Biomedical subjects

F P Rossini

Publications and source records attributed to F P Rossini.

At least 19 recordsLinked to original sources

PubMed2000

Small bowel polyps in Peutz-Jeghers syndrome: management by combined push enteroscopy and intraoperative enteroscopy.

BACKGROUND: Polyps occur throughout the GI tract in Peutz-Jeghers syndrome; the major problem in the management of the syndrome lies in the small bowel. METHODS: From January 1979 to January 1998, seven patients with Peutz-Jeghers syndrome underwent surveillance. Between 1979 and 1992 they were managed with upper and lower endoscopy every 2 to 3 years and surgery when intestinal obstruction occurred. From 1993 they also underwent enteroclysis and, on the basis of radiologic findings, push enteroscopy and/or intraoperative enteroscopy. Push enteroscopy was then performed every 2 years in all patients. RESULTS: During the first period, 5 of 7 patients underwent emergency small bowel resection (2 operated twice). The patients were divided into 2 groups based on enteroclysis findings; the first comprised 4 patients with multiple polyps throughout the small bowel, and the second included 3 patients with polyps only in the proximal small bowel. Three of the 4 patients with diffuse polyposis underwent intraoperative enteroscopy during which on average 16 polyps per patient were removed (range 10 to 25 polyps; mean diameter 16 mm, range 3 to 50 mm). The remaining patient with diffuse polyposis had a single 25 mm polyp in the terminal ileum removed by retrograde ileoscopy; the more proximal polyps were removed by push enteroscopy. The patients with diffuse polyposis remained asymptomatic during follow-up (mean 50 months, range 47 to 57 months) and also underwent periodic push enteroscopy (mean 2.25 enteroscopies per patient, range 2 to 3) at which a mean of 8.5 polyps per patient (range 4 to 13 polyps) were removed (mean diameter 7.2 mm, range 3 to 15 mm). The 3 patients of the second group underwent periodic push enteroscopy alone (mean 3 per patient) during which a mean of 11.7 polyps per patient were removed (range 7 to 15 polyps: mean diameter 10.9 mm, range 3 to 40 mm). Enteroclysis was not repeated in these patients, who remained asymptomatic during follow-up (mean 47 months, range 46 to 48 months). CONCLUSIONS: More effective clearance of small bowel polyps via enteroscopy will help reduce the need for emergency surgery with extensive intestinal resection in patients with Peutz-Jeghers syndrome.

Adolescent↗

PubMed2000

Small-bowel endoscopy.

During the last year, several interesting publications have further confirmed the role of enteroscopy in clinical practice. Of particular interest have been various articles concerning the use of two-way enteroscopy in large series of patients with obscure gastrointestinal bleeding or with radiological abnormalities. Reports continue to appear describing a high incidence of gastroduodenal or colonic lesions that were missed or misinterpreted during previous upper and lower endoscopies in patients with recurrent obscure bleeding. By contrast, there have been few outcome studies on patients with obscure bleeding, and the conclusions reached are not in full agreement. Other important publications have stressed the value of enteroscopy in selected cases of chronic unexplained diarrhea, for diagnosing small-bowel lesions caused by nonsteroidal anti-inflammatory drugs, and in identifying small-bowel tumors. In addition to numerous reports on intraoperative enteroscopy, the results of initial experience with laparoscopically assisted enteroscopy have also been reported.

Diagnosis, Differential↗

PubMed2000

Idiopathic myenteric ganglionitis underlying intractable vomiting in a young adult.

Inflammatory infiltration of intestinal myenteric plexuses (i.e. myenteric ganglionitis), along with severe intestinal motor abnormalities, may accompany paraneoplastic syndromes, neurological disorders and gastrointestinal infections, although rare cases can be idiopathic. In this report, we describe the case of a patient who presented with chronic intractable vomiting and weight loss associated with idiopathic myenteric ganglionitis mainly involving the stomach. Tissue analysis showed that the inflammatory infiltrate comprised T lymphocytes (CD4+ and CD8+), and peptide immunolabelling revealed a marked decrease of substance P/tachykinin immunoreactive staining in nerve fibres and myenteric neurones. Following systemic steroid therapy, the patient's symptoms dramatically improved, and after one year of follow-up his general condition remains satisfactory. The possible mechanisms leading to symptom generation and gastric dysmotility in the context of an idiopathic myenteric ganglionitis are discussed.

