Endoscopic diagnosis and treatment of early colorectal cancer

Colorectal adenomas and early cancers are grossly classified into three groups: protruded, flush or slightly elevated (so-called flat adenomas), and depressed. Protruded lesions and flat adenomas are not invasive until they are rather large, whereas depressed lesions can invade the submucosa even when very small. It is not difficult to detect protruded and flat adenomas, but depressed carcinomas are often overlooked. Keys to the detection of depressed carcinomas are a slight color change, bleeding spots, interruptions of the capillary network pattern, slight deformation of the colonic wall, shape change of the lesion with insufflation and deflation of air, and interruption of the innominate grooves by the lesion. Spraying of indigo carmine dye helps to clarify the lesions. Pit pattern analysis with magnifying colonoscopy is useful for diagnosis of early colorectal cancer. Pit pattern analysis and histologic examination suggest that depressed carcinomas probably have arisen de novo, without going through an adenomatous step. Some adenomas appear at first to have a depression, but such cancer-mimicking adenomas with pseudodepression must be distinguished from depressed carcinomas because they are quite different in nature. Protruded and flat adenomas can usually be removed with polypectomy or hot biopsy techniques. Depressed carcinomas are treated with an endoscopic mucosal resection (EMR) technique; but when they massively invade the submucosa, surgical resection is indicated. Some neoplastic lesions, which we call laterally spreading tumors, extensively and circumferentially spread along the colonic wall, although they are short in height. They tend to have a rather benign nature despite their large size; therefore EMR or a piecemeal EMR method is indicated.     

Colorectal cancer: future population screening for early colorectal cancer

Colorectal cancer (CRC) is one of the most frequent cancers in Western countries. The identification of individuals at risk and the early diagnosis of CRC are of critical importance since a large proportion can be prevented or cured by surgical removal before metastasis has occurred. With increasing understanding of the genetic basis of hereditary and sporadic (non-hereditary) CRC, it becomes feasible to detect genetic alterations by molecular techniques. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), as well as early stages of spontaneous CRC, can be diagnosed by molecular characterisation of the adenomatous polyposis coli (APC) gene, the RAS oncogene and other genes in DNA from peripheral blood, stool or intestinal biopsies. With a better understanding of the genetic events leading to malignant transformation, molecular population screening should allow us to identify individuals at risk as well as patients with an early and potentially curable CRC. At present, careful patient and family history, physical examination and testing for occult blood as well as colonoscopy are still the key elements for clinical patient management. Molecular diagnosis will hopefully soon complement these analyses and should result in a reduction of morbidity and mortality from CRC.     

Diagnostic cytology for detection of early cancer

Cytologic methods for detection of early cancers of the uterine cervix, lung and various other organs are discussed. The scraping smear method using a spatula is more effective than the cotton swab or vaginal pool smear method for detection of preinvasive intraepithelial lesions, such as, carcinoma in situ and dysplasias of various degrees of the uterine cervix. The use of sputum specimens pooled for three to five days is recommended for cytologic examination in population screening of lung cancer. Good cytopreparatory techniques, suitable screening and cytodiagnostic classifications of malignancy are also described and emphasized, especially, the importance of properly fixed cytologic material for correct cytopathological diagnosis.     

