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DNA adduct formation by 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in rat colon.

A food-born carcinogen, 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) induces cancer in the rat colon. The mechanism for colonic DNA adduct formation leading to cancer by IQ was studied using a colostomized F344 rat model. In this model, the transverse colon of the rat was colostomized, which produced a fecal stream-positive proximal colon and a negative distal colon were produced. When IQ (50 mg/kg) was administered into the distal colon of the colostomized rats (n = 5), the ratio of the DNA adduct level of the distal colonic mucosa to the paired muscular layer 24 hr after dosage was 2.02, whereas that was 1.51 and 1.37 when IQ was administered into the stomach (n = 6) and the vein (n = 5), respectively. This suggested that luminal exposure of IQ induced DNA adduct formation. Since IQ (an amine form) has no reactivity toward DNA, these findings suggested that IQ was immediately activated in the absorbed mucosal cells and reacted with DNA. However, most of the IQ absorbed was metabolically activated in the liver, distributed by blood circulation, and formed DNA adducts in the colonic mucosa and muscular layer.

Animals↗

[Total esophagectomy and colon transplantation in treatment of upper neck esophageal carcinoma. Report of 16 cases].

Sixteen patients with carcinoma of the upper neck esophagus were treated by total esophagectomy and replacement with transverse colon in this hospital from 1982 to 1989. The operative morbidity rate was 18.7% and no death occurred. There were 8 patients with lesion longer than 5 cm, 3 less than 3 cm, and 5 between 3 cm and 5 cm. The length between the tumor and the proximal margin of resection was less than 2 cm in 5 patients, between 2 and 4 cm in 8, and more than 4 cm in 3. No residual tumor was found pathologically at stumps. Follow-up study showed that 5 patients survived more than 5 years, 5 patients 3 to 5 years, 6 patients less than 3 years. The maneuver and advantages of the operation were introduced and the problems concerning the prevention of operative complication were investigated.

Aged↗

Obstructing left-sided colon carcinoma. Appraisal of surgical options.

This study is a retrospective analysis over a 10-year period of 37 patients who presented with a large bowel obstruction secondary to a left-sided colon cancer. Our patients were confined to those with clinical evidence of acute obstruction with lesions located from the mid-transverse colon to the rectum. Thirty-eight per cent of these lesions occurred at the sigmoid level. We found 70 per cent of these lesions were treated with resection at their initial operation. Eighty-one per cent of all lesions were classified as Duke's C or D. There was a 33 per cent 5-year survival. These patients were evaluated for their initial surgical therapy and subsequent mortality and morbidity.

Adult↗

Minute lesions of the rectum and sigmoid colon in patients with Crohn's disease.

Sigmoidoscopy with a spray of 0.1% indigocarmine was performed on 20 patients with Crohn's disease whose main lesions were located proximal to the transverse colon and on 10 age-matched healthy volunteers. Minute lesions such as apthoid lesions, areas of erythema, and small ulcers were found in 90% of patients with Crohn's disease and in 0% of healthy volunteers (p less than 0.001). Among the minute lesions, aphthoid lesions were found in the highest incidence (85%). It was difficult to determine the presence of aphthoid lesions without the spray of indigocarmine, which facilitated detection. Histologically, granulomas were found in 15% of patients with Crohn's disease. Aphthoid lesions were not associated with superficial erosions and lymphoid follicles. The presence of aphthoid lesions in the rectum and sigmoid colon would be a strong indication of the presence of Crohn's disease.

Adolescent↗

Phlebosclerosis of the colon with positive anti-centromere antibody.

A 56-year-old woman with symptoms of chronic bowel disease presented a peculiar calcification of the mesenteric vein of the ascending to transverse colon on barium enema study. The resected colon was hard and black. Histo-pathologic examinations demonstrated fibrous change of the colon with a calcified and hyaline-deposited mesenteric vein. No cell infiltration was observed. These findings were compatible with phlebosclerosis and also with systemic sclerosis. Positive anti-centromere antibody and Raynaud's phenomenon, hallmarks of a variant systemic sclerosis, the CREST syndrome were observed. We therefore speculated that the pathogenesis of the phlebosclerosis of the colon is related to the CREST syndrome.

Autoantibodies↗

[Arterial supply in the left colonic flexure].