Adult↗

PubMed1999

Enteroscopic identification of an adenocarcinoma of the small bowel in a patient with previously unrecognized hereditary nonpolyposis colorectal cancer syndrome.

Tumors of the small bowel are uncommon and seldom suspected on a clinical basis. Together with the relative inaccessibility of the small bowel to endoscopic investigation, the rarity of these tumors undoubtedly delays their diagnosis. The case reported is of a patient with an adenocarcinoma of the jejunum presenting as gastrointestinal bleeding of obscure origin. Diagnosis was by push enteroscopy, after several years of unsuccessful radiological and upper and lower endoscopic evaluation. The patient's family fulfilled the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome, which was previously unrecognized. This report emphasizes the value of push enteroscopy and the limits of radiography of the small bowel when investigating patients with obscure GI bleeding. It also underlines the importance of a careful evaluation of the pedigree (concerning history of colorectal and extracolonic cancer) of all patients, including those who present with adenocarcinoma of the small bowel; it is similarly important to consider the possibility of small bowel cancer in members of families with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.

Adenocarcinoma↗

PubMed1999

K-ras2 activation and genome instability increase proliferation and size of FAP adenomas.

The possible role of K-ras2 mutations and aneuploidy toward increase of proliferation and adenoma size in Familial Adenomatous Polyposis (FAP) adenomas is not known. The present study addresses these issues by investigating 147 colorectal adenomas obtained from four FAP patients. The majority of adenomas had size lower than or equal to 10 mm (86%), low grade dysplasia (63%), and were preferentially located in the right colon (60%). Normal mucosa samples were obtained from 19 healthy donors. Three synchronous adenocarcinomas were also investigated. K-ras2 mutation spectrum was analysed by PCR and Sequence Specific Oligonucleotide (SSO) hybridization, while flow cytometry (FCM) was used for evaluating degree of DNA ploidy and S-phase fraction. Overall, incidences of K-ras2 mutations, DNA aneuploidy and high S-phase values (>7.2%) were 6.6%, 5.4% and 10.5%, respectively. In particular, among the adenomas with size lower than 5 mm, K-ras2 mutation and DNA aneuploidy frequencies were only slightly above 1%. Statistically significant correlations were found between K-ras2 and size, DNA ploidy and size and K-ras2 and S-phase (p < 0.001). In particular, among the wild type K-ras2 adenomas, high S-phase values were detected in 8% of the cases versus 57% among the K-ras2 mutated adenomas (p = 0.0005). The present series of FAP adenomas indicates that K-ras2 activation and gross genomic changes play a role toward a proliferative gain and tumour growth in size.

Adenocarcinoma↗

PubMed1999

Dysplastic changes in gastric fundic gland polyps of patients with familial adenomatous polyposis.

BACKGROUND: Fundic gland polyps are the most common gastric lesion in patients with familial adenomatous polyposis and are traditionally considered a condition with no malignancy potential. However, some reports have recently questioned this view. AIMS: To prospectively evaluate their prevalence and the associated dysplastic/malignant changes in a series of affected patients. PATIENTS AND METHODS: Thirty-seven affected patients were carefully investigated by upper endoscopy over a three-year period. Multiple (at least 10) complete excisions of any representative polyp of the body-fundus were performed and a thorough pathological search for microscopic adenomatous/dysplastic changes carried out. RESULTS: Of 37 patients, 19 (51.3%) showed gastric fundic gland polyposis and 18 of them gave consent for polypectomies. Overall, 425 endoscopic polypectomies were performed, with a mean of 23.6 +/- 14.6 per patient. At pathology, all excised polyps of the body-fundus were found to be fundic glandular. Microscopic adenomatous changes within such polyps were identified in 8 (44.4%) patients. All the adenomatous foci revealed mild dysplasia with no case of severe atypia or carcinoma. Patients with microadenomas showed a significantly higher total number of gastric polyps compared with those without microadenomas (p < 0.03). No other differences between the two groups were observed. Two further patients presented microadenomas in apparently normal antral mucosa and one also showed a 6 mm antral adenoma with mild dysplasia. Finally, the search for Helicobacter pylori was always negative. CONCLUSIONS: Patients with familial adenomatous polyposis and gastric fundic gland polyps have a high prevalence of microscopic adenomatous foci within such lesions; nevertheless, these foci seem not to be associated with signs of severe atypia or carcinoma. Moreover, microadenomas are ubiquitous throughout the stomach, as well as in the rest of the gut, and their natural history is still undefined. Thus, their malignancy potential remains uncertain. More extensive follow-up is warranted to better investigate the long-term biological behaviour of these lesions but, at present, our data do not support the need for a change in the usual intervals of upper endoscopy surveillance in familial polyposis patients with or without gastric fundic glands polyps.

