Marta Sandini

The prognostic impact of para-aortic lymph node metastasis in pancreatic cancer: A systematic review and meta-analysis

PURPOSE To evaluate by a meta-analytic approach the long-term prognostic impact of para-aortic lymph node (PALN) involvement in resected ductal adenocarcinoma of the pancreas. METHODS MEDLINE, Embase, PubMed and the Cochrane Library were searched from January 1990 to June 2015. Trials reporting Kaplan-Meier curves and comparing overall long-term survival of negative and metastatic PALN in patients who underwent resection for pancreatic cancer were included. Lymph nodes were classified according to the Japan Pancreatic Society rules and identified using hematoxylin and eosin staining. Hazard ratios (HRs) and 95%CI were estimated for each trial and pooled in a meta-analysis. RESULTS Thirteen eligible studies including 2141 patients (364 positive PALN; 1777 negative PALN) were identified. Most of the studies were retrospective. Heterogeneity among trials was high (I(2) = 98.7%; p < .001). PALN metastasis was associated with increased mortality when compared with patients with negative PALN regardless regional nodal status [HR 1.85, 95%CI 1.48-2.31; p < .001]. Median survival was significantly decreased in patients with positive PALN (WMD = -4.92 months 95%CI -6.40; -3.43; p < .001). Moreover, metastatic PALN affected mortality also when regional lymph nodes were positive [HR 1.67, 95%CI 1.34-2.08; p < .001]. No publication bias was detected. CONCLUSIONS PALN metastasis appears to correlate with poor prognosis in patients with pancreatic adenocarcinoma. The assessment of PALN status may be considered for a more accurate staging of the disease and appropriated subgroup survival reporting. However, the definitive avoidance of the resection in case of intraoperative metastatic PALN needs further investigation.

Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials.

Abstract The role of glutamine (GLN) supplementation in critically ill patients is controversial. Our aim was to analyze its potential effect in patients admitted to intensive care unit (ICU). We performed a systematic literature review through Medline, Embase, Pubmed, Scopus, Ovid, ISI Web of Science, and the Cochrane-Controlled Trials Register searching for randomized clinical trials (RCTs) published from 1983 to 2014 and comparing GLN supplementation to no supplementation in patients admitted to ICU. A random-effect meta-analysis for each outcome (hospital and ICU mortality and rate of infections) of interest was carried out. The effect size was estimated by the risk ratio (RR). Thirty RCTs were analyzed with a total of 3696 patients, 1825 (49.4%) receiving GLN and 1859 (50.6%) no GLN (control groups). Hospital mortality rate was 27.6% in the GLN patients and 28.6% in controls with an RR of 0.93 (95% CI = 0.81–1.07; P = 0.325, I2 = 10.7%). ICU mortality was 18.0 % in the patients receiving GLN and 17.6% in controls with an RR of 1.01 (95% CI = 0.86–1.19; P = 0.932, I2 = 0%). The incidence of infections was 39.7% in GLN group versus 41.7% in controls. The effect of GLN was not significant (RR = 0.88; 95% CI = 0.76–1.03; P = 0.108, I2 = 56.1%). These results do not allow to recommend GLN supplementation in a generic population of critically ills. Further RCTs are needed to explore the effect of GLN in more specific cohort of patients.

Preoperative Computed Tomography to Predict and Stratify the Risk of Severe Pancreatic Fistula After Pancreatoduodenectomy

Abstract The aim of this article is to assess whether measures of abdominal fat distribution, visceral density, and antropometric parameters obtained from computed tomography (CT) may predict postoperative pancreatic fistula (POPF) occurrence. We analyzed 117 patients who underwent pancreatoduodenectomy (PD) and had a preoperative CT scan as staging in our center. CT images were processed to obtain measures of total fat volume (TFV), visceral fat volume (VFV), density of spleen, and pancreas, and diameter of pancreatic duct. The predictive ability of each parameter was investigated by receiver-operating characteristic (ROC) curves methodology and assessing optimal cutoff thresholds. A stepwise selection method was used to determine the best predictive model. Clinically relevant (grades B and C) POPF occurred in 24 patients (20.5%). Areas under ROC-curves showed that none of the parameters was per se significantly predictive. The multivariate analysis revealed that a VFV >2334 cm3, TFV >4408 cm3, pancreas/spleen density ratio <0.707, and pancreatic duct diameter <5 mm were predictive of POPF. The risk of POPF progressively increased with the number of factors involved and age. It is possible to deduce objective information on the risk of POPF from a simple and routine preoperative radiologic workup.

