Villous and tubulovillous adenomas of the colon and rectum. A retrospective review, 1964-1985

The records of 1,040 patients with 1,440 villous and tubulovillous adenomas of the colon and rectum treated at the Cleveland Clinic over a 21 year period were reviewed. The incidence of invasive adenocarcinoma was higher in patients with multiple adenomas at the time of presentation, in patients with a family history of colorectal cancer, and in those with adenomas greater than 4 cm in diameter. Eighty percent of the adenocarcinomas were Dukes' A or B, 15 percent were Dukes' C, and 5 percent presented with distant metastases. Clinical impression on examination was more accurate than biopsy in assessing the presence of malignancy in these tumors. Recurrence after local treatment of both benign and malignant tumors was high. Recurrence was significantly related to the size of the adenoma (more common when the tumor was more than 4 cm in diameter), location (more common when it was located in the rectum), and the type of treatment. Only 4 percent of the patients had died from colorectal cancer at the time of follow-up. The overall 5 year actuarial survival rate was 85 percent.     

Immunohistochemical demonstration of human papilloma virus antigen in human colon neoplasms

The presence of human papilloma virus (HPV) has recently been demonstrated in colon tumors, but the incidence of HPV infection in normal colon mucosa or in benign or malignant neoplasms of the mucosa is unknown. We studied both neoplastic and normal human colon tissue for the presence of HPV antigen using immunohistochemical techniques. Ninety colon specimens were studied. Three consecutive series of normal colon mucosa (N = 30), single benign tubulovillous adenomas (N = 30), and invasive carcinomas (N = 30) were selected and confirmed histologically. Formalin-fixed paraffin-embedded samples of each tissue were prepared using immunohistochemical techniques and resultant slides were read blindly and graded simply as positive or negative for HPV antigen. The presence of HPV antigen varied dramatically between groups, with 97% of the invasive carcinomas, 60% of the benign tubulovillous adenomas, and 23% of the normal mucosa positive for HPV antigen. Groups were statistically significant using chi 2 analysis (P less than 0.001). We conclude that an association exists between the human colon neoplasia and the presence of HPV antigen. This may suggest an etiologic role of the virus in colon cancer.     

Morphology, anatomic distribution and cancer potential of colonic polyps.

The concept of a polyp-cancer sequence is assuming increasing credibility as a factor in the development of colorectal cancer. Colonoscopy permits most colonic polyps to be endoscopically removed and studied pathologically. Of various polyp types encountered in the colon only neoplastic polyps are regarded as having malignant potential. Neoplastic polyps include tubular adenomas (formerly, adenomatous polyps), villous adenomas and villotubular adenomas (formerly, mixed or tuboglandular polyps). Cancerous changes must penetrate the muscularis mucosae for a polyp to be regarded as clinically malignant. The present report analyzes a series of 5,786 adenomas from over 7,000 polyp endoscopically removed. The largest number of each type of adenoma presented in the sigmoid colon, followed by the descending colon in terms of frequency. In all zones tubular adenomas were most common, villous least. Abnormal cellular change, from dysplasia to carcinoma in situ to invasive cancer was most frequently found in the sigmoid colon and, in all colon sectors, increased as the villous componency of the polyp increased. However, all categories of neoplastic polyps showed malignant changes. Polyp size, long recognized as a factor, was shown to be importantly related to malignant change, but invasive cancer was found even in polyps less than 1 cm in diameter. In addition, the incidence of malignancy rose parallel to the frequency of synchronous and metachronous polyps. A vigorous program for detection and endoscopic removal of colorectal polyps is recommended as a means of reducing the incidence of colorectal cancer.     

