[A role for calcium and vitamin D3 in the prevention of colo-rectal tumors].
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Biomedical subjects
Publications and source records attributed to P Lointier.
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Alveolar echinococcosis is a parasitic disease which is relatively rare in humans. It almost exclusively affects patients of rural origin living in enzootic regions (Eastern France, Auvergne) and most lesions are in the liver. Several anatomico-clinical forms have been described; the most frequent is the multilocular form, but the disease may consist of one single cyst or abscess. The liver structure is always deeply altered, with compression, inflammation or superinfection. Jaundice, liver enlargement, abdominal pain or signs of secondary localizations are manifestations that lead to the discovery of hepatic alveolar echinococcosis. The anatomical features of the lesions are demonstrated by ultrasounds and computerized tomography. The main differential diagnosis is tumoral pathology of the liver. In most cases the diagnosis of echinococcosis is confirmed by serological tests, although needle or even surgical biopsy might be necessary. Diagnosed at an early stage, alveolar echinococcosis can be amenable to surgical treatment (hepatectomy), and liver transplantation may even be performed. Medical treatment with benzimidazoles seems to be promising.
Epidemiological and experimental data suggest that dietary calcium and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) are protective against colorectal cancers, while their activity on colon mucosa still remains unknown. Since the presence of receptors is required for steroid action, specific 1,25-(OH)2D3 receptors were investigated in biopsies taken at different levels of the digestive tract from the oesophagus to the rectum and in pancreas. The total study involved biopsies from 152 patients. In 82% of the cases they were paired biopsies in adenocarcinoma tissue and in adjacent normal mucosa (NM). There were 120 operated on for colorectal adenocarcinoma (HCRA). 1,25-(OH)2D3 receptor was assayed in tissue extract by the dextran-coated charcoal (DCC) technique and also characterised by sucrose density gradient centrifugation. Scatchard analyses showed a single class of specific high affinity-low capacity sites binding for 1,25-(OH)2D3 with a Kd = 1.48 +/- 0.8 x 10(-10) M (n = 119). The sedimentation coefficient of the steroid receptor complex was approximately 3.2 S. The incidence of 1,25-(OH)2D3 receptors was significantly higher in NM (82.5%) than in HCRA (34.5%). In HCRA this incidence decreased from right colon (64.7%) to left colon (27.7%) and rectum (15%). All positive HCRA in left colon and rectum (16/76) were histologically well differentiated. The receptor content in NM and HCRA was in the same range: (median) 10-314 (58) and 13-175 (64) fmol/mg protein. These data suggest that 1,25-(OH)2D3 may modulate calcium transport in colon, as in the intestine. Also, loss of receptivity to 1,25-(OH)2D3 is observed as associated with malignant transformation of the human colorectal mucosa.
We have studied and compared the 1,25-dihydroxyvitamin D3 receptor (RD3) content of 154 human digestive carcinoma with the normal mucosa one, removed at distance from the same surgical specimen. The distribution of biopsies is as follows: 5 oesophagus, 10 stomach, 6 small bowel, 35 right colon, 47 left colon, 40 rectum and 11 pancreas. RD3 were measured by the Dextran Coated Charcoal method and characterized by sucrose gradient ultracentrifugation. One single class of high affinity binding sites (kD = 1.5 +/- 0.7 x 10(-10) M) was defined, with a sedimentation coefficient of approximately 3.4 S. The RD3 was present in the 6 samples of small bowel and in 82% of whole normal mucosa, whatever their localization along the digestive tract and pancreas, while in the tumoral tissue, the RD3 was positive in only 32% of the cases. In these tumor specimens the incidence decreases from 64% in the right colon to 27% in the left colon and only 15% in the rectum (P less than 0.001). RD3 rates vary slightly with the localization and are of the same level in normal tissues and in tumors: 10-314 (median = 59) vs 13-175 (median = 64) (P greater than 0.005) respectively. No significative variations relating to age or sex of patients were found. However, all RD3 positive tumors from left colon and rectum were well differentiated histologically. These results show that the normal colonic mucosa is a potential target for 1,25-dihydroxyvitamin D3, which can play a role in the metabolism of calcium and other ions. They also suggest that vitamin D3 could be a modulator of colorectal cell growth and differentiation and its receptor is frequently lost during malignant transformation.
