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PubMed1995

Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines.

PURPOSE: The purpose of this study was the evaluation of various factors in the formulation of guidelines for treatment of early invasive colorectal cancer, in which malignant cells extend through the muscularis mucosa into the submucosa but do not deeply invade the muscularis propria. METHOD: A total of 182 patients were followed for at least five years or until death, with early invasive cancer diagnosed between 1982 and 1989. Patients were grouped according to the level of invasion, as follows: 64 patients with slight carcinoma invasion of the muscularis mucosa (200-300 microns; sm1), 82 with intermediate invasion (sm2), and 36 with carcinoma invasion extending to the inner surface of the muscularis propria (sm3). RESULT: The configuration, diameter, and histologic grade of adenocarcinoma and lymphovascular invasion were correlated with level of invasion. After endoscopic polypectomy or local resection, 4 patients showed local recurrence and 13 patients showed lymph node metastasis. None of these 17 patients had sm1 disease. The level of invasion, configuration, and location were significant risk factors for development of lymph node metastasis or local recurrence (P < 0.05), but lymphovascular invasion, histologic grade, and diameter were not risk factors. CONCLUSIONS: Preoperative assessment of the level of invasion using this classification, in which the submucosa is divided into three depths, may decrease the incidence of unnecessary surgery for sessile polyps. Assessment according to the level of invasion is useful in the formulation of appropriate guidelines for the treatment of early invasive cancer.

Adenocarcinoma↗
PubMed2000

Laparoscopic colectomy compares favorably with colectomy by laparotomy for reduction of postoperative ileus.

PURPOSE: The aim of this study was to compare the length of postoperative ileus in patients undergoing colectomy by either laparotomy or laparoscopy. METHODS: A total of 166 patients were studied. These patients were divided into two groups: Group 1, in which colectomy was done laparoscopically, and Group 2, consisting of patients undergoing laparotomy. Both groups contained 83 patients who were matched for disease severity, indications for surgery, and procedure. Indications for surgery included sigmoid diverticulitis in 12 (14 percent) patients, polyps in 22 (27 percent), Crohn's disease in 21 (25 percent), colorectal cancer in 11 (13 percent), stoma reversal in 8 (10 percent), rectal prolapse in 3 (4 percent), and other indications in 6 (7 percent) in each group. Operations were colectomy with anastomosis (42 ileocolic, 26 colorectal, 6 colocolic, 4 ileorectal, and 2 ileal J pouch) or without anastomosis (3 abdominoperineal resections) performed by the same surgeons during the same time period January 1993 to October 1996). The nasogastric tube was removed from all patients immediately after surgery in both groups. All patients received a clear liquid diet on the first postoperative day, followed by a regular diet as tolerated. The nasogastric tube was reinserted if two or more episodes of emesis of more than 200 ml occurred in the absence of bowel movement. Patients were discharged from the hospital when tolerating a regular diet without evidence of ileus. Statistical analysis was performed using unpaired t-test and Fisher's exact probability test. RESULTS: The male-to-female ratio was 38 to 45 in both groups. A total of 10 (12 percent) and 23 (28 percent) patients in Group 1 and Group 2 had emesis (P = 0.02), and the rate of nasogastric tube reinsertion was 5 (6 percent) and 13 (16 percent), respectively (P > 0.05). There were significant differences between Groups 1 and 2 relative to the lengths of ileus (3.5 +/- 1.3 vs. 5.4 +/- 1.7 days, respectively; P < 0.001), hospitalization (6.6 +/- 3.3 vs. 8.1 +/- 2.5 days, respectively; P < 0.002), and operative time (170 +/- 60 vs. 114 +/- 46 minutes, respectively; P < 0.001). The morbidity rate was 16 (19.2 percent) and 18 (21.6 percent) in the laparoscopy and laparotomy groups, respectively. CONCLUSIONS: Although early oral intake is safe and can be tolerated by 84 percent of patients after colectomy by laparotomy, laparoscopic colectomy reduced the lengths of both postoperative ileus and hospitalization.

Anastomosis, Surgical↗
PubMed2006

Accuracy of high-resolution chromoendoscopy in prediction of histologic findings in diminutive lesions of the rectosigmoid.

