Xiongwei Zheng

The pattern and prevalence of lymphatic spread in thoracic oesophageal squamous cell carcinoma.

BACKGROUNDnOesophageal squamous cell carcinoma (SCC) is a common type of cancer in China. The knowledge of its pattern of lymphatic metastasis would be of clinical value for surgical and radiation oncologists to treat this disease.nnnMATERIAL AND METHODSnA large series of 1850 thoracic oesophageal SCC was retrospectively analysed after extended oesophagectomy with three-field lymphadenectomy (3FL). Specimens were assessed for pattern of lymphatic spread.nnnRESULTnOf the 1850 patients, 1081 (58.4%) developed mediastinal, cervical and/or abdominal node metastases. The lymphatic metastasis rates were 35.6%, 22.2%, 26.5%, 6.1% and 26.5%, respectively, for the cervical, upper, middle, lower mediastinal nodes and abdominal nodes. The adjacent mediastinal node metastasis alone occurred in 5.5% of patients, and the multiple level or skip node spread accounted for 20.9% and 73.6% of patients with node metastases. Upward lymphatic spread developed in 46.4% of patients, both up- and downward in 33.2%, and the downward, 20.5%. For the upper oesophageal SCC, the most common node metastasis was in the cervical (49.5%) and followed by the upper mediastinal (28.7%), middle mediastinal (11.4%), abdominal (8.0%) and lower mediastinal (1.4%) nodes. For the middle oesophageal SCC, the highest incidence of node spread was also in the cervical (35.0%) and similar rates in the middle mediastinal (29.8%), abdominal (27.2%) and upper mediastinal (22.4%) nodes, but the least in the lower mediastinal (6.0%) node. For the lower oesophageal SCC, more node metastasis occurred in the abdominal (51.7%), and followed by the middle mediastinal (25.6%), cervical (17.2%), lower mediastinal (13.9%) and upper mediastinal (10.0%). However, the lymphatic metastasis rates of the upper, middle and lower thoracic oesophageal SCC were similar. The unfavourable factors for lymphatic metastasis were long oesophageal lesion (p<0.000), late T stage (p<0.000) and poor differentiation of tumour cells (p<0.000).nnnCONCLUSIONnThe prevalence was: (1) lymphatic spread prone to the upward in the upper oesophageal SCC, downward in the lower one and both up- and downward in the middle one with in favour of the upward and (2) multiple level and skip node metastases were very often seen. The unfavourable factors for node spread were long oesophageal lesion, late T stage and poor differentiation of tumour cells.

Postoperative Radiotherapy Improved Survival of Poor Prognostic Squamous Cell Carcinoma Esophagus

BACKGROUNDnThe purpose of this study was identify prognostic factors and to investigate the association between postoperative radiotherapy and overall survival of thoracic esophageal squamous cell carcinoma patients.nnnMETHODSnFrom January 1993 to March 2007, 1,715 patients underwent extended esophagectomy with three-field lymph node dissection with or without postoperative radiotherapy and were eligible for analysis. Patients were grouped to surgery only (n = 1,277) and surgery plus postoperative radiotherapy (n = 438). Radiation dose was 50 Gy in 25 fractions.nnnRESULTSnThe overall survival rates at 1, 3, 5, and 10 years were 86.6%, 61.3%, 49.4%, and 36.1%, respectively. Univariate and multivariate analyses showed that age 60 years or more, male sex, tumor more than 5 cm long, poorly differentiated histology, T4 tumor, presence of a vascular cancer thrombus in the surgical specimen, lymph node positivity, 3 or more positive lymph nodes, and disease stage II or higher were negative prognostic factors for overall survival. Postoperative radiation therapy improved overall survival for patients with poor disease-related prognostic factors: positive nodal disease, 3 or more positive lymph nodes, stage III/IV, and large or deeply invading tumor. Postoperative radiation had no survival benefit for patients who did not have the poor disease-related prognostic factors.nnnCONCLUSIONSnPostoperative radiotherapy is indicated for patients with poor disease-related prognostic factors.