The authors study the behaviour of the middle colic, left colic superior, middle and inferior and the first sigmoidal arteries in the territory of the terminal portion of the transverse colon, the left colonic flexure and the descending colon. The study was carried out on 1200 angiographies of the superior and inferior mesenteric aa. and on 150 anatomical specimens, surgically extirpated in the course of left emicolectomy operations. Contrary to what is believed by most authors, the left flexure is a colonic tract very well supplied by blood while the descending colon results to be poorly supplied, being served only by one artery (the left sup. colic a.) often of limited caliber and with branches (the middle and the inf. left colic aa.) sometimes totally or partially lacking. In this last colonic tract the vascular continuity, represented by the arterial arcades, is often interrupted. The Riolan's arcade, variously shaped, is to be considered a constant vascular structure (only once it was lacking in this study). Sometimes it is doubled by a second more internal arcade which must not be confused with the intermesenteric arcade. In four of the observed cases, the Riolan's arcade resulted strengthened by a second retroperitoneal arcade, derived from a branching of the middle colic a., whose branches of division went to the two colonic flexures and descended along the postero-lateral walls of the ascending and descending colon, often parallel to the regular abdominal branches. Exceptionally the colonic flexure is supplied by the only left colic a., which behaves as a specific artery, by us called "dominant artery". The central branches of the artery go to the flexure while the lateral ones join the branches of the middle colic and the first sigmoidal aa., effecting tenuous connections, surgically unreliable. In this case the arterial continuity of the Riolan's arcade can be considered interrupted, at least for the surgical practice. The intermesenteric arcade, in its three forms (direct, mixed and indirect), was observed in 20% of the cases. The colic marginal a. is considered by the authors a tier of arches formed by the colic aa. The left colonic flexure is also supplied by particular vessels originated from the middle colic and the left colic aa. (angular branches and arcades and bridge-branches) or from the superior mesenteric a. (angular artery of Donati) and from other sources, particularly from the splenic a. These vessels then join the colic "vasa recta" through the phrenocolic ligament and the marginal omental vessels. This research shows that the vascular continuity of the left colon is not a constant element, able to reassure the surgeon, for possible interruptions that may occur in its composition.

Colon↗

[Myelodysplastic syndrome (RAEB-T) occurring after adjuvant chemotherapy for colon and rectum cancers].

A 67-year-old man was admitted to our hospital because of bleeding tendency and high fever. The patient had a past history of gastrectomy and transverse colectomy for cancer of transverse colon at age 57, and rectum resection for rectum cancer at age 59. After these operations, Tegafur 645 g, MMC 56 mg, and Ara-C 560 mg were administered for about 6 years. Hematological examinations revealed hemoglobin of 7.7 g/dl, white cell count of 9,500/microliters with 8% myeloblasts, and platelet count of 7,000/microliters. A diagnosis of myelodysplastic syndrome (RAEB-T) was made from the finding of bone marrow smear, which showed 28% myeloblasts, and neutrophils and megakaryocytes with morphologically abnormal nuclei and cytoplasms. Chromosomal banding study of the bone marrow cells revealed -5, -8, 7q- in all analyzed cells. These findings suggest that the preceding adjuvant chemotherapy is probably related to the occurrence of myelodysplastic syndrome.

Aged↗

Placement of a colonic stent by percutaneous colostomy in a case of malignant stenosis.

We present a patient with disseminated stomach cancer who presented with symptoms of acute obstruction of the splenic flexure of the colon caused by tumor spread. During a first attempt to insert a colon stent through the anus under endoscopic guidance as final palliative therapy, it was not possible to reach the region of the stricture, and iatrogenic perforation of the descending colon occurred, which resolved favorably under conservative management. A second attempt to insert a stent was made via percutaneous puncture of the transverse colon, approaching the region of the stricture by a descending route. The procedure was completed without complications and the patient's symptoms improved. Stent placement via percutaneous puncture of the colon has not previously been described in the literature. It may be an alternate route in cases of proximal strictures in which access through the anus has been unsuccessful even with the aid of endoscopic guidance.

Colonic Diseases↗

Brain CCKA receptors mediate the colonic motor response to feeding in dogs.

The influence of central vs. peripheral administration of specific type A and type B CCK receptor antagonists (L364,718 and L365,260, respectively) on colonic motor hyperactivity induced by feeding and CCK8 was investigated in dogs with strain-gauge transducers implanted on the proximal and transverse colon. Intravenous injection of L364,718 (5 and 10 micrograms/kg) reduced by 26.2% and 80.1%, respectively, the 0-4-h postprandial increase in colonic motor index; at similar doses L365,260 had no effect. Intracerebroventricular administration of L364,718, at a dose (1 microgram/kg) not active by the IV route, significantly reduced (p less than 0.01) by 67.5% the feeding-induced colonic hyperactivity. In contrast, L365,260 (1-10 micrograms/kg ICV) injected was inactive. Increase in colonic motility produced by intravenous CCK8 infusion (1 microgram/kg/h) was suppressed by previous ICV and IV administration of L364,718 at doses of 1 and 10 micrograms/kg, respectively, while L365,260 was inactive at similar doses. It is concluded that CCK8 released after a meal is responsible for the postprandial increase in colonic motility and that these effects may be mediated through activation of central CCKA receptors.

