Clinical significance of E-cadherin-catenin complex expression in metastatic foci of colorectal carcinoma.

BACKGROUND AND OBJECTIVES: Reduced expressions of cell adhesion molecules (E-cadherin, alpha-catenin, and beta-catenin) has been reported to be associated with tumor metastasis. However, the clinical significance of such adhesion molecules in the metastatic foci remains unclear. In this study, we evaluated the prognostic significance of E-cadherin, alpha-catenin, and beta-catenin expressions in the metastatic foci of patients with colorectal carcinoma. METHODS: The expressions of E-cadherin, alpha-catenin, and beta-catenin were detected immunohistochemically in 105 primary tumors, in 30 metastatic lymph nodes, and 13 metastatic liver tumors from consecutive patients with colorectal carcinoma. RESULTS: Reduced normal expression of E-cadherin, alpha-catenin, and beta-catenin in comparison with normal epithelium was detected in 78 primary tumors, respectively. Patients who had tumors with reduced expression of adhesion molecules showed unfavorable prognosis and the reduced expression of adhesion molecules was detected as one of the independent prognostic factors for patients with colorectal carcinoma. In 30 patients with lymph node metastasis, the increased expression of adhesion molecules in metastatic lymph nodes compared with primary tumors was detected in 13 patients. The prognosis of these 13 patients was poorer than that of remaining 17 patients (P = 0.0296). Also, in 13 patients with liver metastasis, even no significant difference was observed, the mean survival time of 6 patients who had metastatic liver tumors with increased expression of adhesion molecules (10 months) was shorter than that of the remaining 7 patients (16 months; P = 0.1718). CONCLUSIONS: These results suggest that increased expression of the cadherin-catenin cell-cell adhesion system in metastatic foci may play an important role in progression of metastatic colorectal carcinomas.     

Pattern of distant metastases and predictive nomograms in colorectal mucinous adenocarcinoma: a SEER analysis

BackgroundWe evaluated the metastatic patterns and explored the prognostic value of distant metastasis pattern in patients with metastatic colorectal mucinous adenocarcinoma (MC) using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsBetween 2010 and 2015, newly diagnosed colorectal MC patients were selected using the SEER database. Patient prognosis was compared based on the clinicopathological parameters, treatment method, and the site and number of metastatic organs. Cox analyses were used to identify factors associated with overall survival (OS). A nomogram was built to predict the patient’s survival. Harrell’s concordance index (c-index) and calibration curves were used to analyze the discriminative ability of the prognostic factors.ResultsOf 3,088 patients diagnosed with colorectal MC, the liver was the only metastatic organ in 78.4% (997/1,271) of all liver metastasis cases, the lung was the only metastatic organ in 41.0% (164/400) of all lung metastasis cases, bone was the only metastatic organ in 26.6% (29/109) of all bone metastasis cases, and the brain was the only metastatic organ in 23.5% (4/17) of all brain metastasis cases. Compared with the untreated cases, those treated with chemotherapy, surgery, and radiotherapy had better OS (P<0.001). There were marked OS differences (P<0.001) between patients with and without liver and bone metastases. Patients with bone metastasis had the best survival, while those with brain metastasis had the worst survival (P<0.001). Patients with one metastatic site had better prognosis compared to those with two or three (P<0.001). Patients with liver metastasis had the best survival, while those with bone and brain metastasis had the worst survival (P<0.001). Multivariate analysis showed that age <65 years, non-black race, grade I, N0 stage, chemotherapy, radiation, surgery, liver metastasis, and bone metastasis were independent prognostic factors. A nomogram was constructed to predict survival probability. The c-index value was up to 0.745. The calibration plot showed that the nomogram was clinically useful.ConclusionsMetastatic MC (mMC) patients had a characteristic distant metastasis pattern. This study constructed a new and sufficiently accurate prognostic model of mMC based on population-based data. These findings can be utilized to predict prognosis and guide mMC patient management.     

