DNA-methylation signature accurately differentiates pancreatic cancer from chronic pancreatitis in tissue and plasma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Differentiation from chronic pancreatitis (CP) is currently inaccurate in about one-third of cases. Misdiagnoses in both directions, however, have severe consequences for patients. We set out to identify molecular markers for a clear distinction between PDAC and CP. DESIGN: Genome-wide variations of DNA-methylation, messenger RNA and microRNA level as well as combinations thereof were analysed in 345 tissue samples for marker identification. To improve diagnostic performance, we established a random-forest machine-learning approach. Results were validated on another 48 samples and further corroborated in 16 liquid biopsy samples. RESULTS: Machine-learning succeeded in defining markers to differentiate between patients with PDAC and CP, while low-dimensional embedding and cluster analysis failed to do so. DNA-methylation yielded the best diagnostic accuracy by far, dwarfing the importance of transcript levels. Identified changes were confirmed with data taken from public repositories and validated in independent sample sets. A signature of six DNA-methylation sites in a CpG-island of the protein kinase C beta type gene achieved a validated diagnostic accuracy of 100% in tissue and in circulating free DNA isolated from patient plasma. CONCLUSION: The success of machine-learning to identify an effective marker signature documents the power of this approach. The high diagnostic accuracy of discriminating PDAC from CP could have tremendous consequences for treatment success, once the result from still a limited number of liquid biopsy samples would be confirmed in a larger cohort of patients with suspected pancreatic cancer.

Symptomatic marginal ulcer after pancreatoduodenectomy.

BACKGROUND: Marginal ulcer is a well-known complication after pancreatoduodenectomy. In light of increasing long-term survival after pancreatoduodenectomy, the identification of risk factors and preventive strategies are of utmost importance. We assessed the incidence, clinical impact, and potential risk factors of marginal ulcer after pancreatoduodenectomy. METHODS: A prospectively maintained database of patients undergoing pancreatoduodenectomy was analyzed retrospectively. Univariate and bivariate competing-risk Cox regression analyses were performed to identify risk factors for marginal ulcer. RESULTS: Two hundred and fifty-five consecutive patients underwent pancreatoduodenectomy. The median follow-up was 35.7 months. Marginal ulcer was diagnosed in 19 patients (7.5%), and the median time from pancreatoduodenectomy to marginal ulcer diagnosis was 450 days. Thirteen of these 19 patients presented with abdominal pain, melena, or anemia. In all these 13 patients, marginal ulcer resolved with proton pump inhibitor therapy and endoscopic surveillance. Six patients with marginal ulcer presented with an acute abdomen and underwent emergency laparotomy for marginal ulcer perforation and peritonitis. There was no marginal ulcer-related mortality. Univariate and bivariate competing-risk analyses showed an increased risk for marginal ulcer with discontinuation of proton pump inhibitor therapy, smoking, alcohol intake, and the use of non-steroidal anti-inflammatory drugs. Discontinuation of proton pump inhibitor therapy was an independent risk factor for marginal ulcer development. CONCLUSION: Marginal ulcer is a relevant long-term complication after pancreatoduodenectomy that occurs more frequently after proton pump inhibitor therapy is discontinued. Based on our data, permanent use of proton pump inhibitor after pancreatoduodenectomy is strongly recommended especially for those patients who smoke, consume alcohol, or use non-steroidal anti-inflammatory drugs.

Is MRCP necessary to diagnose pancreas divisum?

BACKGROUND: The purpose of this study is to compare the performance of three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) with non-MRCP T2-weighted magnetic resonance imaging (MRI) sequences for diagnosis of pancreas divisum (PD). METHODS: This is a retrospective study of 342 consecutive patients with abdominal MRI including 3D-MRCP. 3D-MRCP was a coronal respiration-navigated T2-weighted sequence with 1.5 mm slice thickness. Non-MRCP T2-weighted sequences were (1) a coronal inversion recovery sequence (TIRM) with 6 mm slice thickness and (2) a transverse single shot turbo spin echo sequence (HASTE) with 4 mm slice thickness. For 3D-MRCP, TIRM, and HASTE, presence of PD and assessment of evaluability were determined in a randomized manner. A consensus read by two radiologists using 3D-MRCP, non-MRCP T2-weighted sequences, and other available imaging sequences served as reference standard for diagnosis of PD. Statistical analysis included performance analysis of 3D-MRCP, TIRM, and HASTE and testing for noninferiority of non-MRCP T2-weighted sequences compared with 3D-MRCP. RESULTS: Thirty-three of 342 patients (9.7%) were diagnosed with PD using the reference standard. Sensitivity/specificity of 3D-MRCP for detecting PD were 81.2%/69.7% (p < 0.001). Sensitivity/specificity of TIRM and HASTE were 92.5%/93.9 and 98.1%/97.0%, respectively (p < 0.001 each). Grouped sensitivity/specificity of non-MRCP T2-weighted sequences were 99.8%/91.0%. Non-MRCP T2-weighted sequences were non-inferior to 3D-MRCP alone for diagnosis of PD. 20.2, 7.3%, and 2.3% of 3D-MRCP, TIRM, and HASTE, respectively, were not evaluable due to motion artifacts or insufficient duct depiction. CONCLUSIONS: Non-MRCP T2-weighted MRI sequences offer high performance for diagnosis of PD and are noninferior to 3D-MRCP alone. TRIAL REGISTRATION: Not applicable.

