结直肠相关多原发癌临床特点分析

目的研究结直肠相关多原发癌（MPC）的临床特点,并与同期单发结直肠癌（CRC）比较分析,以为早期诊断及治疗提供帮助。方法回顾分析1997年9月至2007年11月收治的病理资料及分期明确的573例CRC及MPC患者的相关临床资料,比较中位生存期（mOS）、肿瘤病理分型、分期、发病部位等。结果573例患者中MPC45例（7．85％）,其中有肠外病灶的MPC好发部位依次是胃、乳腺、卵巢、肺、小肠及其他。肠内多原发结直肠癌（MPCC）病例中,发病部位以升结肠癌最多（34．0％）,而CRC则以直肠癌最多（36．5％）。比较单发CRC与MPC,两者在肿瘤家族史方面无明显差异;中位发病年龄分别为57岁和63岁;有结肠息肉史的MPC患者占20．0％,而单发CRC仅0．9％;单发CRC与MPC的mOS分别为93．7和64．8个月。单发CRC和MPC病理类型都以高一中分化腺癌居多,但MPC中黏液腺癌较多。结论结直肠相关MPC在CRC患者中较常见;MPC特别是MPCC中结直肠息肉更多见;结直肠相关MPC比单发CRC的mOS短,提示结直肠相关MPC的预后可能较单发CRC差;MPCC结直肠息肉多发,肿瘤发病间隔时间短,mOS也短,提示预后较有肠外肿瘤的结直肠相关MPC差。     

137例青年人大肠癌临床病理分析

目的 :探讨青年人大肠癌的临床病理特点与预后的关系。方法 :回顾性研究了 13 7例3 5岁以下青年人大肠癌临床病理资料 ,同时与中、老年人大肠癌做了对比分析。结果 :男性 69例 ,女性 68例 ;其中发生在直肠 10 3例 ;溃疡型 76例 ,隆起型 54例 ,浸润型 7例 ;以中分化腺癌多见有 55例 ,依次为黏液腺癌 3 6例 ,高分化腺癌 19例 ,低分化腺癌 15例 ,印戒细胞癌 9例 ,未分化癌 3例。Dukes A期 3 3例 ,B期 41例 ,C期 63例。结论 :青年人大肠癌男女发病率几乎无差异 ,直肠为大肠癌好发部位。黏液腺癌、印戒细胞癌及未分化癌的比例明显高于中老年人 ,提示青年人大肠癌的预后较差。     

Le cancer colorectal chez le sujet jeune: à propos de 40 cas

Colorectal carcinoma in patients younger than 40 years is a rare affection which has a bad prognosis. Several studies have shown the increase in its impact and the aggressiveness of the tumour. The object of this work is to study the epidemiologic, anatomoclinic, therapeutic and evolutionary characteristics and to evaluate the factors of bad prognosis in this young population. In a retrospective review of 144 patients with colorectal cancer, 40 patients were under the age of 40. The predisposing antecedents of colorectal carcinoma were noted among 20 % of the cases. The clinical symptomatology was dominated by rectal bleeding and rectal pain. The tumour was rectal in 70% and colic in 30 %. The cancers were poorly differentiated in 25 % of the cases, 2.5 % had mucinous adenocarcinoma and 7.5 % had mucosal colloid carcinoma. Stage B was found in 45 %, Stage C in 25 % and Stage D in 30 % of the cases. The overall survival rate was 12.5 % at 5 years. The prognostic and therapeutic improvement requires a family screening, a genetic analysis and an early diagnosis, when predisposing antecedents exist.     