Animals↗

Neutron activation-based gamma scintigraphy in pharmacoscintigraphic evaluation of an Egalet constant-release drug delivery system.

This paper is a report from a pharmacoscintigraphic study with an Egalet constant-release system containing caffeine and natural abundance samarium oxide. First the formulation was tested in vitro to clarify integrity during irradiation in the nuclear reactor. Then six healthy male volunteers were enrolled into the in vivo study. The in vitro release of caffeine obeyed all the time linear zero-order kinetics. The in vivo release of radioactive Sm2O3 consisted of three consequent linear phases with different slopes. The release rate was fastest while the product was in the small intestine and slowest when the product was in the descending colon. In terms of the bioavailability of caffeine, the most important factor seemed to be the residence time in the ascending and transverse colon. A long residence time in these sections led to high AUC values for caffeine.

Adult↗

Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.

AIMS: The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. METHODS: Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. RESULTS: (153)Sm-labelled tablets reached the ascending colon after a mean +/- SD 9.8 +/- 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C(max) values from 1429 +/- 1014 to 1040 +/- 601 pg mL(-1) (P = 0.028) and AUC values from 14 814 +/- 11 254 to 13 486 +/- 9369 pg h(-1) mL(-1) (P = 0.008). Mean residence time and t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. CONCLUSIONS: MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

Absorption↗

Intestinal carcinomas in two tamarins (Saguinus fuscicollis, Saguinus oedipus) of the German Primate Centre.

Two colonic mucoid adenocarcinomas in tamarins from the German Primate Centre are reported. A mucinous mucoid adenocarcinoma occurred in the ascending and the transversal colon of a Saguinus oedipus male more than 8 years old, with metastases in the regional lymph nodes and the pancreas. The tumour corresponded to colon cancer in cotton-topped tamarins of other colonies. The second tumour, a well differentiated tubular mucoid adenocarcinoma, developed at the ileocaecal valve of a 14 1/2 year old Saguinus fusciollis male with metastases to the local lymphatic system.

Adenocarcinoma, Mucinous↗

Universal primary colonic repair in the firearm era.

All patients with colonic trauma treated at King Edward VIII Hospital, Durban, from August 1993 to May 1994 underwent primary repair of the colonic wound. They were evaluated prospectively to assess the mode of injury and outcome variables. Colonic injuries were sustained by 102 patients. These were inflicted by gunshots (62), stabs (22), shotguns (14), and blunt trauma (4). The transverse colon was injured most frequently (53). All shotgun injuries were multiple. Average time from admission to theatre was similar for shocked and non-shocked patients. Eighty-seven patients had simple closure (18 deaths) and 15 required resection and anastomosis (eight deaths). Ten patients died in the first 48 h, and 16 died subsequently owing to multiple-organ systems dysfunction. The mortality rates were stabs 9% (2), gunshots 27% (17), shotguns 50% (7), and 0% for blunt trauma. Septic morbidity was seen in 16 but was not related to breakdown of the colonic repair. Implementation of strategies to reduce preoperative time delays and use damage control principles for the management of massive trauma should be evaluated as methods of reducing mortality.

Adolescent↗

Ogilvie's syndrome (acute colonic pseudo-obstruction): review of the literature and report of 6 additional cases.

PURPOSE: Ogilvie's syndrome is defined as an acute pseudo-obstruction of the colon, characterized by the signs, symptoms and radiological pattern of a large-bowel obstruction, but without a detectable organic cause. The aetiology of Ogilvie's syndrome appears to be multifactorial, with a series of possibly interacting pathogenic noxae all resulting in colon inactivity. Our study reports on six cases of Ogilvie's syndrome diagnosed and treated between 1997 and 2002. MATERIALS AND METHODS: From October 1997 to September 2002 we studied six patients affected by pseudo-obstruction of the colon. The pseudo-obstruction was recurrent in two cases. Acute dilatation of the colon without radiologically-detectable organic obstruction was the inclusion criterion for the study. RESULTS: Plain abdominal radiography revealed colon dilatation that extended to the splenic flexure in three patients, to the hepatic flexure in two patients, and confined to the transverse colon in one patient. None of the patients showed air-fluid levels of the small intestine. CONCLUSIONS: The most relevant clinical finding in Ogilvie's syndrome is abdominal distension, which arises suddenly, has a progressive course and reaches massive levels. The first-line diagnostic investigation is plain abdominal radiography which shows extreme colon dilation without air-fluid levels of the small intestine. In three of our patients, conservative therapy alone was able to restore normal conditions within five days; two patients required decompressive colonoscopy, and one patient died from cardio-circulatory arrest after 48 hours.

