结直肠癌肠系膜肿瘤结节与患者预后的相关性

目的探讨结直肠癌伴发肠系膜肿瘤结节与患者预后的关系。方法回顾性分析105例结直肠癌患者临床病理及随访资料,肠系膜肿瘤结节不作为T或N分期,生存率分析其与预后的关系。结果Dukes分'期:A期13例,B期42例,C期35例,D期15例。共计13(12.4%)例患者出现系膜内转移结节,其中Dukes'A期1例,B期4例,C期4例,D期4例。总5年生存率为71.4%,其中Dukes'A期为92.3%,B期为90.5%,C期为65.7%,D期为13.3%。伴有与不伴有肠系膜肿瘤结节的患者总5年生存率分别为38.5%及76.1%(P0.05),在Dukes'A期为0%和100.0%(P0.05),B期为50.0%和94.7%(P0.05),C期为50.0%和67.7%(P0.05),D期为25.0%和9.1%(P0.05)。伴有肠系膜肿瘤结节的Dukes'A+B期患者5年生存率为50.0%,与Dukes'C期(65.7%,P0.05)差异无统计学意义。结论结直肠癌伴有肠系膜肿瘤结节患者预后不良,其临床意义更类似于淋巴结转移。     

Clinicopathologic Study of Gastric Cancer Based on Dukes' Classification

Dukes' classification is a useful staging system in patients with colorectal cancer. The aim of this study was to present clinicopathologic characteristics and survival of patients with gastric cancer based on Dukes' classification. A total of 273 patients with gastric cancer curatively treated by radical gastrectomy and lymph node dissection (D2, D3) were studied. With the modified Dukes' classification, A includes tumors limited to the mucosa, submucosa, or muscularis propria; B includes tumors extending into the subserosa or serosa; Ca includes tumors with one to six positive lymph nodes; and Cb includes tumors with seven or more positive lymph nodes. Dukes' classification modified by the number of positive lymph nodes well correlated with the tumor size (p < 0.01), depth of wall invasion (p < 0.01), level of lymph node metastasis (p < 0.01), and degree of lymphatic permeation (p < 0.01) and venous permeation (p< 0.01). The 5-year survival rate was significantly different among Dukes' A (98%), Dukes' B (90%), Dukes' Ca (75%), and Dukes' Cb (44%) cases. The results indicate that Dukes' classification modified by the number of positive lymph nodes (Dukes' A, B, Ca, an Cb) significantly correlates with tumor progression and patient survival; and it may be a simple and useful staging system for gastric cancer.     

Role of urokinase in colorectal neoplasia

The biofunctional activity of the plasminogen activators urokinase and tissue plasminogen activator has been measured in extracts from 50 colorectal carcinomas and 21 adenomas using a bioimmunoassay. Compared with control mucosa urokinase activity was significantly elevated in adenomas (P less than 0.001) and carcinomas, levels being significantly higher in carcinomas (P less than 0.05). In contrast tissue plasminogen activator activity was reduced in adenomas (P less than 0.01) and carcinomas, levels being significantly lower in carcinomas (P less than 0.01). Although enzyme activity did not relate to Dukes' stage or histological grade urokinase activity was higher in carcinomas with venous invasion (n = 17, P less than 0.05), in those with moderate or extensive local spread (n = 27, P less than 0.05) and in cases where a palliative resection only was feasible because of advanced disease (n = 8, P less than 0.05). Urokinase has been implicated in tissue degradation as well as fibrinolysis and may play a role in tumour invasion and metastasis in human colorectal neoplasia.     

