食管癌大体肿瘤靶区的体积分级与病理T分期的关系

Objective Using the volume calculating function of treatment planning system of 3DCRT to work out the value of GTV standard classifications and to provide the reference for clinical staging of esophageal carcinoma. Methods Six hundred and seven patients underwent radical resection of thoracic esophageal carcinoma in our hospital, and their pre-operative CT images were transmitted in digital format to the three-dimensional conformal radiotherapy planning system by the network. Esophageal lesion GTV targets were outlined, and their volumes were automatically computed by the planning system. Compared the differences of the GTV volumes in different pathological T stages, and analyzed the relationship between GTV volumes and pathological T stages. According to the median volume of GTV at different pathological T stages, divided the values of GTV volume coresponding to different T stages and selected the suitable classification standard of GTV volume. Results The esophageal carcinoma GTV length, maximum diameter and volume were related to pathological T staging and with a positive correlation (all P < 0. 001 ). The Spearman correlation coefficient (r) was 0.376, 0.466 and 0.464, respectively, P < 0.001. Except that the length, maximum diameter and volume of GTV in pathological T3 and T4 had no significant difference, other indicators of the pathological T stages showed significant differences between the groups (P < 0. 001 ). According to the median volume of GTV at different pathological T stages, the GTV volumes were divided into three grades; ≤5.0 cm3,5. 1-13.0 cm3,and > 13.0 cm3. When compared them with pathological T1, T2, and T3 -T4 stages, the coincidence rate was 73. 8%. The consistency was good between the GTV volume grades and pathological T stages ( Kappa = 0. 40, P < 0. 001 ). Hie overall 5-year survival rates of GTV grades 1,2,3 were 78. 1% , 31.5% and 33. 5% , respectively (P < 0. 0001). If the GTVs were divided into four grades; ≤5.0 cm3,5.1-13.0 cm3,13.1-39.0 cm3 ,and >39.0 cm3, the coincidence rate of GTV volume grades and pathology T staging was only 54. 7% , and the consistency was poor, Kappa = 0.24,P<0.001. The overall 5-year survival rate of GTV 1, 2, 3, 4 were 78. 1% , 31.5% , 36.2% and 27.5%, respectively ( P < 0.0001). Conclusion The length, maximum diameter and volume of esophageal carcinoma GTV are related to pathological T staging with a positive correlation. The classification that esophageal carcinoma GTVs divided into three grades has a good coincidence with the pathological T staging.     

食管腔内超声参与的非手术食管癌临床分期与预后的相关性研究

Objective To investigate the clinical staging of non-surgically treated esophageal cancer based on endoscopic ultrasonography (EUS) and computed tomography (CT) and its prognostic value. Methods A total of 290 patients with esophageal squamous cell carcinoma who received non-surgical treatment in our hospital from November 2003 to March 2012 were retrospectively reviewed. The clinical stage of each patient was evaluated based on EUS and CT according to the 2002 UICC TNM staging system. The survival rates and prognostic factors for patients of different stages were analyzed. The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for survival difference analysis;the multivariate analysis was performed using the Cox model. Results EUS could be completely performed in 178(61.4%) of all patients, and their EUS T and N stages were determined. There were no significant differences in overall survival (OS) between patients with EUS T₁-T₄ diseases (P=0.247);there were significant differences in OS and progression-free survival (PFS) between individuals of different EUS T stages among patients with EUS N₀ disease (P=0.000;P=0.006). OS and PFS also showed significant differences between patients with N₀ and N₁ diseases (P=0.012;P=0.016). EUS could not be completely performed in 112 patients, who had poorer OS and PFS than other patients (P=0.001;P=0.003). CT T and N stages also affected OS and PFS (OS P=0.004, PFS P=0.030;OS P=0.024, PFS P=0.020). The 1-, 3-, and 5-year sample sizes were 290, 174, and 73, respectively. The 1-, 3-, and 5-year OS rates for all patients were 61.7%, 27.8%, and 19.8%, respectively. OS and PFS varied significantly between patients of different 2002 UICC clinical stages (P=0.000 and 0.000). The multivariate analysis showed that sex, age and clinical stage were independent prognostic factors (P=0.004, 0.020, and 0.002).Conclusions The clinical staging based on EUS and CT can predict the survival in esophageal cancer
DOI:10.3760/cma.j.issn.1004-4221.2014.02.010
基金项目:首都特色临床应用研究(Z121107001012004)
作者单位:100021 北京协和医学院,中国医学科学院肿瘤医院放疗科
通信作者:肖泽芬,Email:xiaozefen@sina.compatients treated with non-surgical method. EUS is recommended as a basic means for pretreatment staging of esophageal cancer in China.
     

