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Objectives: The purposes of the study are to describe the incidence trend of malignant polyp of large bowel over a 25-year period in the District of Modena and to assess the effect of an organized colorectal cancer screening program., Material and Methods: Through the data of a specialized colorectal cancer Registry, we evaluate the clinical and pathological features of the polyps. Trend analysis was assessed with the Joinpoint Regression Program., Results: A total of 172 patients with malignant polyps were diagnosed throughout the study (3.5% of 4.835 registered patients); their overall frequency during the registration period increased from zero cases in the initial years (1984-85) to 57 cases in the past 3 years (2006-2008). Crude incidence rate passed from 0.37 in 1986-89 to 10.2 in 2006. Joinpoint trend analysis of crude rates showed a significant increase of incidence during the study period, with percent of annual variation ranging between 38.6% (95% CI 12.5-70.7) and 7.3% (95% CI 2.6-12.1). During the screening period (2005-2008, the past 4 years of registration) there was a significant increase of sessile polyps (p < 0.001), while other clinical and morphological features, including the number of low- and high-risk malignant polyps, remained unchanged. The surgery (after polypectomy) tended to raise both in low- and high-risk subgroups., Conclusion: The incidence of malignant polyps increased significantly from the initial to the most recent periods of colorectal cancer registration. Screening was associated with changes in gross morphology of polyps and with an increased use of the surgery after endoscopic polypectomy.

Background: The analysis of regional lymph nodes is particularly relevant in patients with stage II colorectal cancer, in whom the role of adjuvant chemotherapy remains unclear. The aim of this study was to assess the relationship between number of examined lymph nodes and survival in patients with stage IIA (pT3N0M0) colorectal cancer, and to determine the optimal number of lymph nodes that should be examined., Methods: The study group included all the surgically-treated colorectal cancer patients in stage IIA (n = 657) who were identified through the population-based Cancer Registry of the Province of Modena (Northern Italy), during the period 2002-2006., Results: The median number of harvested lymph nodes was 19 (range 1-68). Considering, as a reference point, patients with 12 or less lymph nodes, subjects with n ≥ 20 lymph nodes examined showed, in univariate analysis, a significantly higher cancer specific (p = 0.01) and relapse-free survival (p = 0.003). The results were confirmed by multivariate analysis (Cox model)., Conclusion: The result suggests that colorectal cancer patients in stage IIA with n ≥ 20 lymph nodes examined exhibit better survival when compared with subjects in whom fewer lymph nodes were examined. The number of 20 lymph nodes is the essential requirement for an oncologic resection of the large bowel.

Objective: Stage I colorectal carcinomas display a highly variable behavior which is not accurately predicted by the available prognostic markers. CD133 is considered a useful marker to identify the so-called cancer stem cells in colorectal cancers (CRCs) and its expression has been shown to have prognostic significance in CRC patients. This study aimed to verify whether immunohistochemical evaluation of CD133 might correlate with the progression risk of stage I CRC patients., Material and Methods: Expression levels of the CD133 molecule were analyzed and compared in two series of stage I surgically resected CRC patients showing disease progression and death for the disease and patients with no evidence of disease progression after at least 6 years after surgery., Results: A positive staining for CD133 was detected in 52% of the cases with poor prognosis and only in 9% of the group with good prognosis, and this difference was highly significant (p < 0.001). A significant correlation was detected between CD133 expression and histological parameters, such as tumor budding, vascular invasion, and presence of lymph node micrometastases but not tumor grading, gender, and age. Disease-free survival and cancer-specific survival of CD133 negative tumors were significantly longer compared to positive cases. In multivariate analyses, CD133 staining confirmed to be a predictor of shorter survival independent from vascular invasion but not from lymph nodes micrometastases., Conclusions: These findings demonstrate that CD133 immunostaining is a useful predictor of high risk progression in stage I CRC patients and might help to identify patients eligible for adjuvant chemotherapy.

Objective: The study reviews the endoscopic and histological features of human cytomegalovirus (HCMV) infections of the upper gastrointestinal (UGI) tract., Materials and Methods: Clinical histories, endoscopic findings and bioptic specimens of 30 cases of HCMV infection of the UGI tract, diagnosed in a University Hospital in a 10-year period, were reviewed. In all cases, viral inclusion bodies were detected in routine histopathological sections and the diagnosis was confirmed with immunohistochemistry., Results: Six patients were HIV+, whereas four had received organ transplantations, one was affected by common variable immunodeficiency and four had a recent history of malignancy. No other pathologic condition was evidenced in the remaining 15 cases. Mucosal alterations were endoscopically observed in the stomach (19 cases), esophagus (9), cardias (6) and duodenum (1), and multiple organs being synchronously affected in five patients (3 HIV+, 2 with history of malignancy). The antropyloric area was the most frequently affected site. Single ulcers were detected in 11 cases and multiple ulcers in 8, whereas mucosal thickenings (in the form of localized thickenings, polyps or rugal hypertrophy) were present in 13 patients. Thickenings of the mucosa were detected only in the stomach. At histology, necrotic material and granulation tissue were associated with moderate or marked lympho-plasmacytic infiltrate and foveolar hyperplasia in ulcerative lesions, whereas lesions labeled as mucosal thickenings showed mild or moderate chronic inflammatory infiltrate and foveolar hyperplasia., Conclusions: Endoscopic manifestations of UGI tract involvement in HCMV infection are not specific, varying from erythematous mucosa to ulcers to mucosal thickenings.

