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Background: A single sigmoidoscopy examination at around age 60 years has been proposed as a cost-effective strategy to prevent colorectal cancer. A multicenter randomized controlled trial, the SCORE trial, is in progress in Italy to estimate the impact of this strategy on colorectal cancer incidence and mortality and the duration of the protective effect. We present the baseline screening outcomes.Methods: A questionnaire was mailed to a random sample of 236 568 people aged 55-64 years to assess their eligibility for and interest in screening. Those reporting a history of colorectal cancer, adenomas, inflammatory bowel disease, recent colorectal endoscopy, or two first-degree relatives with colorectal cancer were excluded. Eligible, interested respondents were assigned randomly to the control group (no further contact) or the intervention group (invitation to undergo sigmoidoscopy). Screenees with colorectal cancer, polyps larger than 5 mm, three or more adenomas, adenomas 5 mm or smaller with a villous component of more than 20%, or severe dysplasia were referred for colonoscopy.Results: Of the 56 532 respondents (23.9% of those invited), 34 292 were enrolled and 17 148 were assigned to the screening group. Of those, 9999 attended and 9911 were actually examined by sigmoidoscopy. Distal adenomas were detected in 1070 subjects (10.8%). Proximal adenomas were detected in 116 of 747 (15.5%) subjects without cancer at sigmoidoscopy who then underwent colonoscopy. A total of 54 subjects was found to have colorectal cancer, a rate of 5.4 per 1000 (54% of which were Dukes' A). The procedures were relatively safe, with two perforations (one in 9911 sigmoidoscopy exams and one in 775 colonoscopies) and one hemorrhage requiring hospitalization after polypectomy during colonoscopy. The pain associated with sigmoidoscopy was described as mild or less than expected by 83.3% of the screenees.Conclusion: Sigmoidoscopy screening is generally acceptable to recipients and safe. The high yield of advanced adenomas is consistent with the projected impact of sigmoidoscopy screening on colorectal cancer incidence. [ABSTRACT FROM AUTHOR]

Objective: to evaluate the use of peripheral venous catheters based on microbiological analysis of devices (dressing and three-way stopcocks) and thus contribute to the prevention and infection control., Methods: this was a prospective study of microbiological analysis of 30 three-way stopcocks (external surfaces and lumens) and 30 dressing used in maintaining the peripheral venous catheters of hospitalized adult patients., Results: all external surfaces, 40% of lumens, and 86.7% of dressing presented bacterial growth. The main species isolated in the lumen were 50% coagulase-negative Staphylococcus, 14.3% Staphylococcus aureus, and 14.3% Pseudomonas aeruginosa. Fifty nine percent of multidrug-resistant bacteria were isolated of the three-way stopcocks, 42% of the lumens, and 44% of the dressing with a predominance of coagulase-negative Staphylococcus resistant to methicillin. Besides, 18% gram-negative bacteria with resistance to carbapenems were identified from multidrug-resistant bacteria on the external surfaces of the three-way stopcocks., Conclusion: it is important to emphasize the isolation of coagulase-negative Staphylococcus and gram-negative bacteria resistant to methicillin and carbapenems in samples of devices, respectively, which reinforces the importance of nursing care in the maintenance of the biologically safe environment as well as prevention and infection control practices.

Half the patients with coronary artery disease present with sudden death - or acute infarction as first symptom, making early diagnosis pivotal. Myocardial perfusion scintigraphy is frequently used in the assessment of these patients, but it does not detect the disease without flow restriction, exposes the patient to high levels of radiation and is costly. On the other hand, with less radiological exposure, calcium score is directly correlated to the presence and extension of coronary atherosclerosis, and also to the risk of cardiovascular events. Even though calcium score is a tried-and-true method for stratification of asymptomatic patients, its use is still reduced in this context, since current guidelines are contradictory to its use on symptomatic diseases. The aim of this review is to identify, on patients under investigation for coronary artery disease, the main evidence of the use of calcium score associated with functional evaluation and scintigraphy., Competing Interests: Potential Conflict of Interest No potential conflict of interest relevant to this article was reported.

