Diagnosis and management of colonic and rectal polyps.
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Colon↗
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Fecal levels of short-chain fatty acids and bile acids as determinants of colonic mucosal cell proliferation in humans.
We studied the correlation between fecal levels of short-chain fatty acids (SCFA), bile acids (BA), and colonic mucosal proliferation in humans on a free diet. Subjects [n = 43: 27 men and 16 women; 61 +/- 7 and 59 +/- 6 (SE) yr old, respectively] were outpatients who previously underwent resection of at least two sporadic colon polyps. Mucosal proliferation was determined by [3H]thymidine incorporation in vitro in three colorectal biopsies obtained without cathartics and was expressed as labeling index (LI). BA were analyzed in feces by mass spectrometry and SCFA by gas chromatography. We found that increasing levels of BA in feces did not correlate with higher LI. On the contrary, higher levels of SCFA were significantly associated with lower LI in the colonic mucosa (P for trend = 0.02). In conclusion, in humans on a free diet, intestinal proliferation seems to be regulated by the levels of SCFA in feces and not by BA. Because a lower intestinal proliferation is associated with a decreased colon cancer risk, treatments or diets that increase colonic levels of SCFA might be beneficial for colonic mucosa.
Aged↗
Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells.
Colorectal cancer is the second leading cause of cancer death in the United States. Nonsteroidal anti-inflammatory drugs including sulindac are promising chemopreventive agents for colorectal cancer. Sulindac and selective cyclooxygenase (COX)-2 inhibitors cause regression of colonic polyps in familial polyposis patients. Sulindac induces apoptotic cell death in cancer cells in vitro and in vivo. In tumor cells, activation of extracellular-regulated kinase (ERK) 1/2 results in phosphorylation of several ERK1/2 effectors, including the proapoptotic protein Bad. Phosphorylation of Ser112 by ERK1/2 inactivates Bad and protects the tumor cell from apoptosis. Sulindac metabolites and other nonsteroidal anti-inflammatory drugs selectively inhibit ERK1/2 phosphorylation in human colon cancer cells. In this study we show that epidermal growth factor (EGF) strongly induces phosphorylation of ERK1/2 and Bad in HT29 colon cancer cells. EGF-stimulated phosphorylation of ERK and Bad is blocked by pretreatment with U0126, a selective MAP kinase kinase (MKK)1/2 inhibitor. Similarly, pretreatment with sulindac sulfide blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels. The ability of sulindac to block ERK1/2 signaling by the EGF receptor may account for at least part of its potent growth-inhibitory effects against cancer cells.
Antineoplastic Agents↗
Cronkhite-canada syndrome associated with gastric cancer: report of a case.
A 71-year-old man with characteristic clinical and pathological pictures of Cronkhite-Canada syndrome associated with gastric cancer is presented. Histological examinations of gastric and colonic polyps which resembled juvenile type revealed no malignant cells. The patient slowly recovered after subtotal gastrectomy and elemental diet supplement with antiplasmin agents. As for as is known to the authors, a total of 69 cases with this syndrome were reported in Japan including our patient. Of these cases 8 had cancer of the gastrointestinal tract. Two of them, including our case, had gastric cancer. Another one was associated with gastric cancer but not intestinal polyposis. The remaining 5 cases were associated with colonic cancer. Caution must be paid to the fact that cachexia or malabsorption in some patients with this syndrome results from gastrointestinal malignancy. The prognosis of this syndrome consisted of 20 deaths including 2 postoperative deaths, 33 of improvement including 4 of natural remission and 4 of remission after gastrectomy or colectomy, 7 unchanged and the remainder not described.
Adenocarcinoma↗
Epidemiology of polyps in the rectum and colon. Recovery and evaluation of unresected polyps 2 years after detection.
