Nodal skip metastasis is not a predictor of survival in middle thoracic esophageal squamous cell carcinoma / 中华胸心血管外科杂志

Objective To investigate the relationship of nodal skip metastasis(NSM) and clinicopathological factors of middle thoracic esophageal squamous cell carcinoma patients.Methods Between January 1999 and December 2007,695 patients with middle thoracic esophageal squamous cell carcinoma who had lymph node metastasis were reviewed.All patients received McKeown esophagectomy.We retrospectively analyzed the clinical characteristics and NSM status.Survival rates were compared using the Kaplan-Meier method and Log-Rank test.Multivariate analysis were also performed to assess the element which affect the survival by Cox regression.Results NSM were present in 226 (32.5％) patients.No significant differences in age,gender,tumor differentiation and extent of lymph node dissection depth of tumor invasion were found between skip metastasis group and continuous metastasis group.The NSM group included more patients with earlier T stage and N stage.Univariate analysis displayed that NSM was beneficial for patients with middle thoracic esophageal tumors (P ＜ 0.001).Cox-proportional multivariate analysis showed NSM was not a significant prognostic factor in overall survival.The overall survival did not differ according to NSM status in subgroups with different N stage.T1-2 patients,no significant difference of 5-year survival rate was found between skip metastasis group and continuous metastasis group(P =0.059).T3-4 patients,significant difference of 5-year survival rate was found between skip metastasis group and continuous metastasis group(P =0.001).NSM patients were then separated into 3 groups based on the extent of metastasis lymph nodes:both cervical and abdominal NSM (n =45,19.9％),cervical NSM (n =120,53.1％) and abdominal NSM (n =61,27.0％).The number of metastasis lymph nodes was significantly different among the three groups.No survival differences were observed among the three groups.Conclusion NSM is more frequently in the earlier stage compared to continuous metastasis.Three field lymphadenectomy can reduce the recurrence of T3-4 patients,and improve the survival rate of five years.The presence of NSM does not predict prognosis.

Establishment of a rat model with pulmonary arterial hypertension and its functioning mechanism / 中华胸心血管外科杂志

Objective To study the alteration of hepatocyte growth factor and c-met in the lungs of rats with pulmonary arterial hypertension and its possible underlying mechanisms.Methods Left pneumonectomy plus monocrotaline injection was used for rat PAH model.Rats were executed after measurement of their pulmonary arterial pressure at 1,2, 3 and 4 weeks after MCT injection.Then the right lung and heart were harvested for further analyses.Expression of HGF and c-met was determined by RT-PCR and Western blot.Expression of eNOS and caspase-3 was analyzed immunohistochemically and intrapulmonary TGF-β and ET-1 was analyzed with ELISA.Results Compared with the normal controls, manifestations of right heart hypertrophy and failure, well-elevated pulmonary arterial pressure were observed 28 days after left lung resection and MCT injection.Pulmonary vascular remodeling (i.e., pulmonary fibrosis, hyperplasia of pulmonary arterial endothelial cells and vascular smooth muscle cells in tunica media, as well as decease of vascular density) was observed.Intrapulmonary HGF expression decreased in a time-dependent manner at both mRNA and protein levels 4 weeks after MCT injection, while c-met stayed unchanged.Immunohistochemically, expression of eNOS was reduced and caspase-3 strengthened.On the contrary, ET-1 and TGF-β were obviously up-regulated(P ＜ 0.01).Conclusion Intrapulmonary HGF expression was obviously downregulated in PAH rats, accompanying with reduction of NO and increase of ET-1 and TGF-β expression, while c-met still unchanged.

Comparison of survival between three-field and two-field lymph node dissections for thoracic esophageal squamous cell carcinoma / 中华胸心血管外科杂志

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.

The relationship between number of metastatic lymph node and prognosis of thoracic-esophageal cancer patients treated with radical resection / 中华胸心血管外科杂志

Objective To analyze the possible prognostic factors of thoracic-esophageal cancer patients with lymph node (LN) metastasis after esophagectomy plus three-field lymphadenectomy.Methods 590 esophageal cancer patients with LN metastasis after esophagectomy plus three-field lymphadenectomy were recruited from Jan.1993 to Mar.2007,and the prognostic factors and causes of postoperative failure were analyzed.Results Five-year survival in the whole sample was 29.6％.While the 5-year survival in different subgroups with 1-2,3-6 or ＞ 7 metastatic LNs were 41.2％,22.2％ and 7.0％ (x2 =62.158,P ＜0.0001),respectively.Univariate analysis showed that tumor site,disease length,T stage,number of metastatic LN and the seventh edition of AJCC staging system were prognostic factors.Multivariate analysis indicated that tumor site and number of metastatic LN were two independent prognostic factors.Conclusion Tumor site and number of metastatic LN were independent prognostic factors influencing the outcome of esophageal cancer.

