The Impact of Postoperative Complications on Long-Term Outcomes Following Curative Resection for Colorectal Cancer

Background This study aimed to investigate the impact of postoperative complications on long-term survival and disease recurrence in patients who underwent curative resection for colorectal cancer. Method Patients who underwent radical resection for colorectal cancer with curative intent from January 1996 to December 2004 were included. Operative mortality and morbidity were documented prospectively. Factors that might affect long-term outcome were analyzed with multivariate analysis. Results Curative resection was performed in 1657 patients (943 men), and the median age was 70 years (range: 24–94 years). The 30-day mortality was 2.4%, and the complication rate was 27.3%. Age over 70 years (P < .001, odds ratio: 2.06, 95% CI: 1.63–2.61), male gender (P = .001, odds ratio: 1.49, 95% CI: 1.19–1.88), emergency operation (P < .001, odds ratio: 3.14, 95% CI: 2.26–4.35) and rectal cancer (P < .001, odds ratio: 1.41, 95% CI: 1.25–1.61) were associated with a significantly higher complication rate. With exclusion of patients who died within 30 days, the median follow-up of the surviving patients was 45.3 months. The 5-year overall survival was 64.9%, and the overall recurrence rate was 29.1%. The presence of postoperative complications was an independent factor associated with a worse overall survival (P = .023, hazard ratio: 1.26; 95% CI: 1.03–1.52) and a higher overall recurrence rate (P = .04, hazard ratio: 1.26; 95% CI: 1.01–1.57). Conclusion The presence of postoperative complication not only affects the short-term results of resection of colorectal cancer, but the long-term oncologic outcomes are also adversely affected. Long-term outcomes can be improved with efforts to reduce postoperative complications.     

Inhibiting glycogen synthase kinase-3 reduces endotoxaemic acute renal failure by down-regulating inflammation and renal cell apoptosis

Background and purpose:

Excessive inflammation and apoptosis are pathological features of endotoxaemic acute renal failure. Activation of glycogen synthase kinase-3 (GSK-3) is involved in inflammation and apoptosis. We investigated the effects of inhibiting GSK-3 on lipopolysaccharide (LPS)-induced acute renal failure, nuclear factor-κB (NF-κB), inflammation and apoptosis.

Experimental approach:

The effects of inhibiting GSK-3 with inhibitors, including lithium chloride (LiCl) and 6-bromo-indirubin-3′-oxime (BIO), on LPS-treated (15 mg·kg⁻¹) C3H/HeN mice (LiCl, 40 mg·kg⁻¹ and BIO, 2 mg·kg⁻¹) and LPS-treated (1 µg·mL⁻¹) renal epithelial cells (LiCl, 20 mM and BIO, 5 µM) were studied. Mouse survival was monitored and renal function was analysed by histological and serological examination. Cytokine and chemokine production, and cell apoptosis were measured by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick-end labelling staining, respectively. Activation of NF-κB and GSK-3 was determined by immunostaining and Western blotting, respectively.

Key results:

Mice treated with GSK-3 inhibitors showed decreased mortality, renal tubular dilatation, vacuolization and sloughing, blood urea nitrogen, creatinine and renal cell apoptosis in response to endotoxaemia. Inhibiting GSK-3 reduced LPS-induced tumour necrosis factor-α (TNF-α) and CCL5/RANTES (released upon activation of normal T-cells) in vivo in mice and in vitro in murine kidney cortical collecting duct epithelial M1 cells. Inhibiting GSK-3 did not block TNF-α-induced cytotoxicity in rat kidney proximal tubular epithelial NRK52E or in M1 cells.

Conclusions and implications:

These results suggest that GSK-3 inhibition protects against endotoxaemic acute renal failure mainly by down-regulating pro-inflammatory TNF-α and RANTES.     

Influence of resection margin on survival in hepatic resections for colorectal liver metastases

Background:

Traditionally a 1-cm margin has been accepted as the gold standard for resection of colorectal liver metastases. Evidence is emerging that a lesser margin may provide equally acceptable outcomes, but a critical margin, below which recurrence is higher and survival poorer, has not been universally agreed. In a recent publication, we reported peri-operative morbidity and clear margin as the two independent prognostic factors. The aim of the current study was to further analyse the effect of the width of the surgical margin on patient survival to determine whether a margin of 1 mm is adequate.

Methods:

Two hundred and sixty-one consecutive primary liver resections for colorectal metastases were analysed from 1992 to 2007. The resection margins were assessed by microscopic examination of paraffin sections. The initial analysis was performed on five groups according to the resection margins: involved margin, 0–1 mm, >1–<4 mm, 4–<10 mm and ≥ 10 mm. Subsequent analysis was based on two groups: margin <1 mm and >1 mm.

Results:

With a median follow-up of 4.7 years, the overall 5-year patient and disease-free survival were 38% and 22%, respectively. There was no significant difference in patient- or disease-free survival between the three groups with resection margins >1 mm. When a comparison was made between patients with resection margins ≤1 mm and patients with resection margins >1 mm, there was a significant 5-year patient survival difference of 25% versus 43% (P < 0.04). However, the disease-free survival difference did not reach statistical significance (P= 0.14).

Conclusions:

In this cohort of patients, we have demonstrated that a resection margin of greater than 1 mm is associated with significantly improved 5-year overall survival, compared with involved margins or margins less than or equal to 1 mm. The possible beneficial effect of greater margins beyond 1 mm could not be demonstrated.     

Dysregulation of protein kinase C activity in chemoresistant metastatic breast cancer cells

This study was performed to evaluate the role of protein kinase C (PKC) activity in the development of chemoresistance in clinical breast cancer cells. To simulate the clinical situation, native tumor cells derived from 10 patients with advanced breast cancer were brought into short-term cultures, and treated with anthracyclines (doxorubicin, mitoxantrone), paclitaxel and combinations, respectively. After 3 days of incubation, we determined total PKC activity relative to each control incubated with blank medium. Furthermore, we determined the chemoresistance against these drugs from each cell population separately. Relative PKC activity ranged from 14 to 249%; 64% (37 of 58) of the breast cancer cell suspensions were considered chemoresistant. There was a non-significant trend to a higher relative PKC activity in resistant cells compared to non-resistant cells (p=0.058), regardless of the antineoplastic agent investigated. The individual variability in both PKC activity and chemoresistance pattern revealed that dysregulated PKC activity mediates resistance to antineoplastics. In order to achieve clinical value, evaluation of more data concerning the PKC signal-transduction pathway is necessary. New protocols of cancer treatment will require this information in order to be successful.