Nutritional assessment in overweight and obese patients with metastatic cancer: does it make sense?

BACKGROUND: Obesity is causally related with tumor development, and thus, many cancer patients are overweight or obese at diagnosis. Whether these patients need regular nutritional assessment is not known. In the present study, we evaluated the utility of Mini Nutritional Assessment (MNA), a nutritional screening/assessment questionnaire, in overweight or obese patients with metastatic tumors. PATIENTS AND METHODS: Overweight or obese patients referred for initiation of systemic therapy in three cancer centers were eligible. Basic demographics and clinical data were recorded. MNA was completed at baseline and patients were divided into three groups: A (well nourished), B (at risk), and C (malnourished). Survival data were subsequently collected. The prevalence of malnutrition and prognostic significance were evaluated. RESULTS: In total, 1469 patients with metastatic primaries were identified. Of them, 594 (41.9%) were overweight or obese and included in the analysis. According to MNA, almost 50% were at risk and around 12% were already malnourished at presentation. A significant difference in overall survival was found between groups [group A 17.8 (15.5-20.1) months, group B 8.2 (7.3-9.3) months, and group C 6.4 (3.2-9.6) months, P < 0.001]. Moreover, MNA was the only independent predictor of survival. CONCLUSIONS: Our findings support that a significant percentage of overweight or obese cancer patients may be at nutritional risk and this is moreover related with adverse prognosis. An MNA score could be used for the identification of this risk.

Home parenteral nutrition improves quality of life and nutritional status in patients with cancer: a French observational multicentre study.

PURPOSE: Malnutrition is a predictor of poor outcomes in patients with cancer. Little is known about the benefit of nutritional support in these patients. The purpose of this study was to assess the impact of home parenteral nutrition (HPN) on quality of life (Qol) in cancer patients. METHODS: We performed an observational prospective study to determine the impact of HPN on Qol in a population of patients with heterogeneous cancer. Physicians, patients and family members had to complete a questionnaire before HPN administration and 28 days after the course of HPN. Qol was evaluated using the self-administered questionnaire FACT-G. RESULTS: We included 767 patients with cancer of whom 437 ended the study. Mean patient age was 63±11.4 years and 60.5% were men. Primary gastrointestinal cancer was reported in 50% of patients and 65.3% were presenting metastases. Malnutrition was reported in 98.3%. After 28 days of HPN intake, significant improvement was observed in the Qol (49.95±5.82 vs. 48.35±5.01 at baseline, p<0.0001). The mean weight, serum albumin and the nutrition risk index had also improved significantly. Most patients (78%) had perceived a positive impact of the HPN. A significant improvement in patient's well-being was perceived also by family members and physicians. CONCLUSIONS: Our data suggest that preventing and correcting malnutrition using HPN in patients with cancer might have a significant benefit on their well-being. Randomized controlled studies are required to confirm this finding.

Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples.

AIMS: The purpose of this study was to investigate the clinical feasibility and utility of low-density array analysis on samples obtained from endoscopic ultrasound-guided fine needle aspiration biopsy in locally advanced and/or metastatic pancreatic ductal adenocarcinoma and chronic pancreatitis. PATIENTS AND METHODS: In this prospective multicenter study, we quantified candidate gene expression in biopsies sampled from 44 locally advanced and/or metastatic pancreatic carcinoma and from 17 pseudotumoural chronic pancreatitis using dedicated low-density array microfluidic plates. RESULTS: We first demonstrated that 18S gene expression is stable and comparable in normal pancreas and pancreatic cancer tissues. Next, we found that eight genes (S100P, PLAT, PLAU, MSLN, MMP-11, MMP-7, KRT7, KRT17) were significantly over expressed in pancreatic cancer samples when compared to pseudotumoural chronic pancreatitis (p value ranging from 0.0007 to 0.0215): Linear discriminative analysis identified S100P, PLAT, MSLN, MMP-7, KRT7 as highly explicative variables. The area under receiver operating curve establishes the clinical validity of the potential diagnostic markers identified in this study (values ranging from 0.69 to 0.76). In addition, combination of S100P and KRT7 gave better diagnosis performances (Area Under Receiver Operating Curve 0.81, sensitivity 81%, specificity 77%). CONCLUSION: We demonstrate that molecular studies on EUS-guided FNA material are feasible for the identification and quantification of markers in PDAC patients diagnosed with non-resectable tumours. Using low-density array, we isolated a molecular signature of advanced pancreatic carcinoma including mostly cancer invasion-related genes. This work stems for the use of novel biomarkers for the molecular diagnosis of patient with solid pancreatic masses.