Prognostic analysis of cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the prognostic factors of cervical lymph node metastasis (CLN) in thoracic esophageal squamous cell carcinoma (TESCC), and to probe and verify the esophageal carcinoma staging of the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system.</p><p><b>METHODS</b>A total of 1 715 TESCC patients underwent radical esophagectomy plus three-field lymph node dissection at Fujian Provincial Cancer Hospital between January 1993 and March 2007. 547 patients had pathological metastasis of CLN, and 296 patients received surgery only (S group) and 251 patients received postoperative radiotherapy (S+R group). The prognostic factors were analyzed and the pattern of recurrence and metastases was studied according to the esophageal carcinoma staging criteria of the 7th edition of AJCC TNM staging system.</p><p><b>RESULTS</b>The metastasis rate of CLN was 31.9% for the entire group, 44.2%, 31.5% and 14.4% for the upper, middle and lower TESCC, respectively (P < 0.001). The 5-year overall survival rate of the patients with metastatic CLN was 27.7%, and the median overall survival time was 27.5 months. The 5-year survival rate was 21.3% in the S group and 34.2% in the S+R group, and the median survival time was 21.9 months in the S group and 35.4 months in the S+R group (P < 0.001). Multivariate analysis showed that gender, lesion length in X-ray, N stage, AJCC stage and treatment modality were independent prognostic factors of CLN metastasis in TESCC. Independent prognostic factors for S group included the primary tumor site, pT stage, N stage and AJCC stage, and N stage was an independent prognostic factor for the S+R group.</p><p><b>CONCLUSIONS</b>TESCC with CLN metastasis have a better prognosis after surgery. It supports that cervical lymph nodes belong to regional lymph nodes classified in the 7th edition of AJCC TNM staging system.</p>

Value of postoperative radiochemotherapy for thoracic esophageal squamous cell carcinoma with lymph node metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively compare the efficacy of postoperative radiotherapy (RT) alone with that of postoperative radiotherapy with concurrent chemotherapy (CRT) for thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes, and to evaluate the clinical value of RT + CRT.</p><p><b>METHODS</b>304 EPC patients underwent esophagectomy with three-field lymph node dissection had pathological lymph node metastases, but no hematogenous distant metastasis. Among them, 140 cases underwent postoperative RT alone, and 164 cases underwent postoperative CRT. The dose of irradiation was 50 Gy, and the chemotherapy regimen was taxol and cis-platinum, and a cycle was 21 days.</p><p><b>RESULTS</b>The 1-, 3- and 5-year total survival rates of the whole group were 90.1%, 56.6% and 43.3%, respectively, with a median survival time of 49.7 months. The 5-year overall survival rates of the CRT and RT groups were 47.4% and 38.6%, respectively (P = 0.030), with a median survival time of 53.5 and 41.7 months, respectively (P = 0.030). The overall survival rates of the patients who underwent 1, 2, 3, 4 cycles of chemotherapy were 24.4%, 53.0%, 58.1% and 43.3%, respectively (P = 0.007). Among them, the 5-year total survival rate of patients with 2-4 cycles of chemotherapy was significantly better than that of patients who underwent one cycle of chemotherapy (P = 0.001). Univariate analysis showed that number of metastatic lymph nodes, pT stage, therapeutic regimen and number of chemotherapy cycles were significantly correlated with the prognosis of the patients (P < 0.05 for all). Multivariate analysis showed that number of metastatic lymph nodes, pT stage, and number of chemotherapy cycles were independent prognostic factors of the patients (P < 0.05 for all). Early toxic effects including neutropenia, radiation esophagitis, and gastrointestinal effects were significantly more severe in the CRT group than that in the RT group (P < 0.05), however, there were no significant differences of late toxic effects between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>Postoperative CRT for thoracic EPC with positive lymph nodes can improve the survival rate, with tolerable adverse effects.</p>