In an endoscopic population screening study for colorectal polyps among 200 men and 200 women, 50-59 years of age, 215 polyps less than 5 mm in diameter were left in situ for the present 2-year follow-up examination. The attendance rate was 102 of 106 (96%) for polyp patients and 77 of 90 (86%) in the control group. Of 194 polyps, 143 (74%) in the 102 polyp-bearing individuals were recovered for histological evaluation and 57 polyps were registered as new. Ninety-nine (50%) of the polyps were hyperplastic, 45 (23%) were adenomas, and 45 (23%) were mucosal tags. Both growth and regression of polyps were registered. Regression was commoner in the distal part of the rectum than in the proximal part or distal sigmoid colon. Growth was similar for recovered adenomas and hyperplastic polyps, whereas mucosal tags more often showed diminution in size. No polyp had reached a size of more than 5 mm in 2 years, and no case of severe dysplasia or carcinoma was registered. The estimated total polyp mass more than doubled both for adenomas and hyperplastic polyps. It is concluded that the time interval between initial examination with removal of polyps 5 mm or larger in diameter and the first follow-up examination may safely be set at 2 years.
Colonic Polyps↗
Increased incidence of neoplasia in females with acromegaly.
OBJECTIVE: Some studies have indicated an increased incidence of neoplasia, particularly breast and colon, in acromegaly. We have determined the incidence of benign and malignant neoplasms in an Australian population of patients with acromegaly. DESIGN: Retrospective review, with comparison against cancer data for the local population obtained from a State Cancer Registry. PATIENTS: Fifty patients with documented acromegaly. RESULTS: There were 7 cases of malignancy (2 in men, 5 in women) in the period of follow-up (435 patient years). With logistic regression analysis, there was a relative risk of malignancy, of 1.2 (95% confidence interval 0.31-5.0) for men (P = 0.8) and 4.3 (95% confidence interval 1.7-10.5) for women (P = 0.001), when compared to the local population. There were 2 cases of breast and renal carcinoma, and one each of prostatic, colonic and parotid carcinoma. Of the most common benign tumours 35% of patients had thyroid nodules, 10% had colonic polyps and 6% had nasal polyps. CONCLUSION: The incidence of malignancy was found to be increased in female patients with acromegaly in this series. Routine screening procedures for malignancy, particularly in female patients, should therefore be considered.
Acromegaly↗
Hepatocellular carcinoma in children associated with Gardner syndrome or familial adenomatous polyposis.
PURPOSE: Gardner syndrome, a variant of familial adenomatous polyposis, is characterized by colonic polyps that undergo malignant change and benign and malignant extracolonic lesions. Tumors frequently associated with Gardner syndrome include carcinoma of the ampulla of Vater, papillary carcinoma of the thyroid, and, in children, hepatoblastoma. The childhood malignancies often precede the appearance of other manifestations by several years. PATIENTS AND METHODS: Two patients are described. Gardner syndrome was diagnosed in a 15-year-old girl with fibrolamellar hepatocellular carcinoma after desmoid tumors and colonic polyposis developed. Classic hepatocellular carcinoma was also diagnosed in a 9 1/2-year-old boy with familial adenomatous polyposis. RESULTS: In patient 1, the diagnosis of fibrolamellar hepatocellular carcinoma preceded the diagnosis of Gardner syndrome by almost 2 years. The diagnosis was confirmed by identifying a germline mutation of the adenomatous polyposis coli (APC) gene. This is the first patient reported with fibrolamellar hepatocellular carcinoma associated with Gardner syndrome. Patient 2 had a strong family history of familial adenomatous polyposis but no manifestations of Gardner syndrome. He was not tested for the APC mutation. The current literature and previously reported cases of hepatocellular carcinoma in patients with Gardner syndrome or familial adenomatous polyposis are reviewed. CONCLUSIONS: Because hepatocellular carcinoma is uncommon in the pediatric and adolescent population, it is important to consider the possibility of Gardner syndrome or familial adenomatous polyposis in these patients.
Adenomatous Polyposis Coli↗
Rectal bleeding in infancy: clinical, allergological, and microbiological examination.