A Study of Molecular Resection Margins for Esophageal Squamous Cell Carcinoma Using Large Pathologic Sections

OBJECTIVE It has been shown that application of molecular biological techniques to surgical margins of some cancers could predict risk of local recurrence. However, the optimal length of surgical resection with tumor-free surgical margins for esophageal squamous cell carcinoma (ES-CC) is unknown. This study was conducted to evaluate the optimal length of surgical resection for ESCC with molecularly tumor-free surgical margins marked by p53 and Ki67. METHODS Surgical specimens from 70 patients with ESCC were collected for study. The lengths of the upper margin, tumor, and lower margin of every specimen were measured during the operation. Each specimen was divided into three large pathologic sections, stained with H&E and immunohistochemically for p53 and Ki67, and examined microscopically. The lengths of the upper and lower resection ends were measured for p53 and Ki67 positive expression. The actual surgical lengths were calculated by the principle of rational shrinkage. RESULTS All surgical margins were histologically tumor-free, while the positive rates of p53 and Ki67 were 66% and 54%. The positive rates of p53 and Ki67 in the upper resection end were 17% and 20%. The mean lengths of the upper resection end showing p53 and Ki67 positive expression were 1.08±1.12 cm and 1.64±1.01 cm, and the maximum lengths were 3.73 cm and 3.26 cm. The positive rates of p53 and Ki67 in the lower resection end were 20% and 23%. The mean lengths of the lower resection end of p53 and Ki67 with positive expression were 1.11±1.15 cm and 1.34±0.94 cm, and the maximum lengths were 3.73 cm and 3.61 cm. CONCLUSION The optimal length of surgical resection with molecularly tumor-free surgical margins of ESCC is not more than 5 cm.     

Differential Diagnoses of Solitary Pulmonary Nodules in Patients with an Extrathoracic Malignant Tumor:CT and Parthologic Correlations

OBJECTIVE To determine the possibility of definitive diagnosis for solitary pulmonary nodules in patients with a primary extrathoracic malignant neoplasm (ETM-SPN), and to further evaluate the value of CT for differential diagnosis in ETM-SPN by a multivariate retrospective study.METHODS Eighty-three patients with pathologically and clinically proven ETM-SPN with a diameter smaller than 3 cm were included in this study.The pathological characteristics of the SPN were correlated with those of the extrathoracic neoplasm, with the patient's age, gender, smoking history, disease-free time interval between the diagnosis of the extrathoracic malignancy and that of the lung lesion. In all 83 cases, CT scans were reviewed to confirm the solitary nature, size, and nodular morphology of the lung lesion.RESULTS Of all 83 cases, the mean age was (57.43±15.34) years. There were 51 males and 32 females, with the ratio of 1.59:1. The lesions included solitary metastasis in 43 cases, pulmonary malignant lesions in 33, and benign lesions in seven. Between the primary lung cancers and solitary metastasis groups, there was no significant difference in the gender ratio (1.20:1 vs 2.31:1, x2=0.0209, P>0.05), but there was a significant difference between the mean age (62.48±11.96 years vs 54.10±16.49 years, t=3.34, P<0.05). in the primary lung cancer and metastasis patient group, the percentage of patients who had a smoking history were 39.3 %(11/17) and 35.9 %(14/39), respectively. Patients with a primary lung cancer had no significant higher frequency of smoking history than did those with a metastatic lesion (x2=0.640, P>0.05). Of 81cases who were followed-up, the mean time of the disease-free interval between extrapulmonary malignancy diagnosis and pulmonary lesion differentiation was 39.73± 6.29 months (range 0～300 months, median 20.00 months), whereas those in the primary lung cancer group and metastatic group were 65.62 ±13.45 months and 22.83 ±4.19 months respectively. This difference was significant between the two groups (Wilcoxon rank sum test, U=2.796, P<0.01). Of all 83 cases, there were ten extrapulmonary squamous carcinomas and 58 adenocarcinomas with ratio of primary lung cancer and solitary metastasis of the tumors were 7:3 and 24:34, respectively (x2 =1.781, P >0.05), without showing a statistically significant relevance between the pathologic patterns of extrapulmonary malignancy and characteristics of the lung nodules. Of all the 83 cases, the mean diameters were (2.77±1.25) cm, whereas the diameters of 33 cases of primary lung cancer and 43 cases of a solitary metastatic lesion were (2.86±1.18) cm and (2.62±1.31)cm, respectively. There was no association between the two groups (t=1.29, P>0.05). There was a statistically significant association between primary lung cancer and the metastatic group with spiculate and smooth edges of the lung lesion (x2=8.562, P<0.01; x2=15.220, P<0.001).The study showed that a lung nodule with a spiculatedmargin correlated with a primary lung carcinoma,whereas those nodules with a smooth edge may more frequently show as a metastastic pulmonary lesion. CT-pathologic correlative analyses of hilar and mediastinal adenopathy were reviewed in 37 patients who underwent Iobectomy and thoracotomy. There was no statistical significant difference between the primary lung cancer group and the metastatic group (x2=2.801,P>0.05).CONCLUSION The likelihood of a primary lung cancer versus a metastasis of ETM-SPN smaller than 3 cm mainly depends on the patient's age, free interval between the two tumors and CT morphological characteristics of the lung lesion. This study showed there was no significant relevancy to factors such as gender, smoking history, pathological patterns of the extrapulmonary neoplasm or whether there has hilar or mediastinal adenopathy.     

