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Supplementary Table S1 from Circumferential Margin Involvement Is the Crucial Prognostic Factor after Multimodality Treatment in Patients with Locally Advanced Rectal Carcinoma

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 (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 therapy-induced regression.

Contains fulltext : 71387.pdf (Publisher’s version ) (Open Access) BACKGROUND: Not all patients with locally advanced rectal cancer (LARC) respond equally to neo-adjuvant radiochemotherapy (RCT). Patients with highly apoptotic less advanced rectal cancers do not benefit from short-term radiotherapy. This study investigates whether this is also the case in the setting of RCT for LARC. PATIENTS AND METHODS: Tissue microarrays were constructed of biopsy and resection specimens of 201 LARC patients. Apoptosis (M30) and several apoptosis-regulating proteins [p53, Bcl-2, Bax, cyclooxygenase-2 (Cox-2) and mamma serine protease inhibitor (maspin)] were studied with immunohistochemistry. Subsequently, predictive values for local recurrence (LR), overall survival (OS) and histological tumour regression were analysed. RESULTS: Apoptotic levels, quantified as the number of apoptotic cells/mm(2) tumour epithelium, were higher in posttherapy tissues compared with biopsies (P < 0.001). Biopsies from clinical T4 stage tumours demonstrated significantly higher levels of apoptosis than clinical T3 stage tumours (P = 0.020). Therapy-induced apoptosis was higher when the interval between the last day of irradiation and surgery increased (P < 0.001, correlation coefficient = 0.355). Pre- and posttherapy apoptosis, p53, Bcl-2, Bax and Cox-2 were not associated with LR, OS or tumour regression. Intense pretherapy cytoplasmatic staining of maspin indicated a higher risk on LR (P = 0.009) only. CONCLUSION: 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.

Purpose: to promote a better understanding of locally recurrent rectal cancer disease among surgeons, radiologists, radiotherapists and medical oncologists. Since 1994, a specialized team in the Catharina Hospital Eindhoven is involved in the treatment of patients with locally recurrent rectal cancer. The complete resection rate increased from 42% to 65%. A 30% crude survival rate for all patients was attainable. After complete resection, a five-year survival rate above 40% was achieved (1). Imaging is the cornerstone for treatment planning. However, not merely the diagnosis, which is itself often difficult to obtain, but also the operative planning of the treatment is of interest to the team. The role of the different imaging modalities during consecutive phases of locally recurrent rectal cancer disease is discussed.

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(+) colon cancer (n = 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 = 0.038) and cancer-specific survival (p = 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 patients' outcome than TS IHC.

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 ( 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 therapy-induced regression.

Three patients, two men aged 54 and 72 years, respectively, and a woman aged 52 years, were treated successfully for (recurrence of a) keratoacanthoma with methotrexate. Since the sixties 11 patients with recurrent keratoacanthoma treated with methotrexate have been described. Dose schedules were widely different and dosages were in general high, resulting in more or less severe side effects. The patients now presented were treated according to the Weinstein schedule, with small doses and during a short period, which minimises the adverse effects.