Microsatellite instability in early onset and familial colorectal cancer

Hereditary non-polyposis colorectal cancer syndrome (HNPCC) is often considered to be the most common form of inherited colorectal cancer, although its precise incidence is unknown. The clinical diagnosis of HNPCC relies on a combination of family history and young age of onset of colorectal cancer, but as many familial aggregations of colorectal cancer do not fulfil the strict diagnostic criteria, HNPCC might be underdiagnosed. The majority of HNPCC families have germline mutations in mismatch repair (MMR) genes, such as MSH2 or MLH1, so that HNPCC cancers characteristically exhibit DNA replication errors (RERs) at microsatellite loci. Although an RER positive phenotype in tumours can also result from somatic mutations in an MMR gene, the prevalence of RER + tumours should provide a maximum estimate of the incidence of germline MMR gene mutations in patients with early onset and familial colorectal cancer. We investigated colorectal cancers for RERs from (1) a population based study of 33 patients with colorectal cancer aged 45 years or less, (2) 65 kindreds with familial colorectal cancer which only partially fulfilled the criteria for the diagnosis of HNPCC, and (3) 18 cancers from 12 HNPCC kindreds. Seven of 33 patients (21%) with colorectal cancer aged 45 years or less had an RER + cancer, with only two of these having a clear family history of HNPCC. A greater proportion of RER + tumours (5/7) occurred proximal to the splenic flexure than RER - tumours (4/26; chi2 = 6.14, p < 0.025). RERs were detected in all 18 cancers from HNPCC patients but in only six of 65 non-HNPCC familial colorectal cancer kindreds (9%; chi2 = 52.2, p < 0.0005). These findings suggest that most cancers in patients diagnosed at 45 years of age or less and familial aggregations of colorectal cancer which do not fulfil HNPCC diagnostic criteria do not have germline mutations in MSH2 and MLH1. Hence population screening for germline mutations in these genes is unlikely to be an efficient strategy for identifying people at high risk of developing colorectal cancer.     

The efficacy of PSA density for the early detection of prostate cancer

OBJECTIVE: We studied on the efficacy of prostate specific antigen density (PSAD) for the detection of prostate cancer among patients with intermediate serum PSA levels. MATERIALS AND METHODS: Transrectal ultrasonography (TRUS) and transrectal prostate biopsy were performed in 103 patients whose PSA levels were 10 ng/ml or less despite positive digital rectal examination(DRE) or whose PSA levels were intermediate (4 to 10 ng/ml). Prostate volume was determined by TRUS and PSAD was calculated (serum PSA divided by volume of entire prostate volume). The rate of positive biopsy was compared with PSAD (more than 0.15 versus less than 0.15), DRE (positive versus negative) and patient's age (more than 61 versus 60 or less). RESULTS: The overall cancer detection rate was 43.7% in this study. There was no apparent correlation between patient's age and cancer detection rate when the patient's age was more than 61. DRE itself was not effective for the detection of prostate cancer in the patients whose PSA level was 10 ng/ml or less. Independent of DRE findings, the rate of positive biopsy was double in the patients whose PSAD was more than 0.15, compared with the patients whose PSAD was less than 0.15. CONCLUSIONS: For the early detection of prostate cancer, PSA density may be useful in the selection of patients for transrectal prostate biopsy.     

The genetics of colorectal cancer

This article reviews the genetic alterations that are thought to play a role in the development of sporadic and hereditary forms of colorectal cancer. It also highlights their potential utility in clinical practice, especially in the field of presymptomatic diagnostic testing for hereditary forms of colorectal cancer.     

Correlates of colorectal cancer screening compliance and stage of adoption among siblings of individuals with early onset colorectal cancer.

Concepts from the health belief, transtheoretical, and dual process models were used to examine how siblings of individuals diagnosed with colorectal cancer (CRC) before age 56 made decisions about CRC screening. Siblings (N=504) were assessed for CRC screening practices and intentions, pros, cons, processes-of-change, perceived risk of CRC, perceived severity of CRC, preventability of CRC, cancer-related distress, and sibling relationship closeness. Physician and family recommendation and knowledge were also assessed. Fifty-seven percent of participants (n=287) were compliant with CRC screening. Logistic regression indicated that perceived pros and cons, perceived risk, commitment to screening, health care avoidance, and sibling closeness were associated with screening compliance. Physician and family recommendation were also strong correlates. A similar set of factors was associated with stage of adoption of CRC screening. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensitivity of immunochemical occult blood testing in detecting early colorectal cancer