大肠癌肝转移的治疗

目的 探讨大肠癌肝转移治疗的有效方法.方法 对大肠癌肝转移86例,在原发灶切除的基础上,分为转移灶单纯切除、栓塞化疗切除、单纯栓塞化疗和全身化疗四组进行治疗,并分析单发性肝转移癌、局限于一段或一叶的多发性转移癌、左右肝均有转移癌的不同疗效.结果 单纯切除组和栓塞化疗切除组的一年生存率,均优于单纯栓塞化疗组(P<0.05);而单纯栓塞化疗组的一年生存率又优于单纯化疗组(P<0.05).在手术切除的两组病例中,单发性转移癌术后一年生存率优于左右肝均有转移灶的术后生存率(P<0.01);而局限于肝脏一段或一叶的多发性转移癌,栓塞化疗切除组的三年生存率,优于单纯切除组(P相似文献   

P53 mutations in primary tumors and subsequent liver metastases are related to survival in patients with colorectal carcinoma who undergo liver resection

BACKGROUND: The appearance of p53 mutations in colorectal carcinoma was determined, independent of differentiation and tumor stage of the primary tumors, in relation to the survival of patients who were scheduled to undergo liver resection. METHODS: Tumor material was analyzed for p53 mutations in primary colorectal tumors and subsequent liver metastases from 41 consecutive patients who were scheduled to undergo surgical liver resection. DNA sequencing and immunohistochemical staining of p53 protein within tumor nuclei were performed. RESULTS: Primary tumors displayed p53 mutations within exons 5-9 in 41% of patients. No mutations were found in exons 4, 10, or 11. Forty-one percent of metastatic lesions had the same single mutation that was found in the primary tumor, whereas 11% of metastatic lesions had one additional mutation within exons 5-9; 22% had mutations only in their liver metastases, whereas corresponding primary tumors displayed wild-type p53. None of the patients had mutated p53 in their primary tumor and wild type in their metastases. Survival after undergoing liver resection was correlated negatively (P < 0.05-0.01) with Duke Stages A-D classification of the primary tumors, tumor differentiation, and radicality (> 0.7-0.8 mm) of resected liver metastases. CONCLUSIONS: The presence of p53 mutations in patients with metastatic lesions was related significantly (P < 0.003) to better survival after the patients underwent liver resection compared with patients with wild type p53 in their metastatic lesions. This finding was not related to covariates, such as Duke classification, tumor differentiation, type of liver metastasis, or metastatic radicality during resections. Explanations for this unexpected finding remain unclear, although the authors speculate that occult tumor cells with p53 mutations may be less responsive to growth factor(s) exposure during hepatic regeneration after resection.     

The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer

The major cause of death in colorectal cancer is related to liver metastasis. Although the metastatic process has been well studied, many aspects of the molecular genetic basis of metastasis remain unclear. Elucidation of the molecular nature of liver metastasis is urgent to improve the outcome of colorectal cancer. We analyzed the chronological gene expression profiles of 104 colorectal samples corresponding to oncogenic development including normal mucosa, localized and metastasized primary tumors, and liver metastatic lesions as fundamental samples using a custom cDNA microarray. The gene expression patterns in 104 samples were classified into four groups closely associated with their metastatic status, and the genes of each group appropriately reflected the metastatic process. To investigate the existence of metastatic potential in primary tumors using metastasis-related genes detected by chronological analysis, we performed a hierarchical cluster and supervised classification analysis of 28 independent primary tumors. Hierarchical cluster analysis segregated the tumors according to their final metastatic status, rather than their clinical stages, and the profile of metastasized primary tumors resembled one of a metastatic lesion apart from a primary lesion rather than one of a non-metastasized primary tumor. Using the supervised classification approach, the expression profile of these genes allowed the classification of tumors diagnosed as localized cancer into two classes, the localized and the metastasized class, according to their final metastatic status. The disease-free survival and overall survival were significantly longer in the localized class than the metastasized class. Chronological analysis of the gene expression profile provides a better understanding of the metastatic process. Our results suggest that the metastatic potential is already encoded in the primary tumor and is detectable by a gene expression profile, which allows the prediction of liver metastasis in patients diagnosed with localized tumors and also the design of new strategies for the treatment and diagnosis of colorectal cancer.     

