Polypoid Neoplasms Research Articles

Assessment of Likelihood of Submucosal Invasion in Non-Polypoid Colorectal Neoplasms

Although of lower prevalence compared with polypoid neoplasms, the non-polypoid neoplasms, especially the depressed type, are important to diagnose because they belong to a distinct biologically aggressive subset, given the high rate of intramucosal or submucosal cancers. The detection and diagnosis of the non-polypoid colorectal neoplasm presents a challenge and an opportunity. Above all, characteristic colonoscopic findings obtained by a combination of conventional colonoscopy and magnifying chromoendoscopy are useful for determination of the invasion depth of non-polypoid colorectal cancers, an essential factor in selecting a treatment modality.

Polypoid or non-polypoid? A novel dichotomous approach to uterine carcinosarcoma

ObjectiveTo examine the impact of the polypoid morphology of uterine carcinosarcoma on clinical outcome, as well as its relationship to well-established prognostic factors. MethodsIn a retrospective study of fifty eight patients with uterine carcinosarcoma treated with hysterectomy, we correlated the polypoid status of tumors with stage, lymphatic vascular invasion, myometrial invasion, size, carcinoma to sarcoma ratio, type of carcinomatous and sarcomatous components, disease free survival and overall survival. ResultsBy multivariate analysis, the polypoid status had no impact on disease free survival (p = 0.8958), but approached significance as a positive predictor for overall survival (p = 0.0569); patients in the polypoid group lived on average 14.9 months longer than those with non-polypoid tumors. Polypoid neoplasms had a smaller average size and grew to a smaller maximum size than the non-polypoid tumors. While non- polypoid tumors were either carcinoma or sarcoma predominant, polypoid tumors were mostly sarcoma predominant (p = 0.0348). Polypoid carcinosarcomas also demonstrated an appreciably lesser extent of myometrial invasion (p = 0.0019), a markedly lower rate of lymphatic vascular invasion (p = 0.0002), and tended to present as early stage tumors (p = 0.0265). Carcinomatous component in polypoid tumors tended to have pure or nearly pure (≥90%) endometrioid histology (p = 0.1608). There was no relationship between polypoid status and type of sarcomatous component (p = 0.5299). ConclusionsPolypoid carcinosarcomas differ from their non-polypoid counterparts in key histological parameters such as the carcinoma to sarcoma ratio, myometrial and lymphatic vascular invasion, stage and type of carcinomatous component. Patients with polypoid tumors may have a better survival outcome than those with non-polypoid tumors.

Image-Enhanced Endoscopy in Practice

The detection, diagnosis and treatment of early cancers offers the best hope for the prevention and cure of gastrointestinal cancers – one of the leading causes of death worldwide (1). The detection of pre- or early cancer using white light endoscopy can be challenging because their morphology can be inconspicuous (ie, nonpolypoid; slightly elevated, flat, or slightly depressed]) and their colour can be minimally altered. Indeed, nonpolypoid neoplasms have been shown to be common and important in the esophagus, Barrett’s mucosa and stomach (Figure 1). Our recent prevalence study (2), highlighted their importance in the colon. We showed that nonpolypoid colorectal neoplasms (NP-CRNs) are relatively common and are potentially more dangerous than polypoid neoplasms of similar size because they have a higher risk of containing in situ or submucosal invasive carcinoma. Some nonpolypoid gastrointestinal neoplasms are fairly easy to detect and diagnose, whereas others can be quite difficult to visualize using white light illumination. The current technique and technology of image-enhanced endoscopy (IEE) is available to augment the detection, diagnosis and treatment of these subtle lesions. Figure 1) Distribution of superficial lesions according to morphological classification showing the relevance and importance of the nonpolypoid types in our endoscopic practice. Data regarding lesions of the upper gastrointestinal tract were derived from the Paris ... Dr Tonya Kaltenbach is a gastroenterologist with the VA Healthcare System in Palo Alto, California, USA There are two methods of IEE: dye-based and equipment-based (3). The objective of these two methods is to increase the contrast of structures, thus making the mucosal topography, morphology and borders of lesions viewable in finer detail. Used alone or in tandem, they may complement the white light examination as well each other (Figure 2). Detailed examination of the mucosa provides a cross-sectional view of the underlying pathology and facilitates discrimination between normal, non-neoplastic and neoplastic tissue. Taken together with size and morphology, and observation during submucosal injection, important information regarding the likelihood of submucosal invasion and whether the patient can undergo a safe and curative endoscopic resection is obtained. Figure 2) The benefit of the detection and diagnosis of pre- and early cancer of the gastrointestinal tract is significantly curtailed if safe and efficacious endoscopic treatment is unavailable. Image-enhanced endoscopy is an integral component of endoscopic diagnosis, ... The present article describes the techniques and applications of IEE and provides readers of the Journal with a resource to begin or to potentially improve on their use of IEE. For critical analysis of the literature, readers are directed toward a comprehensive review of the subject (3,4). We will present a description of the various techniques of IEE, and their specific preparations and properties. We will also include an outline of the supporting data regarding the use of IEE for the detection, diagnosis and therapy of a variety of nonpolypoid gastrointestinal neoplasms.