Number and location of positive nodes, postoperative radiotherapy, and survival after esophagectomy with three-field lymph node dissection for thoracic esophageal squamous cell carcinoma

PURPOSEnTo analyze influences of the number and location of positive lymph nodes and postoperative radiotherapy on survival for patients with thoracic esophageal squamous cell carcinoma (TE-SCC) treated with radical esophagectomy with three-field lymphadenectomy.nnnMETHODS AND MATERIALSnA total of 945 patients underwent radical esophagectomy plus three-field lymph node dissection for node-positive TE-SCC at Fujian Provincial Tumor Hospital between January 1993 and March 2007. Five hundred ninety patients received surgery only (S group), and 355 patients received surgery, followed 3 to 4 weeks later by postoperative radiotherapy (S+R group) to a median total dose of 50 Gy in 25 fractions. We assessed potential associations among patient-, tumor-, and treatment-related factors and overall survival.nnnRESULTSnFive-year overall survival rates were 32.8% for the entire group, 29.6% for the S group, and 38.0% for the S+R group (p = 0.001 for S vs. S+R). Treatment with postoperative radiotherapy was particularly beneficial for patients with ≥3 positive nodes and for those with metastasis in the upper (supraclavicular and upper mediastinal) region or both the upper and lower (mediastinal and abdominal) regions (p < 0.05). Postoperative radiotherapy was also associated with lower recurrence rates in the supraclavicular and upper and middle mediastinal regions (p < 0.05). Sex, primary tumor length, number of positive nodes, pathological T category, and postoperative radiotherapy were all independent predictors of survival.nnnCONCLUSIONSnPostoperative radiotherapy was associated with better survival for patients with node-positive TE-SCC, particularly those with three or more positive nodes and positive nodes in the supraclavicular and superior mediastinal regions.

Postoperative radiation therapy with or without concurrent chemotherapy for node-positive thoracic esophageal squamous cell carcinoma

PURPOSEnTo retrospectively compare the efficacy of radiation therapy (RT) and chemotherapy plus RT (CRT) for the postoperative treatment of node-positive thoracic esophageal squamous cell carcinoma (TESCC) and to determine the incidence and severity of toxic reactions.nnnMETHODS AND MATERIALSnWe retrospectively reviewed data from 304 patients who had undergone esophagectomy with 3-field lymph node dissection for TESCC and were determined by postoperative pathology to have lymph node metastasis without distant hematogenous metastasis. Of these patients, 164 underwent postoperative chemotherapy (cisplatin 80 mg/m(2), average days 1-3, plus paclitaxel 135 mg/m(2), day 1; 21-day cycle) plus RT (50 Gy), and 140 underwent postoperative RT alone.nnnRESULTSnThe 5-year overall survival rates for the CRT and RT groups were 47.4% and 38.6%, respectively (P=.030). The distant metastasis rate, the mixed (regional lymph node and distant) metastasis rate, and the overall recurrence rate were significantly lower in the CRT group than in the RT group (P<.05). However, mild and severe early toxic reactions, including neutropenia, radiation esophagitis, and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P<.05). No significant differences in incidence of late toxic reactions were found between the 2 groups.nnnCONCLUSIONSnOur results show that in node-positive TESCC patients, postoperative CRT is significantly more effective than RT alone at increasing the overall survival and decreasing the rates of distant metastasis, mixed metastasis, and overall recurrence. Severe early toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.

