Telomeric repeat factor 1 protein levels correlates with telomere length in colorectal cancer.

BACKGROUND: colorectal cancer is the third cancer cause of death in Spain. It is important to investigate new tumoral markers for early diagnosis, disease monitoring and prevention strategies. Telomeres protect the chromosome from degradation by nucleases and endto-end fusion. The progressive loss of the telomeric ends of chromosomes is an important mechanism in the timing of human cellular aging. Telomeric Repeat Factor 1 (TRF1) is a protein that binds at telomere ends. PURPOSE: to measure the concentrations of TRF1 and the relationships among telomere length, telomerase activity, and TRF1 levels in tumor and normal colorectal mucosa. METHOD: from normal and tumoral samples of 83 patients who underwent surgery for colorectal cancer we analyzed TRF1 protein concentration by Western Blot, telomerase activity, by the fluorescent-telomeric repeat amplification protocol assay and telomere length by Southern Blot. RESULTS: high levels of TRF1 were observed in 68.7% of tumor samples, while the majority of normal samples (59%) showed negative or weak TRF1 concentrations. Among the tumor samples, telomere length was significantly associated with TRF1 protein levels (p = 0.023). CONCLUSIONS: a relationship was found between telomere length and TRF1 abundance protein in tumor samples, which means that TRF1 is an important factor in the tumor progression and maybe a diagnostic factor.

Telomerase activity and telomere length in the colorectal polyp-carcinoma sequence.

OBJECTIVE: The role of telomerase activity and telomere length in the adenoma-carcinoma sequence of colon carcinogenesis has not been well established. The objective of this study was to determine telomerase activity and telomere length patterns in patients with adenomatous polyps either associated or not with colorectal cancer, as well as the role of telomeric instability in the adenoma-carcinoma sequence. PATIENTS AND METHODS: We included in the study 14 patients who underwent surgery for colorectal cancer and/or polyps. In 6 of these patients fresh samples of tumor tissue, polyps, and normal mucosa were obtained; in the 8 remaining cases, we collected only polyps and normal mucosa. We used the fluorescent-telomeric repeat amplification protocol assay (TRAP-F) to determine telomerase activity and telomere length using Southern-blot testing. RESULTS: Telomerase activity was detected in 86% of polyps and 50% of associated normal mucosa. Mean telomerase activity in polyp tissue was 5.85; in the normal mucosa it was 0.58 TPG. Mean telomere length was 6.78 Kbp and 7.78, respectively. Polyps in patients without synchronous cancer had a telomerase activity that was significantly higher (9.4) than in those with cancer (1.1). CONCLUSIONS: Telomerase activity increases in the colorectal adenoma-carcinoma sequence, concurrently with a decrease in telomere length. The presence of synchronous cancer modifies telomerase activity in polyps.

[Effect of ursodeoxycholic acid in an experimental colon cancer model]. / Efecto del ácido ursodeoxicólico en un modelo experimental de cáncer de colon.

AIMS: The present study was designed to examine the effect of ursodeoxycholic acid as chemoprotective agent in experimental colon carcinogenesis in rats. MATERIAL AND METHODS: One hundred and ten 10-week-old, Sprague-Dawley rats were divided into five groups: group A (20), no treatment. Group B (20), receiving daily both ursodeoxycholic acid (UDCA) 4 mg/kg of body weight and ethanol 1.23 g/kg of body weight added to the drinking water from the beginning of the study through 24 weeks. Group C (30), receiving 18 weekly doses of dimethylhydrazine (DMH) 21 mg/kg of body weight subcutaneously from the beginning of the study, with the same doses of UDCA and ethanol as in group B. Group D (20), ethylen-diamin-tetracetic acid solution alone for 18 weeks. Group E (20), receiving the same doses of ethanol plus DMH injections as in group C. All experimental animals were sacrificed after 25-27 weeks. RESULTS: No tumors developed in dimethylhydrazine-free groups. No significant differences in number of tumor-free animals, number of tumors per rat, and macro-microscopic tumor findings were seen between animals in group C and animals in group E. CONCLUSIONS: We concluded that such an ursodeoxycholic acid supplementation did not modify colorectal carcinogenesis using a dynamic DMH-induced model in rats.

