Systemic oxidative stress and antioxidant capacity in cancer patients

Various factors impact the outcome of patients with the diagnosis of cancer. Common treatment modalities of cancer, including surgery, radiation therapy and cytostatic agents, all lead to a systemic inflammatory reaction. In particular, this reaction is of physiological importance as it is crucial for patient recovery. However, in some patients, a self-perpetuating inflammatory response develops due to the presence of unfavorable risk factors, several of which are still unknown, but might lead to a worse disease prognosis. Inflammation has been intimately associated with oxidative stress, that is characterized by an imbalance between pro-oxidants, also termed reactive species, and antioxidants. Systemically, oxidative stress can be quantified by measuring thiols (R-SH, sulfhydryl compounds), which are considered to be regulatory nodes within the extracellular antioxidant network. Most importantly, thiol measurements in serum or plasma form a robust and powerful read-out of the in vivo reduction-oxidation (redox) status as thiols are highly redox-active and thus readily oxidized by circulating reactive species. Therefore, systemic quantification of thiols might be a valuable addition to the clinically available diagnostic and prognostic armamentarium as it is able to reliably capture the overall balance between oxidants and the antioxidant capacity of patients. In this review, we summarized the currently available literature on thiol levels as amendable markers for oxidative stress in patients with lung, prostate and colorectal cancer. Total thiols, native (free) thiols and disulfide levels are significantly altered in these patients compared to healthy individuals. In general, these findings indicate that the extracellular antioxidant capacity is severely affected in patients with these types of cancer. Moreover, lower thiol levels are associated with a lowered overall survival. Future research should focus on exploration of the clinical significance of thiols in cancer

Neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer:a feasibility and safety study

BACKGROUND: Standard treatment for colorectal peritoneal carcinomatosis typically involves cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and if possible, postoperative adjuvant chemotherapy. However, a substantial percentage of patients never receive adjuvant chemotherapy because of postoperative complications. Neoadjuvant chemotherapy could be beneficial in this setting, so we assessed its feasibility and safety when used before cytoreductive surgery and HIPEC. METHODS: In this non-randomized, single-center, observational feasibility study, patients were scheduled to receive six cycles of capecitabine and oxaliplatin before cytoreductive surgery and HIPEC. Computed tomography was performed after the third and sixth chemotherapy cycles to evaluate tumor response, and patients underwent cytoreductive surgery and HIPEC if there were no pulmonary and/or hepatic metastases. Postoperative complications, graded according to the Clavien-Dindo classification, were compared with those of a historic control group that received postoperative adjuvant chemotherapy. RESULTS: Of the 14 patients included in the study, 4 and 3 had to terminate neoadjuvant chemotherapy early because of toxicity and tumor progression, respectively. Cytoreductive surgery and HIPEC were performed in eight patients, and the timing and severity of complications were comparable to those of patients in the historic control group treated without neoadjuvant chemotherapy. CONCLUSION: Patients with peritoneal metastases due to colorectal carcinoma can be treated safely with neoadjuvant chemotherapy before definitive therapy with cytoreductive surgery and HIPEC. TRIAL REGISTRATION NUMBER: NTR 3905, registered on 20th march, 2013, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3905

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal carcinoma: patient selection and improving outcomes

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal carcinoma: Patient selection and improving outcomes In the Netherlands, colorectal cancer is one of the most common types of cancer in women as well as in men. Every year, around 4500 people die because of this disease. Treatment of colorectal cancer consists of a combination of surgery, medication and in some cases radiotherapy. In case of peritoneal metastases, treatment has been difficult, therefore survival of these patients is limited. In the Netherlands, a selected group of patients with peritoneal metastases can be treated with a CRS+HIPEC procedure. During this procedure all macroscopically visible tumour is removed and heated chemotherapy (oxaliplatin or mitomycin) is flushed through he peritoneal cavity during 1.5 hours. With this treatment a 5-years survival of 35-43% has been reached. Only patients that have no other metastases than peritoneal metastases are eligible for CRS+HIPEC. In consequence of the complexity of the procedure many patients experience complications. Therefore, it is important to select those patients that will benefit from the procedure while experiencing a minimum of complications. In this thesis we focused on a more effective patient selection, optimisation of the treatment and the prediction of the quality of life of patients after a CRS+HIPEC procedure. The aim is to find the best treatment for the individual patient, to discover possible predictors of complications and ultimately improve the quality of life of patients

Oxidative Stress Predicts Post-Surgery Complications in Gastrointestinal Cancer Patients

Introduction : An excessive perioperative inflammatory reaction can lead to more postoperative complications in patients treated for gastrointestinal cancers. It has been suggested that this inflammatory reaction leads to oxidative stress. The most important nonenzymatic antioxidants are serum free thiols. The purpose of this study was to evaluate whether high preoperative serum free thiol levels are associated with short-term clinical outcomes. Methods : Blood samples were drawn before, at the end of, and 1 and 2 days after surgery of a consecutive series of patients with gastrointestinal cancer. Serum free thiols were detected using a colorimetric detection method using Ellman's reagent. Short-term clinical outcomes were defined as 30-day complications (Clavien-Dindo ≥2) and length of hospital stay. Logistic regression was applied to examine the association between serum free thiol levels and short-term patient outcomes. Results : Eighty-one patients surgically treated for gastrointestinal cancer were included in the study. Median age was 68 (range 26-87) years, and 28% were female. Patients in the lowest tertile of preoperative serum free thiols had a threefold higher risk to develop postoperative complications (odds ratio [OR]: 3.4; 95% confidence interval [CI]:1.1-10.7) and a fourfold higher risk to have an increased length of stay in the hospital (OR 4.0; 95% CI 1.3-12.9) compared with patients in the highest tertile. Conclusions : Patients with lower preoperative serum free thiol levels, indicating a decrease in extracellular antioxidant capacity and therefore an increase in systemic oxidative stress, are more likely to develop postoperative complications and show a longer in hospital stay than patients with higher serum free thiol levels