Standardized treatment of colorectal cancer. A prospective study

304 patients with colorectal adenocarcinoma underwent standardized, aggressive treatment which included wide resection, adjuvant radio- or chemotherapy and management of advanced disease. The mean age of the patients was 68 years; 50% were older than 70 years, and 17% above 80 years. The resectability rate was 86.2%. Overall postoperative mortality was 7.3%, in patients operated on for cure 5.7%, and in patients more than 80 years 16.3%. The highest postoperative mortality was seen following right hemicolectomy and deaths were mainly caused by anastomotic leakage and myocardial infarction. In patients with primarily inoperable rectal cancer treated with irradiation and followed by attempted curative surgery, the estimated 5-year survival was 38%. In patients with operable rectal cancer treated with preoperative irradiation followed by surgery the 5 year survival was 69% as compared to 45% for those treated with surgery only. Adjuvant cytostatic therapy in patients with colonic tumours of Dukes B and C stages did not improve survival.     

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.     

A prospective clinicopathologic study of venous invasion in colorectal cancer

We performed a long-term prospective study on venous invasion of colorectal cancer. The degree of venous invasion was divided into four stages (V0 through V3). Venous invasion was classified into three types by location (Vx, Vy, and Vz). Hepatic metastasis occurred in 27%, 33%, and 20% of patients with V2, V3, and Vz tumors, respectively. Local recurrence occurred in 33% and 15% of the V3 and Vz groups, respectively. However, there were no significant differences among the groups in terms of the rate of pulmonary metastasis. The 6-year survival rate for Dukes' stage B tumors was 94%, 88%, and 74% in the V0, V1, and V2 groups, respectively. There was a significant difference in the survival rate between patients with V0 tumors and V2 and V3 tumors. However, no significant difference was noted in the location. In Dukes' stage C tumors, on the other hand, the survival rate was 77%, 56%, and 44% in the V1, V2, and V3 groups, respectively. Also, it was 85%, 73%, and 45% in Vx, Vy, and Vz cases, respectively. Significant differences were noted between V1 and V3 (or V2), and between Vz and Vx (or Vy). It appears that the degree and location of venous invasion influence not only hepatic metastasis, local recurrence, and survival rates but also have prognostic value.     

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)     

A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation.

Patient entry is now complete in a prospective trial of anti-Tac, a murine IgG2a monoclonal antibody directed against the p55 chain of the human IL-2 receptor, for the prevention of renal allograft rejection. Recipients of primary cadaver allografts were randomized to receive either anti-Tac (20 mg q.d. x 10 days beginning POD 1) plus low-dose CsA (4 mg/kg/day), azathioprine (2 mg/kg/day), and prednisone (30 mg q.d.), or conventional triple therapy with CsA (8 mg/kg/day), azathioprine, and prednisone. Forty patients were entered in each group, with current followup from 6 to 26 months. The results show a significant reduction in early rejection episodes in the anti-Tac-treated patients. During the 10-day treatment, 5 of 40 anti-Tac patients had rejection episodes, compared with 21 of 40 control patients (P less than 0.001). Anti-Tac significantly delayed the time to the first rejection (12.5 +/- 6.3 vs. 7.6 +/- 6.7 days) (P less than 0.05). Despite these effects, there were no differences in either actual or actuarial graft or patient survival between the two groups. Pneumonia, primarily CMV, developed in 5 treated and 4 control patients. In patients with functioning grafts mean serum creatinine at 3 months was 1.8 +/- 0.7 in the anti-Tac group and 2.0 +/- 0.8 in the control group (P = NS); at 12 months the values were 2.3 +/- 1.5 and 1.8 +/- 0.5, respectively (P = NS). The peak expression of IL-2 receptors on circulating T-cells was significantly lower in anti-Tac patients (15.1 +/- 3.6%) than in controls (21.9 +/- 4.5%) (P less than 0.05). Seven of 10 patients tested to date developed antimouse immunoglobulin antibodies, with antiidiotype shown in 6. These antibodies do not preclude subsequent treatment with OKT3. Five patients in this and previous anti-Tac protocols have received OKT3 for acute rejection despite known pretreatment antimouse antibodies, with resolution of rejection in all cases.     

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.     

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.     