Sensitivity of immunochemical occult blood testing (IFOBT) for early colorectal cancer (CRC) calculated in known cases is reported to be around 50-60%. Sensitivities of IFOBT for cancer in the preclinical stage were reported based on findings of colonoscopy performed on all screenees. Of 5715 asymptomatic persons who underwent flexible sigmoidoscopy (FS), 13 cases of early cancer were found, within the reach of FS. Sensitivities were 53.8%, 76.9 and 84.6% for one-day test, two-day test and three-day test of IFOBT by immunochemical hemagglutination, respectively. While corresponding figure was only 15.4% for three-day Hemoccult test. Other reports indicated that sensitivity of IFOBT is around 30% for small lesions of early CRC less than 1 cm in diameter. IFOBT is much more sensitive in detecting early CRC than Hemoccult test but is poorly sensitive for tiny early CRC.     

Diagnosis of cancer and early detection. Clinical methods

The etiology of cancer--as one of the most important causes of death--remains unknown. Therapy seems promising only in its early stages and if the exact diagnosis of carcinoma is possible. Diagnostic procedures today have gained a high standard demonstrated on malignancies of the gastrointestinal tract and the lung. The whole spectrum of methods can be employed only after having selected the patients according to "high risk" groups and methods of early cancer detection respectively. Effective and pragmatic progress has been made but is not fully utilized yet. Future trends in the diagnostic development are discussed.     

Clinical outcome of surgical treatment for invasive early colorectal cancer in Japan

BACKGROUND/AIMS: Despite the high frequency of early colorectal cancer, little is known about the clinicopathologic features of invasive early colorectal cancer for which endoscopic polypectomy is not indicated. We wanted to determine the clinicopathologic features of these early colorectal cancers. MATERIALS AND METHODS: From 1973 to 1994, a total of 728 patients with colorectal cancer were reviewed retrospectively from hospital records. The clinicopathologic features of the 90 invasive early colorectal cancer patients who underwent major surgeries were compared with those of 626 patients with advanced colorectal cancer. RESULTS: The frequency of early colorectal cancer increased significantly from the periods 1973-1979 to 1990-1994: 0% in the former period and 18.3% in the later period. Minimally invasive surgery was chosen more frequently for the treatment of early colorectal cancers than for the treatment of advanced cancers (p < 0.005). Lymph node metastasis, lymph vessel invasion, and vascular invasion were more prevalent in advanced cancer cases than in early cancer cases (p < 0.005). Lymph node metastasis was found in 7 patients with early colorectal cancer (7.8%). There was no difference in histologic type between the early and advanced colorectal cancers. The 5-year survival rates of early colorectal cancer patients were higher than those of advanced cancer patients: 97.5% in early colon cancer patients; 93.5% in early rectal cancer patients; 59.8% in advanced colon cancer patients; 55.4% in advanced rectal cancer patients. Three early colorectal cancer patients died of recurrence. CONCLUSION: Minimally invasive surgery such as laparoscopic colectomy should be performed on patients with invasive early colorectal cancer when it is impossible for the cancer to be removed by endoscopic polypectomy.     

Validation of the galactose oxidase-Schiff's reagent sequence for early detection and prognosis in human colorectal adenocarcinoma

Based on the multistage and multifocal nature of colorectal carcinogenesis, it is likely that reduction of cancer mortality through early detection and identification of new prognostic markers is an attainable goal. Well-documented changes occur in mucin glycoconjugates during neoplastic progression in the colon, and the nonneoplastic colonic mucosa in colon cancer patients is morphologically and histochemically abnormal. In this retrospective study, 152 archival colorectal tissues from 49 patients were studied for changes in mucin secretions as detected by the galactose oxidase-Schiff's (GOS) sequence. Intensity of the stain was evaluated in histological sections by semiquantitative analysis, and the area percentage of epithelium stained was quantified by image cytometry. The correlation between gender or tumor size, location and reactivity with peanut agglutinin and quantitative expression of GOS-reactive mucins was determined as well as intratumor and inter individual variability. Reactivity with GOS: (a) decreased during neoplastic progression and malignant conversion in the neoplasm; (b) increased in the normal colonic mucosa of patients with progressively more advanced disease; and (c) was of prognostic significance for patient survival or recurrence both in the normal colon of cancer patients and in invasive neoplasms. These data are consistent with the conclusion that GOS reactivity in the normal colonic mucosa is a dosimeter of exposure to environmental/lifestyle colorectal carcinogens rather than a marker for an oncodevelopmental cancer-associated antigen.     