Clinical impact of lymph node status in rectal cancer.

Lymph node status at the time of diagnosis remains one of the principal indicators of prognosis in patients with rectal cancer. Involvement of loco-regional lymph nodes is relevant to surgical and clinical oncologists and continues to impact significantly upon local and systemic management strategies, in both neo-adjuvant and adjuvant settings. In this review, the clinical impact of lymph node status in the surgical management of rectal cancer is considered, with particular reference to the significance of lymphadenectomy and the potential implications for rectal tumours amenable to trans-anal excision. Current standards of care are reviewed and the extent to which the determination of lymph node status influences oncological decisions regarding neo-adjuvant and adjuvant therapies are discussed with areas of controversy highlighted.

A large-scale candidate gene approach identifies SNPs in SOD2 and IL13 as predictive markers of response to preoperative chemoradiation in rectal cancer.

Neoadjuvant radiochemotherapy followed by total mesorectal excision is now the standard treatment for locally advanced rectal cancer. However, tumor response to chemoradiation varies widely among individuals and cannot be determined before the final pathologic evaluation. The aim of this study was to identify germline genetic markers that could predict sensitivity or resistance to preoperative radiochemotherapy (RT-CT) in rectal cancer. We evaluated the predictive value of 128 single-nucleotide polymorphisms (SNPs) in 71 patients preoperatively treated by RT-CT. The selected SNPs were distributed over 76 genes that are involved in various cellular processes such as DNA repair, apoptosis, proliferation or immune response. The SNPs superoxide dismutase 2 (SOD2) rs4880 (P=0.005) and interleukin-13 (IL13) rs1800925 (P=0.0008) were significantly associated with tumor response to chemoradiation. These results reinforce the idea of using germline polymorphisms for personalized treatment.

Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres.

BACKGROUND: This epidemiological observational study aimed at determining the prevalence of malnutrition in non-selected adults with cancer, to identify risk factors of malnutrition and correlate the results with length of stay and 2-month mortality. METHODS: This prospective multicentre 1-day study conducted in 17 French Comprehensive Cancer Centres included 1545 patients. Body mass index (BMI), weight loss (WL) in the past 6 months and age were routinely recorded according to the French national recommendations for hospitalised patients; malnutrition was rated as absent, moderate or severe according to the level of WL and BMI. Age, sex, tumour site, type of hospitalisation and treatment, disease stage, World Health Organisation performance status (PS) and antibiotic therapy were the potential malnutrition risk factors tested. Follow-up at 2 months allowed to determine the correlation with length of stay and mortality. RESULTS: Malnutrition was reported in 30.9% of patients, and was rated as severe in 12.2%. In multivariate analysis, only pre-existing obesity (BMI> or =30), PS > or =2 and head-and-neck or upper digestive cancers were associated with increased risk of malnutrition. Antibiotics use was significantly higher in malnourished patients (35.5 vs 22.8%; P<0.001). Severe malnutrition was independently associated with mortality. The median length of stay was 19.3+/-19.4 days for malnourished patients vs 13.3+/-19.4 days for others (P<0.0001). CONCLUSION: In French Comprehensive Cancer Centres, one out of three cancer patients are malnourished and this was associated with a longer length of stay. Pre-existing obesity could be identified as a new risk factor for malnutrition in our cancer patient population perhaps because of a misidentification or a delay in nutrition support in this category of patients.

[Nutrition and oncogeriatry]. / Nutrition en oncogériatrie.