Short time to recurrence after hepatic resection correlates with poor prognosis in colorectal hepatic metastasis

BACKGROUND: Early recurrence is a major problem after hepatic resection of colorectal hepatic metastasis (CHM). Our aim was to investigate the relationship between time to recurrence after CHM resection and overall survival. METHODS: A retrospective analysis was performed for 101 consecutive patients who underwent hepatic resection for CHM and have been followed more than 5 years. RESULTS: Among 101 patients, 82 (81%) had a recurrence. Overall survival of patients with recurrence within 6 months after CHM resection was significantly worse than that of patients with recurrence after more than 6 months (P < 0.01). Overall survival was poorer when time to recurrence was shorter. One of the reasons for poor prognosis of patients with recurrence within 6 months was that only a few patients could undergo a second resection for recurrence after CHM resection. Histological type, including poorly differentiated signet ring cell or mucinous adenocarcinoma in the primary tumor, bilobar metastases, microscopic positive surgical margin and carcinoembryonic antigen (CEA) above 15 ng/ml had predictive value for decreased recurrence-free survival after CHM resection. CONCLUSION: Short time to recurrence after CHM resection correlates with a poor prognosis. Histological type of poorly differentiated signet ring cell or mucinous adenocarcinoma in the primary tumor might be a predictor for early recurrence after CHM resection.     

The significance of synchronous carcinoma and polyps in the colon and rectum

The relationship of colorectal carcinoma with polyps was studied retrospectively in 1202 patients. The incidence of synchronous carcinoma (SC) and metachronous carcinoma (MC), prognosis, and recurrence patterns were studied. Synchronous polyps (SP) were found in 36% of the patients. SC was found in 4.4% of the patients, and MC developed in 3.5% of patients. The incidence of SC and of MC increased with SP, and varied according to number, size, and histologic features of the polyps. The adjusted 5-year survival rate was improved in patients with SP compared with those without SP, both overall (79% versus 64%, respectively) and by Dukes' Stage B (87% versus 73%, respectively) and Dukes' Stage C (56% versus 39%, respectively). The pattern of relapse was the same for the SP and non-SP groups. Subtotal colectomy is recommended for colorectal carcinoma and SP in good-risk patients.     

Clinicopathological aspects of pancreatic cancer

Using the nationwide database of the Japan Pancreas Society (JPS), the clinicopathological features of 23,284 cases (1981-2000) and 2,298 cases (2001-2002) with pancreatic neoplasms were compared. Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms were increased in the registry. More detailed histological repertoires of endocrine tumors, intraductal tubular tumors and solid-pseudopapillary tumors were registered in the last two years. The numbers of serous cystadenocarcinomas and carcinomas in situ were decreased. The proportion of less differentiated adenocarcinoma was increased in the more advanced stages of the disease. In Stage IVa, the survival of the patients with papillary adenocarcinoma was not statistically different from that of patients with well or moderate tubular adenocarcinoma, though the difference was significant in earlier stages. The survival of the patients with poorly differentiated adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma was miserable. Histological confirmation is critically important to prospect the outcome and to determine the treatment modality. Integration of the nationwide registry and pathological information will give new insights for the treatment of pancreatic cancer.     

Implication of the Galectin-3 in colorectal cancer development (about 325 Tunisian Patients)

Galectin-3 is a specific soluble lectin of the β-galactoside family. It plays an important role in cell adherence, proliferation, and differentiation. It has also been shown that galectin-3 expression correlates with tumor progression in several types of cancers. We investigated the involvement of galectin-3 in colorectal cancer development. We performed a comparative immunohistochemical analysis of galectin-3 expression in term of intensity and distribution in normal mucosa, in primary tumor and in metastasis from 200 patients with colorectal cancer selected among 325 cases. We also compared the galectin-3 staining according to the histological subtype (mucinous vs non mucinous), tumoral differentiation and stage of tumor. We showed a strong and diffuse positive staining of galectin-3 in both adjacent and distanced normal mucosa, in well differentiated adenocarcinoma and in metastasis. However, we note a progressive decrease of galectin-3 staining according to the decreasing degree of tumoral differentiation. We also observed a loss of this protein in adenocarcinoma with mucinous component < 50%, where the positive staining was limited only to the well differentiated areas of tumor. These data suggest that galectin-3 play an important role in colorectal cancer progression concerning the non mucinous carcinoma and can be used as a prognostic factor to predict poor outcome of patients. In mucinous subtype, galectin-3 might be implicated in one or many step of its genesis perhaps through the control of cellular adhesion and interaction with mucin produced. Adenocarcinoma with mucinous component < 50% would be integrate to mucinous carcinoma, not to non mucinous ones. These investigations could open perspectives for therapeutic means targeted to improve the prognosis of this neoplasm.     

