This prospective study was performed to investigate epidemiological characteristics in terms of the age- and sex-specific incidence in patients with perforated and nonperforated appendicitis. The study population comprised 1486 consecutive patients who underwent appendectomy for suspected acute appendicitis between 1989 and 1993. Two patient cohorts [n = 544 (37%)] were analyzed with regard to prehospitalization duration of symptoms and in-hospital observation time. The crude incidence of acute appendicitis was 86 per 100,000 per year. Although the incidence of nonperforated appendicitis was highest among adolescents and young adults (13-40 years of age), perforated appendicitis occurred at almost the same incidence in all sex and age groups. The diagnostic accuracy was 76%. Perforated appendicitis occurred in 19%, with higher rates in small children and the elderly, irrespective of gender. A high diagnostic accuracy was not associated with an increased rate of perforation. In small children and the elderly, the diagnostic accuracy was low and the perforation rate high. Patients with perforation had a significantly longer duration of symptoms as well as in-hospital observation time than did patients with nonperforated appendicitis. Perforated appendicitis showed a different incidence pattern than nonperforated appendicitis and was associated with a significantly longer duration of symptoms and in-hospital observation time, probably due to patient-related factors. We suggest this observation deserves attention regarding clinical diagnosis and treatment decision-making for patients with suspected acute appendicitis.

BACKGROUND: Enhancer of zeste homologue 2 (EZH2) is a member of the Polycomb group of genes that is involved in epigenetic silencing and cell cycle regulation. METHODS: We studied EZH2 expression in 409 patients with colorectal cancer stages II and III. The patients were included in a randomised study, and treated with surgery alone or surgery followed by adjuvant chemotherapy. RESULTS: EZH2 expression was significantly related to increased tumour cell proliferation, as assessed by Ki-67 expression. In colon cancer, strong EZH2 expression (P ¼ 0.041) and high proliferation (X40%; P ¼ 0.001) were both associated with better relapse-free survival (RFS). In contrast, no such associations were found among rectal cancers. High Ki-67 staining was associated with improved RFS in colon cancer patients who received adjuvant chemotherapy (P ¼ 0.001), but not among those who were treated by surgery alone (P ¼ 0.087). In colon cancers stage III, a significant association between RFS and randomisation group was found in patients with high proliferation (P ¼ 0.046), but not in patients with low proliferation (P ¼ 0.26). Multivariate analyses of colon cancers showed that stage III (hazard ratio (HR) 4.00) and high histological grade (HR 1.80) were independent predictors of reduced RFS, whereas high proliferation indicated improved RFS (HR 0.55). CONCLUSION: Strong EZH2 expression and high proliferation are associated features and both indicate improved RFS in colon cancer, but not so in rectal cancer.

The proliferation factor mitotic activity index is the strongest prognostic factor in early breast cancer, but it may lack reproducibility. We analyzed the prognostic value of phosphohistone H3, a marker of cells in late G 2 and M phase, measuring highly standardized immunohistochemical nuclear phosphohistone H3 expression by subjective counts and digital image analysis. Expression was compared with classical clinico-pathologic prognostic variables and the mitotic activity index in 119 node-negative invasive breast cancers in patients less than 55 years old treated with adjuvant systemic chemotherapy with long-term follow-up (median 168 months). Nineteen patients (16%) developed distant metastases and 16 (13%) died. Strong phosphohistone H3 expression occurred preferentially in the peripheral growing front; counts were highly reproducible between observers (R ¼ 0.92) and highly consistent with digital image analysis (R ¼ 0.96). Phosphohistone H3 correlated (Po0.05) with tumor diameter, estrogen receptor, carcinoma grade, and mitotic activity index. Phosphohistone H3 values were systematically (80%) higher than the mitotic activity index. Receiver-operating curve analysis objectively showed that phosphohistone H3 o13 (n ¼ 53; 45% of all cases) vs phosphohistone H3Z13 (n ¼ 66; 55% of all cases) was the strongest prognostic threshold, with 20-year recurrence-free survival of distant metastases of 96 and 58%, respectively (P ¼ 0.0002, HR ¼ 9.6). Mitotic activity index was the second strongest prognostic variable (P ¼ 0.003, HR ¼ 3.9). In multivariate analysis, phosphohistone H3 o13 vsZ13 exceeded the prognostic value of the mitotic activity index. None of the other classical prognostic factors examined offered prognostic value additional to phosphohistone H3. Phosphohistone H3 is by far the strongest prognostic variable in early invasive node-negative breast cancer patients less than 55 years old with long-term follow-up.

Observer prognostic variability in staging and grading is considerable with potentially strong implications for patients. Interobserver variation did not decrease using the new 1999 WHO grading classification.

We validated and compared the prognostic value of the proliferation marker phosphohistone H3 (PPH3) with classical variables in 241 T(1-2)N(0)M(0) breast cancer patients less than 71 years old with long-term follow-up (median 117 months) and without adjuvant treatment. PPH3 was measured by automated digital image analysis. Thirty-seven patients (15%) developed distant metastases and 29 (12%) died. The previously established PPH3 prognostic threshold H3 <13 (n = 157; 65% of all cases) vs. >or=13 (n = 84; 35% of all cases) was the strongest prognostic threshold exceeding all other characteristics, with 10-year recurrence-free survival of distant metastases of 96 and 64%, respectively (P = < 0.0001, hazard ratio = 7.8, 95% confidence interval = 3.4-17.9). PPH3 is robust as it showed high inter-observer reproducibility and was prognostic over wide range of thresholds around 13 and is the strongest prognostic variable in invasive node-negative breast cancer patients less than 71 years old.