Evaluation of metastatic celiac axis lymph nodes in patients with esophageal carcinoma: accuracy of EUS.

BACKGROUND: Endosonography (EUS) is the most accurate modality for assessing depth of tumor invasion and local lymph node metastasis. However, its accuracy in the identification of metastatic (celiac axis) lymph nodes is less well defined. Our objective in this study was to determine the accuracy of Eus in detecting celiac axis lymph node metastasis in patients with esophageal carcinoma. METHODS: Two hundred fourteen patients with esophageal carcinoma underwent preoperative EUS. Of these, 145 underwent attempted surgical resection and staging, and 4 underwent EUS-guided fine-needle aspiration of mediastinal and celiac lymph nodes. Local (mediastinal) and distant (celiac axis) lymph nodes were assessed for malignancy on the basis of four criteria (larger than 1 cm, round, homogeneous echo pattern, sharp borders). Accuracy of EUS was determined by means of correlating histopathologic findings for the resected lymph nodes or results of EUS-guided fine-needle aspiration cytologic examination. RESULTS: Surgical exploration (n = 145) and fine-needle aspiration cytologic examination (n = 4) revealed metastatic celiac axis lymph nodes in 23 and metastatic mediastinal (local) lymph nodes in 93 of 149 patients with esophageal carcinoma. According to defined criteria for malignant lymph nodes, there were 19 true-positive and 4 falsenegative results. Sensitivity for the diagnosis of celiac lymph node metastasis with EUS was 83% with a 98% specificity. For the diagnosis of mediastinal lymph node metastasis, sensitivity was 79% and specificity was 63%. All patients with malignant celiac axis lymph nodes had local T3 (tumor breaching adventitia) or T4 (tumor invading adjacent organs) disease. CONCLUSION: EUS is an excellent modality in the evaluation of metastatic celiac axis lymph nodes in patients with esophageal carcinoma. These findings should be used in selecting options for treatment. Sensitivity for detecting malignancy is consistent with that of prior studies, and local and regional lymph nodes and specificity is significantly higher.     

食管癌淋巴结转移的危险因素分析

目的探讨食管癌淋巴结转移的危险因素。 方法回顾性分析2015年7月至2017年9月,新疆自治区人民医院胸外科行手术治疗食管癌的224例患者的病例资料,比较淋巴结转移组(转移组)与非淋巴结转移组(非转移组)的关系,并进行多因素Logistic回归进行分析,探讨淋巴结转移的危险因素。 结果患者症状期较长、肿瘤长度、分化程度、肿瘤分期T与淋巴结转移有显著相关性(P<0.05)。 结论肿瘤低分化、肿瘤长度>5 cm、肿瘤侵润深度T₃～T₄、患者症状期>6个月是淋巴结转移的危险因素,应尽可能选择经右胸入路胸腹腔镜辅助下食管癌根治术,并清扫双侧喉返神经淋巴结。     

Micrometastases in the cervical lymph nodes in esophageal squamous cell carcinoma

Few studies have investigated the presence of lymph node micrometastases (MM) in the cervical region of patients with esophageal squamous cell cancer. The present study examines the presence of cervical MM and attempts to determine a way to predict the occurrence and site of such micrometastases. A total of 2203 cervical lymph nodes and 118 mediastinal recurrent nerve nodes obtained from 86 patients with esophageal carcinoma were examined immunohistochemically using cytokeratins. Cervical lymph nodes and mediastinal recurrent nerve nodes metastases were detected histologically in 33 and 41 of the 86 patients respectively. Cervical lymph node and mediastinal recurrent nerve node MM were immunohistochemically detected in 16 (18.6%) and 6 (7.0%) patients respectively. Of these 16 patients with cervical MM, seven were found to have lymph node metastases in different cervical regions, whereas cervical MM only were detected in nine patients. Among the former group of patients, five were diagnosed by ultrasound examination as having cervical lymph node metastases. Mediastinal recurrent nerve node metastases and MM correlated with the presence of cervical MM in all but one patient. Cervical lymph node metastasis, including micrometastasis, can be predicted by preoperative ultrasonography and the routine histologic examination of mediastinal recurrent nerve nodes.     