Nonpolypoid Colonic Lesions Are More Likely Than Polyps to Contain Carcinoma

Flat, nonpolypoid colorectal neoplasms (NP-CRNs) seem to be relatively common and may have a greater association with cancer compared with the more routinely diagnosed type of colorectal polyps, according to a study in the March 5 issue of JAMA. Although colorectal cancer prevention has focused on detection and removal of polypoid neoplasms, recent studies have demonstrated that carcinoma can also frequently arise from NP-CRNs. Still, data are limited on the significance of these lesions. “Nonpolypoid colorectal neoplasms are more difficult to detect by colonoscopy or computed tomography colonography because the subtle findings can be difficult to distinguish from those of normal mucosa [membrane],” state Dr Roy M. Soetikno, and colleagues at the Veterans Affairs Palo Alto Health Care System, Palo Alto, California. “As compared with surrounding normal mucosa, NP-CRNs appear to be slightly elevated, completely flat, or slightly depressed.” The study examined data from a group of 1819 patients undergoing elective colonoscopy to estimate the prevalence of NP-CRNs and to determine the association of NP-CRNs with colorectal cancer. The overall prevalence of NP-CRNs was 9.35% (n = 170). The prevalence of NP-CRNs in the subpopulations of patients who presented for screening, surveillance, and symptoms was 5.84%, 15.44%, and 6.01%, respectively. The overall prevalence of NP-CRNs with cancer that had not metastasized or spread into tissue beneath the mucosal membrane was 0.82%, while in the screening population, the prevalence was 0.32%. Overall, NP-CRNs were nearly 10 times more likely to contain cancerous tissue than polypoid lesions, irrespective of the size. A positive size-adjusted association of NP-CRNs with cancer that had not spread was also observed in subpopulations of persons presenting for screening and surveillance, and the depressed type of NP-CRNs had the highest risk (33%). Nonpolypoid colorectal neoplasms containing cancer were smaller in diameter as compared with cancerous polypoid lesions. “In conclusion, in this population of patients at a single Veterans Affairs hospital, NP-CRNs were a relatively common finding during colonoscopy. They were more likely to contain carcinoma compared with polypoid neoplasms, independent of lesion size. Recent studies have pointed out differences in the genetic mechanisms underlying nonpolypoid and polypoid colorectal neoplasms. Future studies on NP-CRNs should further evaluate whether the diagnosis and removal of NP-CRNs has any effect on the prevention and mortality of colorectal cancer and particularly focus on their genetic and protein abnormalities,” the authors write. See “Prevalence of Nonpolypoid (Flat and Depressed) Colorectal Neoplasms in Asymptomatic and Symptomatic Adults,” JAMA, 2008;299:1027–1035.