Correlation between clinical pathophysiologic factors and expression of orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer

We measured the activity of orotate phosphoribosyl transferase (OPRT), the amount of thymidylate synthase (TS) enzyme, and the activity of dihydropyrimidine dehydrogenase (DPD) for individual tissue types in order to study the contribution of these substances to the effects of the pyrimidine fluoride anticancer drug 5-fluorouracil (5-FU). We also studied the correlation between these 3 enzymes and clinical pathophysiologic characteristics (age, sex, extent of tumor invasion, extent of metastasis to the lymph nodes, lymphatic invasion and the venous invasion of the colorectal wall). Sixty-eight patients with colorectal carcinoma who had undergone surgical resection in our department were studied. There was a significant (p < 0.01) elevation of OPRT activity in the tumor tissue compared with regions of normal tissue. OPRT activity levels in the tumor tissue were lowest in patients with mucinous carcinoma while TS enzyme levels showed the highest activity in tumor tissue in poorly differentiated adenocarcinoma. DPD also showed high activity levels in tumor tissue in poorly differentiated adenocarcinoma and mucinous carcinoma. It is possible that the expression of enzymes with respect to the antitumor effects of 5-FU is a factor contributing to the poor prognosis for patients with poorly differentiated adenocarcinoma and mucinous carcinoma. In the present study of clinical pathophysiologic characteristics, we found that metastasis to the lymph nodes was associated with a significant reduction in the OPRT tumor/normal (T/N) ratio. Our results indicate that it may be possible to predict lymphatic metastasis by determining the T/N ratio for OPRT before surgery.     

Clinicopathological study of colorectal cancer in young adults including a case of cancer family syndrome

During the last 6 years, we examined 402 cases (including 5 cases in their 20's and 17 cases in their 30's) of colorectal cancer. We compared three groups (cases in their 20's, cases in their 30's, and cases over 40 years old), and had the following results. Cases in their 20's had a higher rate of familial history of colorectal cancer, and the cancer was located mainly in the proximal colon. Well differentiated and moderately differentiated adenocarcinoma was dominant in the cases in their 30's and in those over 40 years old. On the other hand mucinous adenocarcinoma and signet ring cell carcinoma was dominant in the cases in their 20's. A case of cancer family syndrome is also presented.     

Budding (sprouting) as a useful prognostic marker in colorectal mucinous carcinoma

PURPOSE: Budding (sprouting) along the invasive margin is reported to be associated with high malignant potential of colorectal carcinoma. We examined the prognostic significance of budding in colorectal mucinous carcinoma. PATIENTS AND METHODS: Surgically resected specimens from 31 patients with colorectal mucinous carcinoma were studied. The median postoperative follow-up was 27 months. The presence of budding was examined according to Morodomi's criteria using hematoxylin-eosin-stained sections. RESULTS: Budding was found in 18 lesions (58%). Budding was more frequently observed in lesions with venous invasion and lymph node metastasis than in those without (P = 0.04, P = 0.03, respectively). The incidence of budding was higher in lesions with distant metastasis than in those without (P < 0.03). Overall recurrence and peritoneal disseminated recurrence were significantly more frequent in patients with budding-positive lesions than in those with budding-negative lesions (P = 0.05, P = 0.04, respectively). The cumulative 5-year survival rate of curative resected cases was lower in patients with budding-positive lesions than in those with budding-negative lesions (25.0% versus 90.9%, P = 0.01, log-rank test). Moreover, both the univariate and multivariate proportional hazard models revealed that the presence of budding was the only significant co-factor of postoperative survival. CONCLUSION: Budding is a pathological marker suggesting high malignant potential and decreased postoperative survival in patients with colorectal mucinous carcinoma.     

