Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3

B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients.     

Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal cancer

Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand-held gamma detecting probe. We report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer. One hundred four patients with primary, suspected, or known recurrent colorectal cancer received an intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4 x 10 Bq of iodine 125. Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined. Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe. The overall sensitivity was 77% and a predictive value of a positive detection was 78%. A total of 30 occult sites in 26 patients were identified. In patients with recurrent cancer, the antibody study provided unique data that precluded resection in 10 patients, and in another eight patients it extended the potentially curative procedure.     

Iodine-131 human-mouse chimeric Fab monoclonal antibody A7 guided surgery for colorectal cancer patients: A pilot study

125 I, rather than ¹³¹I, should be used as a tracer for RIGS to enhance the accuracy of ch-Fab-A7. (Received for publication on Sept. 22, 1997; accepted on May 15, 1998)     

粪便隐血单克隆抗体法在检测结、直肠癌中的临床应用

目的评价粪便隐血单克隆抗体法对检测结、直肠癌的意义。方法对７８例确诊为结、直肠癌病人用单克隆抗体法和联苯胺法检测粪便隐血。结果单克隆抗体法和联苯胺法的阳性率分别为８４．６％、６１．５％（Ｐ＜０．０１）。结论单克隆抗体法检测结、直肠癌敏感性远远超过传统联苯胺法。为了提高对结直肠癌的早期诊断率,我们建议常规采用单克隆抗体法进行粪便隐血检测。     

Localization of radioiodinated monoclonal antibody in colorectal cancer. Initial dosimetry results

HT-29-15 is an IgG1 monoclonal antibody reacting with a neuraminidase-sensitive determinant on a cell-surface antigen (molecular weight, 200,000 daltons) present on the colon cancer cell line HT-29. HT-29-15 was selected for a tumor localization study because the antigen was shown to be present, by immunohistochemical staining, in a high percentage of primary and metastatic colorectal cancers. HT-29-15 labeled with iodine 131 was given intravenously over a dose range of 0.2 to 10.0 mg to 23 patients with colorectal cancer. No significant toxicity was seen. Imaging of hepatic metastases was successful from days 5 to 7. Analysis of tissue radioactivity by biopsy showed that the tumor-liver ratio increased from day 1 to day 7, suggesting more rapid clearance of antibody from normal tissue than from tumor. Thus, tissue biopsy specimens and scintigraphy have shown that imaging of metastatic colorectal cancer is possible with monoclonal antibody HT-29-15. Tissue biopsy specimens are essential for demonstrating specificity of localization. Scans alone provide insufficient evidence of specific localization by monoclonal antibodies. Simultaneous infusion of a nonreactive control antibody would be necessary for specific localization to be demonstrated unequivocally.     

人结直肠癌粘膜下注射125I标记抗CEA单抗CL58放射免疫导向手术的研究

目的探讨125I标记的抗CEA单抗(monoclonal antibody, McAb)CL58在结直肠癌放射免疫导向手术(radioimmunoguided surgery, RIGS)中的应用价值.方法将125I标记单抗CL58在纤维结肠镜直视下注射于29例结直肠癌患者癌周粘膜下;给药后3～14d行根治手术,术中使用手持式γ探测仪(gamma-detecting probe, GDP)对肿瘤、区域淋巴结、手术切缘等靶部位(target, T)进行放射性检测,以正常肠壁为对照本底(normal tissue, NT),以T/NT≥3为判别大肠癌、肠壁浸润及淋巴结转移的标准;全部标本行病理学检验;病理学阴性的淋巴结标本进行免疫组化染色寻找微转移灶.结果 GDP探测判别肿瘤的灵敏度为93.1%,判别切缘的特异度为95.5%.RIGS判别淋巴结的灵敏度及特异度分别为92.0%、87.8%,与临床判别相比差异有显著性意义(χ2=5.84,P＜0.05).免疫组化证实RIGS能够检出部分病例中常规病理检验未发现的淋巴结微转移灶.结论应用125I标记的抗CEA单抗CL58进行结直肠癌RIGS,可有效判断区域淋巴结转移.     

Surgery for colorectal cancer

Colorectal cancer surgery represents a major component of the colorectal service workload. A solid understanding of key anatomical and oncological principles is essential for safe practice. In this article we discuss these fundamental aspects of colorectal cancer surgery. The first part of the article will deal with preoperative staging, surgical planning and principles of oncological surgery. The second part will focus on some of the commonest operations. We will describe key intra-operative principles involved in performing a right hemicolectomy, left hemicolectomy, anterior resection and abdomino-perineal resection. Laparoscopic colorectal cancer surgery is increasingly widespread and therefore our perspective will assume this approach by default. In the final section, we discuss the role of radiotherapy in rectal cancers, transanal surgery, resection of colorectal liver metastases and the rationale behind follow-up.     