Prognostic factors of curatively resected esophageal carcinoma associated with multiple metastatic lymph nodes

BACKGROUND/AIMS: Prognosis of esophageal carcinoma with multiple metastatic lymph nodes is dismal despite radical operation and adjuvant therapy. We investigated prognostic factors for curatively resected esophageal carcinoma with multiple positive nodes. METHODOLOGY: From January 1983 to December 2002, 343 patients with thoracic esophageal carcinoma underwent an esophagectomy with curative intent. Of these patients, 82 patients were associated with 4 or more histopathologically positive nodes. Of these patients, 59 patients underwent a curative resection. Of these 59 patients, 7 patients who died of postoperative complications during the hospital stay were excluded. Therefore, 52 patients were enrolled in this study. Survival curves were compared after stratifications according to 14 clinicopathologic variables. Independent prognostic factors were detected using a multivariate Cox proportional hazard model. RESULTS: The cumulative 5-year survival rate for the subjects was 10.6%. The factors affecting cumulative survival rate by a univariate analysis were intramural metastasis (absence vs. presence) (p=0.03), and postoperative therapy (performed vs. not performed) (p=0.02). A multivariate analysis detected the performance of postoperative therapy (Hazard Ratio= 0.390, p= 0.002) and the absence of intramural metastasis (Hazard ratio=0.429, p=0.01) as positive prognostic factors. CONCLUSIONS: The positive prognostic factors for esophageal carcinoma with multiple lymph node metastases were the absence of intramural metastasis and the performance of adjuvant therapy.     

Dynamic analysis of EUS used for the differentiation of benign and malignant lymph nodes

BACKGROUND: EUS elastography was reported to offer supplemental information that allows a better characterization of tissue, and that might enhance conventional EUS imaging. OBJECTIVE: Our purpose was to apply real-time elastography during EUS examinations and to assess the accuracy of the differentiation of benign versus malignant lymph nodes. DESIGN: Prospective cross-sectional feasibility study. SETTING: Department of Surgical Gastroenterology, Gentofte University Hospital, Hellerup, Denmark. PATIENTS: Patients diagnosed by EUS with cervical, mediastinal, or abdominal lymph nodes were included, with a total number of 78 lymph nodes examined. The final diagnosis of the type of lymph node was obtained by EUS-FNA cytologic analysis or by surgical pathologic examination and by a minimum 6 months of follow-up. INTERVENTIONS: Hue histogram analysis of the average images computed from EUS elastography movies was used to assess the color information inside the region of interest and to consequently differentiate benign and malignant lymph nodes. MAIN OUTCOME MEASUREMENTS: Differentiate between malignant and benign lymph nodes. RESULTS: By using mean hue histogram values, the sensitivity, specificity, and accuracy for the differential diagnosis were 85.4%, 91.9%, and 88.5%, respectively, on the basis of a cutoff level of 166 (middle of green-blue rainbow scale). The proposed method might be useful to avoid color perception errors, moving artifacts, or possible selection bias induced by analysis of still images. LIMITATIONS: Lack of the surgical standard in all cases. CONCLUSIONS: Computer-enhanced dynamic analysis based on hue histograms of the EUS elastography movies represents a promising method that allows the differential diagnosis of benign and malignant lymph nodes, offering complementary information added to conventional EUS imaging.     

Malignant mediastinal lymphadenopathy detected by staging EUS in patients with pancreaticobiliary cancer

BACKGROUND: In patients with pancreatic cancer, the presence of malignant mediastinal lymphadenopathy (MML) would preclude definitive resection. A recent study suggested routine evaluation for mediastinal lymph-node metastases in all patients being evaluated for pancreaticobiliary masses. In our practice, we routinely assess for mediastinal lymph-node metastases in all patients undergoing EUS for pancreaticobiliary cancer. METHODS: We retrospectively evaluated the presence of MML by EUS-guided FNA (EUS-FNA) in 160 consecutive patients with a definite diagnosis of pancreaticobiliary cancer (pancreatic and periampullary cancers) who underwent EUS-FNA by a single operator from 2000 to 2004. Lymph nodes that were round and hypoechoic with sharp margins were considered suspicious and were sampled by FNA. RESULTS: Of the 160 patients included in this study, 78 had peripancreatic lymph nodes (49%: 95% CI[41%, 58%]), 25 had celiac lymph nodes (16%: 95% CI[10%, 22%]), and 14 patients had mediastinal lymph nodes (9%: 95% CI[4%, 13%]) that were suspicious for malignancy by morphologic criteria. In 8 of 14 patients with suspicious mediastinal lymph nodes, FNA documented MML in 5%: 95% CI[2%, 8%]. Only one of these 8 patients with MML had other sites of documented distant metastases by CT and/or positron emission tomography scans. However, 7 of 8 patients had locally advanced cancers. CONCLUSIONS: MML is detected by staging EUS-FNA in 5% of patients with pancreaticobiliary cancer. Because of its important implications, endosonographers should routinely assess for MML in patients who undergo staging EUS for pancreaticobiliary malignancy.     