Colorectal adenomas containing invasive carcinoma represent the majority of early colorectal cancers. The malignant polyp carries a significant risk of lympho-haematic metastasis and mortality due to the penetration of cancerous cells into the submucosal layer. The therapeutic dilemma is whether to perform endoscopic or surgical resection. A thorough assessment of the endoscopic, histological and clinical variables is needed to unravel the best treatment for each patient. In particular, a unique staging of such lesions, based on certain histopathological features, has been deeply implicated in the therapeutic choice. Aim of this article is to review the main endoscopic, histological and clinical features of the malignant polyp in order to propose a systematic management of this lesion.

Background: Endoscopic follow-up is advised in patients operated for colorectal cancer due to a high risk for both metachronous colorectal cancer and adenomas. Such issue has been scarcely addressed in Italy. This study aimed to evaluate the incidence of neoplastic lesions at a scheduled endoscopic follow-up and to identify the patients at higher risk of recurrence., Methods: Colorectal cancer patients diagnosed in the three participating hospitals (one North, one Centre and one South Italy) were scheduled for colonoscopies at 1, 3 and 5 years after surgery. Incidence of adenomas, advanced adenomas and colorectal cancer was assessed in all patients. Neoplastic incidence in patients with and without synchronous lesions at entry was also compared., Results: Overall, 318 consecutive patients were prospectively enrolled including 108 (34%, group A) with a synchronous lesion and 210 (group B) without it. A cumulative neoplastic incidence of 20.1, 32.4 and 44% was observed at 1, 3 and 5 years of follow-up, respectively. The cumulative incidence of all the lesions was 70% in group A and 30.2% in group B at 5-year follow-up, being 39.5 and 15.5% after excluding the lesions detected at 1-year examination. A neoplastic lesion was detected more frequently in group A at 1year (30.5% versus 14.7%; p = 0.0013), 3 years (21.4% versus 7.6%; p = 0.0008) and at 5years (18.1% versus 7.8%; p = 0.02)., Conclusions: Our data showed that the incidence of adenomas in patients operated for colorectal cancer is fairly high. Colorectal cancer patients with synchronous lesions are at higher risk of neoplastic recurrence at follow-up as compared to those without them.

Purpose: The malignant polyp carries a significant risk of lymphohematic metastasis and mortality. Clinical usefulness of histologic risk factors is still controversial. The study was designed to compute the association between the main histologic risk factors and the occurrence of unfavorable outcomes in patients with malignant polyps., Methods: A MEDLINE search regarding malignant polyps was performed. Three histologic risk factors (positive resection margin, poor differentiation of carcinoma, vascular invasion) and five (residual disease, recurrent disease, lymph node metastasis, hematogenous metastasis, mortality) unfavorable clinical outcomes were evaluated. Further analysis was performed by subgrouping polyps in high-risk and low-risk groups., Results: Thirty-one studies enrolling 1,900 patients with malignant polyp were selected. Positivity of resection margin was significantly predictive of the presence of residual disease (odds ratio, 22; P < 0.0001), poorly differentiated carcinoma was associated with an increased mortality (odds ratio, 9.2; P < 0.05), and vascular invasion with a higher lymph node metastasis risk (odds ratio, 7; P < 0.05). Patients with high-risk polyps showed a significantly worse outcome than those with low-risk, especially for mortality (odds ratio, 11; P < 0.05). Surgical-related death was as low as 0.8 percent., Conclusions: All three histologic risk factors are significantly associated with the clinical outcome. Classification in low-risk and high-risk patients may be regarded as a meaningful staging procedure.