Surgery for colorectal cancer

Colorectal cancer surgery represents a major component of the colorectal service workload. A solid understanding of key anatomical and oncological principles is essential for safe practice. In this article we discuss these fundamental aspects of colorectal cancer surgery. The first part of the article will deal with preoperative staging, surgical planning and principles of oncological surgery. The second part will focus on some of the most common operations. We will describe key intra-operative principles involved in performing a right hemicolectomy, left hemicolectomy, anterior resection and abdomino-perineal resection. Laparoscopic colorectal cancer surgery is increasingly widespread and therefore our perspective will assume this approach by default. In the final section, we discuss the role of radiotherapy in rectal cancers, transanal surgery, resection of colorectal liver metastases and the rationale behind follow-up.     

Surgery for colorectal cancer

Colorectal cancer surgery represents a major component of the colorectal service workload. A solid understanding of key anatomical and oncological principles is essential for safe practice. In this article we discuss these fundamental aspects of colorectal cancer surgery. The first part of the article will deal with preoperative staging, surgical planning and principles of oncological surgery. The second part will focus on some of the most common operations. We will describe key intra-operative principles involved in performing a right hemicolectomy, left hemicolectomy, anterior resection and abdomino-perineal resection. Laparoscopic colorectal cancer surgery is increasingly widespread and therefore our perspective will assume this approach by default. In the final section, we discuss the role of radiotherapy in rectal cancers, transanal surgery, resection of colorectal liver metastases and the rationale behind follow-up.     

99mTc-IMMU-4 monoclonal antibody scan in colorectal cancer. A prospective study.

A blinded prospective study of 34 patients with colorectal adenocarcinoma using the Fab' fragment of the anticarcinoembryonic antigen monoclonal antibody type IMMU-4 labeled with technetium 99m was conducted to compare, on a lesion-by-lesion basis, the findings of radioimmunoscintigraphy, preoperative computed tomography, and exploratory celiotomy. Of 115 lesions detected at surgery, 113 were adenocarcinoma. Radioimmunoscintigraphy detected 59 lesions and computed tomography detected 62; both studies combined detected 72. Twenty-nine (54%) lesions missed by radioimmunoscintigraphy and 24 (45%) missed by computed tomography were 1 cm or smaller. When both studies were combined, the sensitivities were 90%, 24%, and 42%, and the specificities were 52%, 86%, and 61% for hepatic, extrahepatic intra-abdominal, and pelvic lesions, respectively. In 10 patients, additional information obtained with the radioimmunoscintigram could have altered the treatment of these patients. In this study, radioimmunodetection scan was complementary to computed tomographic scan in the examination of patients with colorectal carcinoma.     

Flow cytometric evaluation of Thomsen-Friedenreich antigen on transitional cell cancer using monoclonal antibody

Summary In 31 transitional cell cancer (TCC) tissues and 5 normal bladder muscosae (NBM), we compared the results of flow cytometry (FCM) and immunohistochemical examination in evaluating the expression of Thomsen-Friedenreich antigen (T-Ag) using a monoclonal antibody. On immunohistochemical examination, 14 (45%) cancer tissues showed T-Ag, while 7 (23%) cancer tissues and all NBM showed only cryptic T-Ag, which was detected only after neurminidase treatment. Ten (32%) high grade cancer tissues showed neither T-Ag nor cryptic T-Ag. On FCM the T-Ag positive cells (TPC) and the T-Ag positive cells after neuraminidase treatment (nTPC) were counted in fresh cell suspensions. FCM was more sensitive than immunohistochemical study in detecting T-Ag. Additionally, FCM revealed that some tumors had both T-Ag and cryptic T-Ag at the same time. The ratio of nTPC to TPC was well correlated with the stage or grade of the tumor and may be a more reliable marker of TCC than the expression of T-Ag assessed by immunohistochemical techniques.     

Hirschsprung's disease: diagnosis using monoclonal antibody 171B5.