鸟苷酸环化酶C在大肠癌淋巴结中表达的意义

目的:探讨在新鲜淋巴结组织检测鸟苷酸环化酶C(GCCmRNA)对大肠癌淋巴结微转移的诊断意义,以求更准确地评估大肠癌的转移情况。方法:收集本院2001.10～2002.3大肠癌根治术标本42例,计得淋巴结618枚;其中经病理形态学诊断无淋巴结转移者25例,得淋巴结370枚。用RT-PCR法检测GCCmRNA、CEAmRNA及CK20mRNA,分别以形态学证实转移淋巴结、良性大肠疾病淋巴结及正常大肠粘膜组织作为对照。全组病例随访6～26个月。结果:病例中临床分期为:DukesA期14例、B期11例、C期17例。总的阳性检出率为GCC22.65%(140/618)、CEA44.01%(272/618)、CK2043.69%(270/618);而在25例形态学诊断无转移病例中,三者的阳性率分别为12.16%(45/370)、42.16%(156/370)和41.62%(154/370)。25例常规病理阴性病例中14例检出GCCmRNA阳性淋巴结,其中4例出现复发转移,GCC诊断试验的灵敏度及特异度分别为100%、52.38%。淋巴结GCCmRNA阳性与复发/转移有统计学相关,影响无瘤生存率。结论:在传统病理形态学阴性的淋巴结中仍可能存在癌转移,用RT-PCR法检测微转移可提高淋巴结转移检出率,更准确地评估大肠癌患者的临床病理分期。GCCmRNA具有较好的特异性。     

Prognosis of colorectal cancer patients with elevated endothelin-1 concentrations

AIM: Prognostic indicators from clinical, laboratory and pathological data of patients with colorectal cancer are essential to identify high-risk groups in whom adjuvant therapy could be beneficial. Endothelin-1 (ET-1), a growth factor, has been associated with the development and spread fo solid tumours. This prospective study was performed to determine whiter preoperative plasma big ET-1 concentrations might be useful as a prognostic indicator in patients with colorectal carcinoma. METHODS: Overall, 65 consecutive patients with colorectal cancer confirmed by biopsy were include prospectively in this study from 1998 to 2001. Plasma samples from a peripheral vein were obtained prior to surgery. Univariant analysis of survival used age (less than or more than 70 years), gender, Dukes' stage (A/B vs C), tumour size (less than or more than 50 mm), vascular invasion, and plasma big ET-1 concentrations, and significant factors were then analysed using a Cox regression model. RESULTS: Three variables, age, Dukes' tumour stage and plasma big ET-1 concentration, and prognostic significance (p < 0.05). Factors associated with a poorer prognosis were age more than 70 years (p = 0.02), Dukes' C (p = 0.04) and plasma big ET-1 concentration more than 4.2 pg/mL (p = 0.02). The Cox regression model identified the same three variables as having independent prognostic value for overall survival. CONCLUSION: Preoperative plasma big ET-1 concentration may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 concentrations may be useful in the selection of high-risk, lymph node-negative patients with colorectal cancer for adjuvant therapy.     

抑癌基因PTEN在结肠直肠癌中表达的研究

目的：探讨PTEN蛋白在结肠直肠癌组织中的表达及其临床意义。方法：应用免疫组织化学技术检测1998年1月至1999年8月间于我院收治的122例结肠直肠癌组织标本中frrEN蛋白的表达。结果：在122例结肠直肠癌组织标本中有39例为阴性表达，正常结肠直肠黏膜组织、腺瘤组织均为阳性表达（P〈0．01）。无论阳性面积抑或强阳性面积，PTEN蛋白表达与结肠直肠癌病人的性别、年龄无显著相关性（P〉0．05）；而与结肠直肠癌周径、淋巴结转移、远处转移、肿瘤分化程度和Dukes分期存在显著相关（P〈0．01）。肿瘤分化各组两两比较显示，在阳性面积中除高分化与中分化腺癌、在强阳性面积中除低分化与未分化腺癌（P〉0．05）外，其余各组间统计学检验均存在显著性差异（P〈0．01）。Dukes分期各期两两比较，无论是阳性面积还是强阳性面积，除B期与C期（P〉0．05）外，其余各组间统计学检验均存在显著性差异（P〈0．01）。结论：PTEN抑癌基因的蛋白表达低下或丢失与结肠直肠的癌变有关，可能是结肠直肠的癌变过程中一种较晚发生的事件，是进展期结肠直肠癌的一种信号。     