Objective: To assess the efficacy of a hereditary non-polyposis colon cancer (HNPCC) identification and surveillance policy., Methods: Familial clustering of colorectal cancer (CRC) and extracolonic cancers (ECs) was investigated in 1520 consecutive CRC patients and relatives. HNPCC was identified by Amsterdam criteria, and individuals at risk were offered biennial colonoscopy and other examinations, starting from age 25 years., Results: Twenty-two HNPCC families were identified. The CRC prevalence was 27.8% (121/435), decreasing from 59.4% in the first generation to 24.4% and 8% in the second and third generation, respectively. Twenty-nine patients had multiple CRC and 34 patients (in 12 families) had ECs.A total of 199/331 at-risk individuals accepted surveillance. The mean follow-up was 48+/-32 months. CRCs were detected at first surveillance in four out of 199 surveilled individuals (2%); in two surveilled individuals (1%), three CRCs developed during follow-up. The overall CRC incidence was 7/199 (3.5%) in surveilled individuals and 5/132 (3.7%) in unsurveilled individuals. CRCs were less advanced in surveilled than in unsurveilled patients. Eleven individuals had 22 adenomas (one with high-grade dysplasia). Three individuals had adenomas at first surveillance; two of them and eight more individuals during surveillance. Seven surveilled individuals and six unsurveilled individuals, all belonging to families with a history of EC, had EC during the study period. All patients with CRC detected by surveillance are alive. One of the unsurveilled patients who had CRC died 18 months after the diagnosis., Conclusions: Data confirm the importance of the family history collected in each patient with CRC for identification of HNPCC and support the efficacy of repeated colonoscopies for early diagnosis and prevention of CRC in at-risk members. Reasons for surveillance failure could be an accelerated progression of small adenomas and a lesion missing at colonoscopy. Longer follow-up is required to assess the efficacy of surveillance for EC.

The possible relationship between gastric metaplasia and ulcerative lesions in an unusual case of ulcerative jejunitis not related to celiac disease and with extensive gastric metaplasia is discussed. Previous studies have described gastric metaplasia in duodenal ulcers on the basis of endoscopic data, and some authors maintain that acid secretion in metaplastic mucosa could represent a pathogenetic factor of ulcerogenesis, with a self-amplifying mechanism. In the absence of functional evidence, we could provide data, in a case of ulcerative jejunitis, about morphologic signs of acid secretion in gastric metaplastic epithelium using an antibody against HMFG-1, a good marker of acid-secreting fundic cells. Metaplastic areas demonstrated a focal positivity for HMFG-1, and these finding are suggestive of local acid secretion.

Background & Aims: Capsule endoscopy (CE) is a promising diagnostic tool for the study of patients with obscure gastrointestinal bleeding. However, the diagnostic yield of this technique has not been adequately studied. We evaluated sensitivity and specificity of CE and the outcome after CE in patients with obscure gastrointestinal bleeding., Methods: One hundred consecutive patients (all with recent negative upper and lower endoscopy; 26 with ongoing overt bleeding [group A], 31 with previous overt bleeding [group B], and 43 with guaiac-positive stools and iron-deficiency anemia [group C]) underwent CE., Results: The yield of positive findings on CE was 92.3% in group A, 12.9% in group B, and 44.2% in group C (P < 0.0001, A vs. B, A vs. C). Angiodysplasia (29%) and Crohn's disease (6%) were the most common diagnoses. Sensitivity, specificity, and positive and negative predictive values of CE were 88.9%, 95%, 97%, and 82.6%, respectively. CE results led to treatments resolving the bleeding in 86.9% of patients undergoing the procedure while actively bleeding. Capsule retention because of unsuspected stenosis occurred in 5 patients and required surgery, which resolved the clinical problem, in 4 patients., Conclusions: CE is an effective diagnostic tool for patients with obscure GI bleeding. The best candidates for the procedure are those with ongoing obscure-overt bleeding or with obscure-occult bleeding. If done early in the course of the workup, CE could shorten considerably the time to diagnosis, lead to definitive treatment in a relevant proportion of patients, and spare a number of alternative investigations with low diagnostic yield.