A new reliable immunohistochemical method for diagnosing Hirschsprung's disease (HD) using our unique monoclonal antibody (MAb) 171B5 against synaptic vesicles is described. Fresh frozen sections of rectal tissues were used from 13 patients with HD aged 2 weeks to 13 months; 9 had rectosigmoid HD and 4 had total colonic aganglionosis (TCA). Comparable normal colonic and rectal specimens were also obtained from 13 age-matched controls. All specimens were labeled with MAb 171B5, to demonstrate neuronal innervation patterns of both mucosa and submucosa. In all control specimens, many synapses arranged in variciform plexuses were seen in the lamina propria, a moderate number in the muscularis mucosae, and dense clusters in the submucosal plexus. In all aganglionic specimens, only scanty numbers of synapses which were not organized in variciform plexuses were seen in the lamina propria, none in the muscularis mucosae, and a few in the submucosa. These findings suggest that MAb 171B5 immunohistochemistry on the lamina propria alone can differentiate between normal and aganglionic bowel and appears to be a reliable and useful method for detecting HD on suction rectal biopsy.     

腹腔镜结直肠癌手术临床评价

目的　探讨腹腔镜结直肠癌手术的可行性。方法　对比研究腹腔镜治疗结直肠癌 2 4例与同期开腹手术 2 0例。结果　两组手术时间、术后并发症差异无显著性 ,腹腔镜组出血量少 ,康复快 ,住院时间短 ,但不包括中转手术病例。结论　腹腔镜结直肠癌手术能体现其微创优点 ,但应降低并发症及手术中转率     

Efficacy of monoclonal antibody 131I-B72.3 immunoscintigraphy of pancreatic adenocarcinoma xenografts in nude mice.

OBJECTIVE: To assess the efficacy of monoclonal antibody (MoAb) B72.3 for in vivo-immunoscintigraphy of pancreatic carcinoma in nude mice. DESIGN: Experimental controlled animal study. SETTING: University hospital, The Netherlands. SUBJECTS: 11 nude mice with subcutaneously xenografted human pancreatic carcinoma. INTERVENTIONS: Specific MoAb B72.3 and non-specific MoAb MOPC21 were iodinated with 131I and injected intraperitoneally in nude mice. Scintigrams were taken on days 1-10 and tumour:non-tumour ratios of the regions of interest (tumour, thorax, abdomen, background) were calculated. The mice were then killed for in vitro tissue counts. MAIN OUTCOME MEASURES: Tumour:non-tumour ratios in vivo and in vitro. RESULTS: Results of immunoscintigraphy on days 1, 2, and 6 were compared. In the B72.3-group all ratios were only moderately raised, the tumour:background ratio being the highest (2.35 (SD 0.67)) on day 6. There were no obvious differences between the ratios of the B72.3-group and the MOPC21-group. The results of tissue counts done at the end of the study, showed that tumour:non-tumour ratios were twice as high in the B72.3-group, suggesting some specificity of this MoAb. CONCLUSION: The results of our study suggest that MoAb B72.3 is not powerful enough for in vivo detection of pancreatic cancer as assessed in this xenograft model in nude mice.     

Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibodies

Aiming at radioimmunodetection of colorectal cancer, anti-CEA monoclonal antibodies (CEA102) were produced by immunization with purified CEA. CEA102 showed high specificity with colorectal cancer by mixed hemadsorption assay and immunoperoxidase technique. The antigen detected by CEA102 was confirmed to be carcinoembryonic antigen (CEA) and its molecular weight was estimated to be ca. 180,000 by biochemical analysis. The in vivo study using nude mice grafted a human colorectal cancer or a human malignant melanoma showed greater accumulation of 125I-labeled CEA102 in CEA-positive colorectal cancer than in nude mouse tissues and CEA-negative malignant melanoma. Moreover we successfully obtained scans with good localization of the grafted colorectal cancer on FCR (Fuji Computed Radiography). Using 131I-labeled CEA102 liver metastasis in the patient with colorectal cancer was successfully detected by external scanning with gamma-camera. These results suggest that radiolabeled CEA102 is useful for the detection of colorectal cancer.     

Studies using the anti-idiotypic monoclonal antibody 105AD7 in patients with primary and advanced colorectal cancer

The mortality from colorectal cancer has not changed appreciably in the last 30 years and new treatment avenues, such as immunotherapy, are being explored. 105AD7 is a form of active specific immunotherapy that aims to stimulate specific T-cells to target tumour specific antigens on colorectal cancer cells. Results indicate that the cancer vaccine 105AD7 is non-toxic and is capable of stimulating T-cells to target tumour specific antigens, become activated, and kill tumour cells by apoptosis. These immune responses have no effect on survival on a cohort of immunosuppressed patients with advanced disease, but results from a case-control study in patients with minimal residual disease suggest they may confer a slight survival advantage on patients receiving 105AD7.     