OBJECTIVE: Rectal bleeding is an alarming symptom and requires additional investigation. In infants it has been explained mainly by hypersensitivity. In addition to dietary antigens, intraluminal microbial agents challenge the immature gut mucosa. Although controlled in the mature gut, these antigens may induce inflammation in the developing gastrointestinal tract. The objectives of this study were to evaluate prospectively the clinical course of rectal bleeding and evaluate the impact of cow's milk allergy and aberrant gut microbiota on the condition. Because withdrawal of cow's milk antigens from the infants' diet is used as a first treatment without evidence of its efficacy, we also aimed to asses the effect of a cow's milk-elimination diet on the duration of rectal bleeding. METHODS: The study involved 40 consecutive infants (mean age: 2.7 months) with visible rectal bleeding during a 2-year period at the Tampere University Hospital Department of Pediatrics. Most of the infants (68%) were fully breastfed. At enrollment the infants were randomly allocated to receive a cow's milk-elimination diet (n = 19) or continue their previous diet (n = 21) for 1 month. Findings of colonoscopy, fecal bacterial culture, fluorescence in situ hybridization of selected gut genera, specific detection of fecal enteroviruses, rotaviruses, and adenoviruses, fecal electron microscopy for viruses, and mucosal electron microscopy for viruses were assessed. During each visit the severity of atopic eczema, if any, was assessed according to the SCORAD method. In evaluating the extent of sensitization, serum total immunoglobulin E (IgE) and specific IgE and skin-prick tests for cow's milk, egg, and wheat were studied. Cow's milk allergy was diagnosed by elimination and provocation testing. Five patients were hospitalized; all others were treated on an outpatient basis. The follow-up visits were scheduled 1 month later and at the age of 1 year. Sixty-four healthy reference infants were selected as controls according to the following criteria: age and timing of fecal sampling being identical to within 1 month. RESULTS: Altogether, 32 (80%) infants manifested bloody stools during follow-up (mean [range]: 2.1 [1-15] per day). The mean number of days with rectal bleeding on follow-up was 6. Typically, bloody stools occurred irregularly, for which reason the mean time to the last occurrence of rectal bleeding was 24 (range: 1-85) days from admission. Atopic eczema at presentation or during follow-up was diagnosed in 38% of the infants. Increased specific IgE concentrations or a positive skin-prick test were uncommon. The growth of the infants was normal on admission and during follow-up. Colonoscopy revealed typically focal mucosal erythema and aphthous ulcerations. The mucosa appeared normal in less than half of the patients. No anorectal fissures or colonic polyps were found. Light microscopy revealed that the overall architecture of the mucosa was well maintained. Acute inflammation or postinflammatory state and focal infiltration of eosinophils in the lamina propria were the most common abnormalities. A cow's milk-elimination diet did not affect the duration of rectal bleeding. Cow's milk allergy was diagnosed in 7 (18%) patients. Virus-particle aggregates were found in the microvillus layer of the colon epithelium in 8 cases. The surface epithelium of the virus-positive colon biopsy specimens regularly showed degenerative changes in the microvillus layer and epithelial cells. Electron microscopy study of the colon biopsies disclosed virus particles (30 nm in diameter) on the surface of epithelial cells. Virus particles or RNA were present in feces in only a minority of the patients. All fecal cultures were negative for Salmonella, Shigella, and Yersinia. Campylobacter jejuni was found in the feces of 1 patient, and fecal cultures were positive for Clostridium difficile in 4 patients, Staphylococcus aureus in 8 patients, and yeast in 2 patients. Fluorescence in situ hybridization revealed that at the time of admission the total numbers of bacteria and the numbers of bifidobacteria and lactobacilli in feces were lower in the patients compared with controls. The fecal concentrations of microbes characterized in this study (Bacteroides, bifidobacteria, Clostridium, lactobacilli, and enterococci) did not differ significantly between the time of admission and the second visit in the patients or controls. At the age of 1 year, 7 patients still suffered from cow's milk allergy, 5 of whom also suffered from multiple food allergies. Atopic eczema and histopathologically confirmed inflammation of the colonic mucosa at presentation were associated with persistence of cow's milk allergy at the age of 1 year. No patients exhibited gastrointestinal complaints or visible blood in stools. CONCLUSIONS: Rectal bleeding in infants is generally a benign and self-limiting disorder. Bloody stools occurred irregularly for only a few days during the following months. As in a previous report, most infants were exclusively breastfed. In the majority of the patients the cause of the condition remains unknown. An association with viruses can be seen in some patients. The microbes that commonly lead to bloody diarrhea in older children and adults, Salmonella, Shigella, and Yersinia, were absent in the present material. The low bifidobacterial numbers in fecal samples may indicate a significant aberrance that may provide a target for probiotic intervention to normalize gut microbiota. The gut microbiota overall seemed stable, because the numbers of major groups of microbiota tested did not change significantly between the time of admission and after 1 month. Cow's milk allergy among these patients is more uncommon than previously believed. Cow's milk challenge is thus essential in infants who become symptom-free during a cow's milk-free diet to reduce the number of false-positive cow's milk-allergy diagnoses.
