结直肠癌术后腹腔免疫化疗的疗效观察

目的：观察腹腔免疫化疗在结直肠癌术后应用的疗效。方法：对46例结直肠癌术后患（DukesC期、D期）行腹腔免疫化疗，评价患生活质量、免疫指标改善，近期复发转移情况。结果：结直肠癌术后应用腹腔免疫化疗，患免疫指标改善，副反应轻，术后肿瘤复发，转移率下降。结论：腹腔免疫化疗对防治结直肠癌术后复发，转移是一种安全、方便有价值的方法。     

植入用缓释氟尿嘧啶腹腔化疗在结直肠癌术中应用的临床研究

目的 评估植入用缓释氟尿嘧啶腹腔化疗在Ⅱ、Ⅲ期结直肠癌术中应用的疗效和安全性.方法 标准结直肠癌根治性切除术后的Ⅱ、Ⅲ期结直肠癌患者108例,分为腹腔植入缓释氟尿嘧啶组35例和对照组73例(常规处理),腹腔植入组在根治性手术过程中术野植入缓释氟尿嘧啶,对照组仅行常规处理,两组患者术后按NCCN指南进行诊疗.比较两组患者围手术期局部并发症、化疗毒副反应以及2年内复发转移情况和2年无病生存率.结果 两组患者围手术期局部并发症和化疗毒副反应无统计学差异(P>0.05).随访24个月至51个月,2年无病生存率比较,腹腔植入组为85.71%,对照组为60.27%,差异有统计学意义(P<0.05).2年复发转移率比较,腹腔植入组为14.29%,对照组为39.73%,差异有统计学意义.腹腔植入组2年总生存率为94.3%,高于对照组83.6%,但差异未达统计学差异.结论 植入用缓释氟尿嘧啶腹腔化疗在Ⅱ、Ⅲ期结直肠癌术中应用安全有效,在2年内复发转移以及2年无病生存率方面,具有明显优势.     

结直肠癌腹膜转移治疗的临床研究进展

腹膜是结直肠癌转移的第三常见部位。结直肠癌腹膜转移通常被认为是终末期疾病,预后差。随着系统性药物治疗的进展,转移性结直肠癌患者预后明显改善,但腹膜转移患者生存获益仍然较少。腹膜肿瘤细胞减灭术和腹腔热灌注化疗能够显著改善腹膜转移患者的预后。新型治疗方法如腹腔加压气溶胶化疗、腹腔MOC31PE抗毒素治疗等也随之出现。本文将对结直肠癌腹膜转移治疗的临床研究进行综述。     

Dukes C期结直肠癌根治术后复发转移因素的Logistic回归分析

目的:探讨Dukes C期结直肠癌根治术后复发转移的相关因素。方法:应用Logistic回归分析方法，对235例结直肠癌根治术后患者的临床病理资料，进行单因素和多因素回顾分析。结果：单因素分析显示，患者性别、年龄、病程、肿瘤部位、肿瘤大体类型、肿瘤直径、肿瘤组织类型及肠壁浸润深度对结直肠癌术后复发转移无影响。单因素和多因素分析显示，淋巴结转移和肿瘤分化程度是影响结直肠癌术后复发转移的独立预后因素。结论：淋巴结转移(数目或部位)和肿瘤分化程度是影响Dukes C期结直肠癌术后复发转移最重要的独立因素，对于判断预后、指导术后治疗及随访方案的制订具有重要作用。     

腹腔化疗预防结直肠癌术后肝转移及局部复发的临床观察

我院1994年8月～1998年10月收治结直肠癌中Dukes B期手术患者42例.为探讨腹腔内化疗预防结直肠癌术后肝转移及局部复发的价值,我们将病例分为两组,术后腹腔内化疗20例(A组),同期未行腹腔内化疗22例(B组),将两组病例对比分析,现报告如下.     