Prevalence of Nonpolypoid (Flat and Depressed) Colorectal Neoplasms in Asymptomatic and Symptomatic Adults

Colorectal cancer is the second leading cause of cancer death in the United States. Prevention has focused on the detection and removal of polypoid neoplasms. Data are limited on the significance of nonpolypoid colorectal neoplasms (NP-CRNs). To determine the prevalence of NP-CRNs in a veterans hospital population and to characterize their association with colorectal cancer. Cross-sectional study at a veterans hospital in California with 1819 patients undergoing elective colonoscopy from July 2003 to June 2004. Endoscopic appearance, location, size, histology, and depth of invasion of neoplasms. The overall prevalence of NP-CRNs was 9.35% (95% confidence interval [95% CI], 8.05%-10.78%; n = 170). The prevalence of NP-CRNs in the subpopulations for screening, surveillance, and symptoms was 5.84% (95% CI, 4.13%-8.00%; n = 36), 15.44% (95% CI, 12.76%-18.44%; n = 101), and 6.01% (95% CI, 4.17%-8.34%; n = 33), respectively. The overall prevalence of NP-CRNs with in situ or submucosal invasive carcinoma was 0.82% (95% CI, 0.46%-1.36%; n = 15); in the screening population, the prevalence was 0.32% (95% CI, 0.04%-1.17%; n = 2). Overall, NP-CRNs were more likely to contain carcinoma (odds ratio, 9.78; 95% CI, 3.93-24.4) than polypoid lesions, irrespective of the size. The positive size-adjusted association of NP-CRNs with in situ or submucosal invasive carcinoma was also observed in subpopulations for screening (odds ratio, 2.01; 95% CI, 0.27-15.3) and surveillance (odds ratio, 63.7; 95% CI, 9.41-431). The depressed type had the highest risk (33%). Nonpolypoid colorectal neoplasms containing carcinoma were smaller in diameter as compared with the polypoid ones (mean [SD] diameter, 15.9 [10.2] mm vs 19.2 [9.6] mm, respectively). The procedure times did not change appreciably as compared with historical controls. In this group of veteran patients, NP-CRNs were relatively common lesions diagnosed during routine colonoscopy and had a greater association with carcinoma compared with polypoid neoplasms, irrespective of size.

Endoscopic Mucosal Resection in the Setting of Barrett’s Esophagus

Endoscopic mucosal resection (EMR) is a technique that was originally developed in 1978 for early gastric cancer (1). Given the relative simplicity, safety and effectiveness of the technique, it has become an endoscopic alternative to surgery in resecting flat and polypoid neoplasms of the mucosa by longitudinal section through the submucosa for curative intent. Moreover, EMR is increasingly being used in submucosal neoplastic lesions and intramucosal cancers. Still considered a novel procedure by endoscopists outside Japan, the present article will outline the current indications for EMR as it pertains to Barrett’s esophagus and distal esophageal lesions. Other areas where EMR may be used, but not discussed in the present paper, include the stomach for gastric cancers, the colorectum for adenomas and, recently, the duodenum.

Incidence and Malignant Potential of Non-polypoid and Polypoid Colorectal Neoplasms at National Cancer Center, Tokyo

Background: Non-polypoid colorectal neoplasms are suspected of having a higher incidence of invasive carcinoma compared to polypoid lesions of similar size. However, non-polypoid lesions have been scarcely studied. The aim of this study was to clarify the incidence and malignant potential of non-polypoid and polypoid lesions. Materials and Methods: A total of 6437 colorectal adenomas and early carcinomas resected between 1998 and 2002 were retrospectively analyzed. Lesions were classified based on their endoscopic appearance: Non-polypoid (IIc, IIa+IIc, Is+IIc) or Polypoid (Ip, Isp, Is, Is+IIa, IIa). Results: There were 153 (2.4%) non-polypoid and 6284 (97.6%) polypoid lesions. There were 69 (45.1%) adenomas, 12 (7.8%) intramucosal carcinomas (m-ca) and 72 (47.1%) submucosal carcinomas (sm-ca) in the non-polypoid group and 5397 (85.9%) adenomas, 778 (12.4%) m-ca and 109 (1.7%) sm-ca in the polypoid group. Among all adenomas, 69 (1.3%) were non-polypoid and 5397 (98.7%) polypoid neoplasms. Counting all the m-ca, 12 (1.5%) were non-polypoid and 778 (98.5%) polypoid lesions. Among all sm-ca there were 72 (39.8%) non-polypoid and 109 (60.2%) polypoid neoplasms. The rate of submucosal invasion was 85.7% (72/84) and 12.3% (109/887) in the non-polypoid and the polypoid early carcinomas respectively (p<0.0001). There were 20 (27.8%) lesions less than 10mm in non-polypoid sm-ca. Meanwhile there were 18 (16.5%) lesions less than 10mm in polypoid sm-ca (p=0.07). The rate of lymph node metastasis was 13.8% (9/65) and 9.5% (7/74) in non-polypoid and polypoid lesions respectively (p=0.42). Conclusion: In spite of its low frequency, non-polypoid lesions account for almost 40% of submucosal colorectal carcinoma. In cases of non-polypoid lesions associated to early carcinoma the risk of submucosal invasion is remarkably high. Special attention must be paid to these lesions in screening colonoscopy.