Adenomatous Polyposis Coli↗

PubMed1999

Small bowel tumors and polyposis syndromes.

Tumors of the small bowel are uncommon and seldom suspected on a clinical basis. Together with the relative inaccessibility of the small bowel to endoscopic investigation, the rarity of these tumors undoubtedly delays the diagnosis. Small bowel tumors may be an interesting field of application for enteroscopy, which now can be readily performed with dedicated enteroscopic evaluation in patients with suspected small bowel neoplasia could improve prognosis and treatment. Enteroscopy may also play an important role in the surveillance of inherited polyposis syndromes, as in other precancerous condition of the small bowel. In Peutz-Jeghers syndrome it may reduce polyp-induced complications and improve planning for surgery; in familial adenomatous polyposis it may contribute to preventing upper gastrointestinal tract cancer.

Biopsy↗

PubMed1998

STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer.

A potential tumor suppressor gene, STK11 , encoding a serine threonine kinase, has recently been identified on chromosome 19p13. Germ-line mutations of this gene have been found in patients with Peutz-Jeghers syndrome (PJS). To further investigate the relevance of STK11 mutations in PJS, we analyzed its coding sequence in nine patients and identified two deletions and three missense mutations. Because intestinal carcinomas have been observed to develop in association with PJS, we analyzed tumors from 71 patients for allelic deletions (loss of heterozygosity) and STK11 gene mutations, to elucidate the etiological role of STK11 gene in sporadic colorectal cancer. Loss of heterozygosity, evaluated using the microsatellite D19S886, was observed in 10 of 52 informative cases. No somatic mutations were detected except for a missense alteration in one tumor. Our data indicate the heterogeneity of PJS and the infrequent involvement of the STK11 gene in colorectal cancer.

AMP-Activated Protein Kinase Kinases↗

PubMed1998

Correlation between 1p deletions and aneusomy in human colorectal adenomas.

Human sporadic colorectal adenomas are characterized by a relatively high occurrence of aneuploidy. Similarly, 1p deletions have been reported to be an early event in colorectal tumorigenesis, while chromosome 7, 17 and 18 gain/losses were also found. The present study investigated 1p deletions, the numerical aberrations of chromosomes 1, 7, 17 and 18, and the nuclear DNA content as obtained by flow cytometry in a series of 34 human sporadic colorectal adenomas. From these adenomas, 51 intra-adenoma regions were microdissected according to 2 degrees of dysplasia and presence of foci of early cancer. Isolated epithelial nuclei were analyzed by fluorescence in situ hybridization interphase cytogenetics using centromeric probes for chromosomes 7, 17 and 18 and, in a double-target analysis, a centromeric probe for chromosome 1 simultaneously with a telomeric probe mapping to the 1p36 band. Aneuploidy incidence due to presence of numerical aberrations for at least one among the investigated chromosomes and/or abnormal flow-cytometric DNA content was 35%, while 1p deletion incidence was 38%. The correlation of 1p deletions with aneuploidy was statistically highly significant (p = 0.003), suggesting that loss of genes in this region may be implicated in chromosome instability.

Adenoma↗

PubMed1998

Specific K-ras2 mutations in human sporadic colorectal adenomas are associated with DNA near-diploid aneuploidy and inhibition of proliferation.