Surgical treatment of metastatic lung cancer from colorectal cancers

Based on conclusions obtained after the observation of 61 colorectal cancer patients with a lung metastasis, the resection of lung metastasis as a therapy was evaluated. Among these 61 patients, only 5 patients had been identified as having a lung metastasis at the time of resection of the primary lesion, whereas the other 56 patients developed the lung metastasis after the curative resection of the colorectal cancer. Only one patient with a synchronous lung metastasis and twelve patients (eleven with a solitary metastatic lesion and one with multiple metastatic lesions) with metachronous lung metastasis underwent removal of the lung metastasis. The three-year survival rate was 65.2% in the metachronous group.     

Outcome of surgical treatment for bone metastases caused by colorectal cancer

BackgroundCancer of the lower intestinal tract, although relatively common, rarely metastasizes to the skeleton. The treatment of metastatic bone disease due to colorectal cancer has thus been poorly described and treatment decisions are therefore difficult. The aim of this study was to describe the outcome of orthopedic surgery in patients with pathological fractures from colorectal cancer and investigate factors that correlate with patient survival, since it influences treatment decisions.MethodsRetrospective review of data collected in a prospectively collected database. 36 patients (38 fractures) who underwent surgery between 2000 and 2019 for metastatic bone disease caused by colorectal cancer were included.ResultsMost metastases were localized in the axial skeleton and 33/36 patients already had visceral metastases. Patients with pathological fractures from colorectal cancer had poor prognosis, with only 5/36 surviving more than 1 year, median survival being 3 months. Patients presenting with a single skeletal metastasis had a superior overall survival (P≤0.001). Post-operative complications were common, noted in 11 patients, and the surgical failure rate was considerable.ConclusionsAlthough relatively rare, bone metastases should be suspected in patients with colorectal cancer presenting with signs and symptoms of spinal cord compression or skeletal pain. In this case, the presence of a solitary skeletal lesion is a favorable prognostic sign. Awareness for local complications after surgery should be high.     

Prognostic Factors and Survival of Renal Clear Cell Carcinoma Patients with Bone Metastases

In our retrospective study the pathological and clinical factors, influencing the survival of 65 renal clear cell carcinoma patients operated for bone metastasis between 1990 and 2008 were examined. Based on Kaplan-Meier curves age, gender, clinical symptoms, pathological fracture, progression to the soft tissues, localization and size of the metastasis, whether the occurrence of multiplex metastases is multiorganic or only located to the skeletal system and the stage and grade of primary renal cancer did not influence the survival. The survival significantly improved if the bone metastases were solitary, low Fuhrman grade, late onset; and radical surgery was performed. Based on Cox regression analysis, survival after bone surgery was influenced by the multiplicity and grade of metastasis and by the radicality of the surgery, whereas survival after nephrectomy was significantly influenced by onset time and grade of metastasis. When the solitary metastasis was radically removed, 75.0% of the patients survived the first, and 35.5% the fifth postoperative year. If the metastasis was multiple or the surgery was not radical, no patient survived the fifth year. This is the first report on the prognostic significance of the Fuhrman grade of bone metastasis of renal cell cancer. While the Fuhrman grade of the primary tumour did not influence the survival, the lower grade of metastasis was associated with a significant longer survival. Therefore in cases of solitary, operable, late onset metastases with low Fuhrman grade radical removal is recommended, since this way in 35.5% of cases 5 year survival can be expected.     