In oncogeriatric patients, severe malnutrition is associated with increased morbidity and mortality, nosocomial infections, radiotherapy or chemotherapy toxicities, and decreased of quality of life. Therefore, systematic screening and care of malnutrition is mandatory, in accordance with the French guidelines in 2007. Now, dietary counselling should be purposed systematically in malnourish patients and when radiotherapy or radiochemotherapy are considered. Oral supplementation by specific diet (immune-enhancing diets) should be used with cautions, and actually, reserved only in digestive neoplasms and surgery. In cases of severely malnourished patients or if dietary counselling suffers a setback, enteral nutrition should be recommended. In radiotherapy or chemotherapy, used parenteral nutrition is associated with an increase in infectious complications. Artificial nutrition should not be used when Karnofski index is lesser than 50% (or performance status greater than 2) and prognosis lesser at three months.

Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Differential diagnosis between pancreatic adenocarcinoma (PADC) and pseudotumoral forms of chronic pancreatitis remains difficult. Mutation of KRAS oncogene is present in 75% to 95% of PADC. This study aimed to evaluate whether the combined analysis of KRAS mutation with cytopathological findings from endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) might improve discrimination between PADC and chronic pancreatitis. PATIENTS AND METHODS: This prospective multicenter study included 178 patients with solid pancreatic masses (men 104, women 74; mean age 64.5 years). Cytopathological examination and KRAS mutation analysis (codon-12 and codon-13, restriction fragment length polymorphism [RFLP] and direct sequencing) were performed on EUS-FNAB material. Final diagnoses were obtained on EUS-FNAB analysis and/or a second biopsy and/or clinical follow-up and/or surgery: PADC, n = 129; chronic pancreatitis, n = 27; other pancreatic neoplasms, n = 16; and benign lesions, n = 6. RESULTS: KRAS status analysis was successful in all EUS-FNAB samples. Codon-12 KRAS point mutation was found in 66% of PADC samples. No case of chronic pancreatitis displayed KRAS mutation. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of cytopathology alone for diagnosis of PADC versus chronic pancreatitis were 83%, 100%, 100%, 56% and 86%, respectively. When KRAS mutation analysis was combined with cytopathology, these values reached 88%, 100%, 100%, 63% and 90% respectively. CONCLUSION: Although the value of KRAS analysis in addition to EUS-FNAB is limited for distinguishing pancreatic mass lesions, when chronic pancreatitis presented as a pseudotumor a negative finding (wild-type KRAS), was useful in strongly suggesting a benign lesion.

[Is endoscopic ultrasound-guided fine needle aspiration of mesorectal lymph nodes infallible for the locoregional staging of rectal cancer? Report of a false-positive case]. / La biopsie transrectale sous échographie endorectale des ganglions du mésorectum est-elle un examen de certitude lors du bilan d'extension locorégional des cancers du rectum? Rapport d'un cas de faux-positif.

The authors report a case of false-positive ultrasound-guided fine needle aspiration in the initial staging of a rectal cancer. A 46 year-old patient presented with a middle third tumor of the rectum staged T2-T3 by MRI and endorectal ultrasonography. Ultrasound-guided fine needle aspiration of mesorectal nodes showed adenocarcinomatous cells. A subtotal proctectomy was performed without neoadjuvant treatment. Histological report showed a well differentiated adenocarcinoma pT2pN0 (42 examined lymph nodes). The authors discuss the different hypothesis to explain the discordance between preoperative staging and definitive histological results.

A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer.