Prognostic factors and in vitro cytotoxic sensitivity in colorectal cancer

The poor response rates to chemotherapy for colorectal cancer justify attempts to rationalize selection of patients for treatment, and the development of systems to evaluate new cytotoxic agents. Refinement of prognostic indices may identify colorectal cancer patients at a higher risk of recurrence who merit more aggressive treatment. We report our experience with the stem cell assay and pulse thymidine labelling in 43 primary colorectal cancers. Thirty-six tumours were evaluable, and clonogenic growth was obtained in 30 (83 per cent). In 24 tumours (67 per cent) growth was adequate for meaningful interpretation of a cytotoxic drug assay. Frequency of growth and colony forming efficiency did not correlate with histopathological grade, Dukes' stage or tumour cell kinetic indices. Thymidine labelling indices correlated with Dukes' stage (A and B versus C and D, P less than 0.01, Mann-Whitney U test). Cytotoxic assays with 5-fluorouracil and 5'-deoxy-5-fluorouridine were undertaken in 18 cases (14 primary carcinomas, 4 malignant ascites), of which 14 were evaluable and 3/14 (21.5 per cent) were chemosensitive in vitro. Both drugs were equally effective in vitro at clinically attainable plasma concentrations. This is in accordance with the response rates observed clinically with 5-FU chemotherapy in colorectal cancer.     

Causes of late diagnosis in cases of colorectal cancer seen in a district general hospital over a 2-year period.

Our aim in this prospective study was to identify those patients who were found to have a colorectal cancer after a delay we considered unacceptable; this was taken as 6 months or more from initial presentation to a physician to diagnosis. It was then possible to determine the presenting complaints (always multiple) and the reasons for delay, in the hope that recommendations could be made regarding appropriate, rapid and thorough investigation of patients suspected of having a colorectal cancer. Of the total of 141 patients with colorectal cancer (108 elective, 33 emergency cases) under the care of one consultant during the period studied, 17 patients (12%) (10 men and 7 women), satisfied the criteria for late diagnosis. The mean age was 72.4 years (range 43-86 years). Five common presenting complaints were identified. They were, symptomatic iron deficiency anaemia, rectal bleeding, change in bowel habit, abdominal pain and weight loss. Incomplete imaging of the colon in patients with sinister presenting symptoms was the most commonly identified factor in delay of diagnosis. Inappropriate iron therapy and false-negative reporting of double contrast barium enema investigations were both seen in a number of cases. Other causes were, inappropriate surgical treatment and both clerical error and delay. The mean time for delay was 17.6 months (median 15 months). Late diagnosed cancers were most commonly found in the caecum and least commonly in the rectum. Colonic tumours of each Dukes' stage were identified, Dukes' B most common and Dukes' A least.     

Association of ploidy and cell proliferation, Dukes' classification, and histopathological differentiation in adenocarcinomas of colon and rectum.

OBJECTIVES--To find out if there is an association between DNA indexes and DNA synthesis (S) phase measurements and Dukes' classification and histopathological differentiation in colorectal cancers, and to investigate the interrelationship between DNA indexes and S phase measurements. DESIGN--Prospective open study. MATERIAL--182 colorectal carcinomas in 181 consecutive patients. INTERVENTION--Tumours biopsied immediately after resection or at rectoscopy or colonoscopy. RESULTS--One or more aneuploid cell populations were found in 113 of 182 carcinomas (62%). There was no correlation between Dukes' stage and either degree of differentiation or S phase measurements, but there were significant correlations between S phase measurements and histological grading (p less than 0.05), and between the percentage of cells in the S phase and the DNA index when values for both diploid and aneuploid tumours were included (p less than 0.001). CONCLUSION--The degree of aneuploidy indicates how far tumour cells have progressed in their cellular disarrangement, and information about a tumour's proliferative capacity is given by the S phase measurements.     