EUS predictors of long-term survival in esophageal carcinoma

BACKGROUND: EUS is the most accurate nonsurgical modality for the staging of esophageal cancer, but the ability of EUS to predict outcomes or prognosis is unclear. Patients were examined who had EUS performed for esophageal cancer staging to determine which endosonographic features predict survival. METHOD: Data on 203 patients undergoing EUS for esophageal cancer staging were studied retrospectively. Median survival was calculated for each T-stage and N-stage and according to the presence or absence of celiac axis (CAx) lymphadenopathy as determined by EUS. Kaplan-Meier survival curves were generated for each stage and the log-rank test was used to test for significant differences in survival. Multivariate analysis was performed to test for the relative importance in predicting survival of the EUS stages, also considering age, gender, histology, and type of treatment. RESULTS: Significant differences were found in the ability of EUS-determined T-stage (p = 0.0005), N-stage (p < 0.0001), and presence of CAx nodes (p = 0.0049) to predict survival. Multivariate analysis showed N-stage to predict survival. CONCLUSIONS: Pretreatment EUS can predict survival in esophageal cancer based on initial T-stage, N-stage, and the presence of CAx nodes. The presence of lymphadenopathy at EUS is an important predictor of survival. EUS should be performed in all patients with esophageal cancer, not only for staging patients before therapy, but also as a valuable method of determining prognosis.     

内镜超声检查术在食管癌术前分期的临床应用

目的探讨内镜超声检查术(EUS)对食管癌术前分期的作用及其临床意义。方法依据UICC1997年分期标准，对61例食管癌患者术前行EUS临床分期，并与术后病理分期相比较。结果术前EUS对T亚组的临床分期较易，其总准确率为86．9％；而N亚组的临床分期较难，其总准确率为52．5％，敏感性和特异性分别为88．9％及23．5％。结论EUS能较准确的判断食管癌的浸润深度，对N分期的准确性有待于进一步提高。EUS可作为术前治疗方法选择、手术可切除性预测的重要依据。     

Clinical significance of immunohistochemically detected lymph node micrometastasis in patients with histologically node-negative esophageal carcinoma: a multi-institutional study

Background  In esophageal carcinoma, the clinical significance of immunohistochemically (IHC)-detected lymph node (LN) micrometastasis is still controversial. We designed this multicenter study to determine the clinical significance of IHC-detected LN micrometastasis in esophageal carcinoma. Methods  The subjects were 164 patients with histopathologically confirmed LN-negative esophageal carcinoma from eight hospitals. A similar IHC technique was used in all institutions, and micrometastasis was diagnosed by a researcher at each hospital as well as independently by pathologists with special interest in esophageal carcinoma. Results  IHC-related micrometastasis in LN was considered positive in 51 (31%) patients by the researchers and in 25 (15%) by the pathologists. The latter micrometastases were further classified into a single (n = 13) and clusters (n = 12) of immunopositive-LN. Kaplan–Meier analysis showed that researcher-based diagnosis of micrometastasis had no significant impact on prognosis whereas the cluster-type micrometastasis diagnosed by pathologists had a significant impact on prognosis. Conclusions  We speculate that the inconsistent results of IHC analyses reported in the literature are caused by the use of different definitions of micrometastasis and the subjective nature of diagnosis of micrometastasis, i.e., dependence on the examiner. Our multiinstitutional study also indicates that the morphological aspects of immunostained cells should be considered when assessing micrometastasis in LN by IHC and that only LN with clusters of IHC-positive cells are prognostically significant in esophageal carcinoma.     

Risk analysis of lymph node metastasis in 285 patients with superficial esophageal squamous cell carcinoma

<正>Objective To identify risk factors of lymph node metastasis in superficial esophageal squamous cell carcinoma(ESCC),and to provide evidence for treatment choice under endoscope.Methods From January 2007 to December 2011,285 patients with pathologically diagnosed ESCC who received surgery and had clear record of lymph nodes resection were enrolled.The clinical pathological data of these patients were analyzed,including     

Effects of preoperative chemotherapy on metastatic lymph nodes in esophageal squamous cell carcinoma

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.     