BACKGROUND: To assess activity and safety of an experimental combination of irinotecan and oxaliplatin (IRINOX) as first-line treatment in advanced colorectal cancer. PATIENTS AND METHODS: In this randomized phase II trial, 80 patients were treated: arm A (IRINOX) in 40 patients received at day 1 oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) biweekly, standard arm B received a biweekly simplified folinic acid (FA) and fluorouracil (FU), FA 200 mg/m(2) in a 2-h infusion and bolus injection of 5FU 400 mg/m(2) on day 1, then a two 400 mg/m(2) continuous infusion of FU on days 1 and 2 with either oxaliplatin 85 mg/m(2) (20 patients) or irinotecan 180 mg/m(2) (20 patients). RESULTS: Twenty-one partial responses (52.5%, median duration 7.2 months) were observed with the IRINOX arm and two complete and 20 partial responses (55%, median duration 6.4 months) with arm B. Median progression-free and overall survival times were 8.4 and 19 months, respectively, in the IRINOX arm and 8.1 and 20.4 months in arm B. Main grade 3/4 toxic effects were, respectively, neutropenia 42.5% and 32.5%; febrile neutropenia 10% and 5%; diarrhea 32.5% and 7.5%; vomiting 10.0% and 5%; neurosensory toxicity 17.5% and 7.5%. CONCLUSION: The IRINOX arm has a manageable toxicity and is active.

[Total parenteral nutrition for recurrent episodes of acute pancreatitis during pregnancy. A case report and literature review]. / Prise en charge d'épisodes récidivants de pancréatite aiguë par nutrition parentérale exclusive pendant la grossesse. Cas clinique et revue de la littérature.

We report on a 35-year-old woman who underwent at 15 weeks of pregnancy exclusive parenteral nutrition for recurrent episodes of acute pancreatitis. She had a pancreatico-jejunal anastomosis stenosis secondary to cephalic duodenopancreatectomy. Nocturnal exclusive parenteral nutrition was used 79 days during pregnancy and 12 days during post-partum. The fetal growth was normal and the foetal well-being was normal. She presented cholestasis at 30 weeks of pregnancy treated medically. She delivered at 33 weeks of pregnancy by cesarean section a healthy baby girl with normal birth weight.

The value of endoscopic rectal ultrasound in predicting the lateral clearance and outcome in patients with lower-third rectal adenocarcinoma.

BACKGROUND AND STUDY AIMS: The aim of this study was to assess whether preoperative endorectal ultrasound (ERUS) is able to predict histological infiltration of the external anal sphincter or the levator ani muscle in patients with a lower-third rectal neoplasm and so the possibility of treatment by sphincter-saving surgery. PATIENTS AND METHODS: Between May 1996 and May 2003, 66 patients with a lower-third rectal neoplasm that was staged as uT2 or greater were entered into a prospective evaluation of ERUS. All patients underwent neoadjuvant treatment before surgery. RESULTS: The first ERUS (ERUS 1) was performed before neoadjuvant treatment; the second ERUS (ERUS 2) was performed between the end of the radiotherapy and the surgery. An abdominoperineal resection was performed mainly when the lower extent of the tumor was within 3.5 cm from the anal verge (P = 0.011), but no correlation was observed between the lateral clearance determined by ERUS 1 and the histological clearance (P = 0.091). After neoadjuvant treatment, the ERUS 2 lateral clearance was significantly correlated with the type of surgery (P = 0.003) and the histological clearance (P < 0.001). With regard to the performance of ERUS 2 for predicting histological infiltration of the external anal sphincter or the levator ani muscle, the sensitivity was 100%, the negative predictive value was 100%, the specificity was 87%, and the positive predictive value was 53%. In a multivariate analysis, the histological clearance and tumor T stage were statistically correlated with disease-free survival (P = 0.035 and P = 0.05, respectively). CONCLUSIONS: ERUS could help oncologists and surgeons in the management of patients with lower rectal carcinomas. Moreover, ERUS is able to predict lateral histological clearance after neoadjuvant treatment.

p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis.

