结直肠癌脑转移的临床研究进展

脑是常见的恶性肿瘤转移部位之一,多见于肺癌、乳腺癌及黑色素瘤。而结直肠癌脑转移发生率较低,因此临床较为少见。近年来由于诊疗水平的提升及患者生存期的延长,结直肠癌脑转移的发生率逐渐增加。本文将从结直肠癌脑转移的发生机制、高危因素、临床表现和预后因素等方面总结现阶段结直肠癌脑转移的研究现状和进展,以期为结直肠癌脑转移的临床和科研工作提供参考。     

A case report of long-term survival after radiotherapy for a solitary brain metastasis from breast cancer

This is the report of a patient with a solitary brain metastasis from breast cancer who survived more than 8 years after the first brain metastasis. The brain metastasis was treated with partial removal followed by 30 Gy/15 fructions of whole brain irradiation plus 20 Gy/10 fructions of local boost irradiation for 5weeks. Brain metastases from breast cancer are usually a sign of rapid systemic tumor progression and long-term survivors are extremely rare. However, this case demonstrated the possibility of long-term survival in rare cases of brain metastases from breast cancer. This suggests a need for aggressive therapy in patients with a solitary brain metastasis.     

Carcinoma of lung with a solitary cerebral metastasis. Surgical management and review of the literature

During the years 1975 to 1980, 10 male patients and 1 female, with ages ranging between 40 to 61 years, underwent combined resection of primary lung cancer and solitary brain metastasis. In 8 patients the lung cancer was diagnosed and treated first. In those patients, craniotomy for removal of a solitary brain metastasis was carried out 8 to 60 months (mean, 27 months) after excision of the lung tumor. In 3 patients, brain metastasis was diagnosed and treated first and lung excision followed, 2 to 4 weeks after craniotomy. The most common histologic type of the tumor was adenocarcinoma (63.6%). There were no operative deaths. Three patients survived less than 6 months after surgery and were considered as a failure of surgical treatment. Seven patients lived longer than 1 year and three of them are still alive with a follow-up period between 2 to 3 1/2 years after both operations. One of the patients underwent recently successfully second brain intervention for removal of recurrent histologically identical solitary brain metastasis and is well. Our results and those reported in literature encourage the combined surgical removal of primary lung cancer and a solitary brain metastasis.     

Brain metastases of colorectal cancer--a case report

Metastatic brain tumors from colorectal cancers are relatively rate. In previous reports, the incidence, ranged from 1.9 to 3.5 percent of all metastatic brain tumors. We reported 2 cases of metastatic brain tumors from colorectal cancers. Metastasis to the lung and liver were not found in 2 cases at the time of the diagnosis of the single brain metastasis. The CEA levels in the serum were highly elevated in these 2 cases. On a contrast-enhanced CT scan, tumors were equally demonstrated as high density and cystic, with a ring-like mass with surrounding brain edema. Brain metastases of colorectal cancer were discussed with a review of the literature.     

Small cell lung cancer with a brain metastasis controlled for 5 years: a case report

We report a case of small cell lung cancer whose initial presentation was a solitary brain metastasis. On chest radiography the primary tumor was unclear and only detected by bronchofiberscopy. A small single pulmonary metastasis was noted in the right lower lobe. Subtotal resection and external irradiation were applied to the brain tumor and external irradiation was applied to the lung. Concurrently one course of systemic chemotherapy was administered. The tumors in the brain and lung had disappeared by the end of the treatment. The patient has been alive and well for 5 years without recurrence.     

Two cases of lung cancer patients with postoperative brain metastases obtaining long-term survival after gamma knife radiosurgery

We report two cases of lung cancer patients with postoperative solitary brain metastases obtaining long-term survival after gamma knife stereotactic radiosurgery. Both were seventies men and had good performance status without active extracranial disease. In one case, an asymptomatic metastatic brain tumor 1.8 cm in maximum diameter appeared one year and two months after the operation and was irradiated with gamma knife resulting in complete local control for seven years. He is alive with solitary lung metastasis in good performance status. In the other case, gamma knife was employed for a metastatic brain tumor 2.7 cm in maximum diameter that appeared nine months after the operation accompanying incomplete left hemiplegia. Six months later, the tumor was enlarged and gamma knife was repeated, but the tumor growth could not be suppressed. Following deterioration of hemiplegia and appearance of convulsion, he died of neurological disorder three years and two months after the onset of brain metastasis. Gamma knife stereotactic radiosurgery for metastatic brain tumors is less invasive and a repeatable technique, and is expected to provide a good local control and a survival benefit for appropriately selected patients.     

