Limited Role of the Apparent Diffusion Coefficient (ADC) for Tumor Grade and Overall Survival in Resectable Pancreatic Ductal Adenocarcinoma.

This study evaluated the relationship between apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and tumor grades based on WHO, Adsay, and Kalimuthu classifications, using whole-mount pancreatectomy specimens. If glandular formation plays a key role in the degree of diffusion restriction, diffusion-weighted imaging could facilitate non-invasive grading of PDAC. A freehand region of interest (ROI) was drawn along tumor borders on the preoperative ADC map in each tumor-containing slice. Resection specimens were retrospectively graded according to WHO, Adsay, and Kalimuthu classifications and correlated with overall survival and the 10th percentile of whole-volume ADC values. Findings from 40 patients (23 male, median age 67) showed no correlation between ADC p10 values and WHO differentiation (p = 0.050), Adsay grade (p = 0.955), or Kalimuthu patterns (p = 0.117). There was no association between ADC p10 and overall survival (p = 0.082) and other clinicopathological variables. Survival was significantly lower for poor tumor differentiation (p = 0.046) and non-glandular Kalimuthu patterns (p = 0.016) and there was a trend towards inferior survival for Adsay G3 (p = 0.090) after correction for age, tumor location, and stage. Preoperative ADC measurements for determining PDAC aggressiveness had limited clinical utility, as there was no correlation with histological parameters or overall survival in resectable PDAC.

Qualitative flow metabolic phenotype of pancreatic cancer. A new prognostic biomarker?

BACKGROUND: Retrospective analysis to investigate the relationship between the flow-metabolic phenotype and overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC) and its potential clinical utility. METHODS: Patients with histopathologically proven PDAC between 2005 and 2014 using tumor attenuation on routine pre-operative CECT as a surrogate for the vascularity and [18F]FDG-uptake as a surrogate for metabolic activity on [18F]FDG-PET. RESULTS: In total, 93 patients (50 male, 43 female, median age 63) were included. Hypoattenuating PDAC with high [18F]FDG-uptake has the poorest prognosis (median OS 7 ± 1 months), compared to hypoattenuating PDAC with low [18F]FDG-uptake (median OS 11 ± 3 months; p = 0.176), iso- or hyperattenuating PDAC with high [18F]FDG-uptake (median OS 15 ± 5 months; p = 0.004) and iso- or hyperattenuating PDAC with low [18F]FDG-uptake (median OS 23 ± 4 months; p = 0.035). In multivariate analysis, surgery combined with tumor differentiation, tumor stage, systemic therapy and flow metabolic phenotype remained independent predictors for overall survival. DISCUSSION: The novel qualitative flow-metabolic phenotype of PDAC using a combination of CECT and [18F]FDG-PET features, predicted significantly worse survival for hypoattenuating-high uptake pancreatic cancers compared to the other phenotypes.

Patients with Clinically Suspected Gallstone Disease: A More Selective Ultrasound May Improve Treatment Related Outcomes.

This study aimed to quantify the confirmation of gallstones on ultrasound (US) in patients with suspicion of gallstone disease. To aid general practitioners (GPs) in diagnostic workup, a model to predict gallstones was developed. A prospective cohort study was conducted in two Dutch general hospitals. Patients (≥18 years) were eligible for inclusion when referred by GPs for US with suspicion of gallstones. The primary outcome was the confirmation of gallstones on US. A multivariable regression model was developed to predict the presence of gallstones. In total, 177 patients were referred with a clinical suspicion of gallstones. Gallstones were found in 64 of 177 patients (36.2%). Patients with gallstones reported higher pain scores (VAS 8.0 vs. 6.0, p < 0.001), less frequent pain (21.9% vs. 54.9%, p < 0.001), and more often met criteria for biliary colic (62.5% vs. 44.2%, p = 0.023). Predictors for the presence of gallstones were a higher pain score, frequency of pain less than weekly, biliary colic, and an absence of heartburn. The model showed good discrimination between patients with and without gallstones (C-statistic 0.73, range: 0.68-0.76). Clinical diagnosis of symptomatic gallstone disease is challenging. The model developed in this study may aid in the selection of patients for referral and improve treatment related outcomes.

Cost-effectiveness of laparoscopic versus open distal pancreatectomy for pancreatic cancer.

