原发腺瘤的病理学特征预测直肠异时性腺瘤的发生

目的　探讨直肠原发腺瘤的病理学特征与直肠异时性腺瘤再发的关系。方法　自 1977年至 1978年用 15cm直肠镜对海宁县 185 85 1居民进行直肠肿瘤筛查 ,共发现 1490例直肠腺瘤患者。这些患者在直肠腺瘤切除后 ,用内镜检查方法分别于第 2、4、6、11及 16年进行随访 ,观察直肠有无新生的异时性腺瘤。并分析首次筛查发现直肠腺瘤的病理学特征与发生直肠新生异时性腺瘤、重度不典型增生腺瘤和癌的关系及相对危险性。结果　随访中发现 2 80例患者在直肠内发生了新腺瘤。具有 2个以上的原发腺瘤、原发腺瘤直径大于 1cm、绒毛状 /混合型和中、重度不典型增生腺瘤患者发生异时性腺瘤的危险性升高 2～ 3倍 ,具有统计学意义。大于 1cm腺瘤 ,绒毛状 /混合型腺瘤及重度不典型增生腺瘤与发生癌或异时性重度不典型增生腺瘤明显相关 ,其相对危险性分别为 4 2 (1 8～ 9 9)、8 1(4 2～ 15 6 )和 14 4(5 0～ 41 3)。与伴轻度不典型增生、小于或等于 1cm腺瘤的患者相比 ,伴重度不典型增生、超过 1cm腺瘤的患者发生异时性直肠肿瘤的相对危险性为 37(7 8～174 7)。结论　直肠异时性腺瘤的危险性与原发腺瘤的病理学特征密切相关 ,因此 ,在高危组腺瘤患者的原发腺瘤切除后 ,应对他们进行密切监视。     

Incidence of synchronous and metachronous colorectal carcinoma

Two hundred and twenty-three patients with colorectal carcinoma were treated consecutively at the University Hospital of South Manchester from May 1976 to January 1981. Twenty-four patients (10.7 per cent) were found to have more than one colorectal carcinoma. In 18 patients this was recognized either immediately or within 6 months of the initial diagnosis--synchronous carcinoma. In the other six cases a second carcinoma was found at a later time--metachronous carcinoma. The incidence of synchronous, and consequently the combined incidence of synchronous and metachronous carcinoma, was higher than previously documented. The anatomical distribution of the multiple carcinomas and the sex incidence in these patients was similar to that seen in patients with a single carcinoma of the large bowel. A high association of adenomatous polypi with multiple large bowel carcinomas was observed. The possibility of more extensive colonic resection in the younger patient with a favourable carcinoma is discussed.     

Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia

We present the clinicopathologic characteristics of 110 colorectal mixed hyperplastic adenomatous polyps (MHAP) that exhibited the architectural but not the cytologic features of a hyperplastic polyp. They are compared with 60 traditional adenomas, 40 hyperplastic polyps, and five colonic polyps that contained admixed but well-defined hyperplastic and adenomatous glands (HP/AD). The patients with MHAP ranged in age from 15 to 88 years (mean, 63 years). Five patients had two or more (up to seven) lesions. MHAP measured 0.2-7.5 cm in diameter. They were distributed throughout the colorectum, but a slight preponderance of large lesions (more than 1.0 cm) occurred in the cecum and appendix. All MHAP were characterized by a serrated glandular pattern simulating that seen in hyperplasia (27% of MHAP were initially diagnosed as hyperplastic polyps). However, MHAP were distinguished by the presence of goblet cell immaturity, upper zone mitoses, prominence of nucleoli, and the absence of a thickened collagen table. Although surface mitotic activity, nuclear pseudostratification, and nuclear cytoplasmic ratio were greater in MHAP than in hyperplastic polyps, they were slightly less than in traditional adenomas. Thirty-seven percent of MHAP contained foci of significant dysplasia; 11% contained areas of intramucosal carcinoma. We conclude that these lesions reflect a morphologically unique variant of adenoma and suggest that they be termed "serrated adenoma" in order to emphasize their neoplastic nature. We further offer the hypothesis that MHAP may arise from the neoplastic transformation of a more differentiated cell in the crypt than the traditional adenoma.     

