Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality.

OBJECTIVES: To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. METHODS: Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. RESULTS: Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). CONCLUSION: In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. KEY POINTS: • Low-tube-voltage high-iodine-load MDCT improves pancreatic cancer conspicuity compared to a standard protocol. • The pancreas-to-tumour attenuation difference increases significantly by reducing the tube voltage. • The radiation exposure dose decreases by reducing the tube voltage.

Assessing surgical quality: comparison of general and procedure-specific morbidity estimation models for the risk adjustment of pancreaticoduodenectomy outcomes.

INTRODUCTION: The use of outcomes to evaluate surgical quality implies the need for detailed risk adjustment. The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) is a generally applicable risk adjustment model suitable for pancreatic surgery. A pancreaticoduodenectomy (PD)-specific intraoperative pancreatic risk assessment (IPRA) estimates the risk of postoperative pancreatic fistula (POPF) and associated morbidity based on factors that are not incorporated into POSSUM. OBJECTIVE: The aim of the study was to compare the risk estimations of POSSUM and IPRA in patients undergoing PD. METHODS: An observational single-center cohort study was conducted including 195 patients undergoing PD in 2008-2010. POSSUM and IPRA data were recorded prospectively. Incidence and severity of postoperative morbidity was recorded according to established definitions. The cohort was grouped by POSSUM and IPRA risk groups. The estimated and observed outcomes and morbidity profiles of POSSUM and IPRA were scrutinized. RESULTS: POSSUM-estimated risk (62 %) corresponded with observed total morbidity (65 %). Severe morbidity was 17 % and in-hospital-mortality 3.1 %. Individual and grouped POSSUM risk estimates did not reveal associations with incidence (p = 0.637) or severity (p = 0.321) of total morbidity or POPF. The IPRA model identified patients with high POPF risk (p < 0.001), but was even associated with incidence (p < 0.001) and severity (p < 0.001) of total morbidity. CONCLUSION: The risk factors defined by a PD-specific model were significantly stronger predictive indicators for the incidence and severity of postoperative morbidity than the factors incorporated in POSSUM. If available, reliable procedure-specific risk factors should be utilized in the risk adjustment of surgical outcomes. For pancreatic surgery, generally applicable tools such as POSSUM still have to prove their relevance.

Diagnostic value of abdominal drainage in individual risk assessment of pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: The use of prophylactic abdominal drainage following pancreaticoduodenectomy (PD) is controversial as its therapeutic value is uncertain. However, the diagnosis of postoperative pancreatic fistula (POPF), the main cause of PD-associated morbidity, is often based on drain pancreatic amylase (DPA) levels. The aim of this study was to assess the predictive value of DPA, plasma pancreatic amylase (PPA) and serum C-reactive protein (CRP) for diagnosing POPF after PD. METHODS: Patients undergoing PD with prophylactic drainage between 2008 and 2012 were studied prospectively. DPA, PPA and CRP levels were obtained daily. Differences between groups with clinically relevant POPF (International Study Group on Pancreatic Fistula (ISGPF) grade B/C) and without clinically relevant POPF (no POPF or ISGPF grade A) were evaluated. Receiver operating characteristic (ROC) analyses were performed to determine the value of DPA, PPA and CRP in prediction of POPF. Risk profiles for clinically relevant POPF were constructed and related to the intraoperative pancreatic risk assessment. RESULTS: Fifty-nine (18.7 per cent) of 315 patients developed clinically relevant POPF. DPA, PPA and CRP levels on postoperative day (POD) 1-3 differed significantly between the study groups. In predicting POPF, the DPA level on POD 1 (cut-off at 1322 units/l; odds ratio (OR) 24.61, 95 per cent confidence interval 11.55 to 52.42) and POD 2 (cut-off at 314 units/l; OR 35.45, 14.07 to 89.33) was superior to that of PPA on POD 1 (cut-off at 177 units/l; OR 13.67, 6.46 to 28.94) and POD 2 (cut-off at 98 units/l; OR 16.97, 8.33 to 34.59). When DPA was combined with CRP (cut-off on POD 3 at 202 mg/l; OR 16.98, 8.43 to 34.21), 90.3 per cent of postoperative courses could be predicted correctly (OR 44.14, 16.89 to 115.38). CONCLUSION: The combination of serum CRP and DPA adequately predicted the development of clinically relevant pancreatic fistula following PD.