Expression of intercellular adhesion molecule-1 and prognosis in colorectal cancer

Intercellular adhesion molecule-1 (ICAM-1) is a 90-kDa cell surface glycoprotein and is known to be a member of the immunoglobulin gene superfamily of adhesion molecules. It has been suggested that ICAM-1 expression on cancer cells might have a role as a suppressor of tumor progression under the host immune surveillance system. We studied the correlation between the expression of ICAM-1 and clinicopathological factors, as well as infiltration of tumor infiltrating lymphocytes (TILs) in colorectal cancer. Resected specimens from 96 patients with colorectal carcinoma were investigated using immunohistochemical staining with a monoclonal antibody against ICAM-1. As a result, the incidence of lymph node or liver metastasis was significantly lower in patients with ICAM-1-positive tumors than in those with ICAM-1-negative tumors. Infiltration of TILs was more frequently observed in the ICAM-1-positive tumors than in the ICAM-1-negative tumors. The prognosis of the patients with ICAM-1-negative tumors was significantly poorer than that of those with ICAM-1-positive tumors. In conclusion, these findings suggested that ICAM-1 expression is closely associated with metastasis and may be a useful indicator of prognosis in patients with colorectal cancer.     

Metastasis of sigmoid colon cancer in cryptorchid testis: report of a case

Isolated testicular metastasis from colorectal cancer is considered an unusual event. In this case report we describe for the first time a metastasis from an adenocarcinoma of the sigmoid colon to a cryptorchid testis. The patient developed a painless testicular nodule three years after the diagnosis of primary sigmoid colon cancer. Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased over the past 50 years; in particular, cryptorchid testes increase the clinical risk factors for primary or metastatic testicular cancer. In conclusion, there should be awareness of the risk of metastasis of colorectal cancer to the testis in the workup of patients with testicular symptoms. Furthermore, patients with colorectal cancer and cryptorchidism should be managed with a single surgical intervention: when the primary colorectal tumor is removed, the cryptorchid testicle should also be removed to reduce the risk of late metastases.     

Adrenalectomy for solitary adrenal metastasis from colorectal cancer

A 77-year-old man had sigmoidectomy for sigmoid colon cancer. Two years later, a right hepatectomy for a liver metastasis was performed. Two years thereafter, abdominal computed tomography scanning and FDG-PET showed the right adrenal mass. Right adrenalectomy was performed with a diagnosis of solitary adrenal metastasis from sigmoid colon cancer. On pathology, adrenal metastasis was confirmed. The patient underwent adjuvant chemotherapy (IRIS). There have been no signs of recurrence for 6 months after the operation. We conclude that patients with solitary adrenal metastasis from colorectal cancer may benefit from surgical resection.     

Two cases with long-term disease-free survival after resection and radiotherapy for solitary brain metastasis from breast cancer with extensive nodal metastases

Two rare cases, each with a solitary brain metastasis from breast cancer with extensive nodal metastases as the first site of distant metastasis, were locally treated with surgery and irradiation. The outcome of the two treated cases indicated an excellent and non-recurrent post-therapeutic survival period of more than 3 and 8 years, respectively. In a 50-year-old woman (Case 1), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with doxorubicin and tegafur-uracil (UFT) and hormonal therapy with tamoxifen for left breast cancer. The brain metastasis was treated twice surgically followed by radiotherapy. One year and 6 months later, local recurrence of the brain metastasis appeared and was treated surgically again. No other treatment was done thereafter. Since then, no other distant or lymph node metastasis occurred, and to date her outcome has been non-eventful for 8 years and 5 months. In a 63-year-old woman (Case 2), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with cyclophosphamide, epirubicin and fluorouracil (CEF) for right breast cancer. The brain metastasis was treated locally with surgery and irradiation of 50 Gy. She thereafter received no further treatments. Since then neither distant metastases nor local recurrence have developed, and to date the post-treatment outcome has been uneventful for 37 months. Our findings suggest that patients who developed a solitary brain metastasis as the first site of distant metastasis from breast cancer have a chance of achieving long-term disease-free survival when treated with aggressive local therapy, even in the presence of extensive lymph node metastases at the primary surgery site for breast cancer.     