Recent studies indicate that p21ras proteins mediate their multiple cell functions through interactions with multiple effectors and that the number of new effectors is growing. We recently reported that K-ras2 mutations in human colorectal adenomas were associated with chromosome instability and proliferation changes. In the present study, we extend these previous observations. Hereditary and multiple (n > or = 5) adenomas and adenomas with early cancer were excluded. Dysplasia was moderate in 91 cases and high in 25, and the median adenoma size was 1.5 cm. K-ras2 spectrum analysis was done by sequence-specific oligonucleotide hybridization using nuclear suspensions provided by analysis and sorting of multiparameter flow cytometry. In particular, tissue inflammatory cells were separated for DNA diploid tumors, whereas DNA aneuploid epithelial subclones were analyzed separately. K-ras2 mutations and DNA aneuploidy were both detected in 29 of 116 (25%) cases. DNA aneuploid index was in the near-diploid region in the majority of cases. DNA aneuploidy was strongly associated with G-->C/T transversions. An association was also found between low S-phase values and G-->A transitions. These findings were confirmed using multivariate logistic regression analysis to account for the effects of size, dysplasia, site, type, age, and sex. These data suggest that specific K-ras2 mutations in a subgroup of human sporadic colorectal adenomas play a role in chromosome instability and, contrary to expectations, are associated with inhibition of proliferation.

Adenoma↗

PubMed1998

Main issues in push enteroscopy.

Endoscopic evaluation of the small bowel has rapidly evolved over the last ten years, marking an important milestone in the diagnosis and treatment of small bowel diseases. Gradual progress in endoscopic techniques and development of new instruments with full therapeutic options have aided and spread the use of enteroscopy. However, some basic issues concerning its appropriate use in clinical practice remain to be solved. This article stresses the importance of lesions missed at oesophagogastroduodenoscopy in patients with obscure gastrointestinal bleeding who undergo push enteroscopy, focuses on the limits of outcome studies related to therapeutic enteroscopy, and critically reviews the clinically relevant indications to push enteroscopy.

Endoscopy, Gastrointestinal↗

PubMed1997

Extended lymph node dissection for gastric cancer: results of a prospective, multi-centre analysis of morbidity and mortality in 118 consecutive cases.

This study reports interim data on post-operative morbidity, hospital mortality and duration of hospital stay of Italian patients undergoing extended lymph-node dissection combined with a pancreas-preserving technique for gastric cancer. Of the 218 patients admitted to one of eight general and/or university hospitals in North Italy, 118 were enrolled in the trial. Eligible patients presented with proven primary adenocarcinoma of the stomach without clinical evidence of distant, peritoneal and/or liver metastasis, or metastasis in para-aortic and retropancreatic nodes at intraoperative biopsy. Patients underwent the extended procedure as described by the Japanese Research Society for the Study of Gastric Cancer, following the Maruyama pancreas-preserving technique. A strict quality control system was used to ensure the performance of a standard surgical treatment. A surgeon of the reference centre (M.D.), who stayed at the National Cancer Center Hospital in Tokyo to learn the D2 technique from a specialist Japanese surgeon, became the trial supervisor and assisted each surgeon in all the Italian participating centres. The patients were staged according both to the TNM system and to the General Rules for the Gastric Cancer Study in Surgery and Pathology. Post-operative surgical complications developed in 21 patients (17.8%). The non-surgical complication rate was 2.5%. Reoperation was necessary in six patients (5%), all of whom survived. The 30-day mortality rate for the eligible group was 2.5%. The overall hospital mortality was the same. Total gastrectomy was associated with a slightly higher operative mortality (4.5% vs 1.3%). Only one patient died from an anastomotic leak. The rate of leakages was higher after total than after distal gastrectomy (15.9 vs 5.4%); the association of splenectomy and pancreatectomy worsened the morbidity rate. D2 lymphadenectomy with pancreas-preserving technique, when performed at experienced centres, seems a feasible and safe technique for the radical treatment of gastric cancer in selected Western patients.

Adenocarcinoma↗

PubMed1996

Microsatellite instability is associated with the histological features of the tumor in nonfamilial colorectal cancer.