Clinical study of operated nine thymic carcinomas

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.     

Prognosis in Duke's B colorectal carcinoma: the Jass classification revisited.

OBJECTIVE: To assess whether Jass staging enhances prognostic prediction in Dukes' B colorectal carcinoma. DESIGN: A historical cohort observational study. SETTING: A university tertiary care centre, Switzerland. SUBJECTS: 108 consecutive patients. INTERVENTIONS: Curative resection of Dukes' B colorectal carcinoma between January 1985 and December 1988, Patients with familial adenomatous polyposis; hereditary non-polyposis colorectal cancer; Crohns' disease; ulcerative colitis and synchronous and recurrent tumours were excluded. A comparable group of 155 consecutive patients with Dukes' C carcinoma were included for reference purposes. MAIN OUTCOME MEASURES: Disease free and overall survival for Dukes' B and overall survival for Dukes' C tumours. RESULTS: Dukes' B tumours in Jass group III or with an infiltrated margin had a significantly worse disease-free survival (p = 0.001 and 0.0001, respectively) and those with infiltrated margins had a significantly worse overall survival (p = 0.002). Overall survival among those with Dukes' B Jass III and Dukes' B with infiltrated margins was no better than overall survival among all patients with Dukes' C tumours. CONCLUSION: Jass staging and the nature of the margin of invasion allow patients undergoing curative surgery for Dukes' B colorectal carcinoma to be separated into prognostic groups. A group of patients with Dukes' B tumours whose prognosis is inseparable from those with Dukes' C tumours can be identified, the nature of the margin of invasion being used to classify a larger number of patients.     

Sentinel lymph node mapping in colorectal cancer

Sentinel lymph node mapping has already been accepted as part of the treatment for malignant melanomas of the skin and in breast carcinomas. The status of lymph nodes is an important prognostic marker in colorectal carcinoma as well. The authors tried the feasibility of this technique in colorectal carcinomas. The technique is analogous to the one used in breast cancer and melanoma: 2 ml of 2.5% Patentblau dye was given subserosally around the tumor. After resection the specimen was immediately sent to pathology where the lymph nodes were removed. This technique has been tried on 31 patients, 22 with colonic and 9 with rectal tumors. Of these patients, 15 were Dukes stage C, 14 were Dukes stage B and 2 were Dukes stage A. An average 4.3 blue lymph nodes were found in colon tumors and 5.4 in rectal tumors and an average 14 unstained lymph nodes were found in colon tumors, and 7 in rectal tumors. The blue nodes were predictive of the nodal status in 9 of the 15 Dukes stage C patients. In these cases the blue lymph nodes contained metastases and there were 2 cases where metastases were limited to the blue lymph nodes. SUMMARY: The authors found a high false negative rate for lymphatic mapping with the vital dye technique, therefore they try to change the method according to that used by Saha et al. The aim of sentinel node identification in colorectal carcinomas would be improved staging rather than reducing of the extent of lymphadenectomy. The role of lymphatic mapping in large bowel cancers needs further investigations. Until the results are reliable, as many lymph nodes as possible have to be excited and sent for histology.     

Colorectal cancer. Dukes' stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern

Flow cytometric DNA histograms of colorectal carcinomas from 264 patients were evaluated for the association of tumor site, Dukes' stage, tumor grade, and preoperative carcinoembryonic level with patient survival. The DNA nondiploid carcinomas were significantly more common from the left (descending and sigmoid) colon and the rectum. A poorer prognosis was found for patients with DNA nondiploid cancers than for patients with DNA diploid cancers. This was particularly true for patients with Dukes' stages B2 and C tumors with a small number (one to three) of lymph nodes with metastatic deposits. The DNA nondiploid cancers also had a relatively poorer prognosis in patients with unresectable disease. In a Cox multivariate analysis model, the DNA pattern was an independent prognostic variable for this group of 264 patients with resected colorectal carcinoma.     