BACKGROUND: The ability to differentiate adenomatous from nonadenomatous colonic polyps by using chromoendoscopy would obviate the need to remove hyperplastic lesions. The aim of this study was to define the accuracy of high-resolution chromoendoscopy for the determination of colonic polyp histology. METHODS: In 158 patients, 273 polyps (<5 mm) in the rectosigmoid were estimated for their histology. The endoscopists, in two steps, predicted the histopathology of each lesion on the basis of its surface characteristics by using high-resolution colonoscope without any staining and after indigo carmine dye according to the Kudo classification. RESULTS: The resected polyps included 48 adenomatous and 225 nonadenomatous polyps. When histologically confirmed hyperplastic polyps were compared with adenomatous polyps, the prediction of hyperplastic polyps based on endoscopic findings had a sensitivity of 93%, a specificity of 60%, and an overall accuracy of 81%. The corresponding sensitivity, specificity, and overall accuracy after indigo carmine dye were 94%, 64%, and 83%, respectively. CONCLUSIONS: The results suggest that the chromoendoscopy only marginally improves the determination between hyperplastic and adenomatous polyps when using high-resolution colonoscopes. The overall accuracy rate increased after dyeing, from 81% to 83%. The omission of histopathologic analysis cannot yet be achieved by chromoendoscopy.

Adenoma↗
PubMed2005

Performance characteristics and evaluation of an automated-developed and quantitative, immunochemical, fecal occult blood screening test.

OBJECTIVES: Guaiac fecal occult blood colorectal cancer (CRC) screening tests (FOBT) are faulted for low sensitivity and nonspecificity for human hemoglobin (Hb). Automated-developed, immunochemical, human Hb FOBT (I-FOBT) is specific, eliminates diet restrictions, and Hb quantification allows selection of a threshold for colonoscopy. Aims were to determine 1) test reproducibility; 2) test stability; 3) intrapatient daily I-FOBT variation; 4) test sensitivity and specificity for neoplasia in 500 symptomatic/high-risk patients undergoing colonoscopy; and 5) to correlate fecal Hb measurements with findings. METHODS: The desktop instrument OC-Sensor (Eiken, Japan) automatically develops and quantitates 50 tests/h for Hb. Patients prepared three tests, which were quantified and then 1) repeatedly re-examined; 2) stored at 4 degrees C or 20 degrees C or 28 degrees C and repeatedly examined; and 3) fecal Hb levels were correlated with colonoscopic findings. RESULTS: Five I-FOBTs re-examined five times in 1 day had no significant measurement changes. Thirty tests stored for 21 or more days had a decay/day of 0.3%+/- 0.4 at 4 degrees C (NS), 2.2%+/- 1.7 at 20 degrees C (NS), and 3.7%+/- 1.8 at 28 degrees C (p < 0.05). There were intrapatient variations between the three daily I-FOBTs (NS). At the recommended 100 ng Hb/mL threshold, all six cases of CRCs and 20 out of 28 cases of advanced adenomas were detected; evaluated together their sensitivity and specificity were 76.5% and 95.3%. CONCLUSIONS: Desktop, automated-developed, quantitative I-FOBT is now available. Refrigerated OC-Sensor samples are stable for 21 days, easy to prepare and develop and, at the 100 ng Hb/mL threshold, have high sensitivity, specificity, and negative predictive values for significant neoplasia. Suitability for population CRC screening awaits further evaluation.

Adenoma↗
PubMed2001

Genetic pathways in the evolution of morphologically distinct colorectal neoplasms.

Colorectal adenomas can be morphologically classified as exophytic or flat. Polypoid cancers and cancers arising de novo (ie., without any adenomatous component) might be the results of genetic progression from exophytic and flat adenomas, respectively. In this study, we examined 94 morphologically distinct neoplastic specimens for mutations in K-RAS and analyzed 10 microsatellite loci tightly linked to the tumor suppressor genes APC, p53, DCC/SMAD4, hMSH2, and hMLH1. K-RAS mutations were significantly associated with exophytic adenomas [11 of 21 (52%)] compared to flat adenomas [2 of 13(15%), P < 0.03] and polypoid cancers [17 of 25 (68%)] compared to cancers arising de novo [7 of 25 (28%), P < 0.01]. Two polypoid cancer cases demonstrated three and four different K-RAS mutations, respectively, suggesting multiple areas of clonal expansion. Cancers arising de novo were significantly associated with loss of heterozygosity (LOH) at chromosome 3p compared to pol ypoid cancers [6 of 18(33%) versus 1 of 20(5%), P < 0.03], whereas the prevalence of LOH at chromosomes 2p, 5q, 17p, and 18q and microsatellite instability were not different between the groups. For all cancers, LOH at chromosomes 17p and 18q occurred in 47 and 51%, respectively. However, LOH at 17p and 18q occurred in 0 and 16% of benign lesions, respectively, suggesting their role in malignant transformation. There was no difference in LOH at chromosomes 17p and 18q between exophytic and flat lesions. These findings suggest that (a) mutant K-RAS is associated with the exophytic growth of colonic neoplasms, and that (b) some colorectal cancers arising de novo lose chromosome 3p during their evolution, which is not seen in polypoid cancers. Half of all cancers lose chromosomes 17p and 18q at or near the malignant transition of benign lesions as reported previously, irrespective of morphology. There may be more than one genetic avenue for colorectal cancer formation, and this correlates with the morphological characteristics.