Increased incidence of colorectal adenomas in follow-up evaluation of patients with newly diagnosed hyperplastic polyps

Background: Although adenomatous polyps have been established clearly as precursor lesions for most cases of colorectal cancer, the role, if any, of hyperplastic polyps remains uncertain. The aim of the current study was to determine whether a patient with an index finding of hyperplastic polyp on colonoscopy is at increased risk for adenomatous polyps. Methods: We conducted a retrospective cohort study using the records of a single surgeon's colonoscopic experience over a 20-year period (June 1973 to December 1994). Patients found to have hyperplastic lesions on index colonoscopy were compared with those who had "clean" index colonoscopies. The two groups were compared for the subsequent diagnosis of adenomatous polyps on follow-up colonoscopies. Those with cancer or adenomas at index colonoscopy or in their history were excluded. We used Cox proportional hazard modeling with subsequent adenoma or cancer diagnosis at follow-up colonoscopy as the outcome, controlling for age and gender. Results: We identified 42 patients for whom hyperplastic polyps were the only colorectal neoplasms found on the index examination, in contrast to 362 control patients who had a "clean" index examination. In this cohort study, patients found to have only hyperplastic polyps on initial examination had a rate of subsequent adenoma diagnoses (42%) twice that of patients with a clean initial colonoscopy (21%). Mean follow-up time was 4.3 years. The relative rate ratio was 2.0 (95% confidence interval, 1.2-3.4). Conclusions: This study suggests that patients found to have hyperplastic polyps on initial colonoscopic examination may have twice the risk of adenomas on follow-up colonoscopy, as compared with those who have clean initial examinations. If this finding is borne out in larger prospective studies, surveillance strategies may need to be modified accordingly. apd: 14 May 2001     

Comparison of p53 and bcl-2 expression in initial, synchronous, and metachronous colorectal adenomas

To investigate the significance of p53 and bcl-2 expression in metachronous colorectal adenomas arising in the remaining colon after carcinoma resection, we analyzed p53 and bcl-2 expression immunohistochemically in initial adenomas (type I), synchronous adenomas with concurrent carcinoma (type II), and metachronous adenomas arising after resection of initial adenomas (type III) or carcinoma (type IV). The incidence of p53 immunoreactivity in type IV adenomas with mild dysplasia was significantly higher than that in type I, type II, or type III adenomas with mild dysplasia. bcl-2 immunoreactivity was more frequently detected in type IV adenomas with mild dysplasia than in type I or type III adenomas with mild dysplasia. Coexpression of p53 and bcl-2 was detected in 16% of the type IV adenomas, this being a significantly higher frequency than that seen in the type I, type II, or type III adenomas. These results suggest that the evaluation of p53 and bcl-2 in metachronous adenomas in the remaining colon after resection of carcinoma may be a useful biologic marker for assessing the risk of cancer development. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan     

Synchronous polyps predict metachronous colorectal lesions after curative resection of colorectal cancer

Background: The principal aim of endoscopic follow-up programs after curative resection of colorectal cancer (CRC) is to improve survival and identify local recurrence and metachronous CRC. The aim of our study was to identify the possible predictors of metachronous colorectal lesions.

Methods: The records of 348 consecutive patients with CRC and who completed at least 1 year of endoscopic follow-up after surgery were analyzed. In this group, 336 patients underwent surgery for primitive CRC and 12 for metachronous cancer. Patients’ characteristics, operative details, and endoscopical follow-up findings were retrieved. Multivariate survival analyses were used to identify patient categories at risk of metachronous colonic lesions.

Results: 128 patients presented a metachronous lesion: 118 adenomas and 10 adenocarcinomas. At multivariate analysis, active smoke (HR?=?1.84, p?=?0.03), neoadjuvant therapy (HR?=?0.24, p?=?0.01), and presence of synchronous polyps (HR?=?1.55, p?=?0.04) resulted independent predictors of metachronous adenoma after CRC removal while neoadjuvant therapy (HR?=?0.25, p?=?0.02), active smoke (HR?=?1.54, p?=?0.04), and presence of synchronous polyps (HR?=?1.86, p?=?0.02) resulted independent predictors of metachronous lesions after CRC removal.