Telomeres and telomerase in the clinical management of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Our aim is to describe the state of the art about the role of telomeres and telomerase in the clinical management of CRC and its potential utility as prognostic and diagnostic biomarkers and targets of new treatments. Telomere length could be a new diagnostic marker as an anomalous behavior is observed in peripheral blood cells when CRC patients and healthy people are compared. Moreover, telomeres and telomerase may be used as diagnostic markers considering that universal changes appear along the CRC process. Currently, new therapeutic cancer approaches are focused on inhibiting the maintenance of telomere length, choosing as targets telomerase -or its subunits- or the Shelterin complex. The goal of these therapies is the shortening of telomeres and the induction of cell senescence. Telomeres and telomerase emerge as useful molecular tools in the clinical management of CRC.

Effect of defunctionalization on colon carcinogenesis in the rat.

OBJECTIVE: to examine the effect of fecal absence on experimental colon carcinogenesis in both male and female rats. MATERIAL AND METHODS: a total of 138 10-week-old Sprague-Dawley, male and female rats were divided into five groups: A) 20 rats, no treatment; B) 26 rats, colonic defunctionalization; C) 30 rats, 18 weekly doses of dimethylhydrazine (DMH), 21 mg/kg body weight each, from the beginning of the study; D) 20 rats, ethylen-diamine-tetraacetic acid for 18 weeks; and E) 42 rats, same surgical procedure as rats in group B plus DMH injections at the same doses as rats in group C. Animals were sacrificed after 25-27 weeks. Number of tumors, their location, and pathological findings were all compared between groups. RESULTS: no tumors developed in the dimethylhydrazine-free groups. No differences were obtained either in number of tumors or tumors per rat for group C as compared to group E. Fecal absence was associated with smaller-sized tumors (p = 0.007), greater numbers of non-mucinous tumors (p = 0.00009), better differentiation (p = 0.0054), and lesser penetration into the wall (p = 0.015) for group E as compared to group C. In the dimethylhydrazine group, fecal absence altered the number of tumors developing in males as compared to female rats (p = 0.025). Moreover, this fecal absence showed no inhibitory effect on right colonic tumors (p = 0.0065). CONCLUSIONS: fecal absence alters the DMH-carcinogenic pattern in the defunctionalized colon when using an experimental model in both male and female rats.

Effect of ethanol consumption on colon cancer in an experimental model.

AIMS: The present study was designed to examine the effect of an ethanol supplement on experimental colon carcinogenesis. MATERIAL AND METHODS: One hundred and ten 10-week-old Sprague-Dawley rats were divided into five groups: group A (20 rats) received no treatment. Group B (20 rats) received a supplement of ethanol at 1.23 g/kg of body weight per day added to their drinking water for 24 weeks. Group C (30 rats) received 18 weekly doses of dimethylhydrazine (DMH) at 21 mg/kg of body weight from the beginning of the study. Group D (20 rats) received ethylen-diamin-tetracetic acid (EDTA) solution only for 18 weeks. Group E (20 rats) received ethanol at the same dose as group B plus DMH injections at the same dose as the rats in group C from the beginning of the study. All experimental animals were sacrificed after 25-27 weeks. RESULTS: No significant differences in the number of rats that developed tumors, number of tumor-free animals, and number of tumors per rat, as well as in macro-microscopic tumoral findings were observed for animals in group C compared to animals in group E. CONCLUSIONS: We concluded that the addition of an ethanol supplement does not modify colorectal carcinogenesis using a dynamic model of tumor induction with DMH.

Calcium inhibits colon carcinogenesis in an experimental model in the rat.