Adenoma↗
PubMed2001

Diagnostic yield of screening colonoscopies in lung transplant candidates.

BACKGROUND: Colonoscopy has been used to screen lung transplant candidates for colorectal diseases that would preclude transplantation. The diagnostic yield of this procedure is unknown. METHODS: This is a retrospective cohort study of patients 50 years of age and over who underwent lung transplant evaluations from 1996 to 1999. We assessed the prevalence and location of colonoscopic abnormalities, the predictive value of risk factors for colonic neoplasms, and the impact of colonoscopic findings on management. RESULTS: Thirty-one patients were evaluated. Twenty-four patients had at least one abnormal endoscopic finding. Six patients (19%) had adenomatous polyps; no carcinomas were detected. The 13 patients with risk factors were more likely to have adenomas (relative risk=2.8, P=0.2). The negative predictive value of risk factors for adenomas was 89%. One patient's management was altered and none were denied transplant listing because of the colonoscopic findings. CONCLUSIONS: Screening colonoscopy did not substantively alter the management of lung transplant candidates. More selective screening strategies may be warranted.

Adenoma↗
PubMed2000

Tissue transition projection (TTP) of the intestines.

Tissue transition projection (TTP) represents a three-dimensional reconstruction technique for volumetric image data sets. To demonstrate the principle characteristics of TTP, a simple phantom consisting of two pipes with a simulated, wall-adherent polyp was scanned with spiral CT, and images were reconstructed by means of volume rendering for both opaque surface reconstructions and TTP. Tissue transition projection was used in 7 patients for reconstruction of the small intestine or the colon. Unlike three-dimensional reconstructions with opaque surfaces, TTP enhances surface transitions while suppressing homogeneous areas, allowing delineation of the bowel wall similar to conventional double-contrast studies.

Adenocarcinoma↗
PubMed2000

Magnetic resonance colonography and virtual magnetic resonance colonoscopy with the 1.0-T system: a feasibility study.

RATIONALE AND OBJECTIVES: An ex vivo study and a clinical, prospective, patient study were undertaken to evaluate the feasibility of magnetic resonance (MR) colonography with a 1.0-T system. METHODS: An ex vivo colon model was scanned. A cleaned pig colon was prepared with six simulated sessile polyps (diameters of 4-12 mm) and one simulated pedunculated polyp (diameter of 5 mm). Subsequently, five patients (aged 39-81 years; four women, one man) were examined with MR colonography, immediately followed by endoscopic colonoscopy. After preparation for colonoscopy, the colon was filled with a Gd-DTPA/water solution (1:100). A breath-hold 3D gradient-echo sequence was acquired in both the prone and supine positions and after intravenous Gd-DTPA administration. Images were analyzed interactively by using multiplanar projections, maximum-intensity projection, and a virtual endoscopic view. The MR results were compared with the findings of the fiberoptic endoscopy. RESULTS: All seven simulated lesions of the colon model could be detected by MR imaging. In one patient, an advanced colon cancer as well as an additional small polyp was depicted. In the other four patients, single polyps with a diameter of 1 to 2.5 cm and a large adenoma were visualized by MR colonography. Contrast enhancement of the polyps was noted only after subtraction. CONCLUSIONS: The 1.0-T system is feasible for MR colonography. Reduced requirements for hardware could contribute to establish the novel technique as a screening method for colorectal polyps.

Adenoma↗
PubMed2005

Colonic adenocarcinoma and stones in an Indiana pouch.

We report on a 63-year-old woman with adenocarcinoma and stones in an Indiana pouch. Adenocarcinoma of an Indiana pouch is extremely rare. To our knowledge, only four cases with adenocarcinoma in an Indiana pouch have been reported.

