Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium.

Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (pFDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (pFDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.

Are Ergothioneine Levels in Blood Associated with Chronic Peripheral Neuropathy in Colorectal Cancer Patients Who Underwent Chemotherapy?

Objective: Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN) is highly prevalent among colorectal cancer (CRC) patients. Ergothioneine (ET) - a dietary antioxidant -protected against CIPN in experimental models, but human studies are lacking. We explored whether whole blood ET levels were associated with chronic peripheral neuropathy among CRC patients who had completed chemotherapy.Methods: At diagnosis, median ET-concentration in whole blood of 159 CRC patients was 10.2 µg/ml (7.2-15.8). Patients completed questionnaires on peripheral neuropathy 6 months after completion of chemotherapy. We calculated prevalence ratios (PR) to assess associations of ET-concentrations and prevalence of peripheral neuropathy and used linear regression to assess associations with severity of peripheral neuropathy.Results: Prevalence of total and sensory peripheral neuropathy were both 81%. Higher ET-concentrations tended to be associated with lower prevalence of total and sensory peripheral neuropathy, but not statistically significant (highest versus lowest tertile of ET: PR = 0.93(0.78, 1.11) for total neuropathy, and PR = 0.84(0.70, 1.02) for sensory neuropathy). ET-concentrations were not associated with severity of neuropathy.Conclusion: Statistically significant associations were not observed, possibly because of limited sample size. Although data may putatively suggest higher levels of ET to be associated with a lower prevalence of neuropathy, analyses should be repeated in larger populations with larger variability in ET-concentrations.

Multicenter, Prospective, Longitudinal Study of the Recurrence, Surgical Site Infection, and Quality of Life After Contaminated Ventral Hernia Repair Using Biosynthetic Absorbable Mesh: The COBRA Study.

OBJECTIVE: The aim of the study was to evaluate biosynthetic absorbable mesh in single-staged contaminated (Centers for Disease Control class II and III) ventral hernia (CVH) repair over 24 months. BACKGROUND: CVH has an increased risk of postoperative infection. CVH repair with synthetic or biologic meshes has reported chronic biomaterial infections and high hernia recurrence rates. METHODS: Patients with a contaminated or clean-contaminated operative field and a hernia defect at least 9 cm had a biosynthetic mesh (open, sublay, retrorectus, or intraperitoneal) repair with fascial closure (n = 104). Endpoints included overall Kaplan-Meier estimates for hernia recurrence and postoperative wound infection rates at 24 months, and the EQ-5D and Short Form 12 Health Survey (SF-12). Analyses were conducted on the intent-to-treat population, and health outcome measures evaluated using paired t tests. RESULTS: Patients had a mean age of 58 years, body mass index of 28 kg/m, 77% had contaminated wounds, and 84% completed 24-months follow-up. Concomitant procedures included fistula takedown (n = 24) or removal of infected previously placed mesh (n = 29). Hernia recurrence rate was 17% (n = 16). At the time of CVH repair, intraperitoneal placement of the biosynthetic mesh significantly increased the risk of recurrences (P ≤ 0.04). Surgical site infections (19/104) led to higher risk of recurrence (P < 0.01). Mean 24-month EQ-5D (index and visual analogue) and SF-12 physical component and mental scores improved from baseline (P < 0.05). CONCLUSIONS: In this prospective longitudinal study, biosynthetic absorbable mesh showed efficacy in terms of long-term recurrence and quality of life for CVH repair patients and offers an alternative to biologic and permanent synthetic meshes in these complex situations.

An increase in physical activity after colorectal cancer surgery is associated with improved recovery of physical functioning: a prospective cohort study.

BACKGROUND: The influence of physical activity on patient-reported recovery of physical functioning after colorectal cancer (CRC) surgery is unknown. Therefore, we studied recovery of physical functioning after hospital discharge by (a) a relative increase in physical activity level and (b) absolute activity levels before and after surgery. METHODS: We included 327 incident CRC patients (stages I-III) from a prospective observational study. Patients completed questionnaires that assessed physical functioning and moderate-to-vigorous physical activity shortly after diagnosis and 6 months later. Cox regression models were used to calculate prevalence ratios (PRs) of no recovery of physical functioning. All PRs were adjusted for age, sex, physical functioning before surgery, stage of disease, ostomy and body mass index. RESULTS: At 6 months post-diagnosis 54% of CRC patients had not recovered to pre-operative physical functioning. Patients who increased their activity by at least 60 min/week were 43% more likely to recover physical function (adjusted PR 0.57 95%CI 0.39-0.82), compared with those with stable activity levels. Higher post-surgery levels of physical activity were also positively associated with recovery (P for trend = 0.01). In contrast, activity level before surgery was not associated with recovery (P for trend = 0.24). CONCLUSIONS: At 6 month post-diagnosis, about half of CRC patients had not recovered to preoperative functioning. An increase in moderate-to-vigorous physical activity after CRC surgery was associated with enhanced recovery of physical functioning. This benefit was seen regardless of physical activity level before surgery. These associations provide evidence to further explore connections between physical activity and recovery from CRC surgery after discharge from the hospital.

Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality.

BACKGROUND: Higher concentrations of 25-hydroxyvitamin D3 [25(OH)D3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism. OBJECTIVES: We aimed to investigate 25(OH)D3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality. METHODS: The study population included 1169 newly diagnosed stage I-III CRC patients from 2 prospective cohorts. Associations between 25(OH)D3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another. RESULTS: Serum 25(OH)D3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 vs. Q1: 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. Q1: 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (<50 nmol/L) and had a low magnesium intake. No interactions between calcium and vitamin D in relation to all-cause mortality were observed. CONCLUSIONS: Our findings suggest that the presence of an adequate status of 25(OH)D3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings. The COLON study was registered at clinicaltrials.gov as NCT03191110. The EnCoRe study was registered at trialregister.nl as NTR7099.