Radiotherapy in the treatment of hepatocellular carcinoma and its metastases

A study was conducted to evaluate the effect of external radiation therapy on hepatocellular carcinoma (HCC) and its metastatic lesions. A total of 33 patients with cytopathologically proven HCC were subjected to radiation therapy over a 4-year period, and treatment was discontinued in 8 cases due to jaundice, severe discomfort, or early mortality. Thus, 25 patients with 28 lesions underwent irradiation with a total dose ranging between 3000 and 5600. Of these, seven were irradiated for liver tumors, and the results showed that two lesions decreased in size, the symptoms improved in 1 case, and another patient maintained stable disease for 4 months. Among the 21 metastatic lesions treated, only 2 patients failed respond to the treatment. Nine subjects were irradiated for bone metastases, and the bone pain subsided in all but one case. The survival for bone metastasis was as long as 23 months when the primary tumor was treated effectively. Three of the four cases of irradiated skin nodules disappeared and had not recurred after 5 months, 1 year, and 4 years, respectively. Tumor shrinkage or symptoms of relief were noted for three abdominal lymph nodes, one neck lymph node, one pleural tumor, and one lung tumor. Clinical improvement associated with a stable lesion was observed in two patients with brain metastasis. Follow-up revealed regrowth of the tumor or recurrence of symptoms in most of the patients. However, none of the patients died as a direct result of a metastatic lesion. Although external radiation therapy is palliative in intent, it appears to be useful in the treatment of HCC and its metastatic lesions.Presented at The Second International Symposium on Treatment of Liver Cancer. Taipei, 3–4 February 1991     

复发转移性结直肠癌的外科治疗及预后分析

背景与目的:结直肠癌是常见恶性肿瘤之一,其发病率有逐渐增高的趋势.其主要的治疗方法是根治性手术,手术后的复发及转移是导致患者死亡的主要原因.目前复发性结直肠癌的再手术是提高患者生存率和生存质量的主要方法.本文探讨结直肠癌术后复发的原因、诊断和外科治疗方法.方法:回顾性分析2003-2006年35例复发与转移性结直肠癌的外科治疗及预后.结果:手术后1年内复发者9例 (26%),3年内复发者26例(74 %).本组35例复发或转移性结直肠癌均行再次手术,7例复发性直肠癌再切除4例,造瘘3例,28例复发性结肠癌中,根治性切除8例(包括5例肝转移灶切除),姑息性切除10例,盲肠或横结肠造瘘10例.总切除率为63 %(22/35),其中根治性切除率为55%(12/22),姑息性切除45%(10/22).术后随访6～36个月,2例失访,12例根治性切除组中,9例无瘤生存,1例肺转移,2例肝转移;23例姑息治疗组中,5例死亡,4例肝转移,其余14例带瘤生存.结论:结肠癌的手术治疗,应根据其生物学特点,采取规范的手术方式、彻底清除原发灶、转移的肠系膜及淋巴结,术中注意无瘤操作,术后酌情辅以化疗或放疗,定期随访,是预防结直肠癌术后复发的主要措施.而对复发和转移病例,应根据其部位、临床特征,选择以手术为主的综合治疗方案,酌情达到根治或姑息治疗的目的.     

结直肠癌骨转移的临床特点及治疗(附104例)

目的:探讨结直肠癌骨转移的临床特点,提高结直肠癌骨转移诊疗水平.方法:通过对中国医科大学附属盛京医院2012年1月1日至2015年1月1日收治的104例结直肠癌骨转移患者资料进行回顾性分析,分析其临床特征,绘制生存曲线,总结诊疗规律.结果:2012年1月1日至2015年1月1日期间我院共收治结直肠癌骨转移患者104例,占同期结直肠癌患者的10.0%(104/1 038),其中结肠癌骨转移38例,直肠癌骨转移66例.多发骨转移60例(57.7%),单发骨转移44例(42.3%),常见转移部位依次为腰椎(38.5%)、骶骨(32.7%)、胸椎(30.8%)、肋骨(26.9%)、四肢骨(19.2%)、肩胛骨(3.8%)、颌面骨(1.9%).共有74例患者合并有远处脏器转移(71.2%),≥2处者46例,肺脏42例,肝脏40例,腹膜后淋巴结14例,腹股沟淋巴结6例,肾上腺4例,脑2例.确诊骨转移的中位时间为(26.1±3.3)个月.从确诊骨转移之日算起,中位生存期为(22.5±4.0)个月.结论:结直肠癌骨转移患者多合并远处脏器转移;直肠癌比结肠癌更易发生骨转移.     