Conclusions: This study demonstrated a high rate of metachronous lesions in the early follow-up after curative CRC resection. The negative effects of synchronous polyps should be carefully evaluated when planning patients’ follow-up.     

Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea

Abundant recent data suggest that sessile serrated adenoma/polyp (SSA/P) is an early precursor lesion in the serrated pathway of carcinogenesis. It is believed that SSA/Ps develop cancer by an SSA/P-dysplasia-carcinoma sequence. Hyperplastic polyps (HPs) share some histologic and molecular characteristics with SSA/P, but it is unclear whether SSA/Ps are derived from HPs or whether they develop by a different pathogenetic pathway. Previous studies have shown that serrated polyps from Korean patients show different prevalence rates of certain molecular abnormalities compared with similar lesions from American patients, and this suggests that lifestyle and dietary factors may influence the serrated neoplasia pathway. The purpose of this study was to evaluate the molecular features of HPs and SSA/Ps, the latter both with and without dysplasia, from Korean patients and to compare the findings with similar lesions from American patients. One hundred and eleven serrated polyps, consisting of 45 HPs (30 microvesicular, 11 goblet cell, 4 mucin depleted) and 56 SSA/Ps (36 with dysplasia, 20 without dysplasia), were retrieved from the pathology files of a large medical center in Korea and 38 SSA/P from American patients were evaluated for BRAF and KRAS mutations, microsatellite instability, and hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT), hMLH1, adenomatous polyposis coli (APC), p16, methylated in tumor-1 (MINT-1), MINT2, and MINT31. Methylation of hMLH1 was performed using 2 different sets of primers. Twenty-three conventional adenomas from Korean patients were included as controls. The data were compared between polyp subtypes and between polyps in the right versus the left colon. With regard to HP, KRAS mutations were present in 31.1% of polyps and BRAF mutations in 46.7% of polyps. KRAS mutations were significantly more common in goblet cell HP and BRAF in microvesicular HP (MVHP). Methylation of MGMT, hMLH1, APC, p16, MINT1, MINT2, and MINT31 were present in 42.2%, 64.4% (and 24.4%), 37.8%, 60%, 68.9%, 51.1%, and 60% of HPs. CpG island methylator phenotype high was noted in 60% of HPs. Methylation of hMLH1, p16, MINT2, and MINT31 were more frequent in MVHPs compared with other types of HPs. In contrast, SSA/Ps showed KRAS and BRAF mutations in 12.5% and 60.7% of cases, respectively. Methylation of all tumor-related genes, except hMLH1 (23.2% using 1 type of primers) and APC (37.5%), occurred in >50% of lesions, and CpG island methylator phenotype (CIMP) high was noted in 76.8% of cases. None of the molecular findings were significantly more common in SSA/P with, versus those without, dysplasia, but only 2 of the 36 polyps with dysplasia were of the conventional adenomatous type; the remainder (34 of 36) was of the serrated type. Nevertheless, both SSA/P with conventional adenomatous dysplasia showed methylation of MGMT, APC, MINT1, and MINT31 and were CIMP high. BRAF mutations, methylation of most tumor related genes, and CIMP high occurred more frequently in HPs and SSA/Ps in the right colon, compared with the left colon. In fact, no significant differences were observed between HPs and SSPs of the right colon and HPs and SSA/Ps from the left colon. Furthermore, compared with American patients, Korean male individuals were affected more frequently than female individuals, and both BRAF mutations and hMLH1 methylation were less frequent in the latter compared with the former. We conclude that HPs and SSA/Ps in Korean patients share some, but not all, clinical and molecular characteristics to those that occur in Americans. The data support the theory that the right and left colon are biologically different with regard to susceptibility to serrated cancer, and that anatomic location (right vs. left) may be a more significant risk factor of progression than the histologic type of polyp. Our data also support the theory that right-sided MVHPs may be a precursor to SSA/P.     

Characterization and identification of gastric hyperplastic polyps and adenomas by confocal laser endomicroscopy

Background  

Management of gastric polyps depends on their histologic composition. A real-time in vivo histologic diagnosis would be valuable to an “on table” management decision. Confocal laser endomicroscopy (CLE), a new diagnostic tool, allows real-time in vivo histologic evaluations of gastrointestinal lesions. This study aimed to assess the feasibility and practicability of using CLE to identify and differentiate gastric hyperplastic polyps and adenomas.     