Surgical outcome of patients with thoracic esophageal cancer positive for cervical lymph nodes

BACKGROUND/AIMS: Although cervical lymph nodes were classified as distant metastases in patients with thoracic esophageal cancer, not a few patients survive more than five-years. The purpose of this study was to predict patients with good prognosis among thoracic esophageal cancer patients with cervical node metastases. METHODOLOGY: From 1983 to 2002, 312 consecutive patients with thoracic esophageal squamous cell carcinoma underwent curative surgery with 3-field lymph node dissection (3FLD). A total of 88 (28%) of 312 patients were diagnosed with cervical lymph node metastases. Univariate and multivariate analyses were carried out to evaluate the impact of clinico-pathological factors on the survival of these patients. RESULTS: Overall five-year survival rate of 88 patients with cervical lymph node metastases was 26%. Univariate analysis revealed that following groups showed more than 40% overall five-years survival rate; female patients, patients with T1, T2 tumors and patients without thoracic node metastases. These variables were also independent good prognostic factors in multivariate analysis. CONCLUSIONS: Although cervical lymph node metastases was risk factors for worse survival, female patients, patients with T1, T2 tumors and patients without thoracic node metastases showed acceptable overall survival after 3FLD.     

Celiac lymph nodes: distant or regional for thoracic esophageal carcinoma?

Involvement of celiac nodes is defined as distant metastasis in the TNM classification for thoracic esophageal carcinoma. Some textbooks, however, describe dissection of these nodes as a standard technique. The present study was, therefore, undertaken to clarify which celiac nodes are regional for thoracic esophageal carcinoma and whether or not celiac node dissection would provide a survival benefit. Eight hundred and five patients who underwent R0 resection (no residual tumor) with systematic lymphadenectomy including the celiac axis area for thoracic esophageal carcinoma were retrospectively investigated. The frequency of metastasis and the therapeutic value of dissecting celiac nodes were compared to those associated with the left gastric artery area. The frequencies of left gastric and celiac nodal involvement were 15.4% and 9.6%, respectively, for thoracic esophageal carcinoma. As for tumor location, the incidences of metastasis around left gastric artery and celiac axis from the upper, middle and lower portion were 6.7% and 1.0%; 12.3% and 7.7%; and 25.7% and 17.4%, respectively. The 5‐year survivals of patients with celiac but not left gastric metastasis were 36.3% and 41.8% for the middle and lower portions, respectively, while the corresponding values with left gastric involvement but no celiac metastasis were 24.1% and 27.9%. These differences were not significant. The frequency of celiac node involvement was not low. And, their dissection has equivalent therapeutic value to that of left gastric nodes. Revision of the TNM classification to account for celiac node involvement in thoracic esophageal carcinoma, especially of the middle and lower portions, is needed.     

Prognostic significance of perigastric lymph nodes metastases on survival in patients with thoracic esophageal cancer

Several publications have showed that the number of metastatic lymph node (LN) should be taken into consideration in nodal category of esophageal cancer, but seldom considered extent of involved regional LNs. The aim of this study is to evaluate the significance of the extent of regional LN metastasis on survival in patients with esophageal cancer. A total of 245 thoracic esophageal cancer patients underwent transthoracic esophagectomy with standard lymphadenectomy between January 2000 and December 2006 were included in the study. Data including demographic factors, pathologic findings, LN parameters and survival outcomes were collected. The survival experience was depicted using Kaplan‐Meier method. A multivariate Cox proportional hazard model was used to screen the significant prognostic factors. The univariate analysis to further explore the significant prognostic factor was done by log‐rank test. After a median follow‐up of 53.2 months, the 5‐year survival rate was 46.3% for the entire cohort. Cox model regression indicated that the LN status and perigastric nodal status, aside from residual tumor status, histological tumor type and depth of invasion, were the independent prognostic factors. Patients without LN metastasis had better 5‐year survival than those with positive nodes (64.2% vs. 18.9%, X²= 35.875, P < 0.001). However, For those patients with nodal involvement, there was no difference in 5‐year survival between patients with involved nodes <3 and ≥3 (27.8% vs. 0%, X²= 0.925, P= 0.336). When considering the location of LN metastasis, patients could be further stratified according to whether the perigastric nodes were involved or not (37.5% vs. 10.0%, X²= 4.295, P= 0.038). In conclusion, involved LN number had no prognostic implication in nodal involved patients based on our data. Whereas, perigastric nodal involvement should be used to refine the N category (N0, no nodal metastasis, N1, non‐perigastric node metastasis, N2, perigastric node metastasis) for the future esophageal cancer staging criteria.     