Endobronchial Polypoid Tumor

CASE REPORT A 55-year-old man presented with a 6-month history of malaise and cough associated with intermittent fevers, night sweats, and a weight loss of 7 kilograms. He had increased dyspnea with exertion for a year and associated wheezing. Medical history was unremarkable except for active cigarette use, a 70–pack-year history of smoking, and chronic obstructive pulmonary disease. Physical examination was significant for clubbing and diminished breath sounds with mild bilateral expiratory wheezes. Chest radiograph revealed a 1.5-cm nodule in the superior segment of the right lower lobe, a 3.5-cm mass in the right hilum, and bilateral hyperinflation consistent with chronic obstructive pulmonary disease. Chest computed tomography revealed a 2-cm right lower lobe nodule, a large right hilar mass, and mediastinal adenopathy involving right paratracheal and subcarinal regions. On flexible bronchoscopy, a large white mobile endobronchial polypoid lesion extended along the medial wall of the bronchus intermedius (Fig. 1). The distal end was fixed in the right middle lobe. The main and secondary carina appeared to be widened. Pathologic examination of the mass and transbronchial needle aspiration biopsy of the right upper lobe secondary carina was positive for squamous cell carcinoma. Two weeks after bronchoscopy, the patient had a sudden onset of choking and expectorated a piece of tissue measuring 6 cm × 2 cm (Fig. 2). Histologic examination revealed a poorly differentiated squamous cell carcinoma. Mediastinoscopy confirmed mediastinal involvement and stage T3N2M0 disease. He received palliative radiation therapy. Subsequently, he developed progressive right lung collapse and died of respiratory failure 6 weeks later.FIG. 1.: Large mobile endobronchial polypoid lesion.FIG. 2.: Expectorated piece of tissue.DISCUSSION Endobronchial polypoid neoplasms form a small, distinct group of pulmonary neoplasms that invade and metastasize late. 1 Endobronchial polypoid squamous cell carcinoma is rarely reported. Sherwin et al. described only two cases of endobronchial polypoid tumors in a series of 85 resectable lung cancers. 2 In both cases, the endobronchial tumors were less than 2 cm in diameter. Endobronchial polypoid squamous carcinoma was reported to have a frequency of 2% (34 cases) over a 35-year period with a 5-year survival of 62.5%. 3 These tumors were presumed to carry a favorable prognosis. The differential diagnosis of any endobronchial tumor-like lesion is broad, ranging from benign to malignant processes. Benign endobronchial lesions include inflammatory polyps and papillomas as well as a variety of benign tumors. 4,5 Of the neoplastic category, bronchogenic carcinomas are the most common, but soft tissue tumors and metastatic disease from other organs, such as thymoma, thyroid carcinoma, lymphoma, and renal cell carcinoma have been described. 6–9 Treatment of benign or malignant endobronchial lesions may involve surgical resection or local treatment. When curative resection is not possible, endoscopic and local therapy are effective strategies for palliation. Cryotherapy, electrocautery, brachytherapy, and laser therapy can be applied using rigid or flexible bronchoscopy. 10 These modalities may be combined with conventional chemotherapy, external beam radiotherapy, and surgical resection. 11–12 In contrast to historically described cases, our patient presented with endobronchial polypoid squamous cell carcinoma with a large tumor size, mediastinal involvement, and rapidly progressive clinical course. Our observations underscore the value of flexible bronchoscopy and address limitations in staging. Endobronchial polypoid squamous carcinoma may represent a spectrum of bronchogenic carcinomas that includes tumors exhibiting less aggressive behavior as well as those following a more aggressive course as was seen in this case.