Hypercoagulability after distal pancreatectomy: Just meaningless alterations?

BACKGROUND: Perioperative and short-term postoperative parameters are similar comparing spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). But there are no sound data evaluating the long term risk of postoperative thromboses and infectious complications after splenectomy. The present study evaluated whether the coagulation status differs in patients after SPDP and DPS, and whether that matters clinically. METHODS: A total of 41 patients after DP (SPDP = 20; DPS = 21) were followed up, focusing on alterations of patient coagulation and immune status. To assess kinetics of the coagulation process, qualitative tests (multiple platelet function analyzer, rotational thrombelastography) were used in addition to global coagulation tests. RESULTS: Coagulation tests revealed a significant enhanced tendency for blood-platelet aggregation and coagulation activation in patients after DPS compared to patients after SPDP. No septic or thromboembolic events were observed in any patient. CONCLUSION: Hypercoagulability in splenectomized patients persists over years. Thus, a correlation of this finding with thromboembolic events and mortality years after splenectomy should to be performed in a large cohort.

Fluid collection after distal pancreatectomy: a frequent finding.

BACKGROUND: Fluid collections (FC) at the resection margin of the pancreatic stump after distal pancreatectomy (DP) are common radiological findings in follow-up scans. No recommendations exist regarding the management of such findings. The aim was to characterise incidence, risk factors, clinical impact and therapy of FC. METHOD: Data of 209 patients who underwent DP between 07/2009 and 06/2011 were prospectively collected and analysed, regarding follow-up CT or MRI scan findings of FC at the resection margin. FC was defined as a cyst-like lesion >1 cm in diameter. RESULTS: A follow-up with at least two cross-sectional images was available in 159/209 patients. In the first postoperative control, 68 patients showed an FC (43%). FC size was classified as <5 cm (n = 38 pat.), 5-10 cm (n = 24 pat.) and >10 cm (n = 6 pat.). 20 patients (30%) showed clinical symptoms. Six patients (9%) required specific treatment, all other FC showed spontaneous regression. No correlation with stump closure techniques or preceding postoperative pancreatic fistula was found (4/68 patients, 6%). Multivariate analysis revealed standard resections as the only significant factor for FC. CONCLUSIONS: FCs at the resection margin after DP are frequent and harmless findings. Therapeutic interventions are required in only 9% of all FC patients.

Extrapancreatic malignancies in patients with pancreatic cancer: epidemiology and clinical consequences.

OBJECTIVES: To investigate the incidence, characteristics, and prognostic impact of prior extrapancreatic malignancies on patients with pancreatic cancer (PDAC). METHODS: Records from 1733 patients who underwent surgery for PDAC were analyzed for the occurrence of prior extrapancreatic malignancies. Patients' records showing extrapancreatic malignancies were then analyzed for tumor type, epidemiological data, risk factors, PDAC tumor stage, and long-term survival. RESULTS: A total of 239 patients with PDAC (13.8%) had a history of 271 extrapancreatic tumors; 26 patients had a history of two pancreatic cancers, and 3 patients had 3 extrapancreatic cancers. The most common extrapancreatic tumors were breast cancer (56 patients) and prostate cancer (41 patients), followed by colorectal, reno/urothelial, and gynecologic tumors (39, 32, and 23 patients, respectively). No significant difference in overall survival was found between patients with PDAC with or without extrapancreatic malignancies. CONCLUSIONS: Pancreatic cancer is associated with extrapancreatic malignancies in a remarkable number of patients. A history of extrapancreatic malignancies does not influence prognosis and should not be an obstacle to a curative therapeutic approach. Surveillance of patients with extrapancreatic malignancies, especially breast, prostate, and colorectal cancer, could allow for earlier PDAC diagnosis and therefore improve prognosis of these patients.

Reactive hypertrophy of an accessory spleen mimicking tumour recurrence of metastatic renal cell carcinoma.

De novo occurrence of an accessory spleen after splenectomy is worth noting for two reasons. First, it is known that splenectomy can cause reactive hypertrophy of initially inactive and macroscopically invisible splenic tissue. Second, it can mimic tumour recurrence in situations in which splenectomy has been performed for oncological reasons. This might cause difficulties in differential diagnosis and the clinical decision for reoperation. We report the case of a patient with suspected recurrence of renal cell carcinoma after total pancreatectomy and splenectomy for metastatic renal cell carcinoma, which finally revealed an accessory spleen as the morphological correlate of the newly diagnosed mass in the left retroperitoneum.

Intrapulmonal dislocation of a totally implantable venous access device.

BACKGROUND: Totally implantable venous access devices are widely used for infusion of chemotherapy or parenteral nutrition. Device associated complications include technical operative problems, infections, paravasal infusions and catheter or punction chamber dislocation. CASE PRESENTATION: We present the case of a 49-year-old patient with the rare complication of a intrapulmonal catheter dislocation of a totally implantable venous access system. Treosulfane for chemotherapy of metastatic breast cancer was infused via the catheter causing instant coughing and dyspnoea which lead to the diagnosis of catheter dislocation. The intrapulmonal part of the catheter was removed under thoracoscopic control without further complications. CONCLUSION: Intrapulmonal catheter dislocation is a rare complication of a totally implantable venous access device which can not be avoided by any prophylactic measures. Therefore, the infusion system should be tested before each use and each new symptom, even when not obviously related to the catheter should be carefully documented and evaluated by expert physicians to avoid severe catheter-associated complications.