Routine Gastric Decompression after Pancreatoduodenectomy: Treating the Surgeon?

BACKGROUND: The decision to routinely leave a nasogastric tube after pancreatoduodenectomy remains controversial. We sought to determine the impact of immediate nasogastric tube removal versus early nasogastric tube removal (<24 h) on postoperative outcomes. METHODS: A retrospective review of our institution's prospective ACS-NSQIP database identified patients that underwent pancreatoduodenectomy from 2015 to 2018. Outcomes were compared among patients with immediate nasogastric tube removal versus early nasogastric tube removal. RESULTS: A total of 365 patients were included in primary analysis (no nasogastric tube, n = 99; nasogastric tube removed <24 h, n = 266). Thirty-day mortality and infectious, renal, cardiovascular, and pulmonary morbidity were similar in comparing those with no nasogastric tube versus early nasogastric tube removal on univariable and multivariable analyses (P > 0.05). Incidence of delayed gastric emptying (11.1 versus 13.2%) was similar between groups. Patients with no nasogastric tube less frequently required nasogastric tube reinsertion (n = 4, 4%) compared to patients with NGT <24 h (n = 39, 15%) (OR = 3.83, 95% CI [1.39-10.58]; P = 0.009). CONCLUSION: Routine gastric decompression can be safely avoided after uneventful pancreaticoduodenectomy.

Optimal hepatobiliary scintigraphy for gallbladder dyskinesia.

BACKGROUND: The accuracy of hepatobiliary scintigraphy to assess gallbladder function remains controversial. National supply shortages of pharmaceutical-grade cholecystokinin led to the use of an oral fatty meal to stimulate gallbladder contraction during hepatobiliary scintigraphy. The goal of this study was to compare the predictive indices of cholecystokinin and fatty meal ingestion for stimulation of gallbladder contraction. METHODS: Patients evaluated with hepatobiliary iminodiacetic acid scan from 2014 to 2017 were reviewed and grouped based on testing stimulant (fatty meal versus cholecystokinin). Patients who later underwent cholecystectomy were selected for analysis. Hepatobiliary iminodiacetic acid results were correlated with surgical pathology and postoperative resolution of symptoms. Two-way statistical analysis was performed. RESULTS: A total of 359 patients underwent hepatobiliary iminodiacetic acid scan followed by cholecystectomy for biliary dyskinesia. Patients who received fatty meal stimulant (n = 86) were compared to those that received cholecystokinin (n = 273). Mean gallbladder ejection fraction during hepatobiliary iminodiacetic acid was 38% and 44% for the cholecystokinin and fatty meal groups, respectively, P = .073. Predictive metrics were not statistically different between groups with regard to pathology, symptomatic improvement, or accuracy. Symptomatic resolution (cholecystokinin-hepatobiliary iminodiacetic acid 78%, fatty meal-hepatobiliary iminodiacetic acid 68%; P = 0.058) and specificity (cholecystokinin-hepatobiliary iminodiacetic acid 26%, fatty meal-hepatobiliary iminodiacetic acid 44%, P = 0.417) were comparable in both testing groups. CONCLUSION: Stimulation of gallbladder contraction with a fatty meal during hepatobiliary iminodiacetic acid testing is a more affordable and reliable alternative to cholecystokinin for patients undergoing evaluation for gallbladder dysmotility.

Comparison of skin closure techniques in patients undergoing open pancreaticoduodenectomy: A single center experience.

BACKGROUND: This study evaluated closure techniques and incisional surgical site complications (SSCs) and incisional surgical site infections (SSIs) after pancreaticoduodenectomy (PD). METHODS: Retrospective review of open PDs from 2015 to 2018 was performed. Outcomes were compared among closure techniques (subcuticular + topical skin adhesive (TSA); staples; subcuticular only). SSCs were defined as abscess, cellulitis, seroma, or fat necrosis. SSIs were defined according to the National Surgical Quality Improvement Program (NSQIP). RESULTS: Patients with subcuticular + TSA (n = 205) were less likely to develop an incisional SSC (9.8%) compared to staples (n = 139) (20.1%) and subcuticular (n = 74) (16.2%) on univariable analysis (P = 0.024). Multivariable analysis revealed no statistically significant difference in incisional SSC between subcuticular + TSA and subcuticular (P = 0.528); a significant difference remained between subcuticular + TSA and staples (P = 0.014). Unadjusted median length of stay (LOS) (days) was significantly longer for staples (9) vs. subcuticular (8) vs. subcuticular + TSA (7); P < 0.001. Incisional SSIs were evaluated separately according to the NSQIP definition. When comparing rates, the subcuticular + TSA group experienced lower incisional SSIs compared to the other two techniques (4.9% vs. 10.1%, 10.8%). However, this difference was not statistically significant by either univariable or multivariable analysis. CONCLUSIONS: Subcuticular suture + TSA reduces the risk of incisional SSCs when compared to staples alone after pancreaticoduodenectomy.

Growing teratoma syndrome of the ovary presenting with liver metastasis: report of a case.

Growing teratoma syndrome (GTS) is a rare condition among patients with non-seminomatous germ cell tumors who present with enlarging metastatic masses during appropriate systemic chemotherapy in the context of normalized serum markers. This is an infrequent event in the progression of testicular tumors, and is