Minimally invasive treatment of synchronous colorectal tumours

In patients with colorectal cancers synchronous neoplastic lesions are an increasingly frequent finding at preoperative staging; 3% of the cases are other cancers while 33-35% of the synchronous lesions are villous adenomas. The treatment of most colorectal adenomas can be performed by endoscopic poplypectomy. In 5% of cases there are synchronous colorectal lesions also requiring surgical treatment. From January 1995 to June 2007 we treated 5 patients with rectal lesions by transanal endoscopic microsurgery (TEM) together with a laparoscopic colectomy for the presence of synchronous lesions at the "Clinica Chirurgica Generale e d'Urgenza" of the University of Perugia,. Surgical timing involved performing a sequential exeresis characterised by a cancer resection, followed by resection of the voluminous adenoma: TEM for rectal cancer followed by a laparoscopic right hemicolectomy with an extracorporeal anastomosis for a voluminous villous adenoma (1 patient) and laparoscopic right hemicolectomy with an extracorporeal anastomosis for cancer followed by TEM for a voluminous villous adenoma (2 patients). One patient with left colon cancer associated with a voluminous villous rectal adenoma first underwent TEM for the rectal adenoma and then a left laparoscopic hemicolectomy with an extracorporeal anastomosis in order to ease the transit of the circular mechanical stapler. Another patient with rectal and right colon adenomas first underwent TEM for a voluminous rectal sessile adenoma and later a right hemicolectomy. The use of this minimally invasive approach allowed rectum preservation and less invasive surgery.     

Villous adenocarcinoma of the colon and rectum: a clinicopathologic study of 36 cases

Some colorectal adenocarcinomas show villous architecture with morphologic similarities to tubulovillous or villous adenomas. We reviewed 420 consecutive colorectal adenocarcinoma resection specimens and found that 95 tumors (23%) showed areas of villous architecture. Thirty-six tumors (8.6%) in 35 patients showed more than 50% villous architecture and were designated villous adenocarcinomas. Only 42% of the villous adenocarcinomas showed severe atypia and only 44% of the available pre-resection biopsies of these tumors were diagnosed as adenocarcinoma. Epithelial islands in desmoplastic stroma (EIDS) may be helpful in the diagnosis of these tumors. EIDS were found in 97% of the resection specimens for villous adenocarcinomas and none of 62 resection specimens for tubulovillous or villous adenomas. The presence of EIDS showed a 67% sensitivity, 100% specificity, and 100% predictive value in the diagnosis of villous adenocarcinoma in a blinded review of villous tumors. On review of the pre-resection biopsies of villous adenocarcinoma without a final diagnosis of adenocarcinoma, 40% showed EIDS. Clinical follow-up of the 35 patients with villous adenocarcinoma showed that only one died of colorectal adenocarcinoma (median follow-up, 46 months). This sole patient dying of colorectal adenocarcinoma showed a synchronous advanced stage of nonvillous adenocarcinoma at the time of diagnosis. Villous adenocarcinoma is a diagnostically challenging subset of colorectal adenocarcinoma, which appears to be associated with a favorable prognosis. Classifying these tumors as a special type of colorectal cancer may facilitate the development of diagnostic adjuncts and optimal treatment protocols.     

Villous tumors of the duodenum.

Records of 32 patients with 34 villous and tubulovillous adenomas of the duodenum, treated at the Cleveland Clinic over the past 21 years, were reviewed. Twenty-two patients (69%) had complete resection of the adenoma; the incidence of malignancy was 47%. Five patients underwent a Whipple procedure; 4 patients had segmental resection of the duodenum; 12 had wide local excision of the adenoma; 1 had both a segmental resection and a local excision for two separate adenomas; and 5 patients had endoscopic excision alone. The remaining five patients underwent exploratory laparotomy alone or with palliative bypass procedures. A 28% recurrence rate was observed, all of these after segmental resection, local excision, or endoscopic excision. The highest recurrence rate was associated with local excision. The 2- and 5-year survival rates for patients with adenomas containing invasive cancer were 22% and 0%, respectively, compared to 87% and 87%, respectively, for benign adenomas (including those with carcinoma in situ). Twenty-two per cent of patients had intestinal polyposis syndromes. Duodenal adenomas were diagnosed a mean of 17 years after colectomy for polyposis, indicating the need for continued surveillance in these patients.     