CIK细胞过继性免疫治疗对结直肠癌化疗患者免疫指标的影响

目的 探讨 CIK 细胞回输对化疗后结直肠癌患者免疫功能的影响.方法 检测化疗联合 CIK 细胞回输后结直肠癌患者的外周血 CD3+细胞百分率,CD4+细胞百分率,CD4+/CD8+比值,NK 细胞百分率.结果 化疗联合 CIK 细胞回输后肿瘤患者CD3'、CD4+、CD4+/CD8+、NK 均显著高于化疗前组,且 CD8+显著低于对照组(P<0.05).结论 FOLFOX 方案化疗后序贯应用 CIK 细胞过继性免疫治疗,可提高结直肠癌患者的免疫功能,有可能降低术后复发和转移.     

结直肠癌术后门静脉化疗对NK细胞活性的影响

肝脏是结直肠癌远处转移的好发部位,一旦发生转移预后很差。随机临床研究证明结直肠癌术后门静脉灌注化疗(5-FU或5-FU/MMC)可预防肝转移。而门静脉化疗对患者抗肿瘤免疫功能的影响尚不清楚。本文旨在研究门静脉化疗对结直肠癌患者NK细胞活性的影响,进一步阐明结直肠癌术后门静脉化疗的利与弊。 1992～1994年作者将35例进展期结直肠癌患者随机分为2组,19人行术后门静脉化疗,15人作对照组,所有病人均行根治性切除术。伴有远处转移、其他严重疾病和已接受过上腹部手术者未列于本组研究。     

结直肠癌围手术期炎症反应的研究进展

结直肠癌术后复发与转移的比例较高,且缺乏有效的预防手段与治疗方法。围手术期机体炎症功能的改变和手术应激与肿瘤预后密切相关,其中结直肠肿瘤环氧化酶-2 (Cyclooxygenase-2）过度表达在患者免疫功能的转变上发挥了重要的作用。通过调节围手术期患者的免疫状态,控制外科应激,可能成为预防降低术后复发与改善预后的新途径。     

新辅助化疗对直肠癌患者肿瘤标志物与疾病复发转移指标的影响

目的观察新辅助化疗对直肠癌患者肿瘤标志物与疾病复发转移指标的影响。方法选取54例直肠癌患者为研究对象,将其随机分为对照组(常规手术治疗组)27例和观察组(术前新辅助化疗组)27例,然后检测两组患者治疗前和术后不同时间的肿瘤标志物与疾病复发转移相关指标并进行比较。结果治疗前两组患者的肿瘤标志物与疾病复发转移相关指标比较,P均>0.05,而术后不同时间观察组的肿瘤标志物与疾病复发转移相关指标表达均低于对照组,P均<0.05,均有显著性差异。结论新辅助化疗可明显降低直肠癌患者的肿瘤标志物与疾病复发转移指标的表达,因此认为新辅助化疗在直肠癌患者中的应用价值较高。     

麻醉对结直肠癌患者围手术期免疫功能及肿瘤预后影响的研究进展

炎症与结直肠癌的发生和发展密切相关,结直肠癌患者的围手术期手术、麻醉、疼痛等均会导致机体的全身炎症及免疫功能的损伤,这对结直肠癌患者预后有着重要的影响,尤其在术后肿瘤复发和转移方面.麻醉是控制围手术期应激反应的有效途径,部分麻醉技术和麻醉药物具有抗炎特性及保护免疫功能的作用.因此,本研究就目前不同麻醉技术及麻醉药物对结直肠癌患者围手术期免疫功能及其预后影响的相关文献进行综述,以期为麻醉医师优化结直肠癌患者围手术期麻醉技术及麻醉药物的管理,改善其长期预后提供重要的参考价值.     

Evaluation of 1p losses in primary carcinomas, local recurrences and peripheral metastases from colorectal cancer patients

Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of 1p deletions in primary carcinomas (n=28), local recurrences (n=19) and metastases (n=33) from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04). The smallest region of 1p deletion overlap (SRO) defined separately for each group of lesions had the region between markers D1S2647 and D1S2644, at 1p35–36, in common. The genes PLA2G2A (1p35.1–36) and TP73 (1p36.3) were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18) were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%). The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences.     