Molecular biology of colorectal cancer and clinical consequences for colorectal cancer syndromes

Because of the accomplishments in biotechnical research in the past few decades our knowledge about the molecular mechanisms of carcinogenesis has grown rapidly. Colorectal cancer has been one of the most intensively investigated tumor entities, and it seems to be well established that colorectal tumor growth is associated with an accumulation of acquired somatic mutational events in tumor suppressor genes and oncogenes. Recent progress in our understanding of the molecular basis of the most prevalent colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis and therapy. Identification and characterization of the causative genes for these colorectal cancer syndromes have enabled precise presymptomatic detection of mutations in individuals who bear an a priori risk of about 50% of developing colorectal cancer. Genotype-phenotype correlations might further increase the clinical management of hereditary colorectal cancer. Even though developments in cancer research are restricted to the minority of individuals with hereditary cancer syndromes, growing knowledge about the effect of low penetrance variations in tumor suppressor genes may affect the diagnosis and therapy of sporadic colorectal cancer.     

The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99mTc-HMDP. The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformans were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, gamma-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases.     

Programs of early detection of breast cancer and access of mammography in Spain

BACKGROUND: We studied availability to mammography among Spanish women aged 40 to 70 years, variation in use of the mammography by autonomous community, and the situation and importance of breast cancer screening programs among other factors, in the access to mammography. SUBJECTS AND METHODS: A cross-sectional population survey was conducted in 1994 in a sample of 3,218 women. A questionnaire was used to collect data on the variable access (receipt of at least one mammogram in the last 2 years) as well as different access-related variables. Information on breast cancer screening programs was collected by contacting the responsible institutions. We considered that a program had total coverage if it included all the municipalities in the province and partial if it did not include all municipalities. RESULTS: Twenty-eight percent of women had performed a mammogram. This proportion varied among autonomous communities (AACC) from 11.5 to 73.8%. Breast cancer screening programs existed in 8 AACC. The multivariant analysis revealed an association between access to mammography and the existence of a screening program, especially when the later had total coverage (OR = 7.64; 95% CI = 5.24-11.10). An association was also found between access to mammography and physician-related factors, place of residence and attitudes of women toward mammography. CONCLUSIONS: Less than one third of women aged 40-70 have performed a mammography in the last 2 years, and this proportion varies among AACC. Gynecologist visits and the existence of breast cancer screening programs are fundamental factors in the access to mammography in Spain.     

The impact of molecular diagnosis on familial colorectal cancer

Two cases of mesothelial/monocytic incidental cardiac excrescences in a 66-year-old female and an 80-year-old male are presented. Lesions had solid and tubular pattern formations which were composed of two predominant cell types of histiocytoid cells and cuboidal cells arranged in strips. The histiocytoid cells were round and had well-defined nuclei with prominent nuclear grooves. They had a low nuclear to cytoplasmic ratio. There were no atypical mitoses. Immunohistochemically, these cells were positive for leukocyte common antigen (LCA) and CD68 (KP-1) but negative for keratin. The cuboidal cells were present in strips, had haphazardly arranged surface microvilli and had small round non-cleaved nuclei. These cells were positive for keratin but negative for LCA, CD68, p53, proliferative cell nuclear antigen, alpha-smooth muscle actin, Factor VIII, epithelial membranous antigen and vimentin. These lesions are probably reactive because of their heterogeneous components; an expected feature for an essentially artifactual lesion that is related to cardiac surgery and invasive catheterization. Immunohistochemical studies are useful for avoiding misdiagnosis of neoplasms.