Factors affecting survival in breast cancer patients following bone metastasis

AIMS AND BACKGROUND: The purpose of the study was to identify prognostic factors that affect survival following bone metastasis in breast cancer patients with first metastases in the skeletal system. METHODS AND STUDY DESIGN: We analyzed retrospectively the data of 248 metastatic breast cancer patients whose first distant metastasis was in the skeleton. RESULTS: The median age of the patients at diagnosis was 46 years (range, 23-76). Nearly half of the patients were premenopausal (52.4%). The median disease-free survival was 24 months. For most of the patients (221), bone was the sole first metastatic site, and the disease remained confined to the bone in 99 of them. The remaining patients (n = 27) had both bone and visceral metastasis at the time of first relapse. One hundred and fourteen of the patients (46%) had died by the time of analysis. With the median follow-up of 50.5 months from diagnosis, median survival after bone metastasis was 32 months. In univariate analyses, statistically significant predictors for survival after bone metastasis were axillary lymph node status, T stage of disease, hormone receptor status of the primary tumor, the presence of lymphovascular invasion, involvement of skin, the presence of additional nonosseous metastatic sites at the time of bone relapse, and disease-free interval. In multivariate analyses, the presence of additional non-osseous metastatic sites at the time of bone relapse, T stage of disease, hormone receptor status of the primary tumor, and the presence of lymphovascular invasion were found to be significant independent prognostic factors. CONCLUSIONS: In the result of study, for patients with breast cancer, survival following bone metastasis is affected by secondary prognostic factors such as disease-free interval and extent of metastasis besides primary prognostic factors related to the primary tumor.     

后路I期全脊椎整块切除治疗胸腰椎原发和转移性肿瘤的疗效分析

目的探讨后路I期全脊椎整块切除（totalenblocspondylectomy,TES）治疗胸腰椎原发和转移性肿瘤的疗效。方法回顾性分析2007年1月至2012年7月,我科行TES的21例,男11例,女10例,年龄21～66（平均47.8）岁。原发肿瘤8例,孤立性转移瘤13例。原发肿瘤分别为骨巨细胞瘤3例,浆细胞瘤2例,骨肉瘤、软骨肉瘤及上皮样血管内皮瘤各1例;转移性肿瘤原发肿瘤分别为乳腺癌4例,肺癌3例,肾癌2例,甲状腺癌、前列腺癌、膀胱癌和原发灶不明转移性腺癌各1例。肿瘤节段分布于T3～L3,其中胸椎12例、腰椎9例,单一椎体19例、多椎体2例（均位于3个相邻胸椎）。根据Tomita脊柱肿瘤外科分期进行评估：Ⅰ型5例、Ⅱ型10例、Ⅲ型1例、Ⅴ型2例、Ⅵ型3例。术前均有顽固性腰背痛或神经功能损害。切除椎体的骨缺损用钛网＋自体骨或异体骨＋钉棒系统进行固定和重建。手术均经后路I期完成。结果手术时间4.0～8.5h,平均6.4h;出血量1300～11600ml,平均4500ml。本组21例均获12～80个月的随访,平均40个月,术后腰背部局部疼痛均达到缓解。脊髓功能损伤的患者术后Frankel分级均有一级以上恢复,和术前Frankel分级比较,差异有统计学意义（Z＝-2.232,P＜0.05）。3例死亡,平均死亡时间为术后16个月,4例带瘤生存,14例无瘤存活,总生存率为85.7%。局部复发3例,复发率为14.3%,复发时间为平均术后22个月。本组除1例胸腔积液伴肺部感染、1例气胸伴双肺感染、1例左侧L3神经根一过性麻痹外,未出现严重并发症,并发症发生率14.3%。所有病例均无术中由于大血管或节段血管引起的大出血发生,植骨均完全愈合,无内固定失败或钛网移位。结论后路I期TES治疗脊柱原发恶性肿瘤、侵袭性良性肿瘤和孤立性转移瘤能有效降低局部复发率,无严重的并发症,是一种有效的手术方式。     

