Impact of Liver and Whole-Body Diffusion-Weighted MRI for Neuroendocrine Tumors on Patient Management: A Pilot Study.

BACKGROUND: Computed tomography scan is the current standard cross-sectional imaging modality for neuroendocrine tumor (NET) workup. Diffusion-weighted magnetic resonance imaging (DW-MRI) has proven to be more sensitive than standard sequences to diagnose liver metastases; whole-body DW-MRI may be more sensitive than whole-body MRI. Clinical implications have not yet been assessed. Thus, we evaluated radiological and clinical contributions of liver and whole-body DW-MRI to manage NETs. METHODS: Twenty-five abnormal liver and 22 abnormal whole-body standard MRIs were first analyzed retrospectively. MR images were then reanalyzed after adding DW sequences. The standard of reference for metastasis confirmation was a combination of radiological follow-up and histological proof. Clinical impact was defined as MRI changes of liver invasion (unilobar to bilobar and/or <50 to >50% of liver) or therapeutic management changes made during a dedicated multidisciplinary meeting after whole-body MRI. RESULTS: Thirty-two patients with mainly small intestine NETs (24/32) were studied. Adding DW to standard liver MRI yielded additional findings for 45% of the patients with 1.78 times more new lesions, mainly infracentimetric; it induced a management change for 18% of the patients. DW sequences added to whole-body MRI yielded additional findings for 71% of the patients, with 1.72 times more lesions, mainly infracentimetric, and induced a change in management for 19% of the patients. CONCLUSION: Adding DW sequences to standard MRI revealed additional metastases and led to modifications of patient management. Prospective studies are needed to confirm these results.

Radiological imaging markers predicting clinical outcome in patients with metastatic colorectal carcinoma treated with regorafenib: post hoc analysis of the CORRECT phase III trial (RadioCORRECT study).

OBJECTIVE: To identify imaging markers predicting clinical outcomes to regorafenib in metastatic colorectal carcinoma (mCRC). METHODS: The RadioCORRECT study is a post hoc analysis of a cohort of patients with mCRC treated within the phase III placebo-controlled CORRECT trial of regorafenib. Baseline and week 8 contrast-enhanced CT were used to assess response by RECIST 1.1, changes in the sum of target lesion diameters (ΔSTL), lung metastases cavitation and liver metastases density. Primary and secondary objectives were to develop ex novo univariable and multivariable models to predict overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: 202 patients were enrolled, 134 (66.3%) treated with regorafenib and 68 (33.7%) with placebo. In the univariate analysis, PFS predictors were lung metastases cavitation at baseline (HR 0.50, 95% CI 0.27 to 0.92, p=0.03) and at week 8 (HR 0.58, 95% CI 0.36 to 0.93, p=0.02). Baseline cavitation (HR 0.23, 95% CI 0.08 to 0.66, p=0.007), RECIST 1.1 (HR 0.23, 95% CI 0.14 to 0.4, p <0.0001) and ΔSTL (HR 1.16, 95% CI 1.06 to 1.27, p=0.002) predicted OS. We found an increase of 9% of diameter as the best threshold for discriminating OS (HR 2.64, 95% CI 1.61 to 4.34, p <0.001). In the multivariate analysis, baseline and week 8 cavitation remained significant PFS predictors. Baseline cavitation, RECIST 1.1 and ΔSTL remained predictors of OS in exploratory multivariable models. Assessment of liver metastases density did not predict clinical outcome. CONCLUSIONS: RECIST 1.1 and ΔSTL predict favourable outcome to regorafenib. In contrast to liver metastases density that failed to be a predictor, lung metastases cavitation represents a novel radiological marker of favourable outcome that deserves consideration.

Fatty acid composition of adipose tissue and colorectal cancer: a case-control study.