Complementation of intracavitary and intravenous administration of a monoclonal antibody (B72.3) in patients with carcinoma

Monoclonal antibody (MAb) B72.3 has been shown to have selective reactivity for a wide range of carcinomas (colorectal, ovarian, breast, lung, gastric, and endometrial) versus normal adult tissues. 131I-Labeled B72.3 IgG has recently been shown to selectively bind carcinoma lesions when administered i.v. in patients with metastatic colorectal cancer. We report here the first direct comparison of i.p. administered [131I]B72.3 IgG to specifically localize metastatic carcinoma. Three of 10 patients studied were negative for tumor detection by both CAT scan and X-ray but were positive for tumor localization via gamma scanning i.p. administered 131I-labeled MAb B72.3 IgG. Direct analyses of biopsy specimens of carcinoma and normal tissues demonstrated ratios of greater than 70:1 (based on percentage of injected dose/mg) for tumor MAb localization versus normal tissues. Specificity of [131I]B72.3 tumor targeting was demonstrated by the concomitant administration of an equal dose of an 125I-labeled isotype identical (IgG1) control MAb. Simultaneous i.p. administration of [131I]B72.3, and i.v. administration of [125I]B72.3 in individual patients demonstrated: peritoneal implants are targeted more efficiently via i.p. MAb administration, and hematogenously spread and lymph node metastases as well as local recurrences are targeted more efficiently by i.v. administered MAb. No antibody toxicity was observed in any patients. Pharmacokinetics of MAb clearance demonstrated that only 10 to 30% of the i.p. administered MAb was found in plasma. These studies thus demonstrate the efficacy of intracavitary MAb administration as well as the advantage of the concomitant use of intracavitary and i.v. administered MAbs for tumor targeting and for potential MAb guided therapy of metastatic carcinoma.     

Up-regulation of the peripheral benzodiazepine receptor during human colorectal carcinogenesis and tumor spread.

The peripheral benzodiazepine receptor (PBR) is overexpressed in a variety of cancers. In Unio Internationale Contra Cancrum (UICC) III colorectal cancers, a high level of PBR overexpression correlates with poor prognosis. However, little is known about the role of PBR in the development and progression of colorectal cancer. This study addresses the up-regulation of PBR during colorectal carcinogenesis and tumor spread. One hundred sixteen consecutive patients undergoing surgery for colorectal cancer with either regional (59 patients) or distant metastases (57 patients) were followed-up for 5 years or until death. Twenty-four of the 59 patients with initial UICC stage III cancers later developed distant metastases. PBR overexpression in tumor specimens was determined by immunohistochemistry. UICC stage III patients with colorectal primaries highly overexpressing PBR developed metastases significantly more often than patients with low PBR overexpression in their primary carcinoma. In 54 of the 116 patients adenomas and/or metastases and/or recurrences were available to be studied for PBR up-regulation during colorectal carcinogenesis and tumor spread. PBR was found to be overexpressed in 86% of early and late adenomas. Furthermore, 85% of primaries and of 86% of metastases displayed PBR overexpression. PBR overexpression was also detected at the mRNA level as revealed by real-time PCR. The extent of PBR protein overexpression was equivalent in colorectal adenomas and carcinomas but slightly increased in metastases. These data suggest a functional role of PBR during colorectal carcinogenesis and tumor spread. Thus, PBR qualifies as a target for innovative diagnostic and therapeutic approaches.     

Surgical or radiosurgical failures on cervical lymph nodes in treatment of head and neck cancer

From a series of 850 patients with head and neck carcinoma and subjected to lymph node dissection, 80 cases of recurrences in the neck have been collected. Postoperative radiotherapy was performed only in cases with metastatic extranodal spread. Of these recurrences, 56 occurred in the area of lymph node dissection, 7 were marginal and 17 were contralateral. The recurrences occurred prevalently in node-positive (N+) patients (70 of 80). The incidence of recurrences in the dissection area was 41.6% (25 of 60) in cases with metastatic extranodal spread, despite postoperative radiotherapy. The incidence of recurrences in cases with clinically evident metastases at the time of dissection but without extranodal spread and not subjected to postoperative radiotherapy was relatively high (24.1%, or 28 of 116). Since recurrences occurred, despite postoperative radiotherapy, in a relatively high percentage of cases with carcinoma of the oral floor and of the tongue (59.1% and 50%, respectively), it seems justifiable to perform preoperative radiation treatment in cases with clinically evident metastatic lymph nodes. As regards marginal recurrences, which all occurred in patients with carcinoma of the oral floor, it is considered sufficient to extend the surgical treatment to the subhyoid region. The high incidence of contralateral recurrences, which occurred mainly in patients with carcinoma of the larynx (13 of 17), shows the usefulness of radiation treatment of the contralateral region of the neck in these tumors, when dissection is limited to only one side of the neck.     