The correlation between the productive capacity of carcinoembryonic antigen (CEA) and prognosis in gastric cancer

In 130 resected specimens of gastric cancer, CEA was stained by the enzyme labeled antibody method. The positive rate of CEA stain was 74.6% and higher in well differentiated adenocarcinoma, mucinous adenocarcinoma, and signet ring cell carcinoma. The positive rate was lower in poorly differentiated adenocarcinoma. The 5-year survival rate was higher in the CEA (-) group in stage II, and higher in the CEA (+) group in stage III (p less than 0.05) and stage IV. This suggests that the correlation of the CEA stain and the prognosis varies with the stage of cancer.     

雌激素受体与大肠癌生物学行为相关关系

［目的］探讨大肠癌组织中雌激素受体（ＥＲ）表达与大肠癌生物学行为的关系。［方法］采用免疫组织化学法检测９４例大肠癌组织中ＥＲ表达。［结果］ＥＲ的阳性表达与患者性别、年龄、肿瘤发生部位无明显相关性（Ｐ＞０．０５）;Ｄｕｋｅｓ’Ａ、Ｄ组的ＥＲ阳性率显著高于Ｄｕｋｅｓ’Ｃ、Ｄ期（Ｐ＜０．０１）;肿瘤生长于浆膜层内者ＥＲ阳性率显著高于肿瘤已浸润至浆膜层外者（Ｐ＜０．０５）;高分化腺癌ＥＲ阳性率显著高于低分化腺癌者（ｐ＜０．０５）。［结论］研究雌激素受体对探讨大肠癌的发病机制有一定的帮助,可作为判断预后的参考,对大肠癌病人行内分泌治疗具有指导意义。     

Analysis of microsatellite instability and p53 LOH in advanced colorectal cancers--first report of the No. 3 protocol

In order to establish the most appropriate protocol of adjuvant chemotherapy for colorectal cancers, several cooperative studies have been undertaken by the Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma (KCSGCCC). In the No. 3 protocol of KCSGCCC, several cancer-associated molecular markers were analyzed to investigate a possible correlation with chemosensitivity and/or patient's prognosis. Here, we report the preliminary results of the analysis of microsatellite instability (MSI) and p53 LOH in 559 cases of Stage II, III colorectal cancer. The MSI was detected in 51 cases (9%) and was shown to have a significant correlation with right-sided localization and histology (poorly differentiated, mucinous). p53 LOH was positive in 225 cases (40%) and was shown to have a significant correlation with left-sided localization and histology (well to moderately differentiated). These results might support the concept of 2 distinct pathways of colorectal carcinogenesis, e.g., RER pathway and LOH pathway.     

Endocrine carcinoma intermediate cell type of the uterine cervix

Nine cases of endocrine carcinoma, intermediate-cell type of the uterine cervix, were found in a study of 404 cases listed in the files of the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston as adenocarcinoma of the cervix. Based on light microscopic patterns, these cases were divided into pure endocrine carcinoma (six cases), and endocrine carcinoma mixed with adenocarcinoma (three cases). All tumors were 3 cm or larger in at least one dimension. On light microscopic examination, the predominant pattern was trabecular; however, insular, glandular, and spindle patterns were also identified. Argyrophilic granules were demonstrated in all cases by Grimelius stain, and Fontana-Masson (argentaffin) stain was negative. Electron microscopic examination of three cases showed membrane-bound, dense-core granules of the neurosecretory type. Although no endocrine symptoms were found, immunoperoxidase studies demonstrated 5-hydroxytryptamine in seven cases, substance P in three, vasointestinal polypeptide in two, pancreatic polypeptide in one, and somatostatin in one. Clinical behavior of these tumors was extremely aggressive. Although five cases were Stage IB at presentation, two Stage IIB, one Stage IIIB, and one Stage IV, 87.5% of these patients died of their neoplasms within 3 years. This study emphasizes the importance of correctly diagnosing endocrine carcinoma, intermediate-cell type in the uterine cervix, because of the poor prognosis of this tumor when compared with adenocarcinoma of the cervix.     

