Improved overall survival for patients with rectal cancer since 1990: the effects of TME surgery and pre-operative radiotherapy.

Aim: The aim was to study the effects of the introduction of TME surgery and pre-operative radiotherapy on overall survival (OS) by comparing patients treated in the period before (1990-1995), during (1996-1999) and after (2000-2002) the TME trial.

Patients And Methods: Patients diagnosed with rectal carcinoma in the region of Comprehensive Cancer Centres South and West were used (n=3179).

Results: Five-year OS was, respectively, 56%, 62% and 65% in the pre-trial, trial and post-trial periods (p<0.

Prediction of the immunogenic potential of frameshift-mutated antigens in microsatellite instable cancer.

Microsatellite instable (MSI) cancers express frameshift-mutated antigens, the C-terminal polypeptides of which are foreign to the immune system. Consequently, these antigens constitute a unique pool of tumor-specific antigens that can be exploited for patient diagnosis and selective, immune-mediated targeting of cancers. However, other than their sequence, very little is known about the characteristics of the majority of these proteins.

Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902.

Introduction: The Preoperative Chemotherapy in Primary Operable Breast Cancer (POCOB) study was designed to compare preoperative with postoperative chemotherapy in patients with early breast cancer concerning breast conserving therapy (BCT) procedures, disease free survival (DFS) and overall survival (OS).

Methods: Patients (n = 698) with early breast cancer were enrolled between 1991 and 1999 and randomized between preoperative versus postoperative chemotherapy (four cycles of fluorouracil, epirubicin, and cyclophosphamide). Endpoints were BCT procedures, DFS, OS, and tumor response to preoperative chemotherapy.

Level of arterial ligation in rectal cancer surgery: low tie preferred over high tie. A review.

Consensus does not exist on the level of arterial ligation in rectal cancer surgery. From oncologic considerations, many surgeons apply high tie arterial ligation (level of inferior mesenteric artery). Other strategies include ligation at the level of the superior rectal artery, just caudally to the origin of the left colic artery (low tie), and ligation at a level without any intraoperative definition of the inferior mesenteric or superior rectal arteries.

Isolated hepatic perfusion with 200 mg melphalan for advanced noncolorectal liver metastases.

Purpose: The liver is one of the most common sites for metastatic solid tumors. If the liver is the only site of metastatic disease, regional treatment options can offer the benefit of high local exposure with limited systemic toxicity, especially for patients without (further) systemic treatment options. We report the results of our experience with isolated hepatic perfusion (IHP) in patients with isolated liver metastases from a variety of primary tumors.

Quantitative analysis of methylation of genomic loci in early-stage rectal cancer predicts distant recurrence.

Purpose: There are no accurate prognostic biomarkers specific for rectal cancer. Epigenetic aberrations, in the form of DNA methylation, accumulate early during rectal tumor formation. In a preliminary study, we investigated absolute quantitative methylation changes associated with tumor progression of rectal tissue at multiple genomic methylated-in-tumor (MINT) loci sequences.

Controversies of total mesorectal excision for rectal cancer in elderly patients.

The cornerstone of treatment for rectal cancer is resectional treatment according to the principles of total mesorectal excision (TME). However, population-based registries show that improvements in outcome after resectional treatment occur mainly in younger patients. Furthermore, 6-month postoperative mortality is significantly increased in elderly patients (> or = 75 years of age) compared with younger patients (< 75 years of age).

Disrupted expression of CXCL5 in colorectal cancer is associated with rapid tumor formation in rats and poor prognosis in patients.

Purpose: We isolated a subline (CC531M) from the CC531S rat colon carcinoma cell line, which grows and metastasizes much more rapidly than CC531S. We found, using RNA expression profiling, that one of the major changes in the CC531M cell line was a 5.8-fold reduction of the chemokine CXCL5.

Epithelial human leukocyte antigen-DR expression predicts reduced recurrence rates and prolonged survival in rectal cancer patients.

Purpose: The development of local and distant recurrences is a major problem in the treatment of rectal cancer patients. In this study, we investigated whether epithelial human leukocyte antigen-DR (HLA-DR) expression allowed discrimination between high and low tumor recurrence rates, and analyzed the mechanism behind its expression.

Experimental Design: The role of IFNgamma in HLA-DR expression was studied in rectal cancer cell lines and tumors by promoter-specific analyses of class II transactivator (CIITA).

Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.

Materials And Methods: The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib.