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。     

Lumpectomy vs oncoplastic surgery for breast-conserving therapy of cancer. A prospective study about 99 patients

The integration of oncoplastic techniques with a concomitant contralateral symmetrization procedure is a novel surgical approach that allows wide excisions and prevents breast deformities. AIM OF THE STUDY: This prospective study was undertaken to compare the accuracy of breast resection, between standard narrow lumpectomy and oncoplastic surgery. PATIENTS AND METHODS: Ninety-nine consecutive women undergoing breast cancer resection were enrolled in a prospective study comparing oncoplastic surgery (42 women) and standard lumpectomy (57 women). The size of the glandular resection, the width of the nearest margins, the ratio of clear margins and the need for further surgery were recorded. RESULTS: The oncoplastic approach resulted in significantly greater glandular resection and wider free histological margins than did standard lumpectomy. The need for re-exicsional surgery was significantly lower in the oncoplastic group than in the lumpectomy group. Furthermore, a trend towards fewer secondary mastectomies was seen for the oncoplastic approach versus standard lumpectomy. CONCLUSIONS: The use of oncoplastic techniques and concomitant symmetrization of the contralateral breast allows extensive resections for conservative treatment of breast carcinoma achieves accurate tumour resection and reduces the need for further surgery.     

Surgery for colorectal cancer guided by radiodetecting probe. Clinical evaluation using monoclonal antibody B72.3.

Radioactive antibodies that react with tumour-associated antigens to "tag" antigen-positive tumour cell deposits were given to 20 patients with primary or recurrent colorectal cancer. The tumour associated antigen TAG 72-specific monoclonal antibody B72.3 labelled with 125-Iodine was used, and the radioactivity in the tumour was sought during operation with a hand-held gamma detecting probe. Tumour was detected by the probe in 7 of 15 patients with primary cancer, with a mean tumour: normal tissue ratio of 3.9, and in 4 of 5 patients with recurrent disease, with a mean tumour: normal tissue ratio of 2.0. Immunohistochemical analysis of surgical specimens confirmed the results of the intraoperative detection. The incidence of TAG 72-positive tumours (11/20, 55%), detected by immunohistochemistry, was lower than the 80% in the other series, possibly because of sampling errors or because the cases studied were uncomplicated with small primary tumours. Results obtained with the probe were instrumental in modifying the operation in two of the four "positive" patients with recurrences, allowing the removal of tumour masses that would otherwise have been overlooked.     

Preoperative nonspecific immunostimulation with Propionibacterium granulosum KP-45 in patients with colorectal cancer. A prospective randomized study

The effect of preoperative unspecific immunomodulation with Propionibacterium granulosum KP-45 (P.g.) on postoperative complications and patient survival was evaluated in a prospectively randomized trial in patients with colorectal tumor resection. Patients of the therapy group (n = 51) received at least 3 days before operation an infusion of 10 mg P.g., patients of the control group (n = 49) were not treated at all. The wound infection rate and the number of re-explorations were significantly lower in the therapy group, however, patient survival and tumor recurrence rates were not positively affected by this P.g. pre-treatment.     

Screen detection is a survival predictor independent of pathological grade in colorectal cancer. A prospective cohort study

IntroductionPatients with screened detected colorectal cancer (CRC) have a better survival than patients referred with symptoms. This may be because of cancers being identified in a younger population and at an earlier stage. In this study, we assess whether screened detected CRC has an improved outcome after controlling for key pathological and patient factors known to influence prognosis.MethodThis is a cohort study of all CRC patients diagnosed in NHS Grampian. Patients aged 51–75 years old between June 2007 and July 2017 were included. Data were obtained from a prospectively maintained regional pathology database and outcomes from ISD records. All-cause mortality rates at 1 and 5 years were examined. A Cox proportional hazards regression model was used to estimate the effect of screening status, age, gender, Duke stage, tumour location, extramural venous invasion (EMVI) status and lymph node ratio (LNR) on overall survival.ResultsOf 1618 CRC cases, 449 (27.8%) were screened and 1169 (72.2%) were symptomatic. Screened CRC patients had improved survival compared to non-screened CRC at 1 year (88.9% vs 83.9% p < 0.001) and 5-years (42.5% vs 36.2%; p < 0.001). On multivariable analysis of patients who had no neoadjuvant therapy (n = 1272), screening had better survival (HR 0.57; 95% CI 0.44–0.74; p < 0.001). EMVI (HR 2.22; CI 1.76 to 2.79; p < 0.001) and tumour location were found to affect outcome.ConclusionPatients referred through screening had improved survival compared with symptomatic patients. Further research could be targeted to determine if screened CRC cases are pathologically different to symptomatic cancers or if the screening cohort is inherently more healthy.     