术前CEA、CA19-9和CA50的表达水平与结直肠癌临床病理特点的相关性研究--附1 340例病例分析

目的分析手术前血清CEA、CA19-9和CA50在结直肠癌患者中的表达情况,研究其在不同肿瘤临床分期中的表达差异,及其与临床病理学特点的相关性。方法回顾分析2000年1月~2004年9月于肿瘤医院接受治疗的结直肠肿瘤病例1340例,术前采用放射免疫法测定血清CEA、CA19-9和CA50水平,术后综合术前影像学检查、术中探查结果和术后组织病理学检测进行临床分期,应用SPSS12.0统计软件进行相关性分析。结果在1340例患者中,有59例为外院手术后复发或者转移的患者,另外的1281例患者均为初治病例。其中结直肠癌患者1327例。CEA、CA19-9和CA50检测阳性率分别为25.9%、22.3%和22.8%,同手术性质(根治性/姑息性)和脉管侵犯等临床病理指标相关。CEA、CA19-9和CA50在不同肿瘤分期中表达差异显著,主要在D期患者和复发转移患者中出现高阳性率。CEA在粘液腺癌和腺癌组织中表达差异显著。三个指标的表达和患者性别无关。结论CEA、CA19-9及CA50和肿瘤的临床分期密切相关,其阳性表达提示合并淋巴结或者脏器转移可能,是预后不良指标。     

Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone: patterns of recurrence, latent periods, and prognosis

A retrospective analysis was performed with emphasis on the patterns of recurrence, latent period, and prognosis in patients with cervical squamous cell carcinoma of the uterus treated with definitive radiation therapy alone. Late recurrence, which was observed more than 5 years after the initial radiation therapy, was finally focused on and discussed.

Between 1976 and 1994, 256 patients with squamous cell carcinoma of the uterine cervix without hematogenous metastasis were treated with definitive radiation therapy alone. The patients were staged as follows according to the FIGO classification: 26 in Stage I, 56 in Stage II, 124 in Stage III, 28 in Stage IVa, and 22 in Stage IVb. All the patients were treated with external beam irradiation and low-dose-rate intracavitary brachytherapy.

A total of 74 patients had recurrence. The recurrence appeared in 67 cases (90.5%) within 5 years. Metastasis to para-aortic and/or supraclavicular nodes developed later than other types of recurrence. Among patients with lymphogenous metastasis, there were more 5-year survivors after recurrence than with other types of recurrence. Patients with early recurrence, within 2 years of the initial therapy, had a worse prognosis than those with recurrence more than 2 years after treatment. Seven patients (2.7%) in all developed late recurrence more than 5 years after the treatment. The first site of recurrence was an abdominal para-aortic or supraclavicular node in all patients, excluding one patient who developed intrapelvic lymph node metastasis. Six patients had pelvic node metastasis detected with lymphangiography at the initial treatment. Median survival after late recurrence was 16.0 months. Two of 7 patients survived more than 3 years after secondary radiation therapy, and the remainder died of recurrent disease.

Patients with para-aortic and/or supraclavicular node metastasis that developed late after the initial treatment are more likely to survive due to secondary radiation therapy. Careful follow-up is emphasized for long-term survivors.     

Diffusely infiltrating primary colorectal carcinoma of linitis plastica and lymphangiosis types.

A review of 2369 cases of resected primary colorectal carcinoma identified 15 cases of diffusely infiltrating colorectal carcinoma. Depending on the histologic pattern and extent, these cases were classified as linitis plastica (LP) type (seven cases) or lymphangiosis (LA) type (eight cases). The LP type consisted of poorly differentiated adenocarcinoma or signet ring cell carcinoma; it showed an annularly thickened and rigid bowel wall. The LA type consisted of moderately differentiated adenocarcinoma. The colon wall of the LA type was hemilaterally thickened at the mesenteric side. The prognosis was extremely poor for both types. The LP type mainly had peritoneal dissemination (70%), but the LA type frequently had distant metastasis (88%). Early diagnosis and curative operation are important for both types; however, the LA type also requires therapy for distant metastasis.     