Computed tomography staging of pancreatic cancer: a validation study addressing interobserver agreement.

BACKGROUND/OBJECTIVES: Ductal adenocarcinoma in the head of the pancreas (PDAC) is usually unresectable at the time of diagnosis due to the involvement of the peripancreatic vessels. Various preoperative classification algorithms have been developed to describe the relationship of the tumor to these vessels, but most of them lack a surgically based approach. We present a CT-based classification algorithm for PDAC based on surgical resectability principles with a focus on interobserver variability. METHODS: Thirty patients with PDAC undergoing pancreaticoduodenectomy were examined by using a standard CT protocol. Nine radiologists, representing three different levels of expertise, evaluated the CT examinations and the tumors were classified into four categories (A-D) according to the proposed system. For the interobserver agreement, the Intraclass Correlation Coefficient (ICC) was estimated. RESULTS: The overall ICC was 0.94 and the ICCs among the trainees, experienced radiologists, and experts were 0.85, 0.76, and 0.92, respectively. All tumors classified as category A1 showed no signs of vascular invasion at surgery. In category A2, 40% of the tumors had corresponding infiltration and required resection of the superior mesenteric vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in category C required SMV/PV resection. All six patients in category D had both arterial and venous involvement. CONCLUSION: There is almost perfect agreement among radiologists with different levels of expertise in regards to the local staging of PDAC. For tumors in a more advanced preoperative category, an increased risk for vascular involvement was noticed at surgery.

Structured intraoperative assessment of pancreatic gland characteristics in predicting complications after pancreaticoduodenectomy.

BACKGROUND: The morbidity rate after pancreaticoduodenectomy remains high (20-50 per cent) and postoperative pancreatic fistula (POPF) is a major underlying factor. POPF has been reported to be associated with pancreatic consistency (PC) and pancreatic duct diameter (PDD). The aim was to quantify the risk of pancreaticojejunostomy-associated morbidity (PJAM) by means of a structured intraoperative assessment of both characteristics. METHODS: This single-centre prospective observational study included pancreaticoduodenectomies performed between 2008 and 2010 with a standardized duct-to-mucosa end-to-side pancreaticojejunostomy. PC and PDD were assessed during surgery and classified into four grades each (from very hard to very soft, and from larger than 4 mm to smaller than 2 mm, respectively). PJAM was defined as POPF (grade B or C in International Study Group on Pancreatic Fistula classification) or symptomatic peripancreatic collection of either abscess or fluid. PJAM of at least Clavien grade IIIb was considered severe. RESULTS: PJAM and POPF were observed in 24 (21·8 per cent) and 17 (15·5 per cent) of 110 patients respectively. Softer PC and smaller PDD were risk factors for POPF (both P < 0·001), symptomatic peripancreatic collections (P = 0·071 and P = 0·015) and PJAM (both P < 0·001). Combining consistency and duct characteristics in a composite classification the PJAM risk was stratified as 'high' (both risk factors, PJAM incidence 51 per cent), 'intermediate' (softer PC or smaller PDD, PJAM 26 per cent) or 'low' (no risk factors, PJAM 2 per cent). Severe PJAM was observed only in patients with smaller PDD. CONCLUSION: A high-risk pancreatic gland had a 25-fold higher risk of PJAM after pancreaticoduodenectomy than a low-risk gland. This simple classification can contribute to more individualized patient management and allow stratification of study cohorts with homogeneous POPF risk.