BACKGROUND: A recent Cochrane review compared laparoscopic versus open distal pancreatectomy for people with for cancers of the body and tail of the pancreas and found that laparoscopic distal pancreatectomy may reduce the length of hospital stay. We compared the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy for pancreatic cancer. METHOD: Model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service. A decision tree model was constructed using probabilities, outcomes and cost data from published sources. A time horizon of 5 years was used. One-way and probabilistic sensitivity analyses were undertaken. RESULTS: The probabilistic sensitivity analysis showed that the incremental net monetary benefit was positive (£3,708.58 (95% confidence intervals (CI) -£9,473.62 to £16,115.69) but the 95% CI includes zero, indicating that there is significant uncertainty about the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy. The probability laparoscopic distal pancreatectomy was cost-effective compared to open distal pancreatectomy for pancreatic cancer was between 70% and 80% at the willingness-to-pay thresholds generally used in England (£20,000 to £30,000 per QALY gained). Results were sensitive to the survival proportions and the operating time. CONCLUSIONS: There is considerable uncertainty about whether laparoscopic distal pancreatectomy is cost-effective compared to open distal pancreatectomy for pancreatic cancer in the NHS setting.

Diagnostic accuracy of different imaging modalities following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer.

BACKGROUND: Periampullary cancer includes cancer of the head and neck of the pancreas, cancer of the distal end of the bile duct, cancer of the ampulla of Vater, and cancer of the second part of the duodenum. Surgical resection is the only established potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Other imaging methods such as magnetic resonance imaging (MRI), positron emission tomography (PET), PET-CT, and endoscopic ultrasound (EUS) have been used to detect local invasion or distant metastases not visualised on CT scanning which could prevent unnecessary laparotomy. No systematic review or meta-analysis has examined the role of different imaging modalities in assessing the resectability with curative intent in patients with pancreatic and periampullary cancer. OBJECTIVES: To determine the diagnostic accuracy of MRI, PET scan, and EUS performed as an add-on test or PET-CT as a replacement test to CT scanning in detecting curative resectability in pancreatic and periampullary cancer. SEARCH METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, and Health Technology Assessment (HTA) databases up to 5 November 2015. Two review authors independently screened the references and selected the studies for inclusion. We also searched for articles related to the included studies by performing the "related search" function in MEDLINE (OvidSP) and Embase (OvidSP) and a "citing reference" search (by searching the articles that cite the included articles). SELECTION CRITERIA: We included diagnostic accuracy studies of MRI, PET scan, PET-CT, and EUS in patients with potentially resectable pancreatic and periampullary cancer on CT scan. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and quality assessment using the QUADAS-2 (quality assessment of diagnostic accuracy studies - 2) tool. Although we planned to use bivariate methods for analysis of sensitivities and specificities, we were able to fit only the univariate fixed-effect models for both sensitivity and specificity because of the paucity of data. We calculated the probability of unresectability in patients who had a positive index test (post-test probability of unresectability in people with a positive test result) and in those with negative index test (post-test probability of unresectability in people with a positive test result) using the mean probability of unresectability (pre-test probability) from the included studies and the positive and negative likelihood ratios derived from the model. The difference between the pre-test and post-test probabilities gave the overall added value of the index test compared to the standard practice of CT scan staging alone. MAIN RESULTS: Only two studies (34 participants) met the inclusion criteria of this systematic review. Both studies evaluated the diagnostic test accuracy of EUS in assessing the resectability with curative intent in pancreatic cancers. There was low concerns about applicability for most domains in both studies. The overall risk of bias was low in one study and unclear or high in the second study. The mean probability of unresectable disease after CT scan across studies was 60.5% (that is 61 out of 100 patients who had resectable cancer after CT scan had unresectable disease on laparotomy). The summary estimate of sensitivity of EUS for unresectability was 0.87 (95% confidence interval (CI) 0.54 to 0.97) and the summary estimate of specificity for unresectability was 0.80 (95% CI 0.40 to 0.96). The positive likelihood ratio and negative likelihood ratio were 4.3 (95% CI 1.0 to 18.6) and 0.2 (95% CI 0.0 to 0.8) respectively. At the mean pre-test probability of 60.5%, the post-test probability of unresectable disease for people with a positive EUS (EUS indicating unresectability) was 86.9% (95% CI 60.9% to 96.6%) and the post-test probability of unresectable disease for people with a negative EUS (EUS indicating resectability) was 20.0% (5.1% to 53.7%). This means that 13% of people (95% CI 3% to 39%) with positive EUS have potentially resectable cancer and 20% (5% to 53%) of people with negative EUS have unresectable cancer. AUTHORS' CONCLUSIONS: Based on two small studies, there is significant uncertainty in the utility of EUS in people with pancreatic cancer found to have resectable disease on CT scan. No studies have assessed the utility of EUS in people with periampullary cancer.There is no evidence to suggest that it should be performed routinely in people with pancreatic cancer or periampullary cancer found to have resectable disease on CT scan.

Laparoscopic versus open distal pancreatectomy for pancreatic cancer.