Animals↗
[Colonic adenomatous necrotic polyps and subacute bacterial endocarditis].
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Colonic Polyps↗
[Hereditary solitary polyps (adenoma) of the colon].
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Adenomatous Polyps↗
Epidermoid cysts, polyposis coli and Gardner's syndrome.
One hundred and ninety-six members of 15 families with Gardner's syndrome were investigated to determine the type of skin cyst that is part of this syndrome. These were shown to be epidermoid cysts and not pilar cysts or steatocystoma multiplex. They were solitary or multiple and seldom large and disfiguring. The skin cysts often occurred before the intestinal polyps were detectable. The presence of epidermoid cysts in children should be an indication for sigmoidoscopy when the child reaches the age of 14 years, and at 3-yearly intervals thereafter up to the age of 30 years, whether or not there is a family history of polyposis coli. At present it is not possible to say if Gardner's syndrome is the same as, or different from, familial polyposis. Until all patients with colonic polyps have a full clinical examination, looking for skin cysts and osteomas, X-rays of the skull and long bones to detect osteomas and dental X-rays for abnormalities of the teeth this question will remain unanswered.
Adolescent↗
Synchronous adenocarcinoma of the transverse colon, the gallbladder and the vermiform appendix.
According to the literature synchronous adenocarcinomas of both, the colon and the gallbladder or the colon and the appendix are extremely unusual. To our knowledge the simultaneous occurrence of all three tumors has never been published before. Preoperative diagnosis of early stage tumors of the gallbladder and the vermiform appendix is also made very seldom. The following case report records an instance of synchronous adenocarcinomas of the gallbladder, the transverse colon, in a colonic polyp and the appendix. Owing to the patient's advanced age simultane cancer occurrence may be mere coincidence. Nevertheless, this extremely rare entity could also be ascribed to a genetic defect or an unknown carcinogenic agent.
Adenocarcinoma↗
Pinealoblastoma in a patient with familial adenomatous polyposis: variant of Turcot syndrome type 2? Report of a case and review of the literature.
We report a case of a 23-year-old Turcot female patient who was first diagnosed as having a pinealoblastoma. Thyroid papillary carcinoma was diagnosed a few months later, and multiple colonic polyps were detected three years after that. A genetic workup revealed an APC gene mutation in her family. Long-term survival (i.e., >5 years) of pinealoblastoma is considered to be 20 percent. A review of 25 documented Turcot cases determined that the average age at death is 20.3 years, raising the difficult question of whether she should undergo restorative proctocolectomy. Restorative proctocolectomy may itself cause major morbidity but is currently the only way to prevent colon cancer.
Adenomatous Polyposis Coli↗
COX-2 inhibition and colorectal cancer.
Mortality in patients with advanced colorectal cancer(CRC) remains high. Epidemiologic studies show that individuals taking nonselective, nonsteroidal anti-inflammatory drugs, including aspirin, have a significant reduction in CRC mortality, compared with those not taking these agents. The recent characterization of cyclooxygenase- I and -2 (COX- I and COX-2) isoforms has led to an expanded understanding of how nonsteroidal anti-inflammatory drugs may help prevent polyp formation. Cyclooxygenase enzymes are required for the conversion of arachidonic acid to prostaglandins.COX-2 mediates the inflammatory effects of COX activity, is induced by a wide spectrum of growth factors and proinflammatory cytokines, and is overexpressed in numerous premalignant and malignant lesions, including CRC. Treatment with the selective COX-2 inhibitor celecoxib has shown promising results in the prevention of CRC, Numerous studies show that this COX-2 selective inhibitor is a potent suppressor of colon polyps both in animal models for familial adenomatous polyposis and in patients with this condition. This has led to the US Food and Drug Administration approval of celecoxib for the treatment of patients with familial adenomatous polyposis. The role of celecoxib in cancer treatment is still evolving. Recent studies have identified a potential benefit for adding celecoxib to standard CRC chemotherapy regimens to increase their efficacy and reduce their associated toxicity.