Replication errors (RERs) at microsatellite loci were examined in 46 specimens of nonfamilial colorectal cancer. Somatic microsatellite alterations in at least two genetic loci, D11S904, D13S175, D2S123, and D10S197, consistent with a RER(+) phenotype were found in four cases (8.7%). Six additional cases (13%) showed alterations at a single locus. Mucinous differentiation was observed in 3 of 4 (75%) adenocarcinomas with a RER(+) phenotype and only in 19% (8 of 42) of RER(-) adenocarcinomas (P < 0.05). A distinct cap of inflammatory cells at the advancing edge of the tumor and Crohn's-like reaction in peritumoral stroma were histologically identified in 50 and 25% of RER(+) and in 5 and 0% of RER(-) tumors, respectively (P < 0.05). Also, the plexiform pattern of growth of carcinoma turned out to be significantly associated with the RER(+) phenotype (P < 0.05). Mucinous differentiation and stromal inflammatory reactions are frequent features of hereditary nonpolyposis colorectal cancer in which germ-line mutations of mismatch repair genes cause genetic instability. Our results indicate that a link exists between such histological features and somatic genetic instability consistent with a RER(+) phenotype also in nonfamilial colorectal cancer.

Adenocarcinoma↗

PubMed1996

Apoptosis, cell replication, and Western-style diet-induced tumorigenesis in mouse colon.

In this study, feeding Western-style diets (WDs) to mice for a duration of two years without any chemical carcinogen led to the development of gross colonic lesions that were histologically classified as dysplastic crypts and focal hyperplasias with or without atypical nuclei. To better understand early biological events contributing to the development of colonic neoplasia, grossly normal colonic mucosa was investigated; mitotic and apoptotic colonic epithelial cells, atypical mitosis, and atypical nuclei were studied. A significant and transient increase of mitotic activity in the basal and intermediate portions of the colonic crypts was seen in young mice after feeding them the WDs. This was accompanied by diffuse activation of apoptosis of the colonic epithelial cells. In the middle of the rodents' life span, after administration of both the WDs and control diet, the rodents developed a marked depletion of apoptotic epithelial cells in the mid-region of the colonic crypts; this was followed by the expansion of an epithelial cell population containing atypical nuclei, and the emergence of the gross lesions noted above. With this sequence of events, prolonged feeding of WDs to mice produced single-crypt dysplastic lesions and focal hyperplasias indicative of tumorigenesis.

Animals↗

PubMed1996

Deletions at chromosome 1p by fluorescence in situ hybridization are an early event in human colorectal tumorigenesis.

BACKGROUND & AIMS: Deletions at chromosome 1p have been observed frequently in human colorectal adenocarcinomas, suggesting that loss of genes in this chromosome arm is relevant for tumorigenesis. The aim of this study was to investigate whether 1p deletions are already present in adenomas within selected foci of dysplasia and early cancer using two-color fluorescence in situ hybridization. METHODS: Fifty-one sectors characterized by low- and high-grade dysplasia and early cancer were microdissected from 34 adenomas, and isolated epithelial nuclei were subjected to hybridization with probes to the telomeric and centromeric regions of chromosome 1. RESULTS: Deletions of 1p were detected in 13 of 34 adenomas (38%). In particular, low/moderate and high dysplasia and foci of early cancer had 1p deletion frequencies of 31%, 44%, and 50%, respectively. CONCLUSIONS: Compared with classic cytogenetics, fluorescence in situ hybridization seems to be a particularly useful methodology to detect 1p deletions in human colorectal adenomas. The present findings indicate that loss of genes from the 1p chromosome arm may play an important role during the early steps of the colorectal carcinogenesis.

Adenoma↗

PubMed1996

Clinical enteroscopy.

We prospectively evaluated the diagnostic yield of push enteroscopy using either the Olympus SIF 10-LY fiberscope or the SIF-100 video enteroscope in 120 patients suspected of having small-bowel pathology. Insertion beyond the ligament of Treitz, checked by fluoroscopy, ranged from 30 to 150 cm (median 100). The source of bleeding was identified in 25 (41%) of 61 patients referred for gastrointestinal bleeding of obscure origin; vascular malformations were the most common finding, followed by neoplasias. Of 16 patients with inherited polyposis syndromes, multiple distal duodenal or jejunal hamartomas were diagnosed in five of six with Peutz-Jeghers syndrome and multiple duodenal or jejunal adenomas in six of 10 with familial adenomatous polyposis. Overall, isolated vascular malformations were successfully cauterized in three patients, and polypectomy was performed in 12 patients. Endoscopic and histological alterations, in both duodenum and jejunum, were found in 16 of 43 patients with diarrhea and/or malabsorption of unclear origin. The remaining 27 had normal duodenal and jejunal mucosal appearances; six had abnormal histological findings only in the jejunum and one both in the duodenum and in the jejunum. If we take jejunal histology as diagnostic, the sensitivity of duodenal histology was 74% and the specificity was 100%. We conclude that push enteroscopy provides useful diagnostic information and has therapeutic capabilities in patients with small-bowel pathology.