BACKGROUND: Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on other organs, laparoscopic surgery has been shown to reduce complications and length of hospital stay as compared with open surgery. However, concerns remain about the safety of laparoscopic distal pancreatectomy compared with open distal pancreatectomy in terms of postoperative complications and oncological clearance. OBJECTIVES: To assess the benefits and harms of laparoscopic distal pancreatectomy versus open distal pancreatectomy for people undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the pancreas, or both. SEARCH METHODS: We used search strategies to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and trials registers until June 2015 to identify randomised controlled trials (RCTs) and non-randomised studies. We also searched the reference lists of included trials to identify additional studies. SELECTION CRITERIA: We considered for inclusion in the review RCTs and non-randomised studies comparing laparoscopic versus open distal pancreatectomy in patients with resectable pancreatic cancer, irrespective of language, blinding or publication status.. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and independently extracted data. We calculated odds ratios (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence intervals (CIs) using both fixed-effect and random-effects models with RevMan 5 on the basis of intention-to-treat analysis when possible. MAIN RESULTS: We found no RCTs on this topic. We included in this review 12 non-randomised studies that compared laparoscopic versus open distal pancreatectomy (1576 participants: 394 underwent laparoscopic distal pancreatectomy and 1182 underwent open distal pancreatectomy); 11 studies (1506 participants: 353 undergoing laparoscopic distal pancreatectomy and 1153 undergoing open distal pancreatectomy) provided information for one or more outcomes. All of these studies were retrospective cohort-like studies or case-control studies. Most were at unclear or high risk of bias, and the overall quality of evidence was very low for all reported outcomes.Differences in short-term mortality (laparoscopic group: 1/329 (adjusted proportion based on meta-analysis estimate: 0.5%) vs open group: 11/1122 (1%); OR 0.48, 95% CI 0.11 to 2.17; 1451 participants; nine studies; I(2) = 0%), long-term mortality (HR 0.96, 95% CI 0.82 to 1.12; 277 participants; three studies; I(2) = 0%), proportion of people with serious adverse events (laparoscopic group: 7/89 (adjusted proportion: 8.8%) vs open group: 6/117 (5.1%); OR 1.79, 95% CI 0.53 to 6.06; 206 participants; three studies; I(2) = 0%), proportion of people with a clinically significant pancreatic fistula (laparoscopic group: 9/109 (adjusted proportion: 7.7%) vs open group: 9/137 (6.6%); OR 1.19, 95% CI 0.47 to 3.02; 246 participants; four studies; I(2) = 61%) were imprecise. Differences in recurrence at maximal follow-up (laparoscopic group: 37/81 (adjusted proportion based on meta-analysis estimate: 36.3%) vs open group: 59/103 (49.5%); OR 0.58, 95% CI 0.32 to 1.05; 184 participants; two studies; I(2) = 13%), adverse events of any severity (laparoscopic group: 33/109 (adjusted proportion: 31.7%) vs open group: 45/137 (32.8%); OR 0.95, 95% CI 0.54 to 1.66; 246 participants; four studies; I(2) = 18%) and proportion of participants with positive resection margins (laparoscopic group: 49/333 (adjusted proportion based on meta-analysis estimate: 14.3%) vs open group: 208/1133 (18.4%); OR 0.74, 95% CI 0.49 to 1.10; 1466 participants; 10 studies; I(2) = 6%) were also imprecise. Mean length of hospital stay was shorter by 2.43 days in the laparoscopic group than in the open group (MD -2.43 days, 95% CI -3.13 to -1.73; 1068 participants; five studies; I(2) = 0%). None of the included studies reported quality of life at any point in time, recurrence within six months, time to return to normal activity and time to return to work or blood transfusion requirements. AUTHORS' CONCLUSIONS: Currently, no randomised controlled trials have compared laparoscopic distal pancreatectomy versus open distal pancreatectomy for patients with pancreatic cancers. In observational studies, laparoscopic distal pancreatectomy has been associated with shorter hospital stay as compared with open distal pancreatectomy. Currently, no information is available to determine a causal association in the differences between laparoscopic versus open distal pancreatectomy. Observed differences may be a result of confounding due to laparoscopic operation on less extensive cancer and open surgery on more extensive cancer. In addition, differences in length of hospital stay are relevant only if laparoscopic and open surgery procedures are equivalent oncologically. This information is not available currently. Thus, randomised controlled trials are needed to compare laparoscopic distal pancreatectomy versus open distal pancreatectomy with at least two to three years of follow-up. Such studies should include patient-oriented outcomes such as short-term mortality and long-term mortality (at least two to three years); health-related quality of life; complications and the sequelae of complications; resection margins; measures of earlier postoperative recovery such as length of hospital stay, time to return to normal activity and time to return to work (in those who are employed); and recurrence of cancer.