Efficacy evaluation of laparoscopy-assisted surgery for Siewert I adenocarcinoma of the esophagogastric junction / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of laparoscopy-assisted surgery for Siewert I adenocarcinoma of the esophagogastric junction (AEJ).</p><p><b>METHODS</b>Clinical data of 36 patients who underwent left transthoracic dissection of lower mediastinal lymph node followed by laparoscopy D2 lymph node dissection for Siewert I AEJ in the Fujian Provincial Cancer Hospital between March 2008 and March 2013 were analyzed retrospectively. A left thoracic-abdominal single incision was used without transection of costal arch. Celiac lymph nodes dissection was performed laparoscopically followed by left transthoracic dissection of lower mediastinal lymph node. Digestive tract reconstruction was carried out by esophagus-gastric posterior wall end-to-side anastomosis.</p><p><b>RESULTS</b>Laparoscopy-assisted surgery was successfully achieved in all the 36 patients and there were no in-hospital deaths. The mean operation time, blood loss and number of harvested lymph node were (216.4±46.0) min, (252.1±41.1) ml and 30.7±3.2 respectively. All the procedures were R0 resections. The complication rate was 16.7% (6/36). All the complications were managed by conservative treatment, and there were no re-operations. The lymphatic metastasis rate was 50.0% (18/36), and the lymph node groups with high metastatic rate (all >10.0%) were groups 1, 2, 3, 7, 9, 110 and 111. The median follow-up was 25 months. The overall 3-year survival was 48.0%.</p><p><b>CONCLUSION</b>Laparoscopy-assisted surgery for Siewert I AEJ is safe and feasible.</p>

Clinical analysis of the characteristics of cervical lymph node metastasis in thoracic esophageal squamous cell carcinoma / 中国癌症杂志

Background and purpose: Lymph node (LN) metastasis of esophageal cancer of neck rate higher, but there is little bulk reports. This article aimed to analyze the characteristics of cervical lymph node metastasis (CLN) in thoracic esophageal squamous cell carcinoma (TE-SCC) and the clinical role. Methods:A total number of 1 131 TE-SCC patients underwent radical esophagectomy plus three-ifeld lymph node dissection at Fujian Provincial Tumor Hospital between Jan. 1993 to Dec. 2003, during which, 367 patients had pathological metastasis of CLN. Results:The metastatic rate of CLN was 33.2%for the entire group, 43.7%, 33.0%and 16.0%for the upper, middle and lower TE-SCC respectively. Single factor analysis showed that the metastatic rate of CLN was relevant with the tumor site, pathological differentiated degree, lesion length showed in X-ray, pT stage and the number of CLN (P<0.05). But multivariate regression analysis showed that the metastatic rate of CLN was just relevant with the tumor site, pT stage and the number of CLN (P<0.05). Metastasis of cervical paraesophageal lymph nodes was the most common, and Background and purpose: Lymph node (LN) metastasis of esophageal cancer of neck rate higher, but there is little bulk reports. This article aimed to analyze the characteristics of cervical lymph node metastasis (CLN) in thoracic esophageal squamous cell carcinoma (TE-SCC) and the clinical role. Methods:A total number of 1 131 TE-SCC patients underwent radical esophagectomy plus three-ifeld lymph node dissection at Fujian Provincial Tumor Hospital between Jan. 1993 to Dec. 2003, during which, 367 patients had pathological metastasis of CLN. Results:The metastatic rate of CLN was 33.2%for the entire group, 43.7%, 33.0%and 16.0%for the upper, middle and lower TE-SCC respectively. Single factor analysis showed that the metastatic rate of CLN was relevant with the tumor site, pathological differentiated degree, lesion length showed in X-ray, pT stage and the number of CLN (P<0.05). But multivariate regression analysis showed that the metastatic rate of CLN was just relevant with the tumor site, pT stage and the number of CLN (P<0.05). Metastasis of cervical paraesophageal lymph nodes was the most common, and supraclavicular lymph node metastasis was next, and metastasis of cervical profound lymph nodes and retropharyngeal lymph nodes were rare. The ratio of the number of CLN occupied the sum of the segmental CLN were 57.7%, 32.0%and 10.0%for the upper, middle and lower TE-SCC respectively (P<0.05). Right CLN of each segmental TE-SCC was more than left CLN. Conclusion:Independent factors on CLN in TE-SCC are the tumor site, pT stage and the number of CLN. Metastasis of cervical paraesophageal lymph nodes is the most common, and supraclavicular lymph node metastasis is next, and metastasis of cervical profound lymph nodes and retropharyngeal lymph nodes are rare.