Clinical significance of hypoxia inducible factor-1α expression on postoperative adjuvant radiotherapy in esophageal carcinoma

Objective To determine the effects of hypoxia inducible factor-1α(HIF-1α) expression on postoperative adjuvant radiotherapy in esophageal carcinoma. Methods 95 cases with esophageal carcinoms who received radical operation were analyzed with followed-up data from 1995 to 1998.Expression of HIF-1α in 45 patients with esophageal carcinoma who received radiotherapy after radical operation were deternlined by immunohistochemical method in contrast with 50 patients with esophageal carcinoma received surgery alone.Kaplan-Meier method and COX proportional hazard model were used to analyze.Results The positive expression of HIF-1α in esophageal carcinoma was observed mainly in the nucleus of tumor cells.The positive expression rate of HIF-1α in esophageal carcinoma was 58.9%.The expression of HIF-1α had no relationship with age,sex,histologic subtype and T stage,but had positive relationship with recurrence and distant metastasis.There was significant difference between patients with positive and negative HIF-1α protein expression in surgery alone and postoperation radiotherapy group. COX model analysis showed that HIF-1α had separate and significant impacts on prognosis in surgery group and surgery plus radiotherapy group. Conclusion Over expression of HIF-1α protein suggests a poor prognosis,and has tendency to resist radiotherapy in esophageal carcinoma.     

Clinical significance of hypoxia inducible factor-1α expression on postoperative adjuvant radiotherapy in esophageal carcinoma

Objective To determine the effects of hypoxia inducible factor-1α(HIF-1α) expression on postoperative adjuvant radiotherapy in esophageal carcinoma. Methods 95 cases with esophageal carcinoms who received radical operation were analyzed with followed-up data from 1995 to 1998.Expression of HIF-1α in 45 patients with esophageal carcinoma who received radiotherapy after radical operation were deternlined by immunohistochemical method in contrast with 50 patients with esophageal carcinoma received surgery alone.Kaplan-Meier method and COX proportional hazard model were used to analyze.Results The positive expression of HIF-1α in esophageal carcinoma was observed mainly in the nucleus of tumor cells.The positive expression rate of HIF-1α in esophageal carcinoma was 58.9%.The expression of HIF-1α had no relationship with age,sex,histologic subtype and T stage,but had positive relationship with recurrence and distant metastasis.There was significant difference between patients with positive and negative HIF-1α protein expression in surgery alone and postoperation radiotherapy group. COX model analysis showed that HIF-1α had separate and significant impacts on prognosis in surgery group and surgery plus radiotherapy group. Conclusion Over expression of HIF-1α protein suggests a poor prognosis,and has tendency to resist radiotherapy in esophageal carcinoma.     

