Point mutations of the K-RAS gene at codon 12 are found in about 40% of cases with colorectal cancer. The diagnostic implications of the detection of these mutations and their clinical utility are still unclear. The aim of this study was to test both the feasibility of the detection of the mutated K-RAS gene in serum and its potential role in colorectal cancer detection and monitoring. Codon 12 K-RAS mutations were examined in DNA extracted from the serum of 35 patients with colorectal cancer and were compared with the K-RAS status in the corresponding primary tumor. Molecular detection was performed by the mutant-enriched PCR (ME-PCR) assay, a sensitive method capable of distinguishing a small quantity of mutated DNA in the presence of abundant wild-type DNA. The occurrence of mutations was compared with clinicopathological parameters as well as CEA and CA19.9 serum levels. We found codon 12 K-RAS mutations in the tissue of 13/35 (37%) patients. Serum mutations were detected in 5/13 (38.5%) patients with mutated K-RAS in the tissue. 26/35 (74%) patients showed an identical K-RAS pattern in tissue and serum. No codon 12 K-RAS alterations were found in serum samples of 22 patients with benign gastrointestinal diseases. Elevated serum CEA levels were detected in 16 patients, four of whom also presented serum RAS mutations. Our results confirm that K-RAS mutations can be found in circulating DNA extracted from serum samples of patients with colorectal cancer and show that there is a correspondence between serum and tissue K-RAS patterns.

Adult↗

PubMedDate not supplied

Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with distant metastases.

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to cor-relate with prognosis in this patient subgroup.

Adult↗

PubMedDate not supplied

[Non-polyposis colorectal cancer in subjects under 55 years of age: frequency and phenotype of hereditary or familial syndromes].

Young age is believed to be a risk factor for hereditary or familial non-polyposis colorectal cancer. Present study analysed frequency, phenotype and familial cancer risk of 82 subjects with colorectal cancer under 55 years of age. According to age and family history, probands have been subdivided into 5 groups: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) (8.2% of cases); Suspected HNPCC (7.3%); Non-specific familial aggregation of colorectal cancer (AFACC) (19.5%); Early-onset colorectal cancer (diagnosis under 35 years of age) (CCG) (6.1%); Sporadic colorectal cancer (CCS) (58.5%). Proportions of probands with multiple colonic tumours were highest in HNPCC (57.1%), but present in AFACC (12.5%) and CCG (20.0%) groups, as well. Extracolonic, in particular endometrial and ovarian cancers have been found in HNPCC and AFACC probands. Tumours of proximal colon were most frequent in HNPCC, suspected HNPCC, CCG patients. Eleven-years survival rate was higher in HNPCC probands then in CCS group. Familial cancer risk in HNPCC was 3 times as much as in CCG + CCS groups. Diagnosis of colorectal cancer under 55 years of age is associated with an high frequency of hereditary or familial cases. Genetic tests, surveillance and screening programs in these patients must be based on extensive phenotype and pedigree analyses. HNPCC is widely represented in young colorectal cancer patients and is associated with a high risk of multiple synchronous or metacronous colonic and extracolonic tumours. Total colectomy and eventual hysterectomy with bilateral oophorectomy seem therefore recommendable options in these patients.

Adenocarcinoma↗

PubMedDate not supplied

[Gastrin and colorectal cancer].

The aim of present study was to assess preoperative/postoperative serum gastrin level variations and their prognostic value in patients with colo-rectal cancer. Levels have been evaluated in 66 subjects undergoing colo-rectal cancer surgery, with curative intent, from may 1990 to february 1994. Preoperative gastrin analysis was performed on peripheral blood samples in starred patient just prior surgery. Postoperative gastrin assessment was performed 7 day after surgery in starred patients as well. Follow-up ranged from 5 to 8 years. No association between preoperative gastrin levels and tumor site, stage or grading was observed. No significant variation of preoperative gastrin levels (p > 0.05) was ascertained postoperatively neither in the whole patient series nor after correction for tumor stage. Postoperative levels were therefore not affected by surgical removal of cancer. Neither preoperative nor postoperative serum gastrin levels influenced significantly the 5-year survival. In our experience, with the limitation of a small series assessment, serum gastrin level do not seem to have any prognostic value in colo-rectal cancer.

Aged↗

PubMedDate not supplied

[Multifocal gastric carcinoid associated with chronic type A atrophic gastritis. Analysis of 2 clinical cases].