Impact of the number of examined lymph nodes on outcomes in patients with lymph node-negative gallbladder carcinoma

AIM To determine whether the number of examined lymph nodes(LNs) is correlated with the overall survival of gallbladder carcinoma(GBC) patients. METHODS Patients were collected from the Surveillance Epidemiology and End Results database(2004-2013) and categorized by the number of LNs into six groups: 1 LN, 2 LNs, 3 LNs, 4 LNs, 5 LNs, and ≥ 6 LNs. Survival curves for overall survival were plotted with a KaplanMeier analysis. The log-rank test was used for univariate comparisons.RESULTS In a cohort of 893 patients, the median number of examined LNs was two for the entire cohort. The survival for the 1 LN group was significantly poorer than those of the stage Ⅰ and Ⅱ disease groups and for the entire cohort. By dichotomizing the number of LNs from 1 to 6, we found that the minimum number of LNs that should be examined was four for stage Ⅰ, four or five for stage Ⅱ, and six for stage ⅢA disease. Therefore, for the entire cohort, the number of examined LNs should be at least six, which is exactly consistent with the American Joint Committee on Cancer criteria.CONCLUSION The examination of higher numbers of LNs is associated with improved survival after resection surgery for N0 GBC. The guidelines for GBC surgery, which recommend that six LNs be examined at least, are statistically valid and should be applied in clinical practice widely.     

Perihilar lymph nodes in patients with primary sclerosing cholangitis with and without cholangiocellular carcinoma

Objective. Enlarged perihilar lymph nodes have been described in patients with primary sclerosing cholangitis (PSC). The aim of the study was to determine the clinical relevance of perihilar lymph nodes in PSC patients with and without cholangiocellular carcinoma (CCC). Material and methods. The status of perihilar lymph nodes was investigated in 117 patients with PSC using “high-end” ultrasound. Thirty-five of the 117 PSC patients had histologically proven CCC. Lymph node status was correlated with the presence of CCC and inflammatory bowel disease (IBD). Results. Seventy-three percent of PSC patients without CCC and 86% of patients with CCC had enlarged perihilar lymph nodes (NS). In CCC patients, the width of lymph nodes was significantly larger (12±6 mm versus 8±4 mm; p=0.0001), and the length:width ratio (2.15±0.7:1 versus 2.5±0.6:1; p=0.004) of the lymph nodes was significantly lower. Thirty-seven percent of PSC patients without CCC and 57% of patients with PSC and CCC had multiple perihilar lymph nodes (p=0.04). In all patients, the presence versus absence of IBD had no influence on the number (84% versus 74%,) and size of perihilar lymph nodes (length: 21±10 mm versus 19±7 mm). Lymph node status did not correlate with the number of episodes of cholangitis. Conclusions. Enlarged perihilar lymph nodes are characteristic of patients with PSC. Since perihilar lymph nodes are not predictive of the presence of complicating CCC, such patients should not be excluded from liver transplantation.     

Absence of human papillomavirus DNA detected by polymerase chain reaction in French patients with esophageal carcinoma

Recent studies have suggested that esophageal human papillomavirus infection could be a risk factor for esophageal squamous cell carcinoma. The aim of this study was to evaluate the prevalence of human papillomavirus DNA sequences in the esophagus of French patients with esophageal squamous cell carcinoma. Multiplex polymerase chain reactions with consensus primers directed to the L1 gene or specific primers for human papillomavirus types 6, 11, 16, 18, 31, and 33 directed to E6 gene (40 cycles followed by restriction mapping of the amplified products) were used to determine the presence of human papillomavirus DNA sequences in esophageal squamous cell carcinoma (n = 75), normal adjacent mucosa (n = 49), and metastatic lymphadenopathies (n = 5). As an internal control, a target located in the embryonic myosin heavy-chain gene was used in each reaction. Human papillomavirus DNA sequences could not be detected in any of the tumoral samples, the normal adjacent mucosa, or the metastatic lymphadenopathies. Human papillomavirus seems not to be implicated in esophageal carcinogenesis, at least in French patients, because the viral genomes are not associated with esophageal squamous cell carcinomas.     

Caspase-3 expression in metastatic lymph nodes of esophageal squamous cell carcinoma is prognostic of survival

AIM:To assess whether differential expression of caspase-3 in paired metastatic lymph nodes(LNs)is prognostic of survival in patients with resectable esophageal squamous cell carcinoma(ESCC).METHODS:Capases-3 expression was evaluated immunohistochemically in 122 pairs of primary ESCCs and regional metastatic LNs assembled on tissue microarrays.The impact of caspase-3 expression on survival outcomes was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model.RESULTS:The level of caspase-3 expression was significantly higher in LN metastases than in primary tumors(P<0.001).Caspase-3 expression in the primary tumors was associated with longer median survival(23 mo vs21 mo,P=0.033),whereas higher expression in paired metastatic LNs was associated with shorter median survival(20 mo vs 22 mo,P=0.043).Multivariate analysis showed that both were independent prognostic factors.CONCLUSION:Caspase-3 expression in metastatic LNs may be a potential independent predictor of poorer overall survival in patients with resected ESCC and LN metastasis.Protein expression in metastatic tumors may be a biomarker prognostic of survival.