Villous tumors of the rectum. 50 cases treated surgically

The authors report a study of 50 patients who underwent surgery for a villous adenoma between 1978 and 1988 (29 men and 21 women). Mean age was 70 years old. 84% of the lesions were sessile. They ranged from 1 to 15 centimeters in size. They were associated 12 times with colon adenomas and 3 times with adenocarcinomas. All these lesions were biopsied preoperatively. Removal was performed: in 38% of cases vie a transanal approach in 38% of cases by colorectal resection vie an abdominal approach in 12% of cases by rectal amputation vie both an abdominal and perineal approach, in 12% of cases by Kraske's procedure. 22 adenocarcinomas and 28 benign lesions were discovered. 2 patients died in the early post-operative course after colorectal resection performed vie an abdominal approach. At long term (minimum of 2 years) there were 5 complications and 9 recurrences, the later occurring after tumorectomies. It is essential to know the lesions histologic characteristics in order to administer appropriate therapy, but this is not only possible to determine precisely before excision. Even biopsy specimens may miss the malignant portion of a lesion. Only complete pathological examination of the tumor can establish the diagnosis of a malignancy. Surgery remains the principal method of treatment of these lesions because it permits complete histologie examination and properly adapted management: simple removal for benign tumors or those with malignant degeneration in situ, wide excision for invasive tumors.     

Colonoscopy and the management of polyps containing invasive carcinoma.

Experiences with 565 colonoscopic polypectomies and 91 colonic and rectal resections containing infiltrating carcinoma in polyps are reviewed. A plan of management based on pathologic study of resected polyps is formulated to avoid further unnecessary surgery. It was concluded that: (1) Tubular adenomas containing invasive carcinomas have a low incidence of metastatic node involvement. This incidence is related to the depth of carcinomatous involvement. Resection of these polyps with a margin free of carcinoma constitutes definitive and adequate treatment and that (2) Villous adenomas containing invasive carcinoma have a high incidence of metastatic nodal involvement, and operative resection of the involved area of the colon is recommended, and that (3) Pedunculated tubulovillous adenomas containing invasive carcinoma behave like tubular adenomas, and the recommendations for further surgery in the patient with tubular adenomas with carcinoma apply equally well for these lesions. Sessile tubulovillous polyps tend to behave like villous adenomas, and if invasive carcinoma is demonstrated, further operation is recommended.     

S-100 protein in salivary gland tumors: an immunohistochemical study of 129 cases

Immunohistochemical distribution of S-100 protein was evaluated in 129 tumors from major and minor salivary glands. Also, two sensitive immunoperoxidase avidin-biotin methods using either overnight incubation with primary antibody or pretreatment trypsin digestion and half-hour incubation were compared. Tumors with S-100 protein immunoreactivity were demonstrated in numerous benign and malignant histologic categories. Adenoid cystic carcinomas, carcinomas ex pleomorphic adenoma, clear cell carcinomas, and adenocarcinomas NOS showed inconsistent positive staining, whereas all monomorphic and pleomorphic adenomas and polymorphous low grade adenocarcinomas examined stained positively. No staining was observed in mucoepidermoid carcinomas or acinic cell carcinomas. Mesenchymal-like tumor cells with positive immunostaining were seen only in pleomorphic adenomas and trabecular-tubular adenomas. Equivalent results were found with both overnight and same-day digestion techniques. The consistent S-100 protein staining in some histologic tumor categories (pleomorphic and monomorphic adenoma and polymorphous low grade adenocarcinoma) compared to mucoepidermoid carcinoma that is devoid of S-100 protein immunoreactivity has application to some microscopic differential diagnostic situations. Inconsistent staining of adenoid cystic carcinomas and adenocarcinomas did not allow discrimination from other benign and malignant salivary gland tumors with similar histomorphology.     