Objective: Although patients with Stage I colorectal cancer show an excellent prognosis, a few of them die of metastatic disease. In this subgroup of individuals, the search of occult metastasis might reveal that early dissemination of tumor cells could be the cause of cancer progression., Material and Methods: Through a Cancer Registry, we selected all patients with Stage I disease who died of metastatic tumor; a total of 32 patients were identified and in 25 of them paraffin-embedded material was available. The group was matched to 70 Stage I patients with favorable prognosis (controls). In cases and controls resected lymph nodes were cut, and micrometastases were searched using pan-cytokeratin antibodies., Results: Micrometastases were detected in 18 of 25 (72%) Stage I patients who died of the disease, while they were almost absent among controls (1 of 70, p < 0.001 by χ(2) test). Vascular invasion and tumor budding were more frequent among Stage I patients with an unfavorable prognosis than in controls. By regression analyses, micrometastases (HR 12.3, CI 4.8-32) and vascular invasion (HR 3.5, CI 1.4-8.5) maintained an independent association with prognosis (cancer-specific survival)., Conclusion: Micrometastasis in the lymph nodes can be revealed in the majority of patients with early colorectal cancer who die of tumor progression, while they appear extremely rare in Stage I individuals with good prognosis. The selection of patients through histology (vascular invasion) and search of occult metastatic cells might represent a way to identify individuals who might benefit from adjuvant chemotherapy.

Objective: Familial adenomatous polyposis (FAP) is an interesting model for the study of colorectal tumour. Two genes contribute to the FAP phenotype - APC and MUTYH - but their relative role is still undefined. The objective of this study was to evaluate the contribution of the two genes to the pathogenesis of FAP by means of a series of FAP families., Material and Methods: Sixty-one unrelated families with a diagnosis of FAP and a total of 187 affected individuals were evaluated. After extracting DNA, APC and MUTYH genes were sequenced., Results: In the whole series of patients, colectomy with ileorectal anastomosis was the most frequent surgery, although the number of patients treated by total proctocolectomy and ileoanal anastomosis was increasing. Duodenal and jejunal-ileal adenomas were present in more than half of the patients. Constitutional mutations were detected in 37 of the 45 families (82.2%); there were 33 families with APC and 4 with MUTYH alterations. Age at onset of polyposis and age at surgery were 10-15 years delayed for carriers of MUTYH mutations; cancer at diagnosis was frequent, and extracolonic manifestations were diagnosed in the majority of MUTYH-positive families. MUTYH-associated polyposis showed the horizontal transmission expected for recessive inheritance (at variance with the dominant pattern seen with APC mutations)., Conclusions: At least two genes are associated with the FAP phenotype. APC mutations account for the majority of cases, while MUTYH mutations can be observed in 10% of patients. There are few but definite differences between APC- and MUTYH-associated FAP, such as age at diagnosis and pattern of transmission.

Objective: A unique mutation of the MLH1 gene was recently reported in six families living in a small area of Northern Italy. The mutation consists in the insertion of a T base between nucleotides 2269 and 2270 (2269-2270insT), causing the synthesis of an unstable polypeptide. The mutation was not reported by other investigators or outside this small geographic area, thus suggesting a possible founder effect. The main purpose of this investigation was to investigate whether patients (and families) with the 2260-2270insT mutation show relevant clinical differences when compared with individuals with other MLH1 or MSH2 gene alterations., Material and Methods: We identified hereditary non-polyposis colorectal cancer (HNPCC) families through the specialized colorectal cancer registry following a previously described multistep approach. In all, 58 HNPCC families were identified; of these, 38 were detected through the registry, and 20 were referred from other areas in Italy., Results: Small differences were found in the main clinical and pathologic features; however, tumour burden per family tended to be higher in kindred sharing the founder mutation; in addition, multiple primaries (four or five different tumours in some subjects) were significantly more frequent in patients with the 2269-2270insT than in individuals with MSH2, MLH1 gene mutations or sporadic colorectal neoplasms. No significant difference in prognosis was found between patients with the founder mutation and those with other MLH1 or MSH2 mutations. Regardless of the type of mutation, neoplasms of the colon-rectum, stomach and endometrium represented nearly 80% of the tumour burden in families with HNPCC., Conclusions: A proclivity to multiple tumours arising in the same subject and a higher tumour burden per family were the most relevant findings observed in affected patients with the founder mutation compared with other MLH1 or MSH2 mutations. In general, the results of the study underline the difficulty in discriminating between Lynch I and Lynch II syndromes on the basis of specific molecular changes.