Analysis of clinical features of esophageal neuroendocrine neoplasms

Esophageal neoplasms have a wide spectrum of clinical features, pathologic findings, and imaging manifestations. Leiomyomas are the most common benign esophageal neoplasm, typically appearing as smoothly marginated intramural masses. Fibrovascular polyps arise in the cervical esophagus, gradually elongating as they are pulled inferiorly by esophageal peristalsis. Granular cell tumors are generally incidental small intramural masses with an appearance similar to that of leiomyomas. Malignant esophageal neoplasms are a common cause of cancer mortality, particularly squamous cell carcinoma (SCC) and adenocarcinoma. Both of these tumors occur in older men, most often appearing as irregular infiltrative lesions at barium examination, with evidence of tumor spread beyond the esophagus at cross-sectional imaging. Adenocarcinoma arises from Barrett esophagus and is much more likely than SCC to involve the gastroesophageal junction. Esophageal involvement by lymphoma is usually secondary to tumor spread from the stomach or mediastinum. Spindle cell carcinoma is a biphasic malignancy with carcinomatous and sarcomatous elements that forms a bulky polypoid intraluminal mass. Neuroendocrine carcinoma is an aggressive neoplasm that may be hypervascular and is usually associated with metastatic disease at presentation. Understanding the imaging appearances and pathologic bases of esophageal neoplasms is essential for their detection, differential diagnosis, staging, and treatment planning.

Objective To explore the clinical and histopathological features of Barrett esophagus and its related adenocarcinoma as well as the relationship between them.Methods From January 2002 to January 2012,the clinical data of 35 patients with Barrett esophagus,850 patients with esophagus cancer and 218 patients with esophageal-gastric junction cancer were collected,and the histopathological features of all the patients and the follow-up in patients with Barrett esophagus were retrospectively analyzed.Results Among 35 patients with Barrett esophagus,six cases(17.1 ％) had specialized intestinal metaplasia and all of them did not develop into esophageal adenocarcinoma or Siewert type Ⅰ esophageal-gastric junction cancer.Among 850 patients with esophageal cancer,794 cases (93.4％) were squamous carcinoma,19 cases (2.2％) were small cell carcinoma,seven cases (0.8％) were adenocarcinoma.And besides,there were adenosquamous carcinoma,basaloid squamous carcinoma,carcinosarcoma,and neuroendocrine carcinoma.Among 218 patients with esophageal gastric junction cancer,nine cases (4.1％) were Siewert type Ⅰ,150 cases (68.8％) were Siewert type Ⅱ,59 cases (27.1％) were Siewert type Ⅲ.A total of 180 cases (82.6％) were adenocarcinoma and others were signet ring cell carcinoma,mucous adenocarcinoma,squamous carcinoma,adenosquamous carcinoma,small cell carcinoma,neuroendocrine carcinoma,carcinoid and spindle cell carcinoma.Conclusions Specialized intestinal metaplasia is rare in patients with Barrett esophagus in China,and the probability of Barrett esophagus developing into adenocarcinoma is low.Barrett esophagus related adenocarcinoma such as esophageal adenocarcinoma and Siewert type Ⅰ esophageal-gastric junction cancer is rare. Key words: Barrett esophagus; Esophageal neoplasms; Adenocarcinoma; Esophageal-gastric junction; Pathology, clinical

Most prevalent esophageal neoplasm is squamous cell carcinoma and adenocarcinoma. Other tumors are uncommon and poorly studied. Primary neuroendocrine esophageal neoplasm is a rare carcinoma and most of its therapy management is based on lung neuroendocrine studies. Neuroendocrine tumors can be clustered in the following subtypes: high grade (small cell carcinoma or large cell carcinoma) and low grade (carcinoids). The present study aims to assess clinical and pathological neuroendocrine esophageal tumors in a single oncologic center. A retrospective analysis of patients and review of the literatures was performed. Fourteen patients were identified as neuroendocrine tumors, 11 male and 3 female patients. Mean age was 67.3 years old. Ten patients were classified as small cell, 3 as large cell and 1 as carcinoid. Four patients presented squamous cell carcinoma simultaneously and 1 also presented adenocarcinoma. Main sites of metastasis were liver, peritoneum, lung and bones. Most patients died before 2 years of follow-up. Patient with longer survival died at 35 months after diagnosis. Neuroendocrine esophageal tumors are rare; affect mainly men in their sixties or seventies. High grade tumors can be mixed to other subtypes neoplasms, such as adenocarcinoma and squamous cell carcinoma. Most of these patients have poor overall survival rates.