Ampullectomy for adenoma of the papilla and ampulla of Vater

Introduction: The frequency of malignant adenomas of the papilla figures between 15 and 30%. Villous adenoma is considered to be a premalignant lesion. Treatment: Resection of the papilla is indicated in large tubular and small tubulovillous adenoma. Ampullectomy, however, is mandatory in villous adenoma with severe dysplasia and large villous or tubulovillous adenoma. If villous adenoma with a low-risk pT1 N0 M0 G1/2-cancer is treated by ampullectomy, local lymph dissection should also be performed. Ampullectomy includes extirpation of the ampulla of Vater and reinsertion of the common bile duct and the pancreatic main duct into the duodenal wall. Results: Hospital mortality after ampullectomy is less than 0.4%, and surgical morbidity, e.g., cholangitis, below 10%. Received: 2 March 1998     

Adenoma of the papilla and ampulla – premalignant lesions?

Ampullary adenomas arising in the papilla or the ampulla Vateri, are rare, benign, neoplastic lesions. No specific aetiological factors, such as diet, chemical or environmental causes, have been identified yet. An established risk factor which is accompanied by the development of adenoma is the presence of genetically inherited polyposis syndromes, e.g. familial adenomatosis coli (FAP). Adenomas assume tubular, tubulovillous, or villous architecture and are not different from adenomas arising elsewhere in the gastrointestinal tract. The full neoplastic spectrum, ranging from mild to high grade dysplasia, up to invasive carcinoma, resembles the adenoma-carcinoma sequence of the large bowels.     

Almost all infiltrating colloid carcinomas of the pancreas and periampullary region arise from in situ papillary neoplasms: a study of 39 cases.

Colloid carcinomas of organs such as the breast, colon, and prostate have been well characterized. However, up until now there have been only a few studies of colloid carcinomas of the pancreas and periampullary region, and the number of colloid carcinomas in these studies has been limited. A search of our files revealed 39 resections for pancreatic and periampullary carcinomas with colloid differentiation. All neoplasms were extensively sampled. "Carcinomas with colloid differentiation" were defined as tumors associated with abundant extracellular mucin containing free-floating mucinous epithelial cells. Cases with >50% colloid differentiation were classified as "colloid carcinomas," whereas those with less were termed "carcinomas with focal colloid features." Cases with no colloid differentiation at all were designated "carcinomas without colloid differentiation." Of the 39 carcinomas, 31 were colloid carcinomas, and eight were carcinomas with focal colloid features. Twenty-seven were centered in the pancreas, seven were in the duodenum, and five were in the ampulla of Vater. Remarkably, 38 of the 39 carcinomas (97%) arose in association with an intraductal papillary mucinous neoplasm or a tubular/tubulovillous adenoma. Of the patients with colloid carcinomas, the 2-and 5-year actuarial survival rates were 69% and 29%, respectively. There was no significant difference in survival rates between patients with colloid carcinomas and patients with adenocarcinomas without colloid differentiation, whether or not the latter arose in association with intraductal papillary mucinous neoplasms or tubular/tubulovillous adenomas. In a multivariate model colloid differentiation was not an independent predictor of patient survival, while other factors such as tumor location, perineural invasion, vascular invasion, and margin status after resection independently influenced patient survival. Most colloid carcinomas of the pancreas and periampullary region arise in association with a well-defined in situ papillary neoplasm. The diagnosis of a pancreatic or periampullary colloid carcinoma should encourage the pathologist to search for an associated low-grade in situ component. In addition, colloid carcinomas of the pancreas and periampullary region do not necessarily have a better prognosis than carcinomas without colloid differentiation. Instead, other factors such as tumor location, perineural invasion, vascular invasion, and margin status after resection are far more important.     

Results of 10 years' experience with peranal Parks and Stuart extirpation of villous and tubulo-villous adenomas of the rectum

From 1973 to 1983 68 patients with villous and tubulovillous adenomas were operated by the peranal technique of Parks and Stuart. Seven patients had a circumferential adenoma and in ten patients (14.7%) an invasive cancer was found, four patients with Dukes A and six patients with Dukes B. The lethality of the 68 patients was 1.5% and the morbidity 4.5%. By a follow-up between 5 and 15 years the recurrence rate was 20.9%. There was no recurrence of cancer, especially not in the two patients with primary excision of an invasive carcinoma.     

Villous tumors of the duodenum.