Late relapse of small cell lung cancer treated with radiation therapy alone — case report

This report describes an unusual case of a long-term survivor with small cell lung cancer (SCLC), treated with radiation therapy alone having a late relapse with solitary brain metastasis 6.5 years after the initial treatment. He received radiation therapy and died of the brain metastasis 8.5 years after the initial treatment. Autopsy revealed no tumor recurrence at the primary site and no distant metastases except for the brain. The histology of the brain tumor was small cell carcinoma.     

诱导小鼠肝硬化对结肠癌肝转移的抵抗作用

目的:研究诱导小鼠肝硬化对结肠癌肝转移的抵抗作用及其可能的机制。方法:诱导小鼠肝硬化及结肠癌肝转移模型,比较正常肝与肝硬化小鼠肝转移率;免疫组化法测定层粘连蛋白(laminin,LN)、纤维连接蛋白(fibronectin,FN)及E-选择素(E-selectin)在小鼠肝脏的表达。结果:①肝硬化小鼠肝转移率(4/16,25%)低于正常肝小鼠(14/16,87.5%)(P=0.001);②肝硬化后移植瘤小鼠LN、FN表达高于正常肝移植瘤小鼠,E-selectin表达低于正常肝移植瘤小鼠。结论:动物实验证实肝硬化对结肠癌肝转移有抵抗作用;LN、FN及E-selectin在此过程中可能起一定作用。     

Resection of lung metastasis from gallbladder carcinoma: immunohistochemistry of RCAS1 and CD8+T cells in primary and metastatic tumors

Advanced Gallbladder cancer has an extremely poor prognosis. We examined a patient with resectable gallbladder cancer with associated lung metastasis. A 64-year-old female patient, diagnosed with gallbladder cancer and a solitary benign lung tumor by imaging, was subjected to extensive cholecystectomy and extrahepatic bile duct resection. After one year, a follow-up CT indicated enlargement of the lung tumor; video-assisted right middle lobectomy was then performed. The lung tumor was diagnosed as a metastasis derived from the gallbladder cancer by pathology and immunohistochemistry. Expression of RCAS1, an independent unfavorable prognostic indicator in gallbladder cancer, was observed in both the gallbladder and lung tumors. However, infiltration of CD8+T cells was only seen in the lung metastatic tumor. She has remained free of any evidence of recurrence in the 10 months and 4 years after the first surgery. The results that metastasis is solitary and infiltrated by CD8+T cells correspond with the present clinical history.     

大肠重复癌微卫星不稳定性研究

目的　探讨微卫星不稳定性 (MSI)在大肠重复癌与单发大肠癌中的变化规律。方法　PCR SSLP法对 38例大肠重复癌患者的 5 1例癌灶及对照 35例单发大肠癌分别进行 5个碱基序列位点MSI检测。结果　大肠重复癌中复制错误 (RER)阳性率为 5 2 .9% (2 7/5 1) ,对照组为 17.1% (6 /35 ) ,两组差异有非常显著意义 (χ2 =11.2 5 ,P <0 .0 1)。大肠重复癌组中 ,RER阳性与低分化、近端大肠密切关联。RER阳性组与阴性组在年龄、性别、是否伴有转移、Dukes分期上未见异常。结论　MSI在大肠重复癌的发生上起着重要作用 ,MSI可作为预测大肠重复癌发生的有用标志 ,对MSI大肠癌患者应警惕多重癌发生的可能性。     