Gastric carcinoid is a rare disease, representing less than 1% of gastric tumours and 11-41% of all gastrointestinal carcinoids. The recent Solcia's classification distinguishes three subtypes of these neoplasms, which show specific clinical and pathological features. Type one arises in patients with chronic atrophic gastritis (CGA), achlorhydria, hypergastrinemia and consequent enterochromaffin-like cell hyperplasia and dysplasia. Type two is related to Zollinger Ellison syndrome and type three represents the sporadic kind. We report two cases of multifocal gastric carcinoid associated to CGA, one of them with pernicious anemia. Both patients had aspecific abdominal symptoms; the diagnosis was suspected by upper endoscopy and confirmed by histological examination. Patients were submitted to total gastrectomy. They are still alive six years after surgery, without signs or symptoms of recurrences. Treatment of these tumours is controversial, because of their uncertain biological and clinical behaviour. Some Authors propose a conservative strategy (only endoscopic surveillance or removal); others stress importance of surgery (antrectomy or gastric resection). We discuss and underline the role of surgical therapy and the relevance of radical approach.

Adult↗

PubMedDate not supplied

Distribution of 1,2 DMH-induced colonic aberrant crypt foci after administration of a gastrin receptor antagonist (CR2945), in the murine model.

Our previous experimental data demonstrated that a new gastrin receptor antagonist (CR2945) has a chemopreventive effect on dimethylhydrazine-induced colon cancer in mice. The aim of this study is to test the effect of CR2945 on the appearance and distribution of aberrant crypt foci (ACF), proposed as early "preneoplastic" lesions in colon carcinogenesis, in the murine model. 176 CD1 male mice were randomly divided into 4 groups: group 1, sham group received 2 daily intra-peritoneal injections of saline solution; group 2 received 1 weekly intra-peritoneal injection of DMH 20 mg/kg, for 5 weeks, and 2 daily intra-peritoneal injections of equal volume of NaCl 0.9%; group 3 and 4 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/Kg for 5 weeks. The rodents were sacrified 15, 20, 25, and 38 weeks after receiving the first injection. The number of ACF per area (ACF frequency), their multiplicity (number of crypts per focus), ACF frequency according to each colonic site were recorded. No ACF were found in the sham group. No substantial differences were observed in ACF distribution between the remaining groups. Our hypothesis is that CR2945 does not alter the final number of ACF but might induce a regression of some dysplastic ACF.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

[Billiopancreatic diversion with preservation of the duodenal bulb and transitory gastroplasty in the treatment of morbid obesity. Our experience].

We present our experience in malabsorbitive procedure in bariatric surgery based on Biliopancreatic Diversion (BPD) with transitory gastroplasty. Since 1995 we operated on 74 patients with BPD coupled with gastroplasty which is transitory due to the presence of a band in polidioxanone (PDS). The technique, proposed by Vassallo et al. in 1992, involve the respect of the duodenal bulb (5 centimeter from the pylorous) making an end-to-side duodeno-ileal isoperistaltic anastomosis. The initial excess weight loss was satisfactory (69.8% +/- 11.4% after 1 year) and it kept being stable during all the follow-up (75.2% +/- 6.4% after 5 years). The mortality was absence. We didn't observe ipoalbuminemia, diarrhea or halitosis in any patients. Only 1 patient (1.3%) developed an anastomotic ulcer. After 5 years follow-up we observed 2 cases (12.5%) of chronic hypochromic anemia and 1 case (6.2%) of hypocalcemia. We didn't perform any restorative operation. We consider this technique a good malabsortive procedure able to obtain a satisfactory and stable weight loss, with a low incidence of complications. Moreover it could be applied in patients previously treated by an ineffective gastroplasty.

Adolescent↗

PubMedDate not supplied

[Course and natural history of idiopathic ulcerative proctitis in adults].