Adenocarcinoma↗
PubMed2006

Simultaneous fluorescence imaging of protease expression and vascularity during murine colonoscopy for colonic lesion characterization.

BACKGROUND: Molecularly targeted fluorescent probes are currently being developed to improve the endoscopic detection of intestinal pathologic conditions. OBJECTIVE: We report on the development and testing of a novel multichannel microendoscope capable of quantitatively reporting such probes simultaneously at different wavelengths in real time. We assessed the feasibility of detecting and quantifying beacons that can be activated by protease and correlating imaging with disease state. DESIGN: The microendoscope consisted of a 20-gauge fiberoptic catheter and dichroic beam splitters that simultaneously display visible light, 700 nm and 800 nm near infrared (NIR) fluorescent light. NIR interchannel separation was tested on in vitro phantoms. Two mouse models were used (Apcmin(+/-) mice for colonic adenomas and CT26 murine colon cancer). A perfusion probe and one activated by protease at a separate wavelength were injected before endoscopic evaluation. RESULTS: The microendoscope fluorochrome detection limit was approximately 10 fmol; ratio imaging in the NIR was accurate (+/-8% of true probe concentration between 0.3 to 100 microg/ml of a protease sensor). Both colonic adenomas and adenocarcinomas were clearly visible in the NIR channel on protease probe administration in live mice. Ratio imaging of protease activity/perfusion increased from healthy colon to adenomas to adenocarcinomas. LIMITATIONS: Evaluation across additional spontaneous tumor models may provide more data on the translation of these findings. CONCLUSIONS: Our data show the feasibility of multichannel microendoscopic imaging of molecular targets in vivo and that ratio imaging may provide a novel means for characterizing colonic lesions. When scaled up clinically, this could aid in increasing lesion detection and quantitative assessment of distinct molecular markers.

Adenocarcinoma↗
PubMed1996

The polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics.

The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy: age 35 years of more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 years of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (> of = 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T(1)) and 4 (T(4)) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1), given that at least 10-15% of polyps may be missed at baseline. The final (T(4)) colonoscopies are expected to be completed in early 1998.

Adenoma↗
PubMed2002

Malignant colonic obstruction managed by endoscopic stent decompression followed by laparoscopic resections.

BACKGROUND: Acute left-side colonic obstruction is a surgical emergency whose management is controversial. Recently metallic expandable stents have been used to relieve obstruction either to palliate the condition or to prepare for an elective surgical resection. METHODS: We propose a new minimally invasive therapeutic strategy for the management of malignant colonic obstructions: emergency endoscopic stenting followed by elective laparoscopic one-stage resection. The first four cases are presented. RESULTS: The stents were positioned successfully in all cases, and all the patients had an immediate restoration of bowel functions. After a period that varied from 4 to 5 days, they underwent a one-stage laparoscopic resection and were discharged 5 to 7 days after the operation. There were no postoperative complications. CONCLUSIONS: Malignant colonic obstruction can be managed by a sequential minimally invasive endolaparoscopic approach with an excellent postoperative outcome, good patient comfort, and a short hospital stay without the need for diverting stomas. A study involving a larger number of patients is needed to determine whether this approach is superior to traditional open surgery in terms of morbidity, mortality, quality of life, and recurrences.

Acute Disease↗
PubMed2000

Colorectal cancer update. Prevention, screening, treatment, and surveillance for high-risk groups.

Great advances have been made in understanding the cause and molecular genesis of colorectal cancer. The disease can be prevented by a healthful diet and lifestyle or by resecting the precursor of most of these cancers, the advanced adenomatous polyp. Screening the average-risk population plus special surveillance for high-risk groups now is recommended by evidence-based guidelines. Surgery is highly curative for patients without distant metastases, and adjuvant therapy improves survival in selected patients with advanced cancers.

Adenomatous Polyps↗
PubMed1999

Colorectal adenomatous and hyperplastic polyps: smoking and N-acetyltransferase 2 polymorphisms.