Objective To investigate the expressions of AGGF1 in esophageal squamous cell carcinoma (ESCC) and their relationships with clinical features and prognosis of ESCC. Methods The expressions of AGGF1 in 70 cases of ESCC and 30 cases of normal esophageal tissue were examined using SP immunohistochemical staining and were analyzed according to the clinical features and follow-up data. Results The expressions of AGGF1 in 70 cases of ESCC was significantly higher than those in 30 cases of normal esophageal tissue [54.29% (38/70) vs. 23.33% (7/30)](P=0.004). The expressions of AGGF1 in ESCC were significantly related to the TNM stage, clinical stage and prognosis (P all<0.05). The OS was shorter in the positive teams of AGGF1 than that in the negative teams [(19.7 ± 3.5) months vs. (33.2 ± 4.0) months](P=0.015). Cox-proportional multivariate analysis showed that positive expressions of AGGF1 and VEGF (P=0.043, 0.024) and clinical stage (P=0.035) were significant prognostic factors in overall survival. Conclusions AGGF1 has high expressions in ESCC, and it is closely related to the clinical features and prognosis of ESCC. Key words: Esophageal neoplasms; Neoplasms, squamous cell; Disease attributes; Prognosis; AGGF1

GASTRIC NEUROENDOCRINE CARCINOMA IN A BEARDED DRAGON (POGONA VITTICEPS)

Alimentary Tract Neoplasia in Captive Bearded Dragons (Pogona spp)

Esophageal neuroendocrine neoplasms are rare. With the improvement and popularization of diagnostic methods, the morbidity statistics have increased annually in recent years. There are currently no treatment guidelines for esophageal neuroendocrine neoplasms, and surgery is the only cure. This usually involves radical surgery when the tumor is limited to the primary site or when only regional lymph node metastasis occurs. Surgical treatment is key to treating esophageal neuroendocrine neoplasms, but combined treatment with chemotherapy and radiotherapy can significantly improve patient survival. The effect of radiotherapy alone on this disease is poor. However, targeted endocrine therapy can improve endocrine hormone symptoms. The prognosis of patients with esophageal neuroendocrine neoplasms is mainly determined by the pathological stage. With the development of molecular biology techniques, the combination of targeted drugs and traditional chemotherapy is expected to provide novel ideas and directions for the treatment of esophageal neuroendocrine neoplasms in the coming years. In this article, the status of esophageal neuroendocrine tumor treatments was reviewed in detail.

Objective To investigate the clinical significance and characteristics of recurrent laryngeal nerve lymph node metastasis of thoracic esophageal cancer.Methods One hundred and twenty-four patients who had undergone thoracic esophageal resection with recurrent laryngeal nerve lymph node dissection in our hospital from March 2007 to February 2010.All clinical data were retrospectively analysed.Results Recurrent laryngeal nerve lymph node metastasis was found in 34 of 124 cases,with the metastatic rate of 27.41% (34/124).The left recurrent laryngeal nerve lymph node metastasis was 16.13% and the right was 8.06% .The recurrent laryngeal nerve lymph node metastasis was found in 9 patients with the upper segment esophageal cancer,20 with middle third esophageal cancer and 5 with lower segment esophageal cancer,6 patients with T2 disease had recurrent laryngeal nerve lymph node metastasis,while 27 with,T3 disease.Also there were 4,13,17 cases with metastasis in well-differentiated,moderately differentiated,poorly differentiated respectively.Poorly differentiated esophageal carcinoma was more susceptible to recurrent laryngeal lymph node metastasis than well-differentiated and moderately differentiated esophageal carcinoma.Recurrent laryngeal nerve injury was found in 11 cases,7 cases of them recovered.Conclusion Nearly 1/3 of patients with esophageal carcinoma have recurrent laryngeal nerve lymph node metastasis,especially for tumor located in the upper third esophagus,poor differentiation or deep invasion (T2 or more) of esophageal carcinoma were more susceptible to recurrent laryngeal nerve lymph node metastasis. Key words: Esophageal neoplasms; Neoplasm matastasis; Lymph node; Recurrent laryngeal nerve