Adenomatous Polyposis Coli↗

PubMed1996

High prevalence of adenomas and microadenomas of the duodenal papilla and periampullary region in patients with familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are traditionally considered to be at high risk for duodenal-papillary and periampullary adenomas and cancer. AIM: To evaluate prospectively the prevalence, histology and clinical significance of ampullary and periampullary macroscopic and microscopic lesions in our population of affected patients. SETTING: Three gastroenterological departments of northern Italian hospitals. PATIENT AND METHODS: Twenty-five affected patients were carefully investigated over a 24-month period by end-viewing and side-viewing upper panendoscopy. Biopsies were performed on representative macroscopic lesions and randomly on normal-appearing papillary and periampullary mucosa. RESULTS: Seven patients had macroscopic adenomas of the duodenal papilla, three of the periampullary region and five at both sites (cumulative prevalence 40%). An additional six patients had macroadenomas in the rest of the duodenum (overall prevalence 64%). Microscopic adenomas were identified in nine and two patients in the papilla and periampullary region, respectively, and in three at both sites (overall prevalence 44%). Thus, a total of 17 (68%) patients presented macro- or microadenomas at these locations. The prevalence rose to 72%, when a further patient with macroadenomas in the rest of the duodenum only was included. Malignancy was not encountered and severe dysplasia was observed only in a macroadenoma of the second duodenal portion. A higher frequency of macroadenomas in the papilla and periampullary region was significantly correlated with the presence and number of such lesions in the rest of the duodenum (P = 0.04). No other significant association was detected either between micro- or macroadenomas at different sites or with the demographic, clinical and pathological features. CONCLUSION: This study confirms that the duodenal papilla and periampullary region are sites with high prevalence of macro- and microscopic adenomas in patients with FAP. However, our data do not seem to support a higher frequency and malignancy potential of such lesions as compared to polyps in the rest of the duodenum. Nevertheless, these findings warrant a periodic, careful examination of the duodenum with either end-viewing or side-viewing endoscopy, the need for random biopsies of the papilla and periampullary region and the removal of any larger or rapidly growing lesions detected.

Adenoma↗

PubMed1996

Screening for colorectal cancer by once only sigmoidoscopy: a feasibility study in Turin, Italy.

OBJECTIVES: To assess the impact on compliance of three invitation methods, as well as the acceptability and efficacy of two bowel preparation regimens, for endoscopic screening in the general population. METHODS: 1170 subjects (men and women aged 55 to 59, in the rosters of a sample of general practitioners (GPs) in Turin), were randomly allocated to one of three invitation groups (A: personal letter, signed by GP, with a pre-fixed appointment; B: same as for A + letter supporting the study by a well known scientist; C: letter signed by the study coordinator, NS) and two preparation regimens (i: one enema, self administered at home two hours before the test; ii: two enemas, administered the night before and two hours before the test). A postal reminder was mailed to non-attenders. A sample of non-responders was contacted for a telephone interview by a trained nurse. Written consent was obtained from all subjects undergoing the test. RESULTS: A total of 278 subjects attended for sigmoidoscopic screening. An invitation from the GP alone produced the highest response rate (compliance: A = 29.3%; B = 24.9%; C = 26.8%). A single enema was as effective as two enemas in achieving satisfactory preparation for the test: the proportion of subjects invited to repeat the test was 8.1% in the single enema group, and 9.6% in the group receiving two enemas. CONCLUSIONS: Compliance with this screening procedure tends to be low. One enema, self administered two hours before sigmoidoscopy, can ensure a satisfactory bowel preparation.

Colorectal Neoplasms↗