486例结直肠癌同时性和异时性肝转移患者的预后分析

目的 探讨同时性、异时性结直肠癌肝转移的临床特点及不同治疗策略对患者预后的影响.方法 回顾性分析中山大学附属第一医院1994-2006年结直肠癌数据库中肝转移患者的临床及随访资料.采用Kaplan-Meier法绘制生存曲线,Log-Rank法比较生存率,Cox比例风险回归模型进行多因素分析.结果 共有486例患者发生肝转移,其中同时性肝转移191例,异时性肝转移295例,两组5年生存率差异具有统计学意义(9.3%vs.21.5%,P＜0.01);全组患者中267例行手术切除,151例行射频消融治疗,68例保守治疗,三种治疗方法的5年生存率分别为22.1%,10.3%和0,三组之间差异有统计学意义(P＜0.01).单因素分析显示,年龄、肝转移类型、术前CEA、原发瘤N分期、分化程度、肠梗阻、腹水、肿瘤直径、治疗策略等因素与患者预后密切相关;多因素分析显示,肝转移类型、术前CEA、腹水、治疗策略是影响预后的独立危险因素. 结论肝转移的不同类型是决定结直肠癌肝转移患者预后的重要因素;根治性手术切除与射频消融、保守治疗相比更能改善结直肠癌肝转移患者预后.     

Outcomes after resection of synchronous or metachronous hepatic and pulmonary colorectal metastases

BACKGROUND: Surgical resection of isolated hepatic or pulmonary colorectal metastases prolongs survival in selected patients. But the benefits of resection and appropriate selection criteria in patients who develop both hepatic and pulmonary metastases are ill defined. STUDY DESIGN: Data were prospectively collected from 131 patients with colorectal cancer who underwent resection of both hepatic and pulmonary metastases over a 20-year period. Median followup was 6.6 years from the time of resection of the primary tumor. Patient, treatment, and outcomes variables were analyzed using log-rank, Cox regression, and Kaplan-Meier methods. RESULTS: The site of first metastasis was the liver in 65% of patients, the lung in 11%, and both simultaneously in 24%. Multiple hepatic metastases were present in 51% of patients, and multiple pulmonary metastases were found in 48%. Hepatic lobectomy or trisegmentectomy was required in 61% of patients; most lung metastases (80%) were treated with wedge excisions. Median survival rates from resection of the primary disease, first site of metastasis, and second site of metastasis were 6.9, 5.0, and 3.3 years, respectively. After resection of disease at the second site of metastasis, the 1-, 3-, 5-, and 10-year disease-specific survival rates were 91%, 55%, 31%, and 19%, respectively. An analysis of prognostic factors revealed that survival was significantly longer when the disease-free interval between the development of the first and second sites of metastases exceeded 1 year, in patients with a single liver metastasis, and in patients younger than 55 years old. CONCLUSIONS: Surgical resection of both hepatic and pulmonary colorectal metastases is associated with prolonged survival in selected patients. Patients with a longer disease-free interval between metastases and those with single liver lesions had the best outcomes.     

Efficacy of differential mucin staining for predicting synchronous and metachronous colorectal carcinomas

Despite the controversy regarding the significance and usefulness of histochemically differential mucin staining as a marker for colorectal neoplasms, some investigators have used this technique to help define those persons at risk for development of recurrent colorectal carcinoma. To further evaluate the efficacy of this method, we reviewed 85 surgical specimens of the colon and rectum using a high iron diamine-alcian blue staining technique. The group studied included 73 patients with synchronous or metachronous carcinomas and adenomas and 12 patients with no recurrence for more than 5 years who had undergone adequate follow-up, including physical examination; evaluation of serum chemistry findings; and colonoscopy, barium enema, or both. Evaluation of Dukes' staging (A and B1 versus B2 and C2) and distance of the resection margins from the tumor (less than 5 cm versus 5 cm or more) showed no correlation with the amount of sialomucin present. Resection margins from patients with either synchronous or metachronous carcinomas had significantly higher sialomucin ratios than the group without recurrence, whereas those with synchronous or metachronous adenomas did not. The false-negative rate was 4 percent (1 of 23 specimens) and the false-positive rate, 42 percent (5 of 12 specimens). We conclude that this method for evaluating resection margins of colorectal cancer specimens with differential mucin staining is highly reliable for predicting the population with synchronous and metachronous colorectal carcinomas.     

The mechanism of microsatellite instability is different in synchronous and metachronous colorectal cancer

MLH1 promoter hypermethylation has been described as the primary mechanism for high-frequency microsatellite instability (MSI-H) in sporadic colorectal cancers (CRCs). The underlying molecular mechanism for microsatellite instability (MSI) in synchronous and metachronous CRCs is not well described. A total of 33 metachronous CRC patients and 77 synchronous CRC patients were identified from 2884 consecutive patients undergoing cancer surgery in an academic center. Evaluable tumors were tested for MSI, immunohistochemistry for MLH1 and MSH2 protein expression, and hypermethylation of the MLH1 promoter. MSI-H tumors were found in 12 (36%) metachronous CRC patients and 29 (38%) synchronous CRC patients. MSI-H metachronous CRC patients were younger at index cancer diagnosis (64 vs. 76 years, P = 0.01) and more often were diagnosed before 50 years of age (4 of 12 vs. 0 of 29, P = 0.005). Loss of MLH1 expression associated with promoter hypermethylation was common in all patients, although more common in MSI-H synchronous patients (50% metachronous vs. 83% synchronous, P = 0.03). Overall, MLH1 promoter hypermethylation was seen in 7 of 17 (41%) metachronous and 44 of 54 (81%) synchronous MSI-H CRCs tested (P = 0.004). Although MSI occurred with equal frequency among patients with synchronous and metachronous CRCs, the underlying mechanism for MSI was different. Observed differences in MLH1 promoter hypermethylation and patient characteristics suggest most MSI-H synchronous CRCs in our population were sporadic in origin. In contrast, more MSI-H metachronous CRCs were associated with patient and tumor characteristics suggestive of underlying hereditary nonpolyposis CRC. Presented as a poster at Digestive Disease Week 2001, Atlanta, Georgia, May 20–23, 2001.     

Multiple gastric polyps and parathyroid adenomas. Report of two cases.

Two cases of multiple gastric polyps associated with parathyroid adenomas are presented. A review of the literature revealed four patients with multiple gastric polyps and multiple endocrine adenomatosis. The possiblity of multiple gastric polyps as a variant of the MEA syndrome complex is explored. Emphasis is placed on the need for thorough endocrine evaluation in patients with multiple gastric polyps.     

Inverted hyperplastic polyps of the colon

An unusual form of hyperplastic polyp of the colon is described in which endophytic growth can simulate adenoma or carcinoma by penetration of the muscularis mucosae and a complex epithelial growth pattern. These lesions differ clinically from exophytic hyperplastic polyps by being more frequent on the right side than in the left colon and being relatively more common in women.     

Large hyperplastic polyps of the colon

Hyperplastic polyps are the most frequent nonneoplastic lesions of the colon. Typically, they are small sessile polyps (5 mm) located in the rectosigmoid area. Recently, they have been identified as markers of neoplastic polyps. Herein we describe four cases of large (20 mm in size) hyperplastic polyps found at our institution over a 9-year period. All four polyps were excised by endoscopic polypectomy on an outpatient basis without complications. Two polyps were in the right colon; one was pedunculated, none of them was associated with synchronous neoplastic polyps or polyposis. Up to now, follow-up in three patients has been negative for metachronous polyps. We conclude that a large hyperplastic polyp is an unexpected and rare finding, difficult to distinguish, and not related to particular colonic sites or synchronous adenomatous lesions. These polyps should be removed with a standard technique, and patients need to be followed with successive endoscopies.     

Adenomas and hyperplastic polyps in screening studies

A survey is given of colorectal polyps detected in a prospective randomized screening study with the fecal occult blood test. It is demonstrated that colonoscopy in persons with positive Hemoccult-II tests results in detection of and removal of a higher number of adenomas than among controls. The strategy may, therefore, possibly be followed by a reduction of the incidence of colorectal cancer. Screen-detected adenomas were most often in males and were larger than among controls; they were most often in the sigmoid colon, whereas the rectum was the most frequent location for adenomas in controls. Eight percent of persons with screen-detected adenomas had some symptoms, which could be referred to adenomas, in contrast to 50% among controls. Hyperplastic polyps served as markers for adenomas in persons with positive Hemoccult-II as well as in controls with adenomas detected by colonoscopy; however, most persons with adenomas had no hyperplastic polyps. Endoscopic polypectomy did not result in any severe complications, but surgical removal in 2 of 22 patients proved fatal. The results presented are compared with those of other prospective randomized trials. The optimistic view—that the incidence of cancer may be reduced by polypectomy in persons with positive Hemoccult-II tests—stresses the importance of securing optimal colonoscopy service.

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Resumen La presente revisión describe en detalle los hallazgos sobre adenomas y pólipos hiperplásicos en un estudio prospectivo y randomizado de tamizaje mediante prueba de sangre oculta en heces. Se demuestra que la colonoscopia realizada en personas con la prueba Hemoccult-II positiva resulta en la detección y remoción de un mayor nÚmero de adenomas que en los controles. Tal estrategia puede posiblemente dar lugar a una subsiguiente reducción de la incidencia de cáncer colorrectal. Los adenomas detectados mediante tamizaje aparecieron de mayor tamaño y con mayor frecuencia en nombres, que en los controles; se presentaron más frecuentemente en el colon sigmoide, en tanto que el recto fue el lugar donde los adenomas de las personas control exhibieron más frecuente localización. Ocho por ciento de las personas con adenomas detectados mediante tamizaje presentaban alguna sintomatología que pudiera estar relacionada con los adenomas, en coptraste con 50% en los controles.Los pólipos hiperplásicos sirvieron como marcadores de adenomas en personas con prueba Hemoccult-II positiva, así como en personas control con adenomas detectados por colonoscopia. Sin embargo, la mayoría de las personas con adenomas no presentaron pólipos hiperplásicos.La polipectomía endoscópica no resultó en complicaciones severas, pero la resección quirÚrgica realizada en 2 de 22 pacientes résultó fatal.Se comparan estos resultados con los de otros ensayos prospectivos. El punto de vista optimista, que la incidencia de cáncer puede llegar a ser reducida mediante polipectomía en personas con prueba Hemoccult-II, afirma la importancia de disponer de un óptimo servicio de colonoscopia.

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Résumé On a fait une étude prospective randomisée sur les polypes colorectaux détectés à l'examen de sang dans les selles. Il est démontré que la coloscopie permet, chez les patients qui ont des résultats positifs au test Hémoccult-II, la détection et l'exérèse d'un nombre d'adénomes plus grand que celui qu'on a trouvé chez des contrôles. Cette stratégie devrait Être suivie d'une réduction de l'incidence du cancer colorectal. Les adénomes dépistés se trouvaient plus souvent chez l'homme et plus grands que chez les contrôles. Ils étaient localisés la plupart du temps au côlon sigmoÏde alors que la localisation la plus fréquente des adénomes chez les contrôles était le rectum. Huit pour cent des patients ayant des adénomes dépistés avaient des symptômes qui pouvaient Être rapportés à ceux-ci tandis qu'il n'y avait que 50% des contrôles qui avaient des symptômes.Les polypes hyperplasiques servaient de marqueurs pour les adénomes chez les patients ayant un Hémoccult-II positif aussi bien que chez les contrôles avec des adénomes dépistés par coloscopie. Cependant, la plupart des patients ayant un adénome n'avaient pas de polype hyperplasique.La polypectomie endoscopique n'a provoqué aucune complication sévère mais le traitement chirurgical s'est avéré mortel dans 2 cas sur 22.Les résultats présentés ici sont comparés à ceux des autres études prospectives randomisées. La pensée optimiste que l'incidence du cancer peut Être réduite par la polypectomie chez les patients ayant un Hémoccult-II positif souligne l'importance d'un accès facile à l'examen par coloscopie.

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Supported by the Danish Cancer Society, the County of Funen, the Danish Medical Research Council, Sygekassernes Helsefond, Astrid Thaysens Foundation, and several others.