Objective To investigate the clinical significance and expression of microRNA(miR)-561 in esophageal squamous cell carcinoma. Methods From January 2015 to February 2016, 96 specimens of adjacent tissues and cancer tissues from patients with esophageal squamous cell carcinoma who underwent surgery in Dongfeng Hospital Affiliated of Hubei University of Medicine were selected to detect the expression level of miR-561. Cell culture experiments were used to detect the expression level of miR-561 in Het-1a, Kyse150 and Eca109 cell lines. The correlation between clinical features and the expression level of miR-561 was counted. The expression level of miR-561 in patients with esophageal squamous cell carcinoma was analyzed. The relationship between the level of miR-561 and prognosis was investigated. Results Relative expression of miR-561 in esophageal squamous cell carcinoma cell lines Eca109 and Kyse150 (1.61 ± 0.30, 1.21 ± 0.28) was significantly lower than that in Het-1a (2.56 ± 0.51), and the difference was statistically significant (P < 0.05). The relative expression of miR-561 in esophageal squamous cell carcinoma tissues was significantly lower than that in adjacent tissues (0.80 ± 0.17 vs. 1.51 ± 0.42), and the difference was statistically significant (P < 0.05). The expression of miR-561 in esophageal squamous cell carcinoma was correlated with alcohol drinking history, lymph node metastasis, differentiation degree and tumor stage (P < 0.05). Cox multivariate regression analysis showed that the independent risk factors affecting the prognosis of patients were the expression of miR-561, TNM stage and lymph node metastasis (P < 0.05). The survival rate of patients with esophageal squamous cell carcinoma whose expression of miR-561 did not decrease at follow-up was significantly higher than that of patients with decreased expression of miR-561 (P < 0.05). Conclusions In patients with esophageal squamous cell carcinoma, the expression of miR-561 is low, and the development, occurrence and prognosis of esophageal squamous cell carcinoma are closely related with it. Key words: Esophageal neoplasms; MicroRNA-561; Eca109; Kyse150; Het-1a

Objective To investigate the clinical characteristics,diagnosis,treatment and prognosis of limited stage primary esophageal small cell carcinoma (PESC).Methods Clinical data was retrospectively analyzed for 42 patients with pathologically confirmed PESCs who underwent transthoracic esophagectomy with lymphadenectomy from Nov.1990 to Dec.2010 at the Cancer Hospital of Shantou University Medical College.The survival analysis was performed using Kaplan-Meier method.Results The clinical symptoms,imaging and endoscopic features of PESC were similar to those of esophageal squamous cell carcinoma (ESCC).Of the 26 cases that received pre-operative endoscopic biopsy,only five cases were diagnosed as PESC,while the other 21 cases were misdiagnosed as ESCC.The mean follow-up time of this series was 25.3 months (0-123 months).34 patients died of the disease during the follow-up; 7 were still alive and 1 was lost.The median survival time (MST) of the 41 patients was 13.0 months (95 ％ confidence interval 6.3-19.7),and the 6-,12-,24-,36-,and 60-month overall survival rates (OS) were 78.6 ％,57.5 ％,30.8 ％,23.7 ％,10.5 ％,respectively.Conclusion PESC is a rare disease with poor prognosis,and is prone to be misdiagnosed by endoscopic biopsy.Currently no standard treatment has been established. Key words: Esophageal neoplasms; Carcinoma, small cell; Treatment; Prognosis