Preoperative pancreas CT/MRI characteristics predict fistula rate after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula (PF) is considered to be the main cause of morbidity after pancreaticoduodenectomy (PD). A recent study from our institution suggested the risk for pancreatic fistula after distal pancreatectomy to be closely related to the pancreatic remnant volume (PRV). The hypothesis was formulated that after PD the PRV is an important determinant of the risk for PF formation. METHOD: All patients undergoing PD between September 2007 and November 2010 at the Karolinska University Hospital Stockholm were included. Preoperative multidetector computed tomography (CT) or magnetic resonance imaging (MRI) was used to calculate the PRV and the pancreatic duct width (PDW) at the alleged resection line. RESULTS: A total of 182 patients (median age 67 years) undergoing PD were included. The diagnosis was malignant in 144 patients (79.1 %) and benign in 38 (20.9 %). Pancreatic fistula defined according to the International Study Group on Pancreatic Fistula (ISGPF) criteria was diagnosed in 37 patients (20.3 %). The median PRV was 35.2 cm(3) and the median PDW was 3.9 mm. In a univariate analysis a large calculated volume of the pancreatic remnant increased the subsequent risk of PF (odds ratio [OR], 3.71; 95% confidence interval [95% CI], 1.58-8.71; P < 0.01), as did a small duct width (OR, 8.46; 95% CI, 3.11-23.04; P < 0.01). According to the multivariate analysis, the size of the pancreatic remnant and the width of the pancreatic duct maintained their impact on leakage risk. CONCLUSIONS: A large pancreatic volume and small pancreatic duct increase the risk of PF. Preoperative CT and/or MRI therefore are useful in predicting fistula formation before pancreaticoduodenectomy.

Early intraperitoneal metabolic changes and protease activation as indicators of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Ischaemia and local protease activation close to the pancreaticojejunal anastomosis (PJA) are potential mechanisms of postoperative pancreatic fistula (POPF) formation. To provide information on the pathophysiology of POPF, intraperitoneal microdialysis was used to monitor metabolic changes and protease activation close to the PJA after pancreaticoduodenectomy (PD). METHODS: In patients who underwent PD, intraperitoneal metabolites (glycerol, lactate, pyruvate and glucose) were measured by microdialysis, and lactate and glucose in blood were monitored, every 4 h for 5 days, starting at 12.00 hours on the day after surgery. Trypsinogen activation peptide (TAP) was measured in microdialysates as a marker of protease activation. RESULTS: Intraperitoneal glycerol levels and the ratio of lactate to pyruvate were higher after PD and glucose levels were lower in seven patients who later developed symptomatic POPF than in eight patients with other surgical complications (OSC) and 33 with no surgical complications (NSC) (all P < 0·050). TAP was detected at a concentration greater than 0·1 µg/l in six of seven patients with POPF, two of eight with OSC and two of 33 with NSC. Intraperitoneal lactate concentrations were higher than systemic levels in all patients on days 1 to 5 after surgery (P < 0·001). In patients with POPF, high intraperitoneal lactate concentrations were observed without systemic hyperlactataemia. CONCLUSION: Early in the postoperative phase, patients who later developed clinically significant POPF had higher intraperitoneal glycerol concentrations and lactate/pyruvate ratios, and lower glucose concentrations in combination with a TAP level exceeding 0·1 µg/l close to the PJA, than patients who did not develop POPF.

Validation of the harmless acute pancreatitis score in predicting nonsevere course of acute pancreatitis.

BACKGROUND: The Harmless Acute Pancreatitis Score (HAPS) is a scoring algorithm to identify patients with nonsevere acute pancreatitis. The aim of this study was to evaluate the reproducibility of HAPS outside its original study setting. METHOD: Baseline information of all hospitalized patients with acute pancreatitis at Karolinska University Hospital, Stockholm, Sweden, between 2004 and 2009 was collected. The parameters constituting HAPS were signs of peritonitis, hematocrit and serum creatinine levels. Since hematocrit was not available in all patients, complete sample analysis was performed by replacing hematocrit with hemoglobin (strongly correlated with hematocrit; r = 0.86). RESULTS: In total, 531 patients with a first-time or a recurrent attack of acute pancreatitis were included. Among 353 patients with complete information on parameters constituting HAPS, 79 patients were predicted to have a nonsevere course, of whom 1 patient developed severe acute pancreatitis. The specificity of HAPS in predicting a nonsevere course of acute pancreatitis was 96.3% (95% CI: 81.0-99.9) with a corresponding positive predictive value of 98.7% (95% CI: 93.1-100). Complete sample analysis replacing hematocrit with hemoglobin level predicted a nonsevere course in 182 patients, of whom 2 patients had severe acute pancreatitis (94.3% specificity and 98.9% positive predictive value). CONCLUSION: HAPS is a highly specific scoring algorithm that predicts a nonsevere course of acute pancreatitis. Therefore, HAPS might be an additional tool in the clinical assessment of acute pancreatitis where early screening is important to treat the patients at an optimal level of care.