Cervical lymph node metastasis classified as regional nodal staging in thoracic esophageal squamous cell carcinoma after radical esophagectomy and three-field lymph node dissection

BackgroundLymph node metastasis (LNM) is most common in esophageal squamous cell carcinoma (SCC). The bi-directional spread is a key feature of LNM in patients with thoracic esophageal SCC (TE-SCC). The purpose of this study was to analyze the prognostic factors of survival in patients with TE-SCC with cervical lymph node metastasis (CLM) and validate the staging system of the current American Joint Committee on Cancer (AJCC) in a cohort of Chinese patients.MethodsOf 1715 patients with TE-SCC who underwent radical esophagectomy plus three-field lymph node dissection at a single hospital between January 1993 and March 2007, 547 patients who had pathologically confirmed CLM (296 had surgery only and 251 had surgeryu2009+u2009postoperative radiotherapy) were included in this study. The locations of the lymph nodes (LNs) were classified based on the guidelines of the Japanese Society for Esophageal Diseases.ResultsThe rate of CLM was 31.9% for all patients and was 44.2%, 31.5%, and 14.4% for patients with upper, middle, and lower TE-SCC, respectively (Pu2009<u20090.0001). The rates of metastasis to 101 (paraesophageal lymph nodes), 104 (supraclavicular lymph nodes), 102 (deep cervical lymph nodes) and 103 (retropharyngeal lymph nodes) areas were 89.0%, 25.6%, 3.7% and 0.5%, respectively. The 5-year overall survival (OS) rate with CLM was 27.7% (median survival, 27.5xa0months). The 5-year OS rates were 21.3% versus 34.2% (median survival, 21.9xa0months versus 35.4xa0months) for after surgery only versus surgeryu2009+u2009postoperative radiotherapy, respectively (Pu2009<u20090.0001 for both). Multivariate analysis showed that the independent prognostic factors for survival were sex, pT stage, pN stage, number of fields with positive LNs, and treatment modality. In surgery only group, the 5-year OS rates were 24.1%, 16.2% and 11.7%, respectively, when there was metastasis to 101 LN alone, 104 LN alone or both 101 LN and 104 LN. The 5-year OS rates were 17.7%, 22.5% and 31.7%, for patients with upper, middle and lower TE-SCC , respectively (Pu2009=u20090.112). The 5-year OS rates were 43.0%, 25.5%, 10.2% in patients with 1 field (cervical LNs), 2 fields (cervicalu2009+u2009mediastinal, and/or cervicalu2009+u2009abdominal LNs), and 3 fields (cervicalu2009+u2009mediastinalu2009+u2009abdominal LNs) positive LNs, respectively (Pu2009<u20090.0001). The number of fields of positive LNs did not impact the OS according to different pN stage (all Pu2009>u20090.05).ConclusionPatients with TE-SCC with CLM have better prognosis, which supports the current AJCC staging system for esophageal SCC.

An in-depth prognostic analysis of baseline blood lipids in predicting postoperative colorectal cancer mortality: The FIESTA study

BACKGROUNDnDyslipidaemia is key to colorectal carcinogenesis, and the prediction of baseline triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDLC and LDLC) for postsurgical colorectal cancer mortality has not been researched.nnnOBJECTIVESnWe attempted to re-analyse the FIESTA database to assess the prognostic value of three informative lipid derivatives - AI (atherogenic index: (TC - HDLC)/HDLC), THR (TG/HDLC) and LHR (LDLC/HDLC) in predicting colorectal cancer mortality.nnnMETHODSnBased on the FIESTA database, 1318 patients received radical resection from 2000 to 2008, with the latest follow-up completed in December 2015. Median follow-up time was 58.6 months.nnnRESULTSnTotal 1318 patients were randomly evenly divided into the derivation and validation groups. Overall, baseline AI and LHR were associated with the significantly increased risk of colorectal cancer mortality in both derivation (hazard ratio (HR): 1.41 and 1.35, respectively) and validation (HR: 1.37 and 1.32, respectively) groups (all P <u202f0.001). The predictive performance of AI and LHR was remarkably enhanced in patients with female gender, former/current smoking, colon cancer, early stage, positive vein tumor embolus, normal weight, preoperative hypertension or diabetes comorbidities. Calibration/discrimination analyses revealed that adding AI or LHR to the traditional model had a better fit in both groups. A prognostic nomogram was finally constructed with good predictive accuracy and discriminative capability (C-indexu202f=u202f0.814, Pu202f<u202f0.001).nnnCONCLUSIONnWe consolidated the prognostic superiority of AI and LHR in predicting colorectal cancer mortality over TNM stage.