Clinical study of postoperative chemoradiotherapy of thoracic esophageal squamous cell carcinoma with positive lymph nodes / 中华放射肿瘤学杂志

Objective To retrospectively analyze the treatment results and side effects of postoperative chemoradiotherapy and postoperative radiotherapy of thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes.Methods Three hundred and four patients of thoracic EPC were initially treated with three-field lymphadenectomy, with pathological positive lymph nodes and without distant metastases;and randomly divided into two groups:140 patients of the simple postoperative radiotherapy (RT) and 164 patients of postoperative chemoradiotherapy (CRT).The median total dose was 50 Gy.The regimen of concurrent chemotherapy included cisplatin and taxol, and the intermission was 21 days;the median cycles were 2.35.Results The 3-year overall survival rates were 65.7% of CRT and 52.8% of RT (χ2=6.90,P=0.009), and The 3-year disease-free survival rates were 62.5% of CRT and 52.8% of RT (χ2=4.75,P=0.029).The incidences of the supraclavicular lymph-node metastases were 1.8% and 7.1%(χ2=5.21,P=0.022), respectively;and the incidences of distant metastases were 18.3% and 27.9%(χ2=3.94,P=0.047), respectively;and the incidences of overall metastases and recurrences were 27.4% and 39.3%(χ2=4.80,P=0.028), respectively.Early side effects included granulopenia (96.3% and 32.1%,χ2=140.31,P=0.000), radiation-induced esophagitis (37.2% and 26.4%,χ2=4.01,P=0.045),and gastrointestinal toxicity (23.2% and 5.0%,χ2=19.77,P=0.000).Late side effects were 6.1% and 5.0%(χ2=0.17,P=0.678), respectively.Conclusions Postoperative chemoradiotherapy of thoracic EPC with positive lymph nodes can improve the overall survival and disease-free survival, decrease the incidence of the supraclavicular metastases, the distant metastases, the total metastases and recurrences.More severe early side effects were observed in chemoradiotherapy than in the radiotherapy group,but well tolerated.

Lymph node metastasis pattern in patients with T2 and middle thoracic esophageal squamous cell carcinoma / 中华胸心血管外科杂志

Objective To investigate the pattern of lymph node metastasis in patients with 17 and middle thoracic esophageal squamous cell carcinoma( ESCC). Methods Retrospective review the clinical data of 246 cases with T2 and middle thoracic esophageal squamous cell carcinoma who were treated by three-field lymphadenectomy. Analyze the relationship between clinical pathological factors and lymph node metastasis. Results Lymph node metastases were found in 129 of the 246 patients (52.4% ).The average number of resected lymph nodes was 25 per patient (rangel5 -59). The rates of lymph node metastasis were 28.9% in the neck, 28.5% in thoracic mediastinum and 22.0% in abdominal cavity for patients with T2 and middle thoracic ESCC. No significant difference in lymph node metastasis' rate was observed among the neck, thoracic mediastinum and abdominal cavity. Logistic-regression showed the length of tumor, tumor cell differentiation and angiolymphatic invasion were factors influencing lymph node metastasis. Conclusion Lymph node metastasis in T2 and middle thoracic ESCC has the characteristics of upward, downward and skip spreading. Patients with T2 and middle thoracic ESCC should be treated with radical surgery with three-field lymphadenectomy.