Simplified staging system for predicting the prognosis of patients with resectable liver metastasis: development and validation

HYPOTHESIS: Although several staging systems for colorectal liver metastasis have been proposed, simple and generally accepted staging systems are not available for this disease. We hypothesized that more detailed analysis of primary colorectal cancer may make it possible to develop a simple staging system and that its stratification ability may be demonstrated by validation against data from unrelated patients. DESIGN: Retrospective analysis of prospectively documented data, development of a stage, and validation against an unrelated cohort. SETTING: Four tertiary referral centers. PATIENTS: Twenty-two clinicopathologic factors were examined in 369 consecutive patients who underwent curative resection for liver metastasis from colorectal cancer (original cohort). Using the independent prognostic factors, a simplified staging system was developed and was validated by data from 229 unrelated patients (validation cohort). MAIN OUTCOME MEASURES: Kaplan-Meier survival curve analyses between different prognostic groups in the cohorts. RESULTS: Multivariate analysis revealed several independent prognostic variables, including hepatic lymph node metastasis (relative risk 4.39), 4 or more colorectal lymph node metastases (RR 1.50), carcinoembryonic antigen level of 50 ng/mL or higher (RR 1.29), and multiple hepatic metastases (RR 1.27). Patients with hepatic lymph node metastasis were assigned to stage 4, and the remaining patients were divided according to number of factors: none, stage 1; 1, stage 2; 2 or 3, stage 3. In the original cohort, median survival in stages 1, 2, 3, and 4 was 7.2, 3.5, 2.0, and 1.3 years, respectively. In the validation cohort, these values were 9.6, 4.1, 2.8, and 1.6 years, respectively. CONCLUSIONS: The proposed simplified staging system was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups. Although we validated this staging system, further validation and improvements are needed.     

Application of Petersen Index Score for Dukes’B colorectal cancer in a population of 103 consecutive resected patients

Dukes' B colorectal cancer (CRC) represents a wide spectrum of disease from early penetration through the bowel wall to aggressive and extensive tumours with extramural venous spread and involvement of the serosa, surgical margins or adjacent organs. Among Dukes' B cancers, Petersen Index allows stratification to identify those patients whom chemotherapy may benefit. One hundred and three resected patients with CRC Dukes' B were included prospectively in a database and considered in the present study. According to Petersen Index, a score (from 0 to 4) for each patient was calculated on the basis of peritoneal and margin involvement, venous invasion and tumour perforation. Twenty-four out of 103 tumours were located in the rectum and 79 in the colon. According to PI score 59 patients had a score of 0, 30 of 1 and 14 of ≥2. The overall R0 resection was achieved in 95.1?% of cases and the majority of patients with PI score of ≥2 were R1-2. The mean of harvested lymph nodes was 23.6 (±10.7) with no difference according to the PI score. Patients in the high-risk group had a worse 5-year survival rate (66.3?%) compared with the other group (P?相似文献   

Laparoscopic staging of gastric cancer is safe and affects treatment strategy

The accuracy of laparoscopic staging has been documented, but its safety and impact on clinical decision making are less clear. In a prospective series of 64 patients referred to a single consultant, laparoscopy was performed in 49, after exclusion of patients unlikely to derive benefit from laparoscopic staging. The prelaparoscopy treatment plan was altered in 17 (34%). Laparoscopy detected 11 cases of peritoneal and four cases of liver metastasis, of which nine and two, respectively, were not detected by CT scan. Laparoscopy was useful in assessing fitness for major surgery, the planned extent of which was reduced in five cases as a result. Port site metastasis occurred in one case of stage IVB cancer, in conjunction with widespread progressive disease. Laparoscopic staging is recommended in gastric cancer, since it causes important changes to the management plan in one-third of cases, and the risks of port site metastasis appear low.     

