies have shown that the influence of the expression of BMP7 was altered in several tumors. The purpose of the current study was to examine the expression of BMP7 in esophageal squamous cell carcinoma and to clarify the clinical impact of BMP7 expression in esophageal squamous cell carcinoma (ESCC).

Methods

A total of 180 patients with ESCC who underwent surgical resection from 1991 to 2004 were eligible for this study. The expression of BMP7 in esophageal tumor tissues was examined immunohistochemically.

Results

BMP7 expression was found in the cytoplasm of cancer cells. BMP7 positivity was observed in 61.7% of tumors. The BMP7-positive group had deeper progression, more advanced stages, and greater venous invasion than those without BMP7 expression (p?p?p?p?p?Conclusions Patients with expression of BMP7 in ESCC had high malignant potential. BMP7 could be a useful prognostic marker for patients with ESCC.     

Impact of the Number and Extent of Positive Lymph Nodes in 200 Patients with Thoracic Esophageal Squamous Cell Carcinoma after Three-field Lymph Node Dissection

Background Subtotal esophagectomy with three-field lymph node dissection (3FLD) has been reported to improve survival in patients with thoracic esophageal squamous cell carcinoma (SCC). The purpose of this study was to evaluate the prognostic impact of the extent and number of positive lymph nodes for long-term survival of patients who underwent 3FLD. Methods From January 1983 to December 2002, a total of 200 patients with thoracic esophageal SCC underwent 3FLD without any neoadjuvant therapy. The prognostic impact of the extent and number of positive lymph nodes was evaluated by both univariate and multivariate analysis. Results The extent of positive nodes associated with a 5-year survival were as follows: none, 69%; one-field, 50%; two-field, 29%; and three-field, 11%. The number of positive nodes associated with 5-year survival were as follows: single node, 65%; two-nodes, 51%; and more than three-nodes, 20%. Among patients with cervical lymphatic spreading, patients with upper tumors showed significantly better survival than patients with lower tumors (P = 0.036). Multivariate analysis indicated that number of positive nodes and the abdominal node status were independent prognostic factors among lymph node status. Conclusions Together, number and extent of positive lymph nodes can be considered an independent predictor of a high risk of recurrence. Although cervical lymphatic spreading was risk factor for worse survival, patients with upper tumors may have survival benefit after cervical lymph node dissection.     

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。     

Prediction of Lymph Node Status in Superficial Esophageal Carcinoma

Background  Esophageal carcinoma is among the cancers with the worst prognosis. Real chances for cure depend on both early recognition and early treatment. The ability to predict lymph node involvement allows early curative treatment with less invasive approaches. Aims  To determine clinicohistopathological criteria correlated with lymph node involvement in patients with early esophageal cancer (T1) and to identify the best candidate patients for local endoscopic or less invasive surgical treatments. Methods  A total of 98 patients with pT1 esophageal cancer [67 with squamous cell carcinomas (SCC) and 31 with adenocarcinomas (ADK)] underwent Ivor–Lewis or McKeown esophagectomy in the period between 1980 and 2006 at our institution. Based on the depth of invasion, lesions were classified as m1, m2, or m3 if mucosal, and sm1, sm2, or sm3 if submucosal. Results  The rates of lymph node metastasis were 0% for the 27 mucosal carcinomas (T1m) and 28% for the 71 submucosal (T1sm) carcinomas (P < 0.001). Sm1 carcinomas were associated with a lower rate of lymph-node metastasis (8.3% versus 49 % sm2/3, P  = 0.003). As for histotype, the rates of lymph node metastasis for sm1 were 0% for ADK and 12.5% for SCC; for sm2/3 there were no significant differences. On multivariate analysis, depth of infiltration, lymphocytic infiltrate, angiolymphatic and neural invasion were significantly associated with lymph node involvement. Neural invasion was the single parameter with the greatest accuracy (82%); depth of infiltration and angiolymphatic invasion had 75% accuracy. Altogether these three parameters had an accuracy of 97%. Five-year survival rate was 56.7% overall: 77.7% for T1m and 53.3% for T1sm (P  = 0.048). Conclusions  The most important factors for predicting lymph node metastasis in early esophageal cancer are depth of tumor infiltration, angiolymphatic invasion, neural invasion and grade of lymphocytic infiltration. The best candidates for endoscopic therapy are tumors with high-grade lymphocytic infiltration, no angiolymphatic or neural invasion, mucosal infiltration or sm1 (only for ADK), and tumor <1 cm in size. For sm SCC and sm2/3 ADK the treatment of choice remains esophagectomy with standard lymphadenectomy.     

CRP Genetic Polymorphism Is Associated with Lymph Node Metastasis in Thoracic Esophageal Squamous Cell Cancer

Background  Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis. Methods  The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-α and -β, interferon (IFN)-γ, transforming growth factor (TGF)- β, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12β were investigated using the polymerase chain reaction–restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis. Results  For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively. Conclusions  These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.     

Prediction of Lymph Node Metastasis with Use of Artificial Neural Networks Based on Gene Expression Profiles in Esophageal Squamous Cell Carcinoma

Background: The aim of the study was (1) to detect candidate genes involved in lymph node metastasis in esophageal cancers and (2) to investigate whether we can estimate and predict occurrence of lymph node metastasis by analyzing artificial neural networks (ANNs) using these gene subsets.Methods: Twenty-eight primary esophageal squamous cell carcinomas were used. Gene expression profiles of all primary tumors were obtained by cDNA microarray. Lymph node metastasis–related genes were extracted with use of Significance Analysis of Microarrays (SAM). Predictive accuracy for lymph node metastasis was calculated by evaluation of 28 cases by ANNs with leave-one-out cross-n. The results were compared with those of other analyses such as clustering or predictive scoring (LMS).Results: Our ANN model could predict lymph node metastasis most accurately with 60 clones. The highest predictive accuracy for lymph node metastasis by ANN was 10 of 13 (77%) in newly added cases that were not used for gene selection by SAM and 24 of 28 (86%) in all cases (sensitivity: 15/17, 88%; specificity: 9/11, 82%). Predictive accuracy of LMS was 9 of 13 (69%) in newly added cases and 24 of 28 (86%) in all cases (sensitivity: 17/17, 100%; specificity: 7/11, 67%). It was difficult to extract useful information for the prediction of lymph node metastasis by clustering analysis.Conclusions: ANN had superior potential in comparison with other methods of analysis for the prediction of lymph node metastasis. This systematic analysis combining SAM with ANN was very useful for the prediction of lymph node metastasis in esophageal cancers and could be applied clinically in the near future.