The pattern of cervical lymph node metastasis in thoracic esophageal squamous cell carcinoma may affect the target decision for definitive radiotherapy

BACKGROUNDnMetastasis to lymph nodes is a key determinant of thoracic esophageal squamous cell carcinoma (TE-SCC) prognosis. We sought to identify factors linked with cervical lymph node metastasis, which could be used to inform the decision of surgical and definitive radiotherapy.nnnMETHODSnWe retrospectively reviewed records from 1715 patients who had had radical esophagectomy with three-field lymphadenectomy between January 1993 and March 2007 in our hospital. All patients included in the study had pathologically confirmed TE-SCC and no clinical evidence of cervical metastasis.nnnRESULTSnCervical node metastases were found in 547 patients (31.9%); rates of cervical-node positivity were 44.2% for those with upper-thoracic tumors, 31.5% for mid-thoracic tumors, and 14.4% for lower-thoracic tumors. Univariate analysis showed that cervical node metastasis was associated with tumor site, differentiation, and length, pathologic T status, and pN status (P<0.05); however, only tumor site and pN status retained significance in multivariate analysis (P<0.05). Positive cervical nodes were most often found in the paraesophageal region (72.3%), followed by supraclavicular (24.4%); involvement of deep cervical (2.4%) or retropharyngeal nodes (0.9%) was rare (P<0.0001). Positive cervical nodes were most often associated with upper TE-SCCs (60.1%), followed by middle TE-SCCs (31.2%) and lower TE-SCCs (10.6%).nnnCONCLUSIONSnUpper TE-SCC with multiple involved nodes at any site was associated with a high rate of cervical node metastasis. These findings provide critical information for clinical decision-making regarding the extent of nodal dissection or the size of radiation fields in definitive radiotherapy.

Prognostic factors in patients with thoracic esophageal carcinoma staged pT 1-4a N 0 M 0 undergone esophagectomy with three-field lymphadenectomy

BACKGROUNDnTo analyze prognostic factors in patients with thoracic esophageal carcinoma staged pT1-4aN0M0 and undergone esophagectomy with 3-field lymphadenectomy and to evaluate the effect of postoperative radiotherapy.nnnMETHODSnFrom January 1993 to March 2007, 770 patients with stage pT1-4aN0M0 underwent 3-field lymphadenectomy at Fujian Province Cancer Hospital, China were enrolled for analysis. The study consisted of 770 patients with stage pT1-4aN0M0 who underwent 3-field lymphadenectomy at Fujian Province Cancer Hospital, China. A total of 687 had received surgery only, and 83 patients had undergone surgery followed by postoperative radiotherapy. Radiation dose was 50 Gy in 25 fractions.nnnRESULTSnThe overall survival rates at 1, 3, 5, and 10 years were 92.9%, 80.8%, 71.7% and 57.4%, respectively. Univariate analysis showed that age and T staging were two independent factors on prognoses. Five-year survival in cases younger and older than 60 were 76.5% vs. 63.3% (P=0.001), while those of pT1, pT2, pT3 and pT4a were 83.8%, 78.8%, 67.8% and 54.1%, respectively (P=0.000). Five-year survival in group of simple surgery was 71.3%, compared with 74.5% in group of surgery plus postoperative radiotherapy (P=0.763), while stratified analysis indicated that postoperative radiotherapy was able to boost the survival of patients in pT4a which were 72.4% vs. 33.8% (P=0.036) and to lower relapse rate of tumor bed in patients with pT4a (P=0.005). Multivariate analysis showed that age and T staging were two independent factors on prognoses.nnnCONCLUSIONSnPatients with high T staging and at an age more than 60 turned out bad prognoses, neither could postoperative radiotherapy improve their survival.