USPIO-enhanced MR imaging for nodal staging in patients with primary rectal cancer: predictive criteria.

Purpose: To prospectively determine diagnostic performance of predictive criteria for nodal staging with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging in primary rectal cancer patients, with histopathologic findings as reference standard.

Materials And Methods: Institutional review board approval and informed consent were obtained. Twenty-eight rectal cancer patients (18 men, 10 women; mean age, 68 years) underwent USPIO-enhanced MR.

Epigenetic silencing of cyclooxygenase-2 affects clinical outcome in gastric cancer.

Purpose: Overexpression of cyclooxygenase-2 (COX-2) in gastric cancer has been shown to enhance tumor progression. We investigated whether silencing by promoter region hypermethylation of the COX-2 gene contributes to disease outcome in gastric cancer.

Materials And Methods: COX-2 methylation status was initially assessed by capillary array electrophoresis methylation-specific polymerase chain reaction (CAE-MSP) and COX-2 protein expression by immunohistochemistry (IHC) in 40 primary gastric cancer tissues in a pilot study.

The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma.

Objective: To investigate the efficacy of preoperative short-term radiotherapy in patients with mobile rectal cancer undergoing total mesorectal excision (TME) surgery.

Summary Background Data: Local recurrence is a major problem in rectal cancer treatment. Preoperative short-term radiotherapy has shown to improve local control and survival in combination with conventional surgery.

Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis.

Introduction: Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer.

Caspase-3 activity predicts local recurrence in rectal cancer.

Purpose: Radiotherapy followed by total mesorectal excision surgery has been shown to significantly reduce local recurrence rates in rectal cancer patients. Radiotherapy, however, is associated with considerable morbidity. The present study evaluated the use of biochemical detection of enzymatic caspase-3 activity as preoperative marker for apoptosis to preselect patients that are unlikely to develop a local recurrence to spare these patients from overtreatment and the negative side effects of radiotherapy.

DNA copy number profiles of gastric cancer precursor lesions.

Background: Chromosomal instability (CIN) is the most prevalent type of genomic instability in gastric tumours, but its role in malignant transformation of the gastric mucosa is still obscure. In the present study, we set out to study whether two morphologically distinct categories of gastric cancer precursor lesions, i.e.

Clinical impact of HLA class I expression in rectal cancer.

Purpose: To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas.

Experimental Design: Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10).

Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer. A phase I-II multicenter study of the Dutch Colorectal Cancer Group.

Background: We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer.

Methods: T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m(2) twice daily (days 1-14, 25-38) added to RT with 50.4 Gy and surgery after 6-8 weeks.

Quality of surgery in T3-4 rectal cancer: involvement of circumferential resection margin not influenced by preoperative treatment. Results from EORTC trial 22921.

Purpose: The present analyses aimed to determine risk factors for rectal cancer patients associated with circumferential resection margin (CRM) and number of examined lymph nodes (LN) and to correlate these parameters of surgical quality with local recurrence (LR), disease-free and overall survival (DFS and OS).

Materials And Methods: Data of 884 eligible patients, who underwent a resection and had no metastases at time of surgery, were analysed.

Results: Age, period of treatment, distance and pT-stage were associated with surgical quality.

Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo.

The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo, 47 rectal tumors with known apoptotic phenotype (24 low- and 23 high-apoptotic) were analyzed by oligonucleotide microarray technology. We identified several genes differentially expressed between low- and high-apoptotic tumors.

Introduction of a breast cancer care programme including ultra short hospital stay in 4 early adopter centres: framework for an implementation study.

Background: Whereas ultra-short stay (day care or 24 hour hospitalisation) following breast cancer surgery was introduced in the US and Canada in the 1990s, it is not yet common practice in Europe. This paper describes the design of the MaDO study, which involves the implementation of ultra short stay admission for patients after breast cancer surgery, and evaluates whether the targets of the implementation strategy are reached. The ultra short stay programme and the applied implementation strategy will be evaluated from the economic perspective.

Risk factors for adverse outcome in patients with rectal cancer treated with an abdominoperineal resection in the total mesorectal excision trial.

Objective: This study was performed to identify tumor- and patient-related risk factors for distal rectal cancer in patients treated with an abdominoperineal resection (APR) associated with positive circumferential resection margin (CRM), local recurrence (LR), and overall survival (OS).

Background: The introduction of total mesorectal excision (TME) has improved the outcome of patients with rectal cancer. However, survival of patients treated with an APR improved less than of those treated with low anterior resections (LAR).