Endoscopic mucosal resection.

Endoscopic mucosal resection (EMR), or mucosectomy technique, developed by Japanese endoscopists consists of resecting flat and polypoid neoplasms of the mucosa by longitudinal section through the submucosa. This technique is relatively simple and carries a low morbidity. It represents an important advance for endoscopists in both technical and cancer areas. Compared with the endoscopic methods of tumor destruction (laser, plasma coagulation), EMR presents the advantage of obtaining a complete specimen for histologic analysis.

Colorectal carcinogenesis: historical review.

In view of the changing concept of colorectal carcinogenesis during the last 20 years, a historical review of colorectal carcinogenesis is presented. The changing concept of colorectal carcinogenesis was presented in four different periods: 1) carcinogenesis based on surgical materials; 2) carcinogenesis based on polypectomy materials; 3) carcinogenesis based on nonpolypoid neoplasms; 4) carcinogenesis based on molecular biology. In the first period, large adenomas were thought to play the most important role as precursors to colorectal carcinomas; however, in the second period, smaller and nonpedunculated adenomas were found to have a much higher malignancy potential than previously thought. The discovery of nonpolypoid neoplasms, including flat and depressed adenomas/carcinomas, shed light on the new precursor of colorectal carcinomas that were not recognized in the past. Molecular biology clarified a lack of K-ras mutation in nonpolypoid, particularly depressed, neoplasms, suggesting the presence of a novel pathway of colorectal carcinogenesis, different from that in polypoid neoplasms. The concept referred to as the "adenoma-carcinoma sequence" changed because colonoscopic polypectomy specimens were studied, and rather small, nonpedunculated adenomas were found to play an important role as precursors of colorectal carcinomas. The discovery of nonpolypoid neoplasms provides us with new precursors of colorectal carcinomas. The genetic alterations in nonpolypoid neoplasms seem to differ from those in polypoid neoplasms, and genetic alterations in so-called de novo carcinomas need to be clarified.

Immunohistochemical demonstration of p53 protein in colorectal adenomas and adenocarcinomas. Reliable application of the heat-induced antigen retrieval method to formalin-fixed, paraffin-embedded material.

Ninety-nine polypoid neoplasms and eight advanced adenocarcinomas of the colon were studied immunohistochemically for p53 protein expression. For reproducible antigen retrieval, formalin-fixed, paraffin-embedded archival sections were heated at 90 degrees C for 120 min in 0.01 mol/L phosphate-buffered saline, pH 7.2, prior to immunostaining. Proliferating cell nuclear antigen served as a positive control marker for effective antigen retrieval. The 99 polyps were categorized into 24 high-grade adenomas, 60 non-invasive cancer-in-adenomas (CIA), and 15 CIA with stromal invasion. All the polyps contained portions of low-grade adenoma. Positive nuclear staining of p53 protein was observed in none of the non-neoplastic mucosa, nine (9%) of 99 low-grade adenomas, 17 (71%) of 24 high-grade adenomas, 46 (77%) of 60 non-invasive CIA, 10 (67%) of 15 invasive CIA, and five (63%) of eight advanced carcinomas. When the antigen retrieval treatment was omitted, the positivity rates were 0, 2, 17, 35, 40, and 63%, respectively. When the antigen-retrieved staining pattern was classified into (i) 'sparse' (< 25% of the nuclei of neoplastic glands labeled), 'scattered' (25-75%) and 'dense' (> 75%); or (ii) 'focal' (the positively labeled glands occupying < 25% of the tumor area), 'intermediate' (25-75%) and 'diffuse' (> 75%), the sparse and focal patterns predominated in high-grade adenomas and non-invasive CIA with low-grade atypia, while the dense and diffuse patterns predominated in invasive CIA and all the advanced carcinomas revealed the dense and diffuse patterns. Non-invasive CIA with high-grade atypia belonged to an intermediate type between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Studies of Colon Carcinogenesis and Altered Epithelial Cell Differentiation