Analysis of H3K27me3 expression and DNA methylation at CCGG sites in smoking and non-smoking patients with non-small cell lung cancer and their clinical significance

Smoking frequently leads to epigenetic alterations, including DNA methylation and histone modifications. The effect that smoking has on the DNA methylation levels at CCGG sites, the expression of trimethylation of histone H3 at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (EZH2), and their interactions in patients with non-small cell lung cancer (NSCLC) were analyzed. There were a total of 42 patients with NSCLC, 22 with adenocarcinomas and 20 with squamous cell carcinomas enrolled in the present study. Expression of H3K27me3, EZH2 and proliferating cellular nuclear antigen (PCNA) were immunohistochemically detected. DNA methylation at CCGG sites was evaluated via histoendonuclease-linked detection of DNA methylation sites. The apoptotic index of cancerous tissues obtained from patients of different smoking statuses was evaluated via the terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling method. The association with clinicopathological data was calculated relative to different smoking statuses. Compared with the non-smokers, smokers with NSCLC exhibited a significantly lower apoptotic index (P<0.05), and frequently had a lower level of DNA methylation at CCGG sites, lower H3K27me3 expression and a higher EZH2 expression (P<0.05). DNA methylation levels at CCGG sites were negatively correlated to the Brinkman index (P=0.017). Furthermore, there was a parallel association between the H3K27me3 and EZH2 expression levels in the majority of smokers, whereas in the majority of non-smokers, there was a diverging association (P=0.015). There was a diverging association between the PCNA and EZH2 expression levels in the majority of smokers; however, in the majority of non-smokers, there was a parallel association (P=0.048). In addition, the association between the CCGG methylation ratio and immunohistochemical expression of H3K27me3 was a parallel association in the majority of smokers, while in the majority of non-smokers there was a diverging association (P=0.049). Conclusively, patients with NSCLC and different smoking statuses exhibit different epigenetic characteristics. Additionally, DNA methylation levels at the CCGG sites may have the ability to determine associations between the expression levels of H3K27me3, EZH2 and PCNA.

Loss of expression rather than cytoplasmic mislocalization of RUNX3 predicts worse outcome in non-small cell lung cancer

Functional inactivation of human runt-related transcription factor 3 (RUNX3) through mutation or epigenetic silencing has been well-documented in many cancerous entities. In addition to gene mutation and promoter hypermethylation, cytoplasmic mislocalization has emerged as another major manifestation of RUNX3 dysfunction in malignancies including breast, colorectal and gastric cancers. The aim of the present study was to investigate whether patients with non-small cell lung cancer (NSCLC) and different RUNX3 expression patterns would have different overall survival (OS), and the associations between different patterns of clinicopathological parameters and clinical outcome. Expressions of RUNX3 and Ki-67 were immunohistochemically detected in normal lung tissue (n=5) and surgically resected tissues from NSCLC patients (n=188). The optimal cutoff of RUNX3 was determined by X-tile software associated with their survival. Apoptotic index in cancerous tissue was evaluated using the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling method. The prognostic significance of different expression patterns of RUNX3 was determined by means of Kaplan-Meier survival estimates and log-rank tests. It was revealed that loss of RUNX3 expression in NSCLC was correlated with a low cancerous apoptotic index (P<0.001), shorter OS and worse prognosis (P=0.0142), while no statistical difference of apoptotic index (P=0.73) or survival (P=0.3781) was determined between patient subgroups with different localization of RUNX3 expression, which was quite different from the situation demonstrated in other malignancies. In conclusion, loss of expression rather than cytoplasmic mislocalization of RUNX3 predicted worse outcome in NSCLC, which was quite different from what manifested in other cancer types, and thus, the underlying mechanism may deserve further investigation.