408例恶性肿瘤骨转移临床特征分析

  目的  随着抗肿瘤治疗方法的不断进步, 延长了晚期肿瘤患者的生存期, 出现骨转移及骨相关事件的发生率也随之增加, 本文旨在总结分析转移性骨肿瘤的临床特点, 以期进一步提高早期诊断和治疗水平。  方法  回顾性分析2004年5月至2011年4月本院收治转移性骨肿瘤408例, 总结其病史、原发肿瘤来源、好发部位及转移时间等临床特点。  结果  408例转移性骨肿瘤中, 发病年龄最早的是乳腺癌(57.68岁), 最晚是前列腺癌(72.33岁); 原发肿瘤来源依次为肺癌55.88%(228/408)、乳腺癌8.58%(35/408)、食管癌4.66%(19/408)、肾癌4.41%(18/408)、来源不明4.41%(18/408)、肝癌2.94%(12/408)等; 脊柱受累占74.02%(302/408), 肋骨61.27%(250/408), 骨盆38.24%(156/408), 股骨23.53%(96/408), 胸骨15.44%(63/408);平均转移时间为11.41个月, 最短和最长的分别为胰腺癌(3.0个月)和乳腺癌(55.46个月); 276例骨转移患者在初诊时既已发现骨转移; 228例肺癌骨转移中, 腺癌占39.91%(91/228), 鳞癌占24.56%(56/228), 小细胞癌占5.26%(12/228), 腺鳞癌占3.07%(7/228), 大细胞癌占0.88%(2/228), 病理类型不明为26.32%(60/228);全组中位生存期为18.45个月, 6、12和24个月生存率分别为61.27%、27.70%和10.29%。  结论  转移性骨肿瘤好发于41岁以上患者; 肺癌、乳腺癌、食管癌、肾癌最常发生骨转移, 骨转移常见部位依次为脊柱、肋骨、骨盆、股骨、胸骨, 脊柱中胸椎最常见; 男性骨转移以肺癌、肾癌及肝癌为主, 女性以肺癌、乳腺癌癌和食管癌为主; 肺癌骨转移中腺癌最多见; 积极综合治疗, 可改善骨转移患者症状。      

Retrospective analysis of patients with rare-site and metastatic giant cell tumor

A giant cell tumor occurs mainly in the proximal tibia,humerus,distal radius bone and the pelvic bone.It is rarely observed in such sites as the ribs and the temporal bone.The condition is primarily treated with surgical excision and functional reconstruction.The effect of chemotherapy on lung metastases and locally advanced giant cell tumors has remained unknown.We collected and analyzed the data of six patients with rare giant cell tumors located in the head and neck patients.After an average follow-up of 42.6 months after surgery （14 to 90 months）,no local recurrence or metastasis was observed.We also collected and analyzed the data of five patients with metastatic giant cell tumors who were undergoing surgery for the primary tumor before; of three patients who had experienced multiple chemotherapy cycles,one had spontaneous regression,and one survived for long timer despite progression.The other two patients had their major metastatic lesions resected by surgery,and presented long-term survival during the follow up.In addition,this study reports one patient with locally advanced giant cell tumor of the rib,who has undergone successful surgical resection following two cycles of chemotherapy with ifosfamide and liposomal doxorubicin.Complete resection of the lesion at the head and neck is the key to relapse-free survival.The prognosis of lung metastases in patients with giant cell tumors is relatively satisfying.Neoadjuvant chemotherapy is also conducive to the surgery for locally advanced lesions and improvement of the quality of life.     