食管上皮癌变过程中CDK4、p18、p19的表达及意义

Objective To investigate the role of cell cycle regulatory protein CDK4,p18,p19 in the genesis and development of esophageal squamous cell carcinoma (SCC).Methods Tissue microarray and immunohistochemical method (Envision) were used to detect the protein expression of CDK4,p18,p19 in 120 cases of esophageal tissues.The results were statistically analyzed.Results The positive rate of CDK4 protein expression in normal esophageal epithelium was low [28.3 % (34/120)],it increased in esophageal intraepithelial neoplasia [32.5 % (39/120)],and it was high in esophageal SCC [84.2 % (101/120)],which increased with the degree of SCC differentiation decreasing gradually.There was significant differences between the SCC and normal esophageal epithelium or esophageal intraepithelial neoplasia (x2= 76.004,P ＜0.05; x 2= 65.897,P ＜ 0.05).The expression of CDK4 in group with lymphatic metastasis [93.88 % (46/49)]was higher than without it [71.43 % (55/71)] (x2= 5.860,P ＜ 0.05).The positive rates of p18,p19 protein expression in normal esophageal epithelium were high [34.2 % (41/120),29.2 % (35/120)],it decreased in esophageal intraepithelial neoplasia [19.2 % (23/120),15.0 % (1 8/120)] (x 2= 134.481,P ＜ 0.05; x 2 = 141.376,P ＜ 0.05),but it were high in esophageal SCC [63.3 % (76/120) and 61.7 % (74/120)] which decreased with the degree of SCC differentiation gradually increased.There were significant differences between the normal esophageal epithelium and esophageal intraepithelial neoplasia,esophegeal intraepithelial neoplasia and SCC,normal esophageal epithelium and SCC (p 18:x 2 = 6.903,48.296,20.429,P ＜ 0.05; p1 9:x2 = 6.998,55.276,25.565,P＜ 0.05).CDK4 protein expression was correlated with both p18 and p19 (r =0.696,0.630,P ＜0.05),and there was significant positive correlation between the protein expression of p18 and p19 (r =0.833,P ＜0.05).Conclusion Cell cycle regulatory gene CDK4,p18,p19 get involved in the genesis and development of esophageal squamous cell carcinoma.Their protein expressions are closely related to canceration of esophageal epithelium.     

食管上皮癌变过程中CDK4、p18、p19的表达及意义

Objective To investigate the role of cell cycle regulatory protein CDK4,p18,p19 in the genesis and development of esophageal squamous cell carcinoma (SCC).Methods Tissue microarray and immunohistochemical method (Envision) were used to detect the protein expression of CDK4,p18,p19 in 120 cases of esophageal tissues.The results were statistically analyzed.Results The positive rate of CDK4 protein expression in normal esophageal epithelium was low [28.3 % (34/120)],it increased in esophageal intraepithelial neoplasia [32.5 % (39/120)],and it was high in esophageal SCC [84.2 % (101/120)],which increased with the degree of SCC differentiation decreasing gradually.There was significant differences between the SCC and normal esophageal epithelium or esophageal intraepithelial neoplasia (x2= 76.004,P ＜0.05; x 2= 65.897,P ＜ 0.05).The expression of CDK4 in group with lymphatic metastasis [93.88 % (46/49)]was higher than without it [71.43 % (55/71)] (x2= 5.860,P ＜ 0.05).The positive rates of p18,p19 protein expression in normal esophageal epithelium were high [34.2 % (41/120),29.2 % (35/120)],it decreased in esophageal intraepithelial neoplasia [19.2 % (23/120),15.0 % (1 8/120)] (x 2= 134.481,P ＜ 0.05; x 2 = 141.376,P ＜ 0.05),but it were high in esophageal SCC [63.3 % (76/120) and 61.7 % (74/120)] which decreased with the degree of SCC differentiation gradually increased.There were significant differences between the normal esophageal epithelium and esophageal intraepithelial neoplasia,esophegeal intraepithelial neoplasia and SCC,normal esophageal epithelium and SCC (p 18:x 2 = 6.903,48.296,20.429,P ＜ 0.05; p1 9:x2 = 6.998,55.276,25.565,P＜ 0.05).CDK4 protein expression was correlated with both p18 and p19 (r =0.696,0.630,P ＜0.05),and there was significant positive correlation between the protein expression of p18 and p19 (r =0.833,P ＜0.05).Conclusion Cell cycle regulatory gene CDK4,p18,p19 get involved in the genesis and development of esophageal squamous cell carcinoma.Their protein expressions are closely related to canceration of esophageal epithelium.     

脑瘤灌注CT不同层厚CBV与rCBV测量的可重复性研究

Objective： To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume （CBV） and relative cerebral blood volume （rCBV） with different slice thickness in patients with brain neoplasms. Methods： Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation （CV）, and relative paired difference of the measurements were used to determine the levels of inter-and intraobserver reproducibility. Results： The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant （P 〈 0.05） respectively in observer 2, and were not significant in the other two observers （P 〉 0.05）. For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion： High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.     