Different dietary factors can affect colorectal cancer incidence. However, the effect of increased levels of dietary calcium on neoplasms is unclear. The present study was designed to examine the effect of a low calcium supplement on experimental colon carcinogenesis induced by parenteral administration of dimethylhydrazine (DMH). One hundred and twenty 10-week-old Sprague-Dawley rats were divided into five groups of equal sex distribution. The 10 rats in group A (control group) received no treatment; the 30 rats in group B (DMH group) were injected subcutaneously with 18 weekly doses of 21 mg/kg DMH; the 20 rats in group C (EDTA control group) received EDTA solution only; the 30 rats in group D (calcium group) received calcium at 3.2 g/l by adding calcium lactate to the drinking water from the start until the conclusion of the experiment; and the 30 rats in group E (DMH + calcium group) received oral calcium supplements at the same dose as the rats in group D (calcium group) and the same DMH injections as the rats in group B (DMH group). The rats were sacrificed at 25-34 weeks. In group E, we observed a significant diminution in the number of tumours (P = 0.01); an increase in the number of tumour-free animals (P = 0.006); a change in tumour location towards the distal colon (P < 0.025); more adenomas (P = 0.02); and a diminution of adenocarcinomas and mucinous carcinomas, although this was not significant. We conclude that a low dietary calcium supplement in rats inhibits colon cancer carcinogenesis induced by DMH, and changes tumour location towards the distal colon.

[Biliary tract cancer following bilioenteric anastomosis]. / Cáncer de vía biliar después de anastomosis biliodigestivas.

Two cases of carcinoma of bile ducts after bilioenteric anastomosis are presented. The first one arose in the gallbladder eleven years after cholecystojejunostomy; the second, in the common bile duct three years after cholecystectomy and choledocoduodenostomy. The reflux into the bile duct and recurrent infections can be risk factors in tumor development. Although palliative resection was feasible in one case, the early tumor spread and the invasion of the enteric structure, resulted in a poor outcome in the second case.

Complications of colonic diverticular disease. Comparative study of two series.

OBJECTIVE: To compare the form of presentation and management of the disease in two surgical units covering geographically different populations. DESIGN: Observational retrospective study. PATIENTS AND METHOD: 203 cases from the 2nd Chair of Surgery of the Hospital Universitario de Clínicas de Asunción, Paraguay and 150 cases from the Hospital Universitario de Lleida, Spain. We analyzed the cause of admission, medical history, treatment and post-operative morbidity and mortality. RESULTS: Paraguay series: average age: 53 years (range 34-84) for men and 62 years (range 36-92) for women. Fifty-five per cent were hospitalized because of hemorrhagic complications and 45% because of acute diverticulitis. Medical treatment was provided in 109 cases and surgery in 110, 72 of which were emergencies and 38 elective procedures (p < 0.05). Morbidity was 31.8% (40.2% in emergencies and 16% in elective procedures, p < 0.05) and mortality was 15.5% (20.2% in emergencies and 2.6% in elective procedures, p < 0.003). LLEIDA SERIES: Average age: 65.5 years (range 38-85, p < 0.01) for men and 71.4 years (range 30-93, p < 0.01) for women. Eighty-six per cent were hospitalized because of acute diverticulitis and 10.7% because of acute hemorrhage (p < 0.001). Sixteen per cent have had previous attacks (p < 0.001). Medical treatment was provided to 111 patients and surgery to 39 (p < 0.001), 33 of which were emergencies and 6 elective procedures (p < 0.04). Morbidity was 41% and mortality 12.8% (5 cases), all of which were emergencies. The surgical technique was similar in both groups: resection with primary anastomosis in elective procedures and Hartmann's procedure in most emergencies, with a rate of immediate anastomosis of 33 and 21%, respectively. CONCLUSIONS: Factors related to nutrition and quality of life may influence the development of diverticular disease. Emergency surgery should be prevented. Surgeons must adapt their surgical approach to the socioeconomic and cultural medium of the population.

Repetitive mucosal trauma promotes colon cancer in experimental rat model.