胰岛素样生长因子Ⅰ型受体单克隆抗体对结肠癌细胞细胞周期的影响

目的　了解胰岛素样生长因子Ⅰ型受体(IGF- ⅠR)在人结肠癌细胞株HT -29上的表达情况,观察两种胰岛素样生长因子Ⅰ型受体单克隆抗体对HT -29细胞周期的影响。方法　免疫组织化学法检测HT 29的 IGF -ⅠR表达,流式细胞术检测两种 IGF -ⅠR单克隆抗体对 HT- 29 的细胞周期的影响。结果　人结肠癌细胞株HT 29细胞膜高表达 IGF -ⅠR,IGF -ⅠR 单克隆抗体能使 HT 29的细胞周期阻滞于任何一期,诱导凋亡,对结肠癌细胞起抑制作用。结论　IGF -ⅠR单克隆抗体阻断IGF -Ⅰ和 IGF -Ⅱ与 IGF -ⅠR结合,阻滞HT- 29的细胞周期,诱导凋亡。     

Surgery for pulmonary metastases from colorectal cancer

OBJECTIVE: Several investigators have analyzed prognostic factors of surgical treatment for pulmonary metastases from colorectal cancer, but the results remain inconclusive. This study was performed to determine the prognostic implications of the prethoracotomy serum level of carcinoembryonic antigen (CEA) in relation to the postthoracotomy recurrent pattern among patients with this disease. METHODS: A retrospective analysis of prognostic factors was undertaken in 100 patients who had consecutively undergone initial surgical resection for pulmonary metastases of colorectal origin. RESULTS: The overall 3- and 5-year survival rates were 62.2% and 49.4%, respectively. Univariate analysis revealed that the prethoracotomy serum CEA level and operative curability were strongly associated with prognosis, while in multivariate analysis, only the prethoracotomy serum CEA level was a significant prognostic indicator. Patients with a high level of prethoracotomy serum CEA more frequently exhibited recurrence in extrathoracic sites, especially in the brain. CONCLUSION: Before thoracotomy for pulmonary metastases from colorectal cancer, the serum CEA level was the most useful prognostic factor. Patients with elevated serum CEA level should undergo a careful prethoracotomy systemic survey and postthoracotomy follow-up for extrathoracic metastases, in particular brain metastases, and an appropriate combined therapeutic modality should be considered.     

Surgery for pulmonary metastases from colorectal cancer

Objective: Several investigators have analyzed prognostic factors of surgical treatment for pulmonary metastases from colorectal cancer, but the results remain inconclusive. This study was performed to determine the prognostic implications of the prethoractomy serum level of carcinoembryonic antigen (CEA) in relation to the postthoracotomy recurrent pattern among patients with this disease.Methods: A retrospective analysis of prognostic factors was undertaken in 100 patients who had consecutively undergone initial surgical resection for pulmonary metastases of colorectal origin.Results: The overall 3- and 5-year survival rates were 62.2% and 49.4%, respectively. Univariate analysis revealed that the prethoractomy serum CEA level and operative curability were strongly associated with prognosis, while in multivariate analysis, only the prethoractomy serum CEA level was a significant prognostic indicator. Patients with a high level of prethoracotomy, serum CEA more frequently exhibited recurrence in extrathoracic sites, especially in the brain.Conclusion: Before thoracotomy for pulmonary metastases from colorectal cancer, the serum CEA level was the most useful prognostic factor. Patients with elevated serum CEA level should undergo a careful prethoracotomy systemic survey and postthoracotomy follow-up for extrathoracic metastases, in particular brain metastases, and an appropriate combined therapeutic modality should be considered.     

Surgery for colorectal cancer in elderly patients

In 545 consecutive patients undergoing elective or emergency surgery for colorectal cancer (370 colon and 175 rectum), mortality and morbidity were analysed in different age groups with special reference to patients over 80 years old. In that group, 33% had an emergency operation, compared with 18% below that age. Postoperative mortality after elective surgery ranged from 3 to 11% in the different age groups, but was not significantly related to age. In contrast, postoperative in-hospital mortality after emergency surgery was high (38%) among those older than 80 years, compared with 6% below 75 years and 24% between 76 and 80 years. Postoperative morbidity, i.e. infections and cardiovascular disease, increased with age, as did the length of hospital stay. Five-year survival, independent of age, was poorer after emergency surgery than after elective surgery. It is concluded that elective colorectal resection for cancer in elderly patients is a safe procedure.