Recurrences in the soft tissues of the neck after surgery or radiotherapy plus surgery on regional lymph nodes in patients bearing carcinomas of the head and neck

A series of 45 recurrences in the soft tissues of the neck following lymph node dissection in 497 patients bearing carcinoma of the upper aerodigestive passages is reported. Only 22 cases that presented perilymph node metastases and/or in which there were reasons to indicate insufficient surgical radicality had been subjected to radiotherapy after surgical lymph node dissection; the other 23 cases had not been subjected to radiotherapy because the aforementioned premises had been lacking. All the recurrences therefore occurred in patients with clinically and histologically ascertained metastatic lymph nodes. The presence of perilymph node metastases and the judgment of surgical radicality was thus found insufficient criteria to plan future complementary postoperative radiotherapy. However, even in those cases in which postoperative radiotherapy was performed, there was a rather high incidence of recurrences, as high as 64.7% in patients with carcinoma of the tongue. Our data indicate the opportunity of a clinical trial with preoperative radiation therapy in patients with clinically evident lymph node metastases. Thirty-six of these recurrences were situated in the upper parts of the cervical region. The prognosis is very poor in such cases, so much so that only 2 of our series were disease free at 3 years after the treatment.     

The importance of determining androgen receptors in malignant breast tumors

Androgen receptor (AR) level was studied in 254 untreated cases of breast cancer. The occurrence and mean level of AR did not depend upon stage of disease or reproductive status. However, distribution of AR was determined by histologic pattern and grade of malignancy. Increase in degree of anaplasia of ductal invasive carcinoma was matched by decrease in its AR-positive fraction from 75 to 20%. Recurrence-free survival in surgically treated p T1-2 No Mo patients did not depend upon AR status of tumor. In cases of p T1-2 No Mo AR-positive malignancy, recurrences or metastases occurred 2.2 times as rarely when surgery was followed by endocrine therapy. However, in patients with AR-negative tumors (same stage), the best results were obtained with postoperative chemo- and chemoradiation treatment.     

Pulmonary resection for metastatic colorectal cancer

We reviewed the clinical courses of 25 patients who underwent pulmonary resection for metastatic lesions from colorectal cancer between January 1991 and December 2001. The cumulative survivals at 3 and 5 years were 72% and 63%, respectively. Sex, site of the primary tumor, presence of extrapulmonary metastases, disease-free interval, location of pulmonary metastases (PM), number of PM, size of PM, mode of operation, pre-thoracotomy serum carcinoembryonic antigen level, and post-thoracotomy chemotherapy were not found to be statistically significant prognostic factors. Age (70 years < or =) was a predictor of a shorter survival duration by univariate analysis (p = 0.02). Recurrence was observed in 19 patients, 11 of which were lung recurrences. Eight patients underwent repeated pulmonary resection. The median survival in these 8 patients was 23 months after second pulmonary operation. Surgical treatment for pulmonary metastases from colorectal cancer in selected patients might improve prognosis.     