Systematic review and meta-analysis of sutures coated with triclosan for the prevention of surgical site infection after elective colorectal surgery according to the PRISMA statement.

Background:Several randomized clinical trials (RCTs) conducted to evaluate the effect of triclosan-coated suture on surgical site infection (SSI) yield to controversial results. The primary purpose of this systematic review and meta-analysis was to analyze the available RCTs, comparing the effect of triclosan-coated suture with uncoated suture on the incidence of SSI after elective colorectal operations. As secondary endpoint of the analysis, we considered length of hospital stay after surgery. Methods:We performed a systematic literature review through Medline, Embase, Pubmed, Scopus, Ovid, ISI Web of Science, and the Cochrane Controlled Trials Register searching for RCTs published from 1990 to 2015. To conduct these meta-analyses, we followed the guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Study inclusion criteria were as follows: parallel-group RCTs in adult populations reporting the closure of the abdominal wall after elective colorectal operation with triclosan-coated suture or noncoated suture, and reporting the outcomes considered in the meta-analysis. Results:Six trials including 2168 patients (1102 treated and 1066 controls) provided data on SSIs. The overall rate was 11.7% (129/1102) in the triclosan group and 13.4% (143/1066) in the control group (odds ratio 0.81, 95% confidence interval [CI] 0.58–1.13, P = 0.220). Heterogeneity among studies was moderate (I2 = 44.9%). No evidence of publication bias was detectable. Five RCTs (1783 patients; 914 treated and 689 controls) described hospital length of stay with no significant effect (mean difference: −0.02, 95% CI −0.11 to −0.07, P = 0.668). The I2 test for heterogeneity was 0% (P = 0.836). Moderator analyses showed no significant differences were detected in analyses comparing the suture materials (polydioxanone vs polyglactin). In open-label trials, the odds ratio for SSI risk was 0.62 (95% CI 0.20–1.93, P = 0.413), 0.77 in single-blind (95% CI 0.31–1.95, P = 0.583) and 0.85 in double-blind trials (95% CI 0.46–1.54, P = 0.582). Conclusions:Our findings failed to demonstrate a significant protective effect of triclosan-coated sutures on the occurrence of SSI after elective colorectal resections. Further large RCTs are needed before introducing this technology into clinical practice.

Effect of glutamine dipeptide supplementation on primary outcomes for elective major surgery: systematic review and meta-analysis.

To evaluate if glutamine (GLN) supplementation may affect primary outcomes in patients undergoing major elective abdominal operations, we performed a systematic literature review of randomized clinical trials (RCTs) published from 1983 to 2013 and comparing intravenous glutamine dipeptide supplementation to no supplementation in elective surgical abdominal procedures. A meta-analysis for each outcome (overall and infectious morbidity and length of stay) of interest was carried out. The effect size was estimated by the risk ratio (RR) or by the weighted mean difference (WMD). Nineteen RCTs were identified with a total of 1243 patients (640 receiving GLN and 603 controls). In general, the studies were underpowered and of medium or low quality. GLN supplementation did not affect overall morbidity (RR = 0.84, 95% CI 0.51 to 1.36; p = 0.473) and infectious morbidity (RR = 0.64; 95% CI = 0.38 to 1.07; p = 0.087). Patients treated with glutamine had a significant reduction in length of hospital stay (WMD = −2.67; 95% CI = −3.83 to −1.50; p < 0.0001). In conclusion, GLN supplementation appears to reduce hospital stay without affecting the rate of complications. The positive effect of GLN on time of hospitalization is difficult to interpret due to the lack of significant effects on surgery-related morbidity.