Arylamine N-acetyltransferase 2 (NAT2) is involved in both the detoxification and bioactivation of carcinogenic arylamines and other mutagens. This enzyme is polymorphic, and the fast and slow phenotypes are thought to be risk factors for colon and bladder cancer, respectively. Here, we report on a case-control study of adenomatous and hyperplastic polyps, with particular attention to tobacco smoking, a known risk factor for adenomas, and polymorphisms of NAT2. All participants underwent complete colonoscopy and were subsequently divided into case and control groups on the basis of pathology. Cases were diagnosed with confirmed adenomas (n = 527) or hyperplastic polyps (n = 200); controls (n = 633) had no history of colonic neoplasia and no polyps at colonoscopy. NAT2 genotype was determined using an oligonucleotide ligation assay and fast, intermediate, or slow phenotype imputed. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals were computed using logistic regression adjusting for age, sex, nonsteroidal anti-inflammatory drug use, and hormone replacement therapy use. Smoking was associated with an increased risk of adenomas [current versus never smoking OR = 2.0 (95% confidence interval, 1.4-2.9)] and hyperplastic polyps [current versus never smoking OR = 4.1 (2.6-6.5)]. NAT2 status among adenomatous polyp patients and hyperplastic polyp patients, respectively, showed ORs of 1.1 (0.8-1.4) and 1.2 (0.8-1.6; intermediate versus slow) and 1.1 (0.6-1.9) and 0.9 (0.4-1.9; fast versus slow). There were no differences in risk when adenoma patients were stratified on multiplicity, size, or histopathological subtype of polyps. Never-smokers showed no variation in risk across acetylator status for either species of polyp, whereas current smokers showed ORs of 2.0 (1.2-3.2) and 2.3 (1.4-3.9) for adenomas and 3.9 (2.1-7.1) and 4.9 (2.6-9.4) for hyperplastic polyps for slow and intermediate/fast NAT2, respectively, compared with slow-NAT2 never-smokers. Risks of both multiple [OR = 4.3 (2.1-8.8)] and large [OR = 3.8 (1.9-7.5)] adenomas were somewhat elevated in current smokers with an intermediate/fast phenotype compared with smokers with a slow NAT2 phenotype, but the interaction was not statistically significant. Risk of hyperplastic polyps and adenomatous polyps is strongly related to smoking. There is little suggestion of interaction between NAT2 status and smoking and no relationship with NAT2 genotype alone.

Adenomatous Polyps↗
PubMed1994

[Expression and significance of oncoprotein p53, rasp21 and p185 in carcinomas and polyps of the large intestine].

Seventy eight cases of carcinoma and 14 cases of poly of large intestine were examined to observe the expression of p53, rasp21 and p185 oncoproteins with immunogold silver staining method. The positive expressions for p53, rasp21 and p185 were 53.9%, 46.2% and 51.3% respectively. But only poorly positive expression was found in large intestine polyps for p185 staining. The difference between the carcinomas and polyps for p185 staining was significant (P < 0.01). The normal mucoepithelium near the cancer region expressed positive staining for p53, rasp21 and p185 were 0%, 2.6% and 5.1% respectively. These results were also significantly different when compared to cancer tissue (P < 0.01). In addition, of these 78 cases, 33 cases (42.3%) gave coordinately positive expression for p53 and rasp21 oncoprotein; p53 positive expression was obviously stronger in poorly differentiated carcinoma and mucoadenocarcinoma than in highly and moderately differentiated adenocarcinoma (P < 0.01).

Adenocarcinoma↗
PubMed2006

Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer.

Identification of biomarkers could lead to the development of effective screening tests for colorectal cancer. A previous study from our laboratory showed specific alterations of nuclear structure in colon cancer. In an effort to characterize these biomarkers, protein spots were selected from separations made by two-dimensional gel electrophoresis, which were analyzed by mass spectrometry. The sequences obtained from the isolated spots revealed that they have close similarity to creatine kinase B (CKB) isoforms, heterogeneous nuclear ribonucleoprotein F (hnRNP F) and high mobility group box 1 protein (HMGB1) isoforms. To determine the expression of these proteins in colon cancer, expression was studied in 9 tumor and matched adjacent normal pairs, 5 donor colons, 16 polyps, 4 metastatic liver lesions and matched adjacent normal pairs, and 3 liver donors. CKB and hnRNP F were expressed in 78% and 89% of colon tumors, respectively. hnRNP F had a higher frequency of expression than CKB in premalignant polyps. With the establishment of differential expression of the proteins in colon cancer, their subcellular localization was analyzed. The subcellular fractions studied both showed high protein levels of hnRNP F in colon tumors compared with normal colon tissues. Surprisingly, subcellular levels of CKB were decreased in colon tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon tumorigenesis. These results suggest an involvement of hnRNP F and CKB in colorectal cancer. Additionally, they suggest that hnRNP F is a potential marker for colorectal cancer progression.

Adenocarcinoma↗