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The authors report a case of retroperitoneal perforation of a duodenal ulcer. This is a rare condition which is exceptionally responsible for abscess formation. If often has a poor prognosis. In the present case, the abscess was infrahepatic. The diagnosis of the origin of the abscess was established by radiological opacification via percutaneous puncture. Surgical drainage and irrigation performed via an extraperitoneal approach centered over the cavity, combined with triple-agent antibiotic therapy (penicillin, gentamicin, metronidazole) ensured collapse followed by sterilisation of the abscess cavity. The ulcer was cured by medical treatment. This case differs from the published case in terms of the diagnostic procedures classically used (upper gastrointestinal endoscopy and small bowel series), the infrahepatic site of the abscess and the extraperitoneal surgical treatment which avoided dissemination to the peritoneal cavity.
In a 63-year old woman, a surgically removed leiomyoma of the inferior vena cava recurred, 4 years later, as a leiomyosarcoma. These two smooth muscle tumours, one benign the other malignant, seldom involve the inferior vena cava. Both produce few clinical symptoms and therefore are belatedly diagnosed, except for suprarenal or retrohepatic lesions which rapidly exhibit signs of compression. Computerized tomography, angioscans and cavography are necessary to make a provisional diagnosis and determine the operative strategy. The differential diagnosis between leiomyoma and leiomyosarcoma rests on cellular or nuclear atypias, mitotic index and sometimes cytological and staining details showing the myofibril. These tumours develop slowly in the renal segment. Treatment is primarily surgical. The case reported here raises the problem of the leiomyoma-leiomyosarcoma sequence: are we confronted with degeneration, or is there such a thing as a smooth muscle fibre disease?
Spontaneous hepatic haemorrhage is a rare complication in pregnancy. It usually occurs in multiparous women who have toxaemia of pregnancy. We give a case history of a primigravid patient who was not toxemic. The hepatic haemorrhage presented as blood in the peritoneal cavity which in turn gave rise to abdominal pain with hypovolaemic shock. The surgical treatment consisted in removing the segment of the liver that had been bleeding. The physiopathology of hepatic haemorrhage as described in the literature shows that there was evidence of consumptive coagulopathy with coalescence of periportal areas of liver necrosis. Treatment therefore is that of hepatic trauma. Maternal mortality runs at 70%.
At present, laparoscopic cholecystectomy is the treatment of choice for gallbladder stones. The operating technique reported by most authors includes the use of four trocars. We report a group of 710 consecutive patients treated by an original three-trocar technique. The use of the fourth trocar was necessary in only 55 cases (8%). However, among 56 cases of acute cholecystitis the use of the fourth trocar was necessary in 14 cases (25%) (p < 0.01). Twenty-six laparoscopies were converted to open procedures (3.6%). Four common bile duct injuries were observed (0.5%): two of them among the 655 operations with three trocars (0.3%) and two after application of the fourth trocar at the beginning of the procedure because of dissection difficulties. Our results are similar to those using the "classic" four-trocar technique. Moreover, this technique is less expensive and allows one less scar.
The growth effects of tamoxifen (TAM) were studied using normal and malignant colonic epithelial cells. Addition of TAM (0.8 to 10 microM) to cultured normal human colon epithelial cells and Lovo colon adenocarcinoma cells produced a dose response decrease in growth of 42 to 76%. Histamine (1 to 10 microM) did not affect cell growth and did not negate the TAM effect. Calmodulin (2 micrograms/ml) totally blocked growth inhibitory effects of a calmodulin antagonist, trifluoperazine (10 microM), but did not block the TAM inhibitory effect. These data suggest that antiestrogen binding sites (AEBS) may play an important role in the growth-inhibitory effects of TAM on colon cells. Competition with estrogen and antagonism with histamine or calmodulin do not appear to be significant in this regard.