Objective To compare survival according to the extent of lymph node dissection in patients with thoracic esophageal squamous cell carcinoma.To identify the subgroups of patients that could get survival benefit from three-field lymph node dissection.Methods Between January 1999 and December 2007,1551 patients with thoracic esophageal squamous cell carcinoma received esophagectomy plus three-field lymph node dissection (3 FL) (n =1131) or two-field lymph node dissection (2FL) (n =420).We retrospectively analyzed the clinical characteristics and patterns of lymphatic spread of thoracic esophageal squamous cell carcinoma.Survival rates between 3FL and 2FL were compared using the Kaplan-Meier method and Log-Rank test.Multivariate analysis were also performed to assess the element which affect the survival in 3FL and 2FL group by Cox regression.Results No significant differences in age,gender and depth of tumor invasion were found between 3 FL group and 2FL group.The 3FL group included more patients with upper thoracic esophageal tumors(17.6％ vs.9.8％) and patients with lymph node metastasis(LNM) (62.7％ vs.52.9％).Cox-proportional multivariate analysis showed that extent of lymph node dissection(3FL vs 2FL) was a significant prognostic factor in overall survival; 3 FL was beneficial for patients with upper thoracic esophageal tumors(P =0.002,5-year survival rate 53.2％ vs.34.1％).The 3FL group in patients with middle/lower thoracic esophageal tumors who had no LNMs(N0) had better 5-year survival than the 2FL group(5-year survival rate 77.5％ vs.70.7％),but no significant differences were found (P =0.235).or; Among patients with middle/lower thoracic esophageal tumors who had 1-6 LNMs (N1-N2),3 FL was beneficial for patients with mediastinum LNMs (P =0.006,5-year survival rate 41.1％ vs.32.8％) For patients with ≥7 LNMs(N3),cervical lymphadenectomy did not show additional survival benefits.Conclusion Our findings suggest that extent of lymph node dissection(3FL vs 2FL) is a significant prognostic factor for thoracic esophageal squamous cell carcinoma.3FL offers survival benefit over 2FL in patients with upper thoracic esophageal tumors or patients with middle/lower thoracic esophageal tumors who have 1-6 LNMs with mediastinum lymph node metastasis. Key words: Esophageal neoplasms; Lymph node dissection ; Survival

Simple SummaryEsophageal neuroendocrine neoplasms (E-NENs) are a rare malignancy in esophageal carcinoma; their clinical and oncologic characteristics are poorly reported. Additionally, the effect of surgery on E-NENs remains unclear and controversial. In this study, we retrospectively analyzed the clinicopathological characteristics, prognosis, and immune cell infiltration in E-NENs and compared them with those of esophageal squamous cell carcinoma (ESCC) to determine whether surgery has the same therapeutic efficacy for E-NENs as for ESCC based on a cohort who received surgical treatment. According to our results, first, the target population for surgery may be limited to stage I E-NENs patients. Secondly, E-NENs and especially pure NENs were correlated with the cold tumor phenotype because of the less infiltration of immune cells compared with ESCC. The findings suggest that strategies for immune activation should be developed and applied when immunotherapy is considered for E-NENs in the future.Background: Esophageal neuroendocrine neoplasms (E-NENs) are a rare and poorly reported subtype of esophageal carcinoma. We analyzed the differences in clinicopathological features, prognosis, and tumor-infiltrating lymphocytes (TILs) between E-NENs and esophageal squamous cell carcinoma (ESCC). Methods: A total of 3620 patients who underwent esophagectomy were enrolled retrospectively. The study cohort was divided into two groups (E-NENs and ESCC) through propensity-score matching, and the prognosis and TILs were compared between the two groups. The TILs were assessed using tumor specimens (including six cases of ESCC, six cases of neuroendocrine carcinomas [NECs], and six cases of mixed neuroendocrine–non-neuroendocrine neoplasms [MiNENs]). Results: E-NENs accounted for 3.0% (107/3620) of cases, among which there were just 3 neuroendocrine tumor cases, 51 NEC cases, and 53 MiNENs cases. After matching, esophageal neuroendocrine carcinomas (E-NECs) showed both poorer 5-year overall survival (OS; 35.4% vs. 54.8%, p = 0.0019) and recurrence-free survival (RFS; 29.3% vs. 48.9%, p < 0.001) compared with ESCC. However, the differences were not prominent in the subgroup with stage I. No significant survival benefit was observed for E-NECs with multimodal therapy. Multivariate analysis demonstrated that E-NECs are an independent risk factor for OS and RFS. In the exploratory analysis, E-NECs were associated with less infiltration of immune cells compared with ESCC. Conclusion: E-NECs are significantly associated with a poorer prognosis than ESCC except for early-stage disease. The fewer TILs within the tumor microenvironment of E-NECs compared with ESCC results in weaker anti-tumor immunity and may lead to a poorer prognosis.

