Purpose: After preoperative (radio)chemotherapy, histologic determinants for prognostification have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival. Experimental Design: A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems. All patients received neoadjuvant radiochemotherapy or radiotherapy. The prognostic value of all factors was tested with univariate survival analysis of time to local recurrence and overall survival. Results: Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (P < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (P < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (P = 0.02 and 0.03, respectively). Conclusions: Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapyinduced regression.

Thymidylate synthase (TS) is a potentially valuable marker for therapy response since it is the molecular target of 5-fluorouracil (5-FU). TS can be analyzed at the DNA (gene polymorphisms and amplification) and protein level (immunohistochemistry). This study investigated the predictive role of TS at the DNA and protein levels in patients with N 1 colon cancer (n 5 38). Tumor and normal tissues were genotyped using PCR for variable number of tandem repeats (VNTR), a single nucleotide polymorphism (SNP) in the 3R allele and a 6 bp deletion (1494del6) in the TS gene. Tumor tissues were additionally analyzed for loss of heterozygosity (VNTR polymorphism). A newly developed real time PCR assay was used to detect the presence of TS gene amplifications in tumor tissues. VNTR analysis in normal tissue was significantly associated with distant tumor recurrence (8% for 2R/2R vs. 52% for patients carrying a 3R allele, p 5 0.038) and cancer-specific survival (p 5 0.021). IHC was not found to be significantly associated with patients' outcome. No correlations between TS gene polymorphisms and IHC were found. However, TS gene amplification was correlated with a strong IHC staining intensity. In conclusion, this study indicates that DNA based analysis is more predictive for patientsÕ outcome than TS IHC. ' 2008 Wiley-Liss, Inc.Key words: thymidylate synthase; polymorphism; 5-fluorouracil; colon cancer; gene amplification A substantial number of patients with colon cancer who received adjuvant 5-fluorouracil (5-FU)-based therapy will not benefit from it. Therefore, predictive markers are needed in order to discriminate between responsive and nonresponsive patients. Thymidylate synthase (TS) is a central enzyme in DNA synthesis and is a potentially valuable marker since it is the molecular target of 5-FU. TS protein expression is affected by 3 different functional polymorphisms in the untranslated regions (UTRs) of the gene. Sensitivity to 5-FU based therapy might be largely influenced by the intracellular levels of the TS protein.TS protein levels can be studied directly by western blotting, enzyme activity assays, 1,2 ELISA 3,4 and immunohistochemistry (IHC). 5,6 The mainstream method is IHC because it is a relatively cheap, widely implemented technique that enables studying protein expression in situ. At the DNA level, TS protein expression is affected by different underlying functional polymorphisms as shown by several functional studies. [7][8][9][10][11][12] These polymorphisms are the following: a variable number of tandem repeats (VNTR) containing 2 (2R) or 3 (3R) repeats of 28 bp, 7 a single nucleotide polymorphism (SNP) of a G to C substitution in the 3R allele 9 in the 5 0 UTR and a 6 bp deletion at nucleotide 1494 in the 3 0 UTR (1494del6). 12 Recently, a SNP of a G to C substitution in the first repeat of the 2R allele has also been found (hereafter referred to as the 2RC allele). 13,14 TS mRNA with 3 repeats has greater translation efficiency than mRNA with 2 repeats. 7,11 Individuals with a 3R/3R genotype will,...

Combined RCT is also successful in highly apoptotic tumours and is therefore independent of intrinsic apoptosis.

Lipomatous hypertrophy of the interatrial septum is a rare cardiac lesion that is usually limited to the interatrial septum. We report a case of an extensive lipomatous hypertrophy, which protruded into the right and the left atrium as well as the superior and the inferior vena cava and the right ventricle. A 71-year-old woman was referred to us because of a cardiac mass on a transthoracic echocardiogram, performed on a routine check-up because of a known membranous ventricular septum defect. She underwent surgical resection of the mass and closure of the ventricular septum defect. The postoperative period was complicated by superior vena cava syndrome for which she underwent re-operation. The post mortem histopathological diagnosis was a lipomatous hypertrophic interatrial septum.

<div>Abstract<p><b>Purpose:</b> After preoperative (radio)chemotherapy, histologic determinants for prognostification have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival.</p><p><b>Experimental Design:</b> A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems. All patients received neoadjuvant radiochemotherapy or radiotherapy. The prognostic value of all factors was tested with univariate survival analysis of time to local recurrence and overall survival.</p><p><b>Results:</b> Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (<i>P</i> < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (<i>P</i> < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (<i>P</i> = 0.02 and 0.03, respectively).</p><p><b>Conclusions:</b> Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapy-induced regression.</p></div>