Estrogen analogues, moxestrol (10(-8)-10(-5) M) and ethinyl estradiol (10(-8)-10(-6) M), produced a 30% and 15% inhibition of LoVo cell growth, respectively, in serum-free Ham's F-10 medium. Under the same conditions, no growth effects were observed on these cells following the addition of progesterone or testosterone (10(-8)-10(-6) M); however, metribolone (10(-8)-10(-6) M), a synthetic androgen with glucocorticoid receptor-binding properties, moderately stimulated cell growth (18%). The synthetic antiandrogen, RU 23908 (10(-6) M), did not reduce metribolone effects, and hydrocortisone (10(-9)-10(-7) M) stimulated LoVo cell growth by 31% in serum-free medium. In medium containing 10% charcoal-treated fetal bovine serum, the inhibitory effects of estrogens were not observed, and the lower concentrations (10(-11) M) of moxestrol and ethinyl estradiol facilitated cell growth (10 to 15%). The other steroid hormones produced the same results as observed with serum-free medium. These data suggest that estrogen and glucocorticoid hormones may play an important role in the growth of colon carcinoma cells. Androgen and progesterone hormones appear to be less significant in this regard. Serum factors alter the effects of estrogen, but not of glucocorticoids.
Because it is a common prerequisite for steroid responsiveness in target tissue, we investigated the presence of specific 1,25-DR in spontaneous human colorectal adenocarcinomas (ADC) and adjacent normal-appearing mucosa (NAM) from 23 operative specimens (12 male and 11 female patients). 1,25-DR was determined in cytosol by a DCC assay technique. 1,25-DR was present in 21 of 23 NAM and in only 4 of 23 HCRA. All positive ADC were well differentiated. Receptor content expressed in femtomoles/mg of protein (mean +/- SEM) was respectively 63.9 +/- 7.6 for right colon NAM and 51.3 +/- 12.9 for left colon or rectum NAM. When we compared all NAM specimens, receptor content was 56.7 +/- 8.0 femtomoles/mg of protein. No difference in 1,25-DR NAM level was observed between right colon and left colon or rectum. In adenocarcinoma the mean content was 66.5 +/- 14 fmoles/mg of protein. Scatchard analysis showed a single class of specific high-affinity saturable 1,25-DR with a dissociation constant (Kd) of 0.97 +/- 0.57 and 1.03 +/- 0.39 chi 10(-10) M in NAM and ADC respectively. These preliminary data represent the first demonstration of 1,25-DR throughout the entire human colon and indicate that the receptivity for this hormone is often lost during malignant transformation of the human colorectal mucosa. In addition, 1,25-DR could be a marker of differentiation in ADC. These preliminary results provide evidence supporting the addition of Vitamin D to the roster of developmental cancer chemopreventative agents.
LoVo, a cultured colon cancer cell line, is shown to possess a receptor for 1,25-dihydroxy vitamin D3 (1 alpha,25(OH)2D3) with a low capacity (28 fmol/mg protein) and high affinity (Kd: 1.9 x 10(-21)0M). When these cells were grown in monolayer culture in a chemically defined serum-free medium, a significant inhibition of proliferation was seen in the presence of 10 nM to 1 microM of 1 alpha,25(OH)2D3 (p less than 0.005. Furthermore, 1 alpha,25(OH)2D3 delayed early attachment of cells. After 8 days of treatment, aggregated cuboidal cells showed a marked change to an apparently spindle like morphology. The 1 alpha,25(OH)2D3 growth-inhibitory effect was modulated by verapamil (1 microM), a calcium channel blocker, hydrocortisone (1 microM), and moxestrol (1 mM), an estrogen analogue, and 2% charcoal-treated fetal bovine serum. This study represents the first demonstration of 1 alpha,25(OH)2D3 modulation of growth of human colon cells.