Several chromosome defects parallel morphologic evolution in colorectal tumor progression. Allelic losses in the short arm of chromosome 17, the majority encompassing the 17p13.3 band, have been found in advanced cancer in the absence of TP53 mutations, suggesting that loss of genes in this chromosome region is relevant for tumorigenesis. The aim of this study was to investigate 17p13.3 deletions throughout the colorectal tumor progression using two-color fluorescence in situ hybridization. Histologic sections from 20 colorectal adenomas containing early invasive carcinoma were analyzed by interphase fluorescence in situ hybridization using a centromeric probe for chromosome 17 simultaneously with a subtelomeric probe mapping to the 17p13.3 band. Separate evaluation was made for sectors corresponding to adenoma tissue with low-grade dysplasia, high-grade dysplasia, and early cancer. The same technique was also used in 20 cases of advanced adenocarcinoma of the large bowel. Loss of one centromeric signal was observed in 20, 40, 50, and 10% of low-grade dysplasia, high-grade dysplasia, early cancer, and advanced cancer, respectively (P<0.02 early vs. advanced cancer). Subtelomeric 17p deletions were seen in 60% of advanced cancer and in 15% of early cancer (P<0.01). These findings indicate that loss of genes from the 17p13.3 chromosome region may play an important role in sustaining the transition from early to advanced cancer in colorectal tumor progression.

Here we report a case of Pyoderma gangrenosum (PG) associated with Crohn's disease successfully treated with infliximab. The efficacy of this drug in many inflammatory diseases has already been reported, but its use in PG has only been seen in very few cases. Our study confirms that this therapy is a valid alternative solution for treating PG, which is often unresponsive to conventional therapies.

Germline mutations in APC tumor suppressor gene are responsible for familial adenomatous polyposis (FAP). A major role of these genetic changes is the constitutive activation of beta-catenin-Tcf-4 mediated transcription of nuclear target genes, but other cellular functions can be misregulated. To assess how different APC mutations can drive the early steps of colonic tumorigenesis, we studied the effect of 10 different germline-truncating alterations on the phenotype of the corresponding adenomas. A significant reduction of apoptosis, uncoupled with an increased c-myc and cyclin-D1 expression, was seen with a frameshift mutation on codon 1383, in the 20-aa repeats of the beta-catenin degradation domain, independent of a somatic alteration on the wild-type allele. The decreased apoptotic level was associated with a higher incidence of cancerization. No other APC mutation was linked with a similar effect, even in presence of a somatic allelic loss. These findings suggest that mutations in critical sites of the beta-catenin degradation domain of APC gene can convey a selective advantage to the colonic neoplastic clones by altering the apoptotic surveillance rather than enhancing the beta-catenin-Tcf-4 transcription of growth-promoting genes.

Background: Success achieved in two subtypes of Crohn's disease has persuaded a few investigators to experiment the monoclonal anti-tumour necrosis factor antibody infliximab in the treatment of ulcerative colitis. So far, however, the results (achieved in some 30 steroid-refractory patients included in two independent full-papers) indicate a rate of initial response of 50% and of remission of 25%., Aims: To analyse data of an open trial conducted on consecutive steroid-refractory severely ill patients admitted to our referral Unit., Patients and Methods: In 9 months, infliximab was given to 8 patients (4 male, 4 female aged 20-60 years) with uncontrolled ulcerative colitis of whom 6 were non-responders to parenteral steroids. All received the first infliximab dose as an intravenous infusion of 5 mg/kg., Results: Of the 8, 4 (50%) did not respond to the first injection and were submitted to urgent colectomy; the other four responded clinically. Two have maintained clinical remission for 7 months, without the need for steroids; both have received daily azathioprine at 2 mg/kg, and only one has received two further infliximab injections. Of the other two, one received a second injection at week 5, despite this relapsed, and underwent elective colectomy at that time; the other relapsed at 6 months and showed a partial response to a repeat infliximab infusion. Thus, the rate of sustained response is 2/8 (25%) in this study., Conclusion: These results, achieved in an open uncontrolled fashion, seem to reflect those of other independent studies. In our opinion, these findings warrant an in-depth reappraisal of the indication to use infliximab as rescue treatment for refractory ulcerative colitis.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disorder with variable expression and incomplete penetrance characterized by mucocutaneous pigmentation, predisposition to hamartomatous intestinal polyposis, and various other neoplasms. It occurs in approximately 1 in 8,300 to 29,000 live births. In nearly 50% of patients PJS is caused by germ line mutations in the STK11/LKB1 serine/threonine kinase gene, the only kinase gene currently known to act as a tumor suppressor. We have performed a mutation search in the STK11/LKB1 gene in 8 sporadic cases and 3 PJS families using a combination of different screening techniques. We have identified four mutations, two of which I177N and the IVS2+1A->G, were previously unreported. We have also evaluated the presence of cDNA alterations by means of RT-PCR analysis and direct cDNA sequencing and have found two aberrant transcripts in a single PJS case despite the lack of any apparent genomic alteration. Finally, we report the presence of a novel STK11/LKB1 cDNA isoform observed in all the normal subjects studied as well as in the majority of the PJS patients., (Copyright 2002 Wiley-Liss, Inc.)