Scores for Prediction of Fistula after Pancreatoduodenectomy: A Systematic Review

Background/Aim: Different scoring systems to predict the occurrence of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy have been described, but the considered risk factors often suffer subjective scaling. The aim of this review is to evaluate and compare all published risk metrics predictive of POPF. Methods: All existing scores were retrieved by literature web search. Inclusion criteria were ISGPF classification of POPF and the development of a risk score metric. Results: From a total of 286 publications, 10 studies were selected. Most of them were retrospective and single center. The models considered a median number of 3 items (range from 2 to 5); in 5 of 10 trials only pre or intraoperative variables were included. The median number of patients/study was 186 (IQR 111.1-229.0). External validation was performed in 6 of 10 studies. The most recurrent items were abdominal fat (4/10), main pancreatic duct diameter (in 4/10), and pancreatic texture (3/10). Conclusion: POPF risk estimation should be easy, accurate, and objective. It should consider preoperative patient-related and gland-related features, and intraoperative events. None of the published systems completely adhere to these principles. Large heterogeneous multicentric validations should be endorsed, to account for the case-mix and evaluate the reproducibility of each scoring system.

Preoperative Oral Carbohydrate Load Versus Placebo in Major Elective Abdominal Surgery (PROCY): A Randomized, Placebo-controlled, Multicenter, Phase III Trial

Objective: To explore whether preoperative oral carbohydrate (CHO) loading could achieve a reduction in the occurrence of postoperative infections. Background: Hyperglycemia may increase the risk of infection. Preoperative CHO loading can achieve postoperative glycemic control. Methods: This was a randomized, controlled, multicenter, open-label trial. Nondiabetic adult patients who were candidates for elective major abdominal operation were randomized (1:1) to a CHO (preoperative oral intake of 800 mL of water containing 100 g of CHO) or placebo group (intake of 800 mL of water). The blood glucose level was measured every 4 hours for 4 days. Insulin was administered when the blood glucose level was >180 mg/dL. The primary endpoint was the occurrence of postoperative infection. The secondary endpoint was the number of patients needing insulin. Results: From January 2011 through December 2015, 880 patients were randomly allocated to the CHO (n = 438) or placebo (n = 442) group. From each group, 331 patients were available for the analysis. Postoperative infection occurred in 16.3% (54/331) of CHO group patients and 16.0% (53/331) of placebo group patients (relative risk 1.019, 95% confidence interval 0.720–1.442, P = 1.00). Insulin was needed in 8 (2.4%) CHO group patients and 53 (16.0%) placebo group patients (relative risk 0.15, 95% confidence interval 0.07–0.31, P < 0.001). Conclusions: Oral preoperative CHO load is effective for avoiding a blood glucose level >180 mg/dL, but without affecting the risk of postoperative infectious complication.

Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS)

Background The optimal nutritional therapy in the field of pancreatic surgery is still debated. Methods An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group. Results The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery‐related complications. In addition to patients weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short‐term and long‐term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so‐called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase‐1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement. Conclusion The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short‐ and long‐term outcomes.

Prognostic Factors Affecting Long-Term Survival after Resection for Noncolorectal, Nonneuroendocrine, and Nonsarcoma Liver Metastases

Aim To evaluate feasibility and long-term outcome after hepatic resection for noncolorectal, nonneuroendocrine, and nonsarcoma (NCNNNS) liver metastases in a single center. Methods We retrospectively reviewed our experience on patients who underwent surgery for NCNNNS liver metastases from 1995 to 2015. Patient baseline characteristics, tumor features, treatment options, and postoperative outcome were retrieved. Results We included 47 patients. The overall 5-year survival (OS) rate after hepatectomy was 27.6%, with a median survival of 21 months. Overall survival was significantly longer for patients operated for nongastrointestinal liver metastases when compared with gastrointestinal (41 versus 10 months; p = 0.027). OS was significantly worse in patients with synchronous metastases than in those with metachronous disease (10 versus 22 months; p = 0.021). The occurrence of major postoperative complication negatively affected long-term prognosis (OS 23.5 versus 9.0 months; p = 0.028). Preoperative tumor characteristics (number and size of the lesions), intraoperative features (extension of resection, need for transfusions, and Pringles maneuver), and R0 at pathology were not associated with differences in overall survival. Conclusion Liver resection represents a possible curative option for patients with NCNNNS metastases. The origin of the primary tumor and the timing of metastases presentation may help clinicians to better select which patients could take advantages from surgical intervention.

Secondary endpoints: surrogate interest or supplementary table?

The article by Matthews and colleagues (1) emphasizes the potential impending consequences of underreporting secondary endpoints in studies addressing surgical site infection rates. Generally speaking, this may be a very crucial question about clinical trial methodology and rigor.