Immunohistochemically detected hepatic micrometastases predict a high risk of intrahepatic recurrence after resection of colorectal carcinoma liver metastases

BACKGROUND: Hepatic metastases from colorectal carcinoma frequently recur after resection and hepatic micrometastases most likely are important in the development of such recurrences. The objectives of the current study were to assess the feasibility of the immunohistochemical detection of hepatic micrometastases from colorectal carcinoma and to determine their clinical significance. METHODS: Fifty-three patients underwent curative hepatic resection for colorectal carcinoma metastases. Multiple tissue sections were cut from the advancing margin of the largest hepatic metastasis in each patient and were stained with an antibody against cytokeratin-20 to detect hepatic micrometastases, which were defined as discrete microscopic cancerous lesions surrounding the dominant metastasis. RESULTS: Normal hepatocytes and intrahepatic bile duct epithelia stained negative for cytokeratin-20 in all patients, whereas the largest hepatic tumors stained positive in 46 patients (86.8%). Among the 46 patients with hepatic tumors that were positive for cytokeratin-20, hepatic micrometastases were found immunohistochemically in 32 patients (69.6%). The presence of hepatic micrometastases was associated with a larger number of macroscopic hepatic metastases (P = 0.047) and patients with hepatic micrometastases were found to demonstrate a higher probability of intrahepatic recurrence (P = 0.003) compared with those patients without hepatic micrometastases. In addition, patients with hepatic micrometastases demonstrated a worse survival (10-year survival rate of 21.9%) compared with those patients without hepatic micrometastases (10-year survival rate of 64.3%) (P = 0.017). CONCLUSIONS: Immunohistochemical detection of hepatic micrometastases is feasible in patients with colorectal carcinoma liver metastases. Hepatic micrometastasis indicates widespread hepatic involvement and thus predicts an increased risk of intrahepatic recurrence after hepatic resection and a poorer patient prognosis.     

甲状腺癌组织c-erbB-2/neu蛋白表达及其临床意义

目的：探讨甲状腺癌中c-erbB-2蛋白（p185）的表达与临床预后因素的相关性及意义。方法：运用免疫组化SP法检测45例甲状腺癌石蜡标本中,p185的表达并与临床预后因素进行相关分析。结果：45例患者中p185蛋白的阳性表达率为71．1％（32／45）。其中乳头状癌的p185为71．0％（22／31）;滤泡癌及髓样癌的p185阳性表达分别为2／4和2／4;未分化癌的p185阳性表达分别为5／6。p185表达与甲状腺癌的组织学类型之间存在明显相关性;与性别及年龄无相关;在有淋巴结转移及有复发、远处转移或死亡的患者中,p185的表达呈明显增强趋势,与无复发组相比较差异有统计学意义,P〈0．05。结论：在甲状腺癌中,p185存在着不同程度的表达,在一定程度上反映了甲状腺癌的组织学分化程度、淋巴结转移和复发倾向;p185的强阳性表达暗示着淋巴结转移概率的增加,将对甲状腺癌的手术方式选择有指导意义;p185的阳性表达可作为判断甲状腺癌预后的临床病理指标。     

Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma

BACKGROUND: Measurement of carcinoembryonic antigen (CEA) has been widely applied to detect recurrence, especially of colorectal carcinoma. The validity however, is still controversial. We investigated serial changes in CEA values to calculate whether the CEA doubling time and half-life time could predict metastatic progression or prognosis in colorectal carcinoma. METHODS: Pre- and post-operative serial serum CEA contents were determined in 22 cases of colorectal cancer with or without metastasis. CEA values were determined by enzyme immunoassay (EIA). Patients were assigned depending upon survival time (within vs. more than 18 months after primary resection) for assessment of CEA doubling time. From the gradient of the semi-logarithmic CEA graph, the preoperative doubling time was calculated and the postoperative half-life time was estimated according to the diagnosis of metastases within 2 years after primary resection [metastasis (+) or (-)]. RESULTS: In spite of the effect of curative re-operation of metastatic lesions or of postoperative adjuvant chemotherapy, the CEA doubling time of the groups showed a relation with prognosis (p = 0.045, Student's t-test) when the patients were divided into >18 and < or =18 months survival time. The CEA half-life time of the groups without overlooked metastases was statistically longer than those with (mean +/- SD 8.01 +/- 2.07 and 4.33 +/- 1.11, respectively, p < 0.01, one-factor ANOVA test). Clearance (k) showed a significant difference between the groups (p < 0.001, Student's t-test). CONCLUSION: The CEA doubling time appeared to be a less independent prognostic factor, whereas prolongation of the CEA half-life time might potentially suggest the existence of overlooked synchronous metastases from colorectal carcinoma.