Expression of placental alkaline phosphatase in gastric and colorectal cancers. An immunohistochemical study using the prepared monoclonal antibody

The authors developed monoclonal antibodies (MoAb) against human placental alkaline phosphatase (PLAP). Four specific MoAb reacting only with PLAP and two nonspecific MoAb reacting equally with isozymes of alkaline phosphatase (hepatic, intestinal, and placental) were obtained. Immunohistochemical staining with the specific MoAb showed that the cell membrane and cytoplasm of cancer cells were stained in gastric and colorectal carcinoma. The incidence of PLAP positivity was 23% (25 of 107) of all gastric carcinomas. Among gastric carcinomas, the 42% (13 of 31) positivity of highly differentiated carcinoma (papillary adenocarcinoma and well-differentiated tubular adenocarcinoma) was a significantly higher rate than that found in poorly differentiated carcinoma (poorly differentiated adenocarcinoma and signet-ring cell carcinoma, five of 41, 12%). The incidence of PLAP positivity was 11% (four of 35) in colorectal carcinoma. In contrast, gastric adenoma, intestinal metaplasia, and noncancerous tissue adjacent to cancer did not show staining. These results indicated that expression of PLAP was apt to occur in more highly differentiated gastric carcinoma and was highly specific for carcinoma in the gastrointestinal tract, although its incidence was not high.     

Choice of chemotherapeutic drugs for colorectal cancers by DPD and OPRT activities in cancer tissues

5-FU is the most widely used anticancer drug for digestive system cancers, and it has been recently reported that the effect of 5-FU varies with the amount of enzymes that are involved in the drug metabolism in the cancer tissue. In this report, we measured DPD and OPRT activities in the normal mucosa and colorectal cancer tissues and compared them with clinicopathological factors to examine the choice of chemotherapy for colorectal cancers. Forty-six patients with colorectal carcinoma (28 colon and 18 rectal cancers), which were resected in our department from 1999 to March 2003, were examined. There was no significant difference in the DPD activities between the normal and cancer tissues, whereas OPRT showed significantly higher activity in the cancer tissues. Although we did not find a relation between the DPD activity and clinicopathological factors, the OPRT activity showed a significant difference between gender and classification of tumor, and mucinous adenocarcinoma showed significantly lower OPRT activity than differentiated adenocarcinoma. The DPD activity of mucinous adenocarcinoma is related to catabolism of 5-FU is equal to that of adenocarcinoma, however, the OPRT activity is related to a main pathway of 5-FU phosphorylation is significantly lower. Thus, mucinous adenocarcinoma of the colon was more resistant to 5-FU than the differentiated adenocarcinoma. Therefore, for chemotherapy of mucinous adenocarcinoma, anticancer agents other than 5-FU should be selected.     

GP方案治疗手术后局部复发或肺内转移非小细胞肺癌的临床研究

目的观察GP方案治疗手术后局部复发或肺内转移非小细胞肺癌的疗效及毒性反应。方法对48例手术后局部复发或肺内转移病例应用GP方案化疗,给药方法:吉西他滨1000mg/m2,第1、8、15天,静脉点滴:DDP 20 mg,第1~5天,静脉点滴,28 d为一个周期,均常规化疗4个周期以上。结果CR 4例(鳞癌),PR 23例(其中鳞癌9例,腺癌14例),NC 14例,PD 5例,总有效率56.2%(其中鳞癌40.7%,腺癌76.2%)。局部复发病灶有效率58.3%(7/12),肺内多发转移结节可测病灶共238处,有效率63.9%(152/238)。结论GP方案对晚期及术后复发、转移NSCLC疗效满意,毒副反应可以耐受。