Lymph node retrieval in pancreaticoduodenectomy specimens: does educating the pathologist matter?

AbstractBackgroundMany previous studies have suggested that the number of lymph nodes retrieved should serve as a benchmark for assessing the adequacy of the resection. The aim was to retrospectively observe the impact of nodal retrieval after educating the pathologist.MethodsPatients undergoing a pancreaticoduodenectomy (PD) between September 2005 and March 2009 were included in the study. The PDs performed between September 2005 and March 2008 were designated as Group A. The pathologists were educated regarding the importance of nodal counts in PD by the surgeon on the 1st April 2008. PDs performed between April 2008 and March 2009 were designated as Group B.ResultsNinety-eight PDs performed by a single surgeon (D.R.J.) for peri-ampullary malignancy were evaluated. The median number of lymph nodes retrieved in Group A was 11(3–32) nodes. The median number of lymph nodes retrieved in Group B was 22 (10–29) nodes (P < 0.001).The lymph node ratio (positive/total nodes), median number of positive nodes retrieved, and the node positivity (node positive compared to node negative) rate did not change.DiscussionA single intervention with the pathologists did impact the number of lymph nodes retrieved from PD specimens. However, the lymph node ratio and lymph node positivity rate remained unchanged. The pathologist is critical to nodal retrieval in PD, but the use of this lymph node number for benchmark of surgical adequacy may be simplistic

Training Paradigms in Hepato-Pancreatico-Biliary Surgery: an Overview of the Different Fellowship Pathways

Hepato-pancreatico-biliary (HPB) surgery, and the training of HPB surgeons, has evolved significantly over the last several decades. The current state of training in HPB surgery in North America is defined through three main pathways: the Complex General Surgical Oncology (CGSO) ACGME fellowship, the American Society of Transplant Surgeons (ASTS) fellowship, and the Americas Hepatopancreaticobiliary Association (AHPBA) fellowship. These fellowships offer variable experiences in pancreas, liver, and biliary cases, and each pathway offers a unique perspective on HPB surgery. The CGSO ACGME, ASTS, and AHPBA fellowships represent decades of work by the three major surgical leadership stakeholders to improve and ensure quality training of future HPB surgeons. The best care is provided by the HPB surgeon who has been trained to understand the importance of all available treatment options within the context of a multidisciplinary setting. The three fellowship pathways are outlined in this paper with the nuances and variations characteristic of the different training programs highlighted

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ABSTRACT Context Synchronous cystic neoplasms of pancreas are a highly rare occurrence. Case report We report a very rare case of coexistent serous cystadenoma and multi-side branch intraductal papillary mucinous neoplasm (IPMN). Conclusion To our knowledge, there has been only one previous case report in the literature of a synchronous serous cystadenoma and a solitary IPMN lesion. This case report is intended to increase the awareness of this condition while alluding to the need for diligent examination by endosonographers. It also highlights the clinical impact of endosonography on the diagnosis and management of cystic legions in the pancreas

Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: An evidence-based expert consensus algorithm

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments)

The adequacy of Hepato‐Pancreato‐Biliary training: how closely do perceptions of fellows and programme directors align?

BackgroundHepatopancreatobiliary fellowship programmes have recently undergone significant changes with regards to training standards, case‐volume thresholds and multimodality educational platforms. The goals of this study were to compare the perspectives of fellows and programme directors (PDs) on perceptions of readiness to enter practice and identify core Hepato‐Pancreato‐Biliary (HPB) procedures that require increased emphasis during training.MethodsThis survey targeted PDs and trainees participating in the Fellowship Council/AHPBA pathway. Data related to demographics, education and career plans were collected. Analysis of PD and fellow opinions regarding their confidence to perform core HPB procedures was completed.ResultsThe response rate was 88% for both fellows (21/24) and PDs (23/26). There was good agreement between PDs and fellows in the perception of case volumes. Select differences where PDs ranked higher perceptions included major hepatectomies (PDs: 87% versus fellows: 57%, P = 0.04), pancreaticoduodenectomies (100% versus 81%, P = 0.04) and laparoscopic distal pancreatectomies (78% versus 43%, P = 0.03). ‘Good or excellent’ case volumes translated into increased fellow readiness, except for some pancreatitis procedures, laparoscopic distal pancreatectomies and potentially major hepatectomies.ConclusionsThis study provides insight into content domains that may require additional attention to achieve an appropriate level of proficiency and confidence upon completion of training.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113116/1/hpb12457.pd

High Betaine, a Trimethylamine N-Oxide Related Metabolite, Is Prospectively Associated with Low Future Risk of Type 2 Diabetes Mellitus in the PREVEND Study