Nineteen cases of villous tumors of the duodenum are reported. They have a predilection for the ampullary region, tend to present with obstructive jaundice, especially if malignancy is present, and have a high prevalence of cancer (12 of 19, or 63%). Even when biopsies are available, the diagnosis of cancer is frequently missed (5 of 9 proven cancers, 56% false-negative rate), and it may be impossible to assess the presence of carcinoma in situ or invasive carcinoma without complete excision of the lesion. The authors' experience suggests that some small benign ampullary villous adenomas or those with carcinoma in situ can be excised locally but that pancreaticoduodenectomy is preferable in the fit patient for better local control both of extensive benign lesions and cancers without distant metastases.     

Villous adenoma of the duodenum: A case report and review of the literature

A case of villous adenoma of the duodenum, with focal in situ carcinomatous changes, has been described with a review of forty-two other case reports from the world literature. Occult bleeding, resulting in anemia, and vague obstructive symptoms appear to be the most common presenting findings. The average age was 56.4 years, which was seven years younger than the average age for villous tumors of the colon. Adequate radiologic studies should establish the diagnosis preoperatively. These tumors obtain relatively large size before causing significant symptoms. Approximately one third showed carcinomatous changes, and approximately one half of these were in situ changes. Local segmental resection for duodenal villous tumors is desirable when possible. However, in areas where this is not feasible, local mucosal excision is acceptable for benign tumors and for those with in situ carcinoma. If invasive carcinoma is found in the excised specimen, pancreatoduodenectomy is recommended. Insufficient evidence is available to adequately evaluate survival for malignant villous tumors of the duodenum, but the available data suggest that the survival after treatment of malignant villous tumors is comparable to other malignant lesions originating in the duodenum.     

Villous tumors of the duodenum: Reappraisal of local vs. extended resection

Benign villous tumors of the duodenum are often managed by transduodenal local excision. Risk of local recurrence, coupled with improving safety of radical pancreaticoduodenectomy, has prompted reexamination of the roles of conservative and radical operations. The aim of this study was to determine long-term outcome after local and extended resection in order to identify factors to consider in planning operative strategy. Eighty-six patients (mean age 64 years) with villous tumors of the duodenum managed surgically from 1980 to 1997 were reviewed. Histologic findings, size, presence of polyposis syndromes, and extent of resection were correlated with outcome. Villous tumors were benign adenomas in 64 patients (74%), contained carcinoma in situ in three (4%), and invasive carcinoma in 19 (22%). The presence of cancer was not known preoperatively in 9 (47%) of the 19 with invasive carcinoma. Operative treatment included transduodenal local excision in 53 patients, pancreaticoduodenectomy in 20, pancreas-sparing duodenectomy in five, full-thickness excision in four, and other in six. Among the 50 patients with benign tumors managed by local excision, 17 had a recurrence with actuarial rates of 32% at 5 years and 43% at 10 years; four of the recurrences (24%) were adenocarcinomas. The recurrence rate was influenced by the presence of a polyposis syndrome but not by tumor size. Recurrence of benign villous tumors after local excision is common and may be malignant. Pancreaticoduodenectomy is appropriate for villous tumors containing cancer and may be considered an alternative for select patients with benign villous tumors of the duodenum. If local excision is performed, regular postoperative endoscopic surveillance is mandatory. Presented at the Fortieth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Fla., May 16–19, 1999, and published as an abstract in Gastroenterology 116:A1310, 1999.     

Large villous adenoma of the colon in carcinomatous transformation: colonic resection after endoscopic excision

Large colonic villous adenomas are benign neoplasms capable of malignant transformation with a higher frequency than other adenomas. Such transformation often requires surgical therapy after endoscopic resection. The aim of the present study was to establish the indications for surgery in a series of 13 cases of large colonic villous adenomas initially submitted to endoscopic resection. The patients (8 males and 5 females; mean age; 62 years) were observed over the period 1993-2000. All endoscopic resections were performed using the piecemeal technique. In 7 cases there were 2 endoscopic sessions and in one case 3; a single case of post-endoscopic bleeding was treated conservatively. In 5 cases, endoscopic resection was deemed not to be radical and these patients were submitted to surgical resection. Histology on the surgical specimens revealed 2 cases of carcinoma (T1 and T2, respectively), confirmation of colonic villous adenoma in 2 cases and the presence of inflammatory tissue in 1 case. Among the patients treated with endoscopic resection alone one death occurred at two years due to lung and systemic metastases probably due to the malignant adenoma. After a review of the literature and on the basis of their own experience, the authors stress the importance of a combined pathological and endoscopic approach to establish when surgery is required.     