Adenomatous Polyposis Coli↗
Turcot syndrome in an elderly adult.
A 67-year-old woman presented with hematochezia and an episode of transient expressive dysphasia. She was found to have multiple colonic polyps with adenocarcinomatous changes. Computed tomography brain scan and computed tomography-guided biopsy revealed a left frontoparietal glioblastoma multiforme. This case illustrates the rare presentation of Turcot syndrome-a hereditary colorectal polyposis syndrome-in an older adult.
Adenomatous Polyposis Coli↗
Enhanced secretion of prostaglandin E2 by tissue-fixed macrophages in colonic carcinoma.
Prostaglandin E2 (PGE2) secretion by peripheral blood and tissue-fixed macrophages from patients with colorectal carcinoma was assessed. There was no significant difference between PGE2 production by peripheral blood mononuclear cells between patients with colorectal carcinoma and normal controls. However, secretion of PGE2 by tissue-fixed macrophages from within the colorectal carcinomata in response to opsonised zymosan was significantly higher than in the uninvolved colonic tissue. PGE2 production by tissue-fixed macrophages from within colonic polyps was found to be normal. These results could not be explained on the basis of increased availability of substrate arachidonic acid since addition of excess arachidonic acid resulted in similar findings. The enhanced production of PGE2 correlated with Dukes staging but not the level of differentiation. The production of PGE2 from epithelial cells in response to ionophore A23187 was not significantly enhanced. Leukotriene B4 secretion by intestinal macrophages in response to opsonised zymosan was not significantly elevated in the colonic tumour tissue. Modulation of levels of prostaglandin production within colonic tumours may play a role in the rate of growth and vascularity of these tumours and in the regulation of the local immune response to malignancy.
Calcimycin↗
K-ras gene mutation related to histological atypias in human colorectal adenomas.
To investigate the relationship of oncogene analysis to morphology, we analyzed K-ras gene mutations by dot-blot hybridization with and without consideration of histological atypias in individual colorectal adenomas. Each of 54 colon polyps were divided into two parts after fixation. One part was used as a mass to assess point mutations; the remaining portion of each polyp was paraffin-embedded, stained with hematoxylin and eosin, and examined for point mutations related to histological atypias. In the first part of our study, K-ras gene mutations at codon 12 were detected in 13 cases (24%). In the second part of our study, 12 cases had distinctly different histological atypias. From each of these 12 cases, two areas, one with higher or one with lower grade atypia in the same polyp were excised to analyze for K-ras gene mutation. Two of these 12 cases (17%) had the mutation in different areas of the same tumor. These two cases contained the mutation only in the areas with higher grade atypia, and only one case added information regarding ras mutation upon microdissection when compared to the entire biopsy. These results suggest that oligonucleotide hybridization can identify the majority of cases containing ras mutations despite regional morphologic variation. Individual cases, however, may contain clonal subpopulations within adenomas with different ras sequences from other regions within the same adenoma.
Adenoma↗
[Peutz-Jeghers syndrome: variability of gastrointestinal expression at pediatric age].
Peutz-Jeghers syndrome is a rare autosomal dominant condition, characterized by gastrointestinal polyposis, mucocutaneous pigmentation and high risk of neoplasia in multiple organs. At pediatric age, major clinical impact is related to complications associated to intestinal polyps, but neoplasic risk isn't negligible. Though clinical surveillance is recommended since the age of 10 years, relevant lesions may occur before that age. Conventional radiology and endoscopy have recognized limitations at this age group, and new diagnostic and intervention tools, such as video-capsule and per-operative enteroscopy, are not yet widely used. We present 5 pediatric cases (age under 10 years) with diversity of gastrointestinal expression (including one case with histologic evidence of dysplasia in a large colonic polyp), emphasizing the need of specific guidelines concerning young children.
Child↗