大肠癌组织p16基因甲基化与临床病理特征的关系

目的：研究p16基因启动子CpG区甲基化的改变与大肠癌发生及其临床病理特征的关系。方法：采用甲基化特异PCR技术（MSP法）研究大肠癌组织p16基因甲基化,并分析其与临床病理特征的关系。结果：30例大肠癌组织中有12例（40．0％）呈p16CpG区甲基化阳性。DukesC、D期组织p16CpG区甲基化发生率明显高于DukesA、B期。有转移的大肠癌组织p16甲基化发生率（84．6％）明显高于无转移者（5．9％）。结论p16启动子区甲基化导致p16抑癌基因失活,参与大肠癌的发生和发展。大肠癌组织p16CpG区甲基化与Dukes分期、肿瘤转移有关。p16甲基化可作为评估大肠癌患者预后的1个指标。     

Case report--efficacy of short-term intraarterial 5-fluorouracil for liver metastasis from colorectal cancer

Hepatectomy has the highest cure rate among the various methods for treating liver metastasis from colorectal cancer. We previously reported that continuous hepatic arterial infusion (HAI) of 5-FU is effective for improving the prognosis of patients with liver metastasis. In this study, we examined the efficacy of short-term continuous HAI of 5-FU for treating liver metastasis from colorectal cancer. A 57-year-old woman with a solitary liver metastasis from rectal cancer was treated by continuous HAI of 5-FU (1,000 mg/day) for 6 days. Her elevated serum CEA level (20.7 ng/ml) then returned to normal. Computed tomography revealed a decrease of 55.6% in the size of the liver tumor. Partial segmentectomy (S7) was subsequently performed. Histological examination of the resected tumor showed marked degeneration, necrosis, fibrosis, and calcification with viable moderately differentiated adenocarcinoma cells. These results suggest that preoperative HAI of 5-FU is safe and worth trying in patients with liver metastasis from colorectal cancer.     

长链非编码RNA CCAT2与消化系统肿瘤关系的研究进展

长链非编码RNA-结肠癌相关转录本2（CCAT2）是一种近年来发现的新型lncRNA，最早从微卫星稳定型的结直肠癌中鉴定出来。之后相继在胃癌、胆管癌、肝细胞肝癌、胰腺癌中发现，并在其中发挥重要作用。它能够诱导肿瘤生长、转移和染色体不稳定，被认为是致癌性lncRNA。CCAT2能够通过与miRNA或E-钙黏蛋白等蛋白质相互作用促进肿瘤生长与转移，尤其在消化系统肿瘤中起重要调控作用，为肿瘤的治疗提供了新的思路。     

Brain Metastases from Colorectal Cancer: Risk Factors,Incidence, and the Possible Role of Chemokines

BackgroundBrain metastases from colorectal cancer (CRC) are uncommon. There has been relatively little published on the host and tumor factors that might lead to this clinical scenario. We reviewed all cases of brain metastases from CRC at Dartmouth-Hitchcock Medical Center over a more than 20-year period to establish incidence and to identify patient and cancer characteristics which were associated with their development.Patients and MethodsWe present a retrospective review of 39 confirmed cases of brain metastases from CRC diagnosed between 1984 and 2006. Immunohistochemical staining for CXCR4 was performed on all available brain metastasis biopsy specimens.ResultsThe incidence of brain metastases from CRC was 2.3%. Left-sided primary colon tumors predominated. The majority of patients had pulmonary metastases at the time brain metastases were identified, and those with preexisting pulmonary metastases had progression of that disease. All patients were symptomatic from brain metastases, and the cerebellum was the most common area of brain involvement. Immunohistochemical analysis confirmed strong expression of CXCR4 in all brain metastases sampled.ConclusionThe incidence of brain metastases from CRC is low. Primary tumor in the left colon, long-standing pulmonary metastases, especially those with recent progression, and CXCR4 expression by tumor cells are all associated with increased risk of brain metastases. Increased survival among patients with metastatic CRC will likely result in an increased incidence of brain metastases. Further characterization of the role of tumor and host factors might yield better insight into the development, and potentially the prevention, of this devastating situation.