Pancreatic cancer cells expressing hypoxia-inducible factor-1α tend to be adjacent to intratumoral blood vessels.

We investigated whether cells expressing hypoxia-inducible factor-1α (HIF-1α) are specially related to blood vessels in human pancreatic tumors. HIF-1α and blood vessels were stained in 7 pancreatic ductal adenocarcinomas (PDAC) and 3 nonmalignant tumors. HIF-1α(+) cells accounted for 37 ± 5% of the total PDAC cells and increased to 52 ± 4% in perivascular PDAC cells and to 67 ± 4% in PDAC cells found in intratumoral blood vessels. In nonmalignant tumors, 12 ± 3% of the total tumoral cells examined were HIF-1α(+), and HIF-1α(+) cells decreased to 2 ± 0.3% in perivascular cells examined in the tumors. In conclusion, HIF-1α(+) cells in PDAC and nonmalignant pancreatic tumors differ not only in their amounts but also in their relation to intratumoral blood vessels. HIF-1α(+) cells usually are adjacent to intratumoral blood vessels in PDAC tumors, but are farther away from the vessels in nonmalignant pancreatic tumors.

Impact of chronic and acute high-fat feeding on acute experimental pancreatitis complicated by endotoxinaemia.

BACKGROUND: Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet-induced obesity on outcome in a 'two-hit' model of AP. METHODS: Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose-response experiment, 2) chronic high-fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed. RESULTS: LPS dose-dependently decreased survival rate and increased morphological severity. HF increased weight, intra-abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72-h survival rate was not statistically different in either high-fat experiment. CONCLUSION: An addition of LPS to AP decreases survival rate and intensifies the peri-pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra-abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.

Obstructive jaundice results in increased liver expression of uncoupling protein 2 and intact skeletal muscle glucose metabolism in the rat.

BACKGROUND: A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown. METHODS: Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro. RESULTS: The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats. CONCLUSIONS: Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2, rapid weight loss, and intact insulin action on skeletal muscle glucose metabolism. Obstructive jaundice, by upregulated liver UCP2, may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients.

Obesity increases the severity of acute experimental pancreatitis in the rat.

BACKGROUND: Studies in patients with acute pancreatitis have shown a correlation between obesity and serious complications or a fatal outcome. However, the mechanisms by which obesity aggravates acute pancreatitis are not known. In the present study we used the sodium taurocholate model of pancreatitis to examine the effect of obesity on severity and outcome in acute experimental pancreatitis (AEP). METHODS: AEP was induced at two degrees of severity by retrograde infusion of sodium taurocholate (0.2 ml x 3% or 0.4 ml x 3.5%) into the pancreatic duct of rats with obesity induced by high-fat diet, genetically obese (GO) rats or lean control rats. Surviving animals were sacrificed 72 h after induction of pancreatitis. RESULTS: In the low-dose experiment, there were no significant differences in pancreatic histology or survival rate between the groups. In the high-dose experiment, the GO rats had a significantly lower 72-h survival rate than the high-fat obese (HFO) or lean control (LC) groups (GO 25% versus HFO 73%, P < 0.05; GO 25% versus LC 100%, P < 0.001). Survival rates in the high-dose experiment correlated strongly with basal liver fat content (R2 = 0.86). Pancreatic histology showed significantly more fat necrosis and a higher total pathological mean score in the HFO rats than in the LC animals (both P < 0.05). CONCLUSIONS: Obesity had a negative influence on the outcome of necrotizing pancreatitis that was related to the magnitude of the pancreatic insult. The sodium taurocholate model in obese rats would be useful for future mechanistic studies of the effect of obesity on pancreatitis.