HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation.

Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects

Podocalyxin-like protein expression in primary colorectal cancer and synchronous lymph node metastases

Aims: Previous studies have shown that membranous expression of podocalyxin-like protein (PODXL) is associated with poor prognosis in colorectal cancer (CRC). In this study, we compared PODXL expression in primary CRC and synchronous lymph node metastases. We further analyzed whether its expression changed in rectal tumours after neoadjuvant radiation therapy. Methods and results: The studied cohort consists of 73 consecutive patients from the South-Swedish Colorectal Cancer Biobank. Immunohistochemical PODXL expression was examined on full-face sections from all primary tumours and all 140 available lymph node metastases from 31 cases. Membranous PODXL expression was denoted in 18/73 (24,7%) primary tumours, with a high concordance between primary and metastatic lesions. While all negative primary tumours had negative metastases, some PODXL positive primaries had a varying proportion of positive and negative metastatic lymph nodes. PODXL expression was also found to be mainly unaltered in pre- and post-irradiation surgically resected tumour specimens in rectal cancer patients (n=16). Conclusions: The findings in this study suggest that analysis of PODXL expression in the primary tumour is sufficient for its use as a prognostic and treatment predictive biomarker in CRC, also in patients with metastatic disease

High resection rates of colorectal liver metastases after standardized follow-up and multimodal management:an outcome study within the COLOFOL trial

Background: Outcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy. Methods: In the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS. Results: Of 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46–0.85). Conclusion: A high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients

Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden

<p/> <p>Background</p> <p>Acute surgery in the management of malignant colonic obstruction is associated with high morbidity and mortality. The use of self-expanding metal stents (SEMS) is an alternative method of decompressing colonic obstruction. SEMS may allow time to optimize the patient and to perform preoperative staging, converting acute surgery into elective. SEMS is also proposed as palliative treatment in patients with contraindications to open surgery. Aim: To review our experience of SEMS focusing on clinical outcome and complications. The method used was a review of 75 consecutive trials at SEMS on 71 patients based on stent-protocols and patient charts.</p> <p>Findings</p> <p>SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months.</p> <p>Conclusion</p> <p>Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.</p

Systemic and Local Inflammatory Mediator Response to Major Surgery

Cell-signalling via cytokines modulates the local response to surgical trauma, directs the immunologic response and initiates the healing process. Surgical trauma induces a systemic cytokine response and a down-regulation of the antigen presentation capacity of monocytes (HLA-DR expression), which is associated with a poor prognosis if pronounced. The aims with the studies in this thesis were to identify factors that modulate the cytokine and the immune-cell responses to major surgery and to evaluate the role of collagenases in colonic healing. Major surgery evoked a cytokine response in the systemic circulation, which was enhanced by the presence of a cancer, in colorectal resections. The IL-6 response in colorectal surgery originated from the bowel and enhanced concentrations of IL-6 in tissue of colorectal cancers, emanating from an IL-6 expression in the malignant epithelium, might be the source. Open surgery for abdominal aortic aneurysm (AAA) repair induced higher IL-6 responses than transfemorally placement of endoluminal grafts (TPEG), lower peri-operative sigmoidal pH but equal down-regulation of the HLA-DR expression on monocytes. These findings suggest that tissue destruction influences the systemic IL-6 response in trauma, but not the down-regulation HLA-DR expression on monocytes. Experimental colonic obstruction in rats implied a local inflammatory response and an increased break-down of collagen by matrix metalloproteinases in the colonic wall, leading to a decrease in collagen concentration, assessed as hydroxyproline concentration. Inhibition of MMPs in the early phase of anastomotic healing in the colon, resulted in increased breaking strength of the anastomoses in inhibitor-treated animals compared to controls, confirming a negative role of MMPs in this phase of colonic healing. The knowledge on cytokine response to surgical trauma and interactions with the healing process needs to be expanded by studies on local events in tissue. The information on collagenase up-regulation in the local inflammatory response in the colon and the results of MMP-inhibition in anastomotic healing are promising in the efforts to improve healing in colorectal surgery

Short- and long-term outcomes following bridge to surgery and emergency resection in acute malignant large bowel obstruction

Aim: Bridge to surgery (BtS) aims to decrease perioperative morbidity and mortality in emergency resection (ER) of the colon. Previous results are inconsistent, and long-term comparisons are scarce. The aim of this study was to compare the short- and long-term outcomes of BtS and ER. Method: This retrospective study examined data from the Swedish Colorectal Cancer Registry for patients treated for acute malignant large bowel obstruction from 2007 to 2009. Patients were grouped by treatment strategy: BtS (using a self-expanding metallic stent or diverting stoma) or ER. Medical records were scrutinized for all patients in the BtS group. The primary endpoints were 5-year overall survival (OS) and 3-year recurrence-free survival (RFS). The secondary endpoints were postoperative mortality and morbidity rates and stoma permanence. Results: Overall, 143 patients were treated using BtS versus 1302 patients treated with ER. The 5-year OS was higher in the BtS group than in the ER group (53.8% vs. 37.4%; p < 0.05). No difference was noted in the 3-year RFS (75.7% vs. 75.0%; p = 0.38). The postoperative mortality rate was lower in the BtS group than in the ER group (0.7% vs. 7.3%; p < 0.05). Complications occurred in 46.9% of patients in the BtS group (both procedures) versus 35.9% of patients in the ER group (p < 0.05); the rate of severe complications was 23.1% and 16.9%, respectively (p = 0.07). Conclusion: This retrospective population-based registry study showed higher long-term survival and lower postoperative mortality rates among patients treated with BtS versus ER for acute malignant large bowel obstruction