Value of the number and distribution of metastatic lymph nodes in postoperative radiotherapy for thoracic esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To analyze the relationship between the number as well as distributions of positive lymph nodes, and the clinical outcomes of postoperative radiotherapy for thoracic esophageal squamous cell carcinoma (TESCC) , And to evaluate the efficacy of postoperative radiotherapy . Methods From January 1993 to March 2007,945 patients with TESCC treated with three-field lymphadenectomy were involved in this study. All patients were with lymphoid metastasis but without distant metastasis. Among them, 590 patients received surgery alone and the other 355 received surgery plus postoperative radiotherapy. The radiotherapy were begun in the third or fourth week after operation and the median total radiation dose was 50 Gy in 25 fractions of 2 Gy, 5 fractions per week. Results The follow-up rate was 94.5%. 189 patients finished minimal follow-up of five years. The 5-year survival rates in the surgery alone group and in the postoperative radiotherapy group were 29.6% and 38.0%, respectively (χ~2 = 10.44 ,P = 0.001). In stratification analysis, compared with the surgery alone, postoperative radiotherapy could increase the 5-year survival rate of the patients with 3 to 5 (30.5% : 23.1%, χ~2 = 4.11, P = 0.043) or > 5 positive nodes (16.7% : 8.9%, χ~2= 6.87, P= 0.009) , or metastastatic node in the region of supraclavicular or upper mediastinum (45.5% : 34.9%, χ~2= 5.37, P = 0.020). In patients with positive nodes number less than 3, or with medium mediastinum or lower mediastinum lymph nodes metastasis, postoperative radiotherapy could not increase the 5-year survival rates (50.7% : 41.2%, χ~2 = 3.30, P = 0.069 ; 32.0% : 27.7% , χ~2= 2.22 , P = 0. 137) , Though could decrease lymph nodes metastasis in supraclavicular and medium-upper mediastinum (15 : 76, χ~2 = 18.10, P = 0.000; 18 : 97, χ~2= 26.81, P = 0.000). Conclusions In TESCC patients with positive lymph nodes number ≥3 or nodes in the region of supraclavicular and upper mediastinum, postoperative radiotherapy can improve the survival after three field lymphadenectomy. And the rate of metastastatic lymph nodes in the supraclavicular region or upper-medium mediastinum can also be decreased.

Postoperative prophylactic radiotherapy for N0 esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the value of postoperative prophylactic radiotherapy for N0 e-sophageal squamous carcinoma. Methods From January 1993 to December 2006,859 patients with patho-logically staged N0 and M0 esophageal squamous cell carcinoma were included in this study. Among them, 760 received surgery alone, and 99 received surgery followed by postoperative radiotherapy. Radiotherapy started within 3 to 4 weeks after surgery. The median total dose was 50 Gy(2 Gy/F,5 F/w). Results In surgery alone group and postoperative radiotherapy group,the 5-yeur overall survival rotes were 72.2% vs 77.4% (X2 =0. 13,P >0.05) for all patients,34.6% vs67.1% (X2 =7.72,P <0.05) forpT4 disease,and 70.2% vs 81.3% (X2 =4.01 ,P <0.05) for tumor length >5 cm. Postoperative radiotherapy could lower the recurrence rate for pT4 patients. Conclusions For patients with NO esophageal squamous carcinoma, postoperative radiotherapy can significantly improve the survival for pT4 and tumor length > 5 cm,and also re-duce the recurrence for pT4 patients.

Accuracy study of using CT to delineate tumor target volume of thoracic esophageal carcinoma / 中华放射肿瘤学杂志

Objective To compare the accuracy of CT with other methods to measure the length of thoracic esophageal carcinoma. Methods 598 patients with thoracic esophageal squamous carcinoma were enrolled in this study.All the patients received three-field(cervical,thoracic:and abdominal)radical surgery without pre-operative radiotherapy or chemotherapy.The length of each Iesion was recorded and compared by measuring intraoperative specimen,formalin-fixed specimen,X-ray barium meal examination and CT,respectivelv. Results By the measurement of intraoperative specimen,formalin-fixed specimen,Xray barium meal examination and CT,the mean lengths of lesion were(5.22±1.94),(4.28±1.71),(5.12±1.92)and(6.71±2.52) cm,respectively.The measured length was significantly different between intraoperative specimen and formalin-fixed specimen or CT(t=16.01,P＜0.01;t=-15.54,P＜0.01),but not between intraoperative specimen and X-ray barium meal examination(t=1.62,P＞0.05).The measured lengths gradually decreased in the order of CT,intraoperative specimen,X-ray bailam meal examination and formalin-fixed specimen.For different pathological type(except intracavitary type)and different T staging,there was significant difference in lesion length between intraoperative specimen and CT(P＜0.05),but not between intraoperative specimen and X-ray barium meal examination(P＞0.05). Conclusions The length of esophageal carcinoma measured by intraoperative specimen is shorter than by CT,but longer than by X-ray barium meal examination.Specimen could shrink after foriBalin fixation.X-ray barium meal and other examinations should be referred when using CT to delineate tumor target volume of esophageal carcinoma for radiotherapy.