Prognostic value of CA 19.9 levels in colorectal cancer.

Pretreatment serum levels of carbohydrate antigen 19.9 (CA 19.9) and carcinoembryonic antigen were measured in 293 patients with colorectal cancer. Carbohydrate antigen 19.9 was above the cut-off limit of 37 U/mL in 35% of patients. Carbohydrate antigen 19.9 sensitivity was related to tumor stage. Carcinoembryonic antigen was above the cut-off level of 3.5 ng/mL in 61% of patients, and the simultaneous use of two markers increased sensitivity to 66%. The main use of pretreatment levels of CA 19.9 in locoregional cancer is in prognosis. Carbohydrate antigen 19.9 provided more prognostic information than that obtained by conventional staging methods. In patients with Dukes' C tumors, additional information was obtained for allocation of these patients into groups at low or high risk of recurrence. Prognostic significance of carcinoembryonic antigen was not independent of Dukes' classification.     

Screening relatives of patients with colorectal cancer: the need for continuing education

Individuals at risk of familial colorectal cancer may be identified from their pedigree but screening guidelines are limited. We wished to assess the opinion of consultants in the region of the value of screening for familial colorectal cancer. All consultant general surgeons and consultant gastroenterologists in South (West) Thames received a questionnaire. This considered the current screening practice of the consultant for colorectal cancer, their opinion of screening patients with a positive family history, and their screening regimen for particular family history scenarios. Seventy-one (62.8%) of consultants replied. Forty-two consultants regularly performed screening colonoscopy (72%) with a median of 15 patients each year (range 2-130). Of these, 23 said that the number screened was limited by resources. Three percent thought regular screening of individual at increased risk of developing colorectal cancer should be yearly, 42% 3 yearly, and 42% 5 yearly. Regarding the risk of dying from colorectal cancer, 14% would screen for a risk of greater than 1 in 6, 45% 1 in 10, 18% 1 in 20, and 10% 1 in 50. Only half of the consultants agreed with published guidelines regarding the age of an index case of colorectal cancer below which they would screen 1st degree relatives. There was substantial variation in suggested screening regimens for the sample family pedigrees. There is wide variation in indications for and clinical practice of screening for familial colorectal cancer and evidence-based refinement of guidelines and increased specialist referral could rationalise resources.     

Immunohistochemical assessment of lymphovascular invasion in stage I colorectal carcinoma: prognostic relevance and correlation with nodal micrometastases

Several studies have suggested that the presence of occult nodal metastases (micrometastases) is related to adverse clinical course in stage I colorectal carcinoma. Herein we analyzed the correlation between nodal micrometastases and lymphovascular invasion (LVI) or lymphatic vessel density (LVD) in a series of stage I colorectal carcinomas; the cohort included cases characterized or not characterized by disease progression during the follow-up. In these cases, LVI and LVD were evidenced through the immunohistochemical detection of the specific marker for lymphatic vessels, D2-40. LVI was significantly more frequent in colorectal carcinomas characterized by the presence of micrometastases (P<0.0001), high peritumoral LVD (P<0.0001), and disease progression (P<0.0001). The analysis for progression risk indicated that nodal micrometastases and LVI were significant, negative, independent prognostic parameters associated with shorter disease-free survival of stage I colorectal cancer (P=0.0001; P=0.0242). In conclusion, in this study we demonstrated for the first time that LVI is significantly associated with nodal occult metastases in stage I colorectal carcinoma. In the light of its significant, independent, prognostic value in this neoplasia, the detection of LVI may represent a faster and cheaper tool compared with the time-consuming evaluation of micrometastases to select high-risk patients who may benefit from adjuvant systemic treatment. Furthermore, the assessment of LVI may be applied to establish the likelihood of nodal involvement from carcinomas treated with conservative local excision techniques, which provide no regional nodes for histologic examination.