食管平滑肌瘤10例临床治疗体会

我院１９７５年６月～１９９０年７月共收治食管平滑肌瘤１０例，占同期食管肿瘤总数的０．１９２％（１０／１０９２）。位于食管上段２例，中段５例，下段３例。Ｘ线食管钡餐造影是诊断本病的主要方法。行食管粘膜外肿瘤摘除９例，食管部分切除１例，效果良好。本文就其诊断与手术治疗进行了讨论。     

仙人掌原液毒性的初步研究

背景与目的： 研究仙人掌原液的毒性。 材料与方法： 小鼠急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验、大鼠30 d喂养试验。 结果： 仙人掌原液雌、雄小鼠LD50均大于20.0 g/kg,属无毒物质;Ames试验、微核试验和精子畸形试验结果均为阴性;大鼠30 d喂养试验结果显示该样品30 d喂养对大鼠各项观察指标未见毒性作用。结论： 在本次实验条件下,仙人掌原液为无毒物质,未显示有遗传毒性和亚急性毒性作用。     

胰头癌手术切除可能性的术前评价

目的通过总结胰头癌病人的临床表现和影象学检查结果来评价手术切除的可能性。方法总结32例胰头癌病人的临床表现和CT、磁共振（MRI）检查结果,判断肿瘤是否已发生邻近浸润或远处转移,以此来评价其手术切除的可能性。结果在22例作CT检查的病例中,判断正确的为17例,准确率为77．3%。作MR检查9例,全部判断正确,准确率为100%。结论某些特殊的临床表现和CT、MR检查对判断肿瘤是否发生邻近浸润或转移有较大价值,为术前评价手术切除的可能性提供依据。     

Assessment of the degree of carcinogenicity of small doses of nitrites

Chronic experiments on CBA and C57B1 mice and acute experiments on CBA mice established: (a) carcinogenic effect of sodium nitrite given continuously with drinking water (0.1; 1.0 and 10.0 maximum allowable concentration) in combination with morpholine fed with bread, and (b) endogenous synthesis of nitrosomorpholine as a result of simultaneous intragastric administration of same doses of sodium nitrite and morpholine. Also, nitrosomorpholine and N-nitrosodimethylamine synthesis was observed in vitro following addition of low-dose sodium nitrite, morpholine and amidopyrine to human gastric juice. Carcinogenic hazard associated with low-dose nitrite consumption in humans is discussed.     

仙人掌原毒性的初步研究

背景与目的:研究仙人掌原液的毒性。材料与方法:小鼠急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验、大鼠30 d喂养试验。结果:仙人掌原液雌、雄小鼠LD50均大于20.0 g／kg,属无毒物质;Ames试验、微核试验和精子畸形试验结果均为阴性;大鼠30 d喂养试验结果显示该样品30 d喂养对大鼠各项观察指标未见毒性作用。结论:在本次实验条件下,仙人掌原液为无毒物质,未显示有遗传毒性和亚急性毒性作用。     

胆囊癌29例分析

目的探索胆囊癌的防治方法。方法分析29例胆囊癌病人临床资料、治疗方法及结果。结果术前诊断明确者21例，剖腹探查发现已属晚期，9例为Ⅳ期行根治术，12例为Ⅴ期未行根治术，均于术后1年内死亡。术前怀疑胆囊癌者5例，剖腹探查冰冻切片证实为Ⅴ期及Ⅳ期者各1例，Ⅴ期未行根治术，Ⅳ期行根治术，均于术后1年内死亡；Ⅲ期者3例，行胆囊癌根治术分别于术后10月、13月、17月死亡。2例术中冰冻切片发现的Ⅱ期胆囊癌，行胆囊癌根治术，分别于术后23月、26月死亡。1例意外胆囊癌属Ⅰ期胆囊癌，术后5年半死亡。结论要减少胆囊癌危害，重在及时治疗胆囊结石。     

中晚期贲门癌148例的外科治疗

目的　总结贲门癌手术治疗影响生存率的因素 ,提供今后工作参考。方法　对 14 8例经手术治疗的贲门癌患者进行术后并发症、绝对生存率的X2 检验。结果　本组切除率为 94.5 9% ,近半胃切除占 72 .14 % ,1、3、5年生存率分别为 67.9%、45 %和 2 4.3 %。病期、外侵程度和淋巴结转移等因素对 5年生存率有显著影响 (P <0 .0 1)。术后并发症以吻合口瘘及肺癌并发症为多见 ,其发生率为 3 .6% ,手术死亡率 1.4%。结论　提高生存率的关键在于早期诊断 ,根治手术和术后积极综合治疗。