BACKGROUND AND AIMS: Epidemiological studies have shown that ulcerative proctitis represents 25-55% of ulcerative colitis. In western countries, the incidence of ulcerative proctitis has been increased, while the incidence of more extensive colitis remained unchanged. Compared with extensive ulcerative colitis, the idiopathic proctitis seems to be a benign disease, with an extension to proximal segments in less than 30% of cases, low surgical and cancer risk. On the basis of epidemiological studies, not confirmed by endoscopic and histological features, it has been hypothesized that ulcerative colitis and proctitis could represent two different clinical entities. The aim of the study was to evaluate some clinical and demographic features related to the two different localizations, colitis and proctitis, in the attempt to clarify the above mentioned issues. METHODS: Demographic data of 156 patients observed in our institution from 1982 to 1999, were retrospectively analysed. Diagnosis, extension and severity of ulcerative procto-colitis were based on endoscopic and histological criteria. Local and systemic symptoms, extraintestinal manifestations, surgical and cancer risk, were also recorded. RESULTS AND CONCLUSIONS: Ulcerative proctitis has shown to be a benign disease, with a prevalence of local symptoms, less systemic and extraintestinal manifestations, and low endoscopic grades of activity. Furthermore no surgical intervention and cancer development were recorded. Extension to proximal segments was observed in 10.25% of cases. Young age of onset of symptoms,-smoking and appendectomy were associated to an higher risk of extension of the disease.

Adolescent↗

PubMedDate not supplied

[The role of color-Doppler ultrasonography in preoperative study of hyperparathyroidism].

The different diagnostic modalities (MIBI scan, ultrasound, CT, MNR) applied in the preoperative study of hyperparathyroidism, have given excellent sensitivity results, only slightly lower than those obtained by surgical exploration performed by experienced surgeons. Yet, their only limitation lies in a lower level of specificity. Other cervical tumours, such as thyroid nodules, lymphoadenopaties, vascular and macular lesions, can in fact be erroneously taken as hyperfunctioning parathyroids. The present paper shows a clinical experience of 27 patients affected by IPT (14 primary IPT, 10 secondary, 3 terziary) who underwent Color-Doppler Ultrasonography and US before surgical exploration. As a result, global sensitivity level reached 81.5%, specificity 100%. In IPT I and III, sensitivity reached 100% while in IPT II it was only 72.2%. In conclusion, Color-Doppler associated with conventional US increases the specificity rate of IPT pre-operative diagnosis.

Adult↗

PubMedDate not supplied

[DNA index of colorectal carcinoma and follow-up].

In relation to DNA index we have studied 18 cases of differently evoluted carcinoma of the colon, some incoherently (8) other in agreement (10) with staging. Static and flow cytometric techniques have been employed, the first by means of densitometric study on paraffin sections with the Feulgen method, the second based on application of Hedley method on paraffin included material. DNA content, pressed by the DNA index, is inversely proportional to survival with similar results in both techniques, from which the possible prognostic significance is argued.

Carcinoma↗

PubMedDate not supplied

[The role of color flow-Doppler ultrasonography in the diagnosis of nodular goiter].

Sixtysix patients were submitted to color Doppler ultrasonography, with flowmetric analysis, in the preoperative work up of their thyroid nodules. Three different groups (and two subsets) were so identified, corresponding to the different pathological nodule types: hyperplasia, adenoma, and cancer. The data obtained were then compared to the final pathological results. The color Doppler ultrasonography showed a diagnostic accuracy rate of 87.8%. An evaluation of the peak systolic velocity proved to be very useful in the differential diagnosis between adenomas and cancers. The color Doppler ultrasonography represents a sound method for evaluating thyroid nodules.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

[Surgery in severe ulcerative colitis: our experience].

BACKGROUND AND AIMS: The mortality in severe episodes of ulcerative colitis (UC) has been reduced from 31-61% in the 1950 to 1-3%. Nevertheless it remains high in non specialist centers. Simple criteria are necessary to predict the outcome of severe ulcerative colitis. METHODS: 14 patients hospitalized for severe disease (Truelove and Witts criteria) from 1996 to 2000 were retrospectively analyzed. Patients were divided into two groups: 1. Group A: patients with severe disease surgically treated. 2. Group B: patients with severe disease responders to medical therapy Sex, age, length of steroids medical therapy, fever, stool frequency, CRP, ESR, haemoglobinemia, leukocytes, serum albumin values in the three days before the operation or during the hospitalization were collected. RESULTS: Total colectomy with ileostomy was necessary in 8 patients (57.1%), while 6 patients (42.90%) were responders to medical therapy. No perioperative mortality was recorded. Stool frequency, CRP, ESR, haemoglobinemia, serum albumin were significantly related to surgical operation. CONCLUSIONS: 1. No uniform criteria off severe attacks, are clearly defined in Literature. 2. The length of pre-operative medical therapy has a tendency to be too high (in our series 19 + 8.2 days). 3. Stool frequency, CRP, ESR, haemoglobinemia, serum albumin were significantly modified in operated patients.

Adult↗