Permeability of human brain tumor to 99mTc-gluco-heptonate and 99mTc-albumin. Implications for monoclonal antibody therapy

The variable penetration of chemotherapeutic drugs into brain and tumor is more dependent upon lipid solubility than upon size. In contrast, the molecular weight of virus- and tumor-specific monoclonal antibodies appears to limit uptake. The authors have studied eight patients with malignant brain tumors in order to compare tumor uptake of an iodinated contrast agent evaluated by computerized tomography scanning with uptake of the low and high molecular weight imaging agents technetium-99m (99mTc)-glucoheptonate and 99mTc-albumin, respectively, measured by radionuclide brain scanning. The agent 99mTc-labeled albumin was chosen for evaluation because its molecular weight (68,000) is similar to that of the most clinically promising monoclonal antibody fragment, the immunoglobulin (Ig) G Fab monomeric fragment. The radionuclide brain scans in the eight patients showed highly variable permeability of brain tumor to these markers, with uptake of the high molecular weight marker in the tumor being much less than that of the low molecular weight radionuclide. A clinical implication of these studies is that the success of monoclonal antibody therapy in the treatment of malignant brain tumors may require techniques to increase permeability of the blood-brain barrier and blood-tumor barrier to protein.     

Feasibility of colorectal surgery without colonic preparation. A prospective study

INTRODUCTION: Mechanical bowel preparation (MBP), aimed at reducing the infectious complications of colorectal surgery, was considered as indispensable. This benefit is actually disputed. The aim of this study was to report an experience of colorectal surgery without MBP. MATERIALS AND METHODS: Hundred ninety patients without MBP and without low residue diet, who underwent colorectal surgery with primary anastomosis not requiring a diverting stoma were included. The main outcome were the rate of mortality, anastomotic leak, wound infection and intra-abdominal abscess. Secondary outcomes were duration of intravenous perfusion, nasogastric aspiration, total hospitalisation stay and time to realimentation. RESULTS: The procedure was performed by laparotomy (n=142) or laparoscopy (n=48). Forty-eight patients underwent emergency surgery. Ninety-two patients were operated for malignancy. The rate of mortality was 6.3% in correlation with the scale of AFC. The rate of anastomotic leak was 3.7%. The rate of specific morbidity was independent of scale of AFC on the contrary to the frequency of non-specific complications. The mean duration of intravenous perfusion and nasogastric suction were 6 days and 0.3 day. The patient had normal diet to the 4th day (4+/-3 days). The mean hospital stay was 13.4 days. CONCLUSION: The colorectal surgery without MBP may be safely performed and could improve the quality of life of patients in the perioperatory period.     

胰岛素样生长因子Ⅰ型受体单克隆抗体对结肠癌细胞生长的影响

目的探讨胰岛素样生长因子Ⅰ型受体（insulin-like growth factorⅠ receptor,IGF-ⅠR）在人结肠癌细胞株HT-29上的表达,以及两种胰岛素样生长因子Ⅰ型受体单克隆抗体（IGF-ⅠRMcAb）对HT-29细胞增殖的影响.方法免疫组织化学法检测HT-29的IGF-ⅠR表达,MTT法检测两种IGF-ⅠR McAb对HT-29的抑制增殖作用及诱导凋亡情况.结果人结肠癌细胞株HT-29细胞膜高表达IGF-ⅠR.IGF-ⅠR McAb能抑制HT-29细胞增殖,McAb对HT-29细胞的抑制作用随抗体浓度增大而增大.IGF-ⅠR McAb诱导HT-29凋亡,与对照组相比差异有统计学意义（P＜0.01）.结论IGF-ⅠR McAb通过阻断IGF-ⅠR抑制结肠癌细胞增殖、诱导细胞凋亡.     

Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study.

Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients.     

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.     

The recognition of cancer-associated fucosylated antigens in colorectal cancer by a novel monoclonal antibody,YB-2

A monoclonal antibody, YB-2, which has a novel epitope for fucosylated antigens and shows cross-reactivity with Y/Le^b/H type 2 antigens, was used in an immunohisto-chemical study of human neoplastic and normal colorectal tissues. Of 64 colorectal cancers, 59 (92.2%) were stained by the YB-2 antibody; however, only 3 (12.0%) of 25 samples of normal colon mucosa and 13 (50.0%) of 26 adenomas expressed the antigens recognized by YB-2. Clinicopathologically, the YB-2-negative colon cancers were exclusively in Dukes stage A. These results indicate that the monoclonal antibody, YB-2, could detect cancer-associated antigens, and the degree of YB-2-reacted antigen expression might be correlated with the progression of colorectal carcinogenesis.