Dietary Intake of Magnesium or Calcium and Chemotherapy-Induced Peripheral Neuropathy in Colorectal Cancer Patients.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side-effect in colorectal cancer (CRC) patients. This study assessed the association between habitual dietary intake of magnesium or calcium and prevalence and severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For this prospective cohort study, 196 CRC patients were considered. Magnesium and calcium intake was determined using a food frequency questionnaire at diagnosis, during and after chemotherapy. Chronic CIPN was assessed 12 months after diagnosis using the quality of life questionnaire CIPN20. Prevalence ratios were calculated to assess the association between magnesium or calcium intake and the prevalence of CIPN. Multivariable linear regression analysis was used to assess the association between magnesium or calcium intake and severity of CIPN. CIPN was reported by 160 (82%) patients. Magnesium intake during chemotherapy was statistically significantly associated with lower prevalence of CIPN (prevalence ratio (PR) 0.53, 95% confidence interval (CI) 0.32, 0.92). Furthermore, higher dietary intake of magnesium during (ß -1.08, 95% CI -1.95, -0.22) and after chemotherapy (ß -0.93, 95% CI -1.81, -0.06) was associated with less severe CIPN. No associations were found for calcium intake and the prevalence and severity of CIPN. To conclude, we observed an association between higher dietary magnesium intake and lower prevalence and severity of CIPN in CRC patients.

Laparoscopic vs. open incisional hernia repair: a randomized clinical trial.

IMPORTANCE: Incisional hernia is the most frequent surgical complication after laparotomy. Up to 30% of all patients undergoing laparotomy develop an incisional hernia. OBJECTIVE: To compare laparoscopic vs open ventral incisional hernia repair with regard to postoperative pain and nausea, operative results, perioperative and postoperative complications, hospital admission, and recurrence rate. DESIGN: Multicenter randomized controlled trial between May 1999 and December 2006 with a mean follow-up period of 35 months. SETTING: All patients were operated on in a clinical setting at 1 of the 2 participating university medical centers or at the other 8 teaching hospitals. PARTICIPANTS: Two hundred six patients from 10 hospitals were randomized equally to laparoscopic or open mesh repair. Patients with an incisional hernia larger than 3 cm and smaller than 15 cm, either primary or recurrent, were included. Patients were excluded if they had an open abdomen treatment in their medical histories. INTERVENTION: Laparoscopic or open ventral incisional hernia repair. MAIN OUTCOME MEASURES: The primary outcome of the trial was postoperative pain. Secondary outcomes were use of analgesics, perioperative and postoperative complications, operative time, postoperative nausea, length of hospital stay, recurrence, morbidity, and mortality. RESULTS: Median blood loss during the operation was significantly less (10 mL vs 50 mL; P = .05) as well as the number of patients receiving a wound drain (3% vs. 45%; P < .001) in the laparoscopic group. Operative time for the laparoscopic group was longer (100 minutes vs. 76 minutes; P = .001). Perioperative complications were significantly higher after laparoscopy (9% vs. 2%). Visual analog scale scores for pain and nausea, completed before surgery and 3 days and 1 and 4 weeks postoperatively, showed no significant differences between the 2 groups. At a mean follow-up period of 35 months, a recurrence rate of 14% was reported in the open group and 18%, in the laparoscopic group (P = .30). The size of the defect was found to be an independent predictor for recurrence (P < .001). CONCLUSIONS AND RELEVANCE: During the operation, there was less blood loss and less need for a wound drain in the laparoscopic group. However, operative time was longer during laparoscopy. Perioperative complications were significantly higher in the laparoscopic group. Visual analog scores for pain and nausea did not differ between groups. The incidence of a recurrence was similar in both groups. The size of the defect was found to be an independent factor for recurrence of an incisional hernia.

Repair of parastomal hernias with biologic grafts: a systematic review.

BACKGROUND: Biologic grafts are increasingly used instead of synthetic mesh for parastomal hernia repair due to concerns of synthetic mesh-related complications. This systematic review was designed to evaluate the use of these collagen-based scaffolds for the repair of parastomal hernias. METHODS: Studies were retrieved after searching the electronic databases MEDLINE, EMBASE and Cochrane CENTRAL. The search terms 'paracolostomy', 'paraileostomy', 'parastomal', 'colostomy', 'ileostomy', 'hernia', 'defect', 'closure', 'repair' and 'reconstruction' were used. Selection of studies and assessment of methodological quality were performed with a modified MINORS index. All reports on repair of parastomal hernias using a collagen-based biologic scaffold to reinforce or bridge the defect were included. Outcomes were recurrence rate, mortality and morbidity. RESULTS: Four retrospective studies with a combined enrolment of 57 patients were included. Recurrence occurred in 15.7% (95% confidence interval [CI] 7.8-25.9) of patients and wound-related complications in 26.2% (95% CI 14.7-39.5). No mortality or graft infections were reported. CONCLUSIONS: The use of reinforcing or bridging biologic grafts during parastomal hernia repair results in acceptable rates of recurrence and complications. However, given the similar rates of recurrence and complications achieved using synthetic mesh in this scenario, the evidence does not support use of biologic grafts.