Adult↗

[The role of segmental transit time in the large intestine in the diagnosis of severe constipation].

Segmental small and large bowel transit time of 25 healthy volunteers have been studied, as a control group, by means of radio-opaque markers prepared and administered according to an original method. The same study has been subsequently carried out on 37 patients suffering for chronic non organic constipation. The resulting data, though poorly homogeneous, may however, be plotted in 8 classes; each class groups subjects presenting very similar segmental transit time whose changes are less than 4 hours. The first class gathers the 8.1% of the cases, presenting in increased small bowel transit time; the patients of the second class (5.4%) has resulted affected by "right colon constipation syndrome"; another 5.4% of patients, plotted in the third class have shown a permanence time of the markers in the transverse colon of about 190 hours, while the 10.8% fourth class and the 16.2% fifth class have presented a 97 and 150 hours' one respectively. The patients of the sixth class (21.6%) have shown long lasting permanence of markers in the left colon and in the rectum. The 13.5% of cases, gathered in seventh class, has shown an increased transit time through the whole colon, while at last the eight class (19.0% of patients) has resulted affected by dischezia. The described method has thus revealed useful in the study of bowel segmental transit time from a topographic diagnostic point of view.

Adolescent↗

[Primary lymphomas of the large intestine].

Primary colorectal lymphomas are rare tumors that comprise 0.5 to 2% of large bowel malignancies and 10 to 20% of gastrointestinal lymphomas. Between 1982-1993 ten patients were treated in the Colorectal Unit of the "Hospital das Clínicas" of the University of São Paulo, representing 2% of the neoplasms in this period. Age varied from 22 to 76 years, with median around 50 years, and male/female ratio 8:2. Weight loss, right iliac palpable mass and bowel habit alterations were the most common symptoms. Definitive diagnostic was only set with histological evaluation of the surgical specimen in all colon tumors. Four patients had advanced disease classified as stages III or IV. The tumors were located in ileocecal region (7 cases), transverse colon (1 case), sigmoid colon (1 case) and rectum (1 case). Colon lymphomas were treated by radical surgical resection and chemotherapy; the patient with rectal lymphoma received radiotherapy and chemotherapy because of local tumor spread. Histological data showed 6 large cell lymphomas and 4 small cleaved cells lymphomas. Lymphnodal involvement and tumor size were the main prognostic factors in the series: 80% of the patients in advanced stage (III or IV) and 66% of those with tumors larger than 10 cm died during the first year of the follow-up.

Adult↗

Intraoperative photoplethysmographic diagnosis of ischemic colitis.

Intraoperative evaluation of ischemic colitis presents several problems related to diagnosis, severity, and extension. The aim of this study was to determine the usefulness of photopletysmography (PPG) to detect colonic arterial wave amplitude changes in patients operated on for ischemic colitis, comparing the affected area with a control area on the transverse colon. Four patients were studied, two with gangrenous colitis, and two with protracted "transient" ischemic colitis. All four patients survived. PPG is a useful method for intraoperative diagnosis and surgical assessment of ischemic colitis.

Aged↗

Endoscopic resection of a large colonic leiomyoma.

A 48-year old man suffered from intermittent hematochezia and abdominal cramping over a period of four weeks. A colonoscopy revealed a 4.5 cm semi-pedunculated tumor in the transverse colon. Using a 2-channel colonoscope, the tumor was successfully removed with an electro-surgical snare after normal saline submucosal injection. Microscopic examination revealed it to be a smooth muscle tumor without mitosis. The patient recovered well, and did not have a residual tumor in a follow-up colonoscopy. We found no reports of a colonic leiomyoma larger than 3 cm which was completely removed by a colonoscope. According to the case presented here, intraluminal colonic leiomyoma can be completely resected with skillful manipulation of a colonoscope, even if the tumor is as large as 4.5 cm. Successful endoscopic polypectomy of colonic leiomyoma reduces the cost of treatment and eliminates unnecessary surgery.

Colonic Neoplasms↗