OBJECTIVE: To investigate the effect of repetitive mucosal trauma, anastomosis and intestinal content on experimental colonic carcinogenesis as there is the possibility than non-specific colon lesions can promote cancer. MATERIAL AND METHOD: We performed to sixty female Sprague-Dawley rats a 4 cm colon loop defunctionalization with double colostomy (traumatic site). Intestinal continuity was restored with an end-to-end colo-colic silk anastomosis. The surviving 47 rats were divided in 3 groups: Group A: 27 rats treated with DMH. Group B: 10 rats treated with EDTA and Group C: Control of 10 rats. Animals were sacrificed 31-32 weeks after surgery for macro and micropathological studies. RESULTS: In group A appeared 60 tumours: 44 in the functional colon, 20 of them in the anastomotic site; 8 in the non traumatised defunctionalized segment and 18 in the traumatised segment (p < 0.05). CONCLUSIONS: a) Continuous microtraumas on colonic mucosa in rats are cancer promotional factors; b) silk suture in anastomosis promotes cancer.

Teaching through clinical cases: a good method to study bioethics. Experience at the Lleida Faculty of Medicine.

This paper summarises our experience in the teaching of bioethics during the final course in medicine at the Universitat de Lleida. Teaching has been based on the discussion of real clinical cases, the ethical implications of which have been extracted and presented by the professor, and analysed under his supervision. We present here the objectives, the programme and the course and evaluation methodology used, as well as the results of an inquiry carried out among the 55 students attending the course. The acceptance level was 92% and the attendance 95%. We believe the methodology used to be successful, since it makes possible the introduction of theoretical aspects of bioethics in order to solve actual cases, as well as encourage wide discussion. At the same time it emphasises that the students discover the values involved.

[A double aorto-enteric fistula secondary to an aortic pseudoaneurysm. Its anatomical correction]. / Doble fístula aorto-entérica secundaria a pseudoaneurisma aórtico. Corrección anatómica.

A very rare case of double fistula aorto-enteric jejunal and ileal, draining to an aortic pseudoaneurysm, is presented. There were not evidence of sepsis, and by this reason pseudoaneurysm and prosthesis were removed, a new prosthesis was inserted by reconstruction "in situ", and intestinal fistulas were closed. The short- and large-term postoperatory was satisfactory. A review about possible mechanisms implicated in a fistula, diagnosis and therapeutic alternatives was made.

[A spontaneous hematoma of the rectus abdominis sheath]. / Hematoma espontáneo de la vaina de los rectos.

The spontaneous hematoma of rectus abdominis sheath is a rare condition which usually presents as acute abdomen. We report our experience with 19 patients, most of them on treatment with oral anticoagulants. The most common symptoms were abdominal pain and palpable tumor. Twenty-six percent required blood transfusion. Echography and computerized tomography, were useful for diagnosis. Treatment was mainly conservative and was the mode of choice; surgery was left only for those patients who had hemodynamic changes or infection of the hematoma.

Appearance of ear tumors in Sprague-Dawley rats treated with 1,2-dimethylhydrazine when used as a model for colonic carcinogenesis.

One of the models of colon carcinogenesis in rats is produced by s.c. injections of 1,2-dimethylhydrazine (DMH). This specific colon carcinogen provokes other tumors in the rat, notably intestinal tumors. Ear tumors are just marginally mentioned in the literature. We have studied the appearance and histologic characteristics of ear tumors produced by 19 s.c. injections of 21 mg/kg of DMH in 18 Sprague-Dawley rats: 15 tumors appeared in 13 ears of 10 rats (55% of the animals). Simultaneously there were 23 colonic tumors: four (26.6%) of the tumors were carcinomas, 10 (66.6%) papillomas and one (6.6%) pseudoepitheliomatous hyperplasia. We conclude that ear tumors induced by DMH appear in 55% of the rats and that it is not possible to distinguish macroscopically in terms of size and aspect between benign and malignant lesions.