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Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature.We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance.The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-92 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-937 U/mL, 39.7%, 94.1%, and 76.3%, respectively.The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.

Chronic pancreatitis (CP) often leads to the development of diabetes. To understand better this pathogenic mechanism, we investigated whether islet cell area and pancreatic volume are reduced in CP patients, islet cell turnover increases in CP patients, and islet cells are less vulnerable to apoptosis than acinar cells.Pancreatic tissues from 43 patients with CP and 27 controls were examined by immunohistochemistry and quantitative morphometry. Pancreas volume was determined using abdominal computed tomography data.The pancreatic volumes were 64.9 +/- 4.3 cm(3) in CP patients and 82.3 +/- 6.7 cm(3) in controls (P = .035). beta-cell areas were 0.69% +/- 0.08% in CP patients and 0.97% +/- 0.08% in controls (P = .017), whereas alpha-cell areas did not differ between the groups (P = .47). There were no differences in the frequencies of replication among groups of alpha-cells, beta-cells, duct cells, or acinar cells nor were there differences in numbers of apoptotic alpha-cells or beta-cells between CP patients and controls. However, CP patients had an approximately 10-fold increase in numbers of apoptotic acinar cells compared with controls (P.0001).Pancreatic volume was reduced by 21%, and the area comprising beta-cells was reduced by 29% in patients with CP. The lack of increased beta-cells turnover in CP patients, despite an approximately 10-fold increase in the number of apoptotic acinar cells, suggests that the damage to the pancreas is highly specific for the exocrine compartment and affects the endocrine islets to a lesser extent.

Until today, surgery remains the treatment of choice for hydatid liver disease. However, new insights into the natural course of the disease and treatment alternatives are known. Since 1998 we have treated all patients with hydatid disease of the liver according to a disease stage specific, multimodai treatment regimen. The present study compares this new interdisciplinary approach with the surgical results from 19861997. Methods: Ultrasonographic classification of cyst morphology and activity (WHO grade 1-3) is mandatory for a stage adapted therapy: Calcified cysts (WHO 3) are inactive and need no treatment. Uncomplicated cysts (WHO 1 + 2) are pnw~arily treated with albendazole with subsequent sonographic controls. In case nf persisting activity and progression of the cyst we performed an endocystectomy with instillation of ethanol or in case of large cystobiliary fistula a liver resection. All complicated cysts were treated surgically. Results: Since 1998 we have screened 37 patients with hydatid disease. 12 were inactive and have been observed (32%). 25 were primarily treated with albendazole (67%), and in 19 of those (76%) cyst involution has been observed sonographically (16) or avitality directly proven by puncture (3). Only 6 patients (16%) needed surgery for cyst complications. So far recurrence rate and mortality are zero and no reintervention was necessary. 3 temporary biliary fistulas have been observed postoperatively, and the overall complication rate of all patients was low (8%). 67 cases with hydatid disease were treated surgically between lgl86-1997 (58 endocystectomies, 9 resections). Postoperatively we observed local complications (bile leakage, bilioma, hematoma, abscess) in 14 cases (21%). Recurrence was observed in 3 patients (4%). However, 43 of all treated cysts were calcified (64%) and would not be treated surgically anymore, as they are inactive. Conclusions: The new stage specific treatment regimen for hydatid disease lowers the number of necessary operations and at the same time morbidity. This therapeutical concept should he ideally performed by an expert team (infectious diseases, radiology, surgery) with a regular follow-up of all patients.