The aim of this study was to evaluate, in a prospective study, the predictive role of p53 status analysed at four different levels in identifying the response to preoperative radiotherapy in rectal adenocarcinoma. Before treatment, 70 patients were staged and endoscopic forceps biopsies from the tumour area were taken. p53 status was assessed by total cDNA sequencing, allelic loss analysis, immunohistochemistry, and p53 antibodies. Neoadjuvant treatment was based on preoperative radiotherapy or radiochemotherapy. Response to therapy was evaluated after surgery by both pathologic downstaging and histologic tumour regression grade. In all, 35 patients (50.0%) had p53 gene mutations; 44.4% of patients had an allelic loss; nuclear p53 overexpression was observed in 39 patients (55.7%); and p53 antibodies were detected in 11 patients (16.7%). In the multilevel analysis of p53 status, gene mutations correlated with both nuclear protein overexpression (P < 0.0001) and loss of heterozygosity (P = 0.013). In all, 29 patients (41.4%) were downstaged by pathologic analysis, and 19 patients (29.2%) were classified as tumour regression grade 1. Whatever the method of evaluation of treatment response, no correlation between p53 alterations and response to radiotherapy was observed. Our results do not support the use of p53 alterations alone as a predictive marker for response to radiotherapy in rectal carcinoma.

Dietary patterns and the adenomacarcinoma sequence of colorectal cancer.

BACKGROUND: Food components of a diet are highly related, so that building up dietary patterns may help understand the relationship between chronic diseases and diet, and identify high risk groups that need preventive advice. AIM: The aim of this study was to determine dietary patterns associated with the colorectal adenoma-carcinoma pathway. METHODS: We performed a two-step analysis using first principal component analysis to select the most appropriate food groups, then a hierarchical agglomerative clustering method, in order to determine dietary patterns in 1372 subjects included in a case-control study. Patients with hyperplastic polyps (n = 103), adenomas < 10 mm, (n = 154) or larger adenomas (n = 208) were then compared with polyp-free controls (n = 426), and colorectal cancer cases (n = 171) compared with population controls (n = 309) using unconditional logistic regression adjusted on age and gender. RESULTS: Cluster analysis determined five food patterns. Cluster 1 identified a low-energy diet; cluster 2 a high-starch, highfat, and low-fruit diet; cluster 3 a high-processed meat, -energy, -alcohol, and -starchy foods diet; cluster 4 a high-fish, -cereals, -honey, -olive oil, -fruit and -vegetables diet; and cluster 5 a high-flour, -sugar, -chocolate, -animal fats, and -eggs diet. Logistic regression identified cluster 2 [corrected] as significantly associated with risk of small adenomas (OR = 1.7; 95% confidence interval 1.0-2.7), large adenomas (OR = 1.9; 1.2-3.0) and cancers (OR = 1.7; 1.1-2.8) compared with cluster 1 [corrected] Cluster 4 diet was inversely associated with risk of small adenomas (OR = 0.4; 0.2-1.0). There was no relationship between patterns and risk of hyperplastic polyps. Multiple adjustment decreased the strength of the relationships with cluster 2 [corrected] which remained significantly associated with adenomas, but not cancer. CONCLUSION: A lowenergy diet appeared as protective all along the adenoma-carcinoma sequence, contrary to a high-energy, high-processed meat and -animal fat diet.

Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.

This study assessed the efficacy of combined prophylactic and curative anti-diarrhoeal medication in advanced colorectal patients treated by irinotecan. Thirty-four pre-treated eligible patients were evaluated. There were 44% women, the median age was 65 and 38% of the patients had a 0 performance status. The patients received sucralfate(4g/d) and nifuroxazide(600 mg/d) prophylactic treatment on days 0-7. In the case of severe diarrhoea, preventive treatment was replaced by loperamide(12 mg/d) and diosmectite (9 g/d). Grade 3 delayed diarrhoea occurred in 18% of patients (90% CI: [9.5-28.9]) and 4.6% of cycles. No grade 4 delayed diarrhoea was observed. Twenty-nine patients (85%) received the preventive treatment at cycle 1, while 14% (90% CI: [6.2-25.7]) experienced grade 3 delayed diarrhoea in 3.7% of cycles for a median 4.5 days. The objective response rate was 8% (90% CI [1.4-23.1]) among the 25 assessable patients. Preventive combined treatment is effective in reducing the incidence of severe delayed diarrhoea, and it should be proposed to patients treated with mono-therapy Campto(r) and evaluated in poly-chemotherapy protocols.