Object To investigate the expression of inducible nitric oxide synthase(iNOS) and vascular endothelial growth factor(VEGF) in human esophageal squamous cell carcinoma and their clinical significances,and to evaluate the correlation between the expression of iNOS and VEGF.Methods Immunohisto-chemical SABC methond was used to detect the expression of iNOS and VEGF in 52 cases of esophageal squamous cell carcinoma and 20 cases of paired para-carcinama.The correlation between the expression of iNOS and VEGF was analyzed statistically.And the correlation between the expression of iNOS and VEGF and the clinical pathological features of the patients was analyzed statistically.Results The positive expression rates of iNOS and VEGF in esophageal squamous cell carcinoma were 63.46％ (33/52) and 67.31％ (35/52),respectively.The positive expression rates of iNOS and VEGF in paired para-carcinama tissues were 10％ (2/20) and 20％ (4/20)respectively.The positive expression rates of iNOS and VEGF in esophageal squamous cell carcinoma were significantly higher than those in paired para-carcinama tissues(x2 =14.455 6,P ＜ 0.01;x2 =9.508 9,P ＜ 0.01).There was significiat correlation between the expression of iNOS,VEGF and the pathological grade (P ＜ 0.01),clinic TNM stage(P ＜ 0.05),lymph noed metastasis(P ＜ 0.05),but there was no correlation between the expression of iNOS,VEGF and the patients sex (P ＞ 0.05).Expression of iNOS was positively correlated with that of VEGF(r=0.748 2,P ＜ 0.01).Conclusion iNOS and VEGF are highly expressed and correlated in esophageal carcinoma.It is speculated that a common activation mechanism may coexists between the two genes.The expression of iNOS and VEGF plays an important role in the malignant progression. Key words: Esophageal neoplasms; Nitric oxide synthas; Vascular endothelial growth factors

Objective To investigate the correlation between the expression of activated CDC42-associated tyrosine kinase 1 (ACK1) and invasion and metastasis of esophageal squamous cell carcinoma (ESCC). Methods RT-PCR technique and immunohistochemical (IHC) assay were used to determine the expression levels of ACK1 mRNA and protein in 45 cases of freezing stored fresh ESCC tissues and ESCC-adjacent normal mucosa tissues. Western blotting was used to determine the expression of ACK1 in 5 ESCC cell lines. The correlation between the different expression levels of ACK1 mRNA and protein and ESCC clinical and pathological features was analyzed. Results Low expression of ACK1 mRNA and protein was found in ESCC-adjacent normal mucosa tissues. In ESCC tissues, the expression levels of ACK1 mRNA and protein were up-regulated in 60% (27/45) and 64.4% (29/45) ESCC tissues, respectively, with good consistency (P=0.02). Statistical analysis showed high expression of ACK1 mRNA and protein, which were significantly correlated with the metastasis of lymph node and tumor staging (P<0.05). Immunohistochemistry showed up -regulated expression of ACK1 in most ESCC cytoplasm, and high expression of ACK1 protein in ESCC nest surrounding invaded tumor cells, indicating positive correlation between ACK1 high expression and tumor cell invasiveness. Conclusion ACK1 high expression is positively correlated with malignant phenotype and poor prognosis of ESCC. Measuring the expression level of ACK1 may predict the ratio of tumor invasion, lymphonode metastasis, and prognosis in ESCC, to provide evidence for individualized cancer therapy. Key words: Esophageal neoplasms; Lymphonode metastasis; Prognosis

Objective To examine the expression of angiopoietin-2(Ang-2) in squamous carcinoma of esophagus,and discuss the relationship between Ang-2 and microvessel density(MVD)and clinical pathological features of squamous carcinoma of esophagus.Method The expression of Ang-2 and CD34 in 80 squamous careinoma of esophagus and 25 normal esophagus were detected by immunohistochemistry SABC technique,and the MVD of tissues signed by CD34 was counted.Results The expression of Ang-2 in squamous carcinoma of esophagus was,higher than that in normal esophagus (P<0.05).The expression of Ang-2 in the stage O-I and II squamous carcinoma of esophagus was lower than that in stage Ⅲ and lV(P<0.05).The expression of Ang-2 in squamous carcinoma of esophagus was correlated with differentiation of esophageal carcinoma and lymph node metastasis and infiltrative deepness.There was a remarkable posidve correlation between the expression of Ang-2 and MVD in squamous carcinoma of esophagus (r=0.603,P<0.05). Conclusion The expression of Ang-2 may be elated to the development of squamous carcinoma of esopha- gus,and may promote the development of squamous carcinoma of esophagus by promoting angiogenesis in tumor. Key words: Esophageal neoplasms; Angiopoiedn-2; Antigens,CD34; Microvessel density