Background: Patients with longstanding ulcerative colitis are at increased risk of colorectal cancer. In the literature, no agreement has yet been reached regarding prevention strategies. Our report sums up a prospective study started in 1980., Methods: A total of 65 patients affected by ulcerative colitis for more than seven years were admitted to a regular colonoscopic and biopsy follow-up programme., Results: Some 20 years after the beginning of the study, 23 (35.3%) patients have been operated upon, 2 patients have died but not from cancer 29 (44.66%) patients have abandoned the programme. Only 11 (16.9%) patients have remained under colonoscopic surveillance., Conclusion: These results cast some doubts on the significance of such a programme and on its long-term feasibility.

During the last year, promising results with the first clinical applications of capsule endoscopy have been reported; this is a new, revolutionary diagnostic method for endoscopic study of the small bowel. The method has chiefly been used in patients with obscure gastrointestinal bleeding, and in some cases has allowed additional diagnoses to be made in comparison with push enteroscopy, with a positive influence on patient management. New therapeutic possibilities have also been developed in push enteroscopy, emphasizing the role of this technique as an essential component of gastrointestinal endoscopy. Important innovations in enteroscopy technique have been described, aimed at increasing the depth of examination, and these will probably make it possible to extend endoscopic treatments to include the entire small bowel. Finally, numerous articles are still being published concerning intraoperative enteroscopy. It is to be hoped that, in future, the use of this invasive procedure will be based on data acquired by capsule endoscopy.

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.

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.

Western-style diets (WDs) trigger and sustain the early phases of tumorigenesis in mouse colon, and when continued throughout the life span lead to the development of dysplastic crypts. In order to evaluate the roles both of cell proliferation and programmed cell death (PCD) in WD-induced tumorigenesis, immunohistochemical detection of proliferating nuclear antigen (PCNA), in situ end labeling (TUNEL) of DNA breaks, and p53 protein were carried out in mouse colonic mucosa during prolonged feeding of two WDs. PCNA Labeling Index of colonic crypts was significantly higher in WD-treated animals than in controls only at the beginning of the nutritional study, the gap rapidly bridged by increased cell proliferation spontaneously occurring in the colonic mucosa during aging. A transient early homeostatic activation of PCD at the base of the crypt also was observed in WD groups. No changes in PCD were seen in the upper third of the crypt or in surface epithelium throughout the study, indicating that PCD in that colonic crypt segment produces a constant flux of cell loss, uninfluenced by homeostatic fluctuations. A major finding was an irreversible, progressive, age-related decline of PCD at the crypt base in both control and treated animals that occurred during the second half of the rodents' life span. p53 protein was not immunohistochemically detected, suggesting that neither overexpression of wild-type nor mutated forms of the protein are involved in the above mentioned changes.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.