Background: Gut microbiota-related metabolites, trimethylamine-N-oxide (TMAO), choline, and betaine, have been shown to be associated with cardiovascular disease (CVD) risk. Moreover, lower plasma betaine concentrations have been reported in subjects with type 2 diabetes mellitus (T2DM). However, few studies have explored the association of betaine with incident T2DM, especially in the general population. The goals of this study were to evaluate the performance of a newly developed betaine assay and to prospectively explore the potential clinical associations of betaine and future risk of T2DM in a large population-based cohort. Methods: We developed a high-throughput, nuclear magnetic resonance (NMR) spectroscopy procedure for acquiring spectra that allow for the accurate quantification of plasma/serum betaine and TMAO. Assay performance for betaine quantification was assessed and Cox proportional hazards regression was employed to evaluate the association of betaine with incident T2DM in 4336 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Results: Betaine assay results were linear (y = 1.02X - 3.75) over a wide range of concentrations (26.0-1135 mu M). The limit of blank (LOB), limit of detection (LOD) and limit of quantitation (LOQ) were 6.4, 8.9, and 13.2 mu M, respectively. Coefficients of variation for intra- and inter-assay precision ranged from 1.5-4.3% and 2.5-5.5%, respectively. Deming regression analysis of results produced by NMR and liquid chromatography coupled to tandem mass spectrometry(LC-MS/MS) revealed an R-2 value of 0.94 (Y = 1.08x - 1.89) and a small bias for higher values by NMR. The reference interval, in a cohort of apparently healthy adult participants (n = 501), was determined to be 23.8 to 74.7 mu M (mean of 42.9 +/- 12.6 mu M). In the PREVEND study (n = 4336, excluding subjects with T2DM at baseline), higher betaine was associated with older age and lower body mass index, total cholesterol, triglycerides, and hsCRP. During a median follow-up of 7.3 (interquartile range (IQR), 5.9-7.7) years, 224 new T2DM cases were ascertained. Cox proportional hazards regression models revealed that the highest tertile of betaine was associated with a lower incidence of T2DM. Hazard ratio (HR) for the crude model was 0.61 (95% CI: 0.44-0.85, p = 0.004). The association remained significant even after adjusting for multiple clinical covariates and T2DM risk factors, including fasting glucose. HR for the fully-adjusted model was 0.50 (95% CI: 0.32-0.80, p = 0.003). Conclusions: The newly developed NMR-based betaine assay exhibits performance characteristics that are consistent with usage in the clinical laboratory. Betaine levels may be useful for assessing the risk of future T2DM

Persistent changes in lipoprotein lipids after a single infusion of ascending doses of MDCO-216 (apoA-IMilano/POPC) in healthy volunteers and stable coronary artery disease patients

Background and aims: Effects of single ascending doses of MDCO-216 on plasma lipid and lipoprotein levels were assessed in human healthy volunteers and in patients with stable coronary artery disease (CAD). Methods: MDCO-216 was infused at a single dose of 5, 10, 20, 30 or 40 mg/kg over 2 h and blood was collected at 2, 4, 8, 24, 48, 168 and 720 h after start of infusion (ASOI). Lipoprotein lipids were assessed by FLPC and by 1H NMR. Results: Plasma concentrations of free cholesterol (FC) displayed a rapid and dose-dependent rise, peaking at 8 h, but remaining above baseline until 48 h ASOI, whereas levels of esterified cholesterol (CE) increased at lower doses but not at higher doses, and even decreased below baseline at the highest dose. Plasma cholesterol esterification rate (CER) decreased with a first nadir between 4 and 8 h and a second nadir at 48 h ASOI. Taken over all subjects receiving MDCO-216, the increase in FC at 8 h correlated inversely with the drop in CER at 4 h but positively with the increase in basal and scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux capacities at 2 h ASOI. Upon FPLC analysis, FC was found to increase first in high density lipoproteins (HDL) and very low density lipoproteins (VLDL) and later (at 48 or 168 h ASOI) in low density lipoproteins (LDL). CE initially decreased in LDL and HDL but after 24 h started to increase in VLDL and LDL whereas HDL-CE was still below baseline at 48 h. Phospholipids (PL) showed the same pattern as FC. Triglycerides (TG) also rose rapidly, most prominently in VLDL, but also in LDL and HDL. Apolipoprotein E (Apo-E) in VLDL increased at 4-8 h but returned to baseline at 24 h ASOI. 1H NMR analysis showed a rapid and dose-dependent increase in HDL particle size, peaking at 2 h and returning to baseline at 24 h, and a small increase in HDL particle concentration. After infusion of the 40 mg/kg dose, LDL and VLDL-particles also increased in number and size. Conclusions: A single administration of MDCO-216 caused rapid changes in lipid levels and lipoprotein composition, some of which persisted for at least 7 days

Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay

Background: Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (2) evaluate the assay performance, (3) isolate LP-Z particles and characterize them by lipidomic and proteomic analysis, and (4) quantify LP-Z in subjects with various liver diseases. Methods: Assay performance was assessed for linearity, sensitivity, and precision. Mass spectroscopy was used to characterize the protein and lipid content of isolated LP-Z particles. Results: The assay showed good linearity and precision (2.5-6.3%). Lipid analyses revealed that LP-Z particles exhibit lower cholesteryl esters and higher free cholesterol, bile acids, acylcarnitines, diacylglycerides, dihexosylceramides, lysophosphatidylcholines, phosphatidylcholines, triacylglycerides, and fatty acids than low-density lipoprotein (LDL) particles. A proteomic analysis revealed that LP-Z have one copy of apolipoprotein B per particle such as LDL, but less apolipoprotein (apo)A-I, apoC3, apoA-IV and apoC2 and more complement C3. LP-Z were not detected in healthy volunteers or subjects with primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, or type 2 diabetes. LP-Z were detected in some, but not all, subjects with hypertriglyceridemia, and were high in some subjects with alcoholic liver disease. Conclusions: LP-Z differ significantly in their lipid and protein content from LDL. Further studies are needed to fully understand the pathophysiological reason for the enhanced presence of LP-Z particles in patients with cholestasis and alcoholic liver disease