Chronic inflammatory bowel disease (IBD) appears to predispose to subsequent colon cancer. Factors that influence the degree of this risk require definition since the reported incidence of malignant change varies widely. Differing environmental factors such as diet may be critical, and several approaches have been used to explore the role of specific variables in colon cancer pathogenesis; one has employed the use of animal models. Naturally occurring models of colon cancer exist including cotton-topped tamarins with colitis. Best studied, however, are animal models of colon cancer induced with specific chemical carcinogens. Cycasin and hydrazine derivatives, eg, 1,2-dimethylhydrazine, are most widely used. After parenteral administration of an active carcinogen, metabolic activation occurs, resulting in colonic adenocarcinomas. Sessile and polypoid neoplasms may be induced, particularly in the distal colon, similar to human colon cancer. Using this model, the effect of differing dietary and therapeutic variables has been explored. Studies with purified single dietary fibres, such as microcrystalline cellulose and hemicellulose, but not pectin, have demonstrated reduced numbers of colonic tumours; these in vivo observations correlate with in vitro effects of fibres on rat luminal and fecal mutagenic activities. Specific therapies used in IBD have also been evaluated - metronidazole, for example, a bacterial mutagen, enhances the development of chemically induced rodent colon cancer. In addition, a significant increase in colonic tumour development occurs after intestinal resection or bypass, two procedures used in the surgical management of IBD. In this setting, surgical sutures, particularly nonabsorbable materials including stainless steel, may play a critical role. Although the extent and duration of disease in patients with chronic IBD may be important in colon cancer pathogenesis, other variables, including diet and treatment, may be critical modulating factors.

Colonic cleansing for radiographic detection of neoplasia: efficacy of the magnesium citrate-castor oil-cleansing enema regimen.

To optimize detection of colonic polyps, we instituted a cleansing regimen of dietary restriction, hydration, magnesium citrate, castor oil, and a cleansing enema. We then conducted a review of serially performed barium enemas to determine the percentage of patients with clean colons in a mixed population of 500 inpatients and outpatients in whom this regimen had been used. The same regimen also was used before single- and double-contrast barium enemas were performed in 139 patients with 234 polyps, and radiologic-endoscopic correlation was used to determine the percentage of polypoid neoplasms detected. The review indicated that a clean colon had been achieved in 97% of the 500 cases. In an additional 1.4% of patients, fecal residue was limited to small amounts in the cecum or ascending colon. In only two cases (0.4%) did fecal material prevent an examination that was suitable for detection of large polypoid or circumferential lesions. The single- and double-contrast barium enemas detected 80% and 91%, respectively, of polypoid lesions of all sizes. Single-contrast examinations detected 94% of polyps 10 mm or larger and 72% of polyps 5-9 mm. Double-contrast studies detected 96% of polyps 10 mm or larger and 88% of those 5-9 mm. The results of this study indicate that with this regimen, fecal residue does not significantly interfere with the detection of colonic polyps via barium enema examination.

Dimethylhydrazine-induced colon tumors in rats fed diets containing beef fat or corn oil with and without wheat bran

Male rats of the Sprague-Dawley strain were fed semisynthetic diets containing either 20% beef fat or corn oil with and without 20% wheat bran. Half of the animals received four weekly doses and the other half received eight weekly doses of dimethylhydrazine, 30 mg/kg, by intragastric intubation. The percentage of rats with tumors of the colon of all types was significantly higher in animals fed no bran than in those fed bran. Likewise, the percentage of rats with polypoid neoplasms of the colon was higher in rats fed no bran, but there was no significant difference in the percentage of rats with malignant tumors of the colon with respect to the feeding of bran. No significant differences were found between rats fed corn oil and those fed beef fat with respect to either the incidence or the kinds of colon tumors. Malignant tumors of the colon, causing death, occurred earlier in rats fed corn oil as compared to those fed beef fat. The percentage of rats with tumors of the colon and the numbers of tumors per tumor-bearing rat were significantly increased in rats given eight doses of dimethylhydrazine or compared to those given four.