BACKGROUND: Unlike experimental results, epidemiologic studies that used dietary questionnaires were not convincing as regards the relations between dietary fatty acids (FAs) and risk of colorectal cancer (CRC). The FA composition of adipose tissue, which is considered to be an indicator of dietary intake over 2-3 y because of the slow turnover rate, appears promising but has so far been rarely used to explore the relation between CRC and exogenous or endogenously produced FAs. OBJECTIVE: In this case-control study, we aimed to investigate associations between risk of CRC and the FA composition of subcutaneous adipose tissue and product-to-precursor ratios as indexes of enzymatic activities. DESIGN: From 2008 to 2011, we recruited 203 cases with newly diagnosed CRC and elective surgery with a curative intent and 223 control subjects with planned abdominal surgery for benign disease and no history of CRC or polyp resection. During surgery, abdominal subcutaneous adipose tissue samples were optimally collected, stored, and analyzed by using high-performance gas chromatography. Multivariate logistic regression was used to estimate ORs for CRC in relation to individual FAs divided into tertiles according to the FA distribution in controls. RESULTS: After adjustment, significant positive associations with CRC risk were observed in highest compared with lowest tertiles of 16:1n-9 (OR: 1.75; 95% CI: 1.00, 3.06; P-trend = 0.045), 20:3n-6 (OR: 1.79; 95% CI: 1.01, 3.17; P-trend = 0.038), 22:5n-3 (OR: 1.82; 95% CI: 1.06, 3.12; P-trend = 0.023), and the ratio of 18:2n-6 to 18:3n-3 (OR: 2.34; 95% CI: 1.37, 3.98; P-trend = 0.001). Significant inverse associations were observed for 18:3n-3 (OR: 0.48; 95% CI: 0.29, 0.81; P-trend = 0.007). Several product-to-precursor ratios showed significant differences between cases and controls in particular ratios that reflected elongase 2/5 activity. CONCLUSIONS: CRC patients presented higher concentrations of some FAs but lower concentrations of α-linolenic acid in their subcutaneous adipose tissue than did controls. These results may reflect both dietary patterns and altered FA metabolism but require mechanistic explorations.

A case-control study of pre-operative levels of serum neutrophil gelatinase-associated lipocalin and other potential inflammatory markers in colorectal cancer.

BACKGROUND: Chronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP). METHODS: The AGARIC multicenter case-control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n=224) or for benign causes (n=252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured. RESULTS: Median values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p<0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR=2.44 (95% CI : 1.34-4.45, p=0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case-control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p=0.028) but this association was reduced after adjustment for CRP (p=0.11). CONCLUSION: Despite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.

Preoperative adipocytokines as a predictor of surgical infection after colorectal surgery: a prospective survey.

BACKGROUND: Infections are the leading cause of morbidity and mortality after colorectal surgery. Obesity is a well-known risk factor for wound infection, but it does not seem to increase the risk of other infectious complications. The aim of this study was to look for a relationship between the fatty tissue metabolism measured by adipocytokine levels and the risk of postoperative infection. PATIENTS AND METHODS: Preoperative plasma levels of eight adipocytokines, cholesterol, triglycerides, insulin and C-reactive protein (CRP) were measured in consecutive patients undergoing elective colorectal surgery between June 2008 and June 2011. Information about epidemiological and clinical characteristics was obtained for each patient. All infections in the 30 days following surgery were recorded. RESULTS: Among the 174 patients included, 49 (28 %) presented with a postoperative infection: 41 surgical site infections and 8 other infections. Preoperative leptin, insulin and CRP were significantly higher in patients with postoperative infection (p = 0.025, p = 0.020 and p = 0.044, respectively), but only leptin was predictive of infection in multivariate analysis (odds ratio (OR) = 1.89, 95 % confidence interval (CI) 1.18-3.03, p = 0.008). The predictive value of leptin was slightly lower for surgical site infection (OR = 1.65, 95 % CI 1.06-2.55, p = 0.025). Leptin levels were independent of the other adipocytokine levels but not of the body mass index. CONCLUSION: Although markers of inflammation and insulin resistance are also related to the onset of surgical infection, leptin correlates more closely with the risk of infection than does any other factor. However, its effect could be partially mediated by the body mass index.

Pancreas cancer-associated polymyositis of the legs regressing after cephalic duodenopancreatectomy: case report and review of the literature.

CONTEXT: Inflammatory myopathy, such as polymyositis, has been widely reported as paraneoplastic syndrome associated with various malignancies. However, its association with pancreas adenocarcinoma is very uncommon. CASE REPORT: A case of a patient with paraneoplastic polymyositis of both legs associated with pancreatic adenocarcinoma is reported here. The diagnosis of polymyositis was highlighted by MRI and confirmed by histopathological examination. The surgical resection of the primary tumor led to the complete resolution of polymyositis with no further recurrence despite later metastases. CONCLUSION: The association between pancreatic cancer and paraneoplastic polymyositis is very uncommon and has to be recognized by clinicians.