Allelic losses associated with the metastatic potential of colorectal-carcinoma

The aim of this study was to define the association of allelic losses with the metastatic potential of colorectal carcinoma and to determine whether allelic losses can be genetic markers for the prognosis of patients with colorectal carcinoma. Eighty primary colorectal tumors and 31 liver metastases from 95 patients were examined for loss of heterozygosity (LOH) at the APC, p53, RB, DCC and chromosome 14q loci by using polymerase chain reaction-single strand conformation polymorphism analysis and restriction fragment length polymorphism analysis. The incidence of LOH at the DCC and RB loci and on chromosome 14q in liver metastases was significantly higher than that in primary tumors. DCC and RB alterations were detected more frequently in primary tumors with higher metastatic potential. Although no statistically significant association was found between these losses and survival or distant metastasis, patients with DCC losses showed poorer survival by multivariate analysis (p=0.056). Thus, inactivation of the DCC and RB genes and gene(s) on chromosome 14q seem to be critical genetic events for the acquisition of metastatic potential in colorectal carcinoma. However, further studies will be required to utilize these genetic alterations as valuable prognostic markers.     

Sarcomas (other than Ewing's) of flat bones in children and adolescents. A clinicopathologic study

The clinicopathologic features and response to therapy of 28 patients with non-Ewing's flat bone sarcoma treated at St. Jude Children's Research Hospital, Memphis, Tennessee, over a 25-year period were reviewed. Twenty-two patients had osteosarcoma, four malignant fibrous histiocytoma, one chondrosarcoma, and one fibrosarcoma. Ages at diagnosis ranged from 3 to 24 years (median, 15 years). Primary sites were craniofacial bones in ten patients, pelvis eight, scapula four, ribs two, metatarsal bones two, clavicle one, and vertebra one. All primary tumors were associated with soft tissue extension; none of the patients had metastatic disease at presentation. Six cases represented second malignancies that arose 5 to 16 years after irradiation for an unrelated tumor. Complete excision was possible in ten patients, eight of whom received postoperative chemotherapy. Five of these patients remain free of disease 1.8+ to 13+ years (median, 8.1 years) from diagnosis. Prolonged remissions after adjuvant chemotherapy were achieved in only two of 18 patients after incomplete surgical resection or biopsy. The median survival time in this group was 1 year (range, 0.2-7.7+ years). The remaining 16 patients had progressive local disease, but only two developed concurrent metastases. Thus, complete surgical resection appears to maximize disease-free survival in patients with non-Ewing's flat bone sarcoma. For the large percentage of patients in whom total resection is not possible, because of soft tissue extension and local invasion of bulky tumors, preoperative chemotherapy may increase the likelihood of complete excision and improve long-term survival.     

Genetic alterations in metastatic renal cell carcinoma detected by comparative genomic hybridization: correlation with clinical and histological data

In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disease. We analyzed 46 renal tumors along with their metastases, and 15 non-metastatic renal tumors. Tumors were classified pathologically according to the Heidelberg classification of RCC, and staged according to the TNM-system. Standard CGH was performed using microdissected archival tissues and DOP-PCR. The average numbers of chromosomal aberrations per tumor were 3.0, 2.1 and 3.9 in patients without metastasis, in patients who developed metastases after a two-year latency period (late onset of metastatic disease) and in patients who developed metastases within two years after therapy of the primary tumor (early onset of metastatic disease). CGH revealed chromosomal aberrations in 91% of primary metastatic tumors. Deletions or losses of chromosomes 9 (26% vs 6%), 10 (21% vs 6%) and 18 (23% vs 0) and 17 (28% vs 7%) occurred more often in metastatic tumors than in non-metastatic tumors. Furthermore, these aberrations were more common in patients with early metastases. CGH analysis of 40 pairs of primary RCCs and their corresponding metastasis revealed similar aberrations in 70% of cases. In 30%, however, metastases showed additional chromosomal aberrations not detected in the corresponding primary tumors. In conclusion, we identified genetic alterations associated with metastatic disease in RCC which could be useful for predicting prognosis. Genetic changes leading to metastases occurred early in tumorigenesis of metastatic tumors.