Local resection of ampullary tumors

There is no consensus on the appropriateness of local resection for ampullary tumors, because malignant recurrence of what were thought to be benign tumors has been reported. This study examined the role of local resection in the management of ampullary tumors. Thirty patients (mean age 66 years) had transduodenal local resections performed at UCSF-Moffitt Hospital or the San Francisco VA Medical Center (February, 1992 to March, 2004). Mean follow-up time was 5.8 years. Preoperative biopsies (obtained in all patients) showed 18 adenomas, four adenomas with dysplasia, five adenomas with atypia, one adenoma with dysplasia and focal adenocarcinoma, and two tumors seen on endoscopy, whose biopsies showed only duodenal mucosa. In comparison with the final pathology findings, the results of frozen section examinations for malignancy in 20 patients, during the operation, were false-negative in three cases. The final pathologic diagnosis was 23 villous adenomas, six adenocarcinomas, and one paraganglioma. On preoperative biopsies, all patients who had high-grade dysplasia and one of five patients with atypia turned out to have invasive adenocarcinoma when the entire specimen was examined postoperatively. Two (33%) adenocarcinomas recurred at a mean of 4 years; both had negative margins at the initial resection. Among the 23 adenomas, three (13%) recurred (all as adenomas) at a mean of 3.2 years; in only one of these cases was the margin positive at the time of resection. Tumor size did not influence recurrence rate. Ampullary tumors with high-grade dysplasia on preoperative biopsy should be treated by pancreaticoduodenectomy because they usually harbor malignancy. Recurrence is too common and unpredictable after local resection of malignant lesions for this to be considered an acceptable alternative to pancreaticoduodenectomy. Ampullary adenomas can be resected locally with good results, but the recurrence rate was 13%, so endoscopic surveillance is indicated postoperatively. Frozen sections were obtained during the operation, but they were less reliable than expected. No adenomas recurred as carcinomas, suggesting that local resection is appropriate for these tumors in the absence of dysplasia or atypia on preoperative biopsies. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (poster presentation).     

细胞增殖标记物微型染色体维持蛋白2在结肠腺瘤和腺癌中的表达差异及意义

目的 探讨细胞增殖标记物MCM2在结肠癌、结肠腺瘤及正常结肠黏膜中的表达差异及在不同临床病理特征的结肠腺瘤巾的表达差异.方法 应用免疫组织化学(免疫组化)SP法检测MCM2在正常结肠黏膜、结肠腺瘤及结肠癌中的表达部位;应用实时荧光定量聚合酶链反应法检测MCM2 mRNA在12例结肠癌、33例结肠腺瘤及5例正常黏膜中表达量的差异并分析其意义,同时用REST-XL(C)软件分析不同临床病理特征的腺瘤之间MCM2的表达差异及其意义.结果 MCM2在正常黏膜中仅表达在腺凹底部,而在结肠腺瘤及腺癌组织中均呈全层上皮表达,但两者在MCM2 mRNA水平上的表达量差异有统计学意义(P=0.001).结肠腺瘤与正常黏膜相比较,MCM2表达上调,但差异无统计学意义(P＞0.05).不同临床病理特征的结肠腺瘤之间MCM2表达差异无统计学意义(P＞0.05).结论 MCM2在正常黏膜和结肠肿瘤中表达部位不同,且在结肠腺瘤及结肠癌中的表达量差异显著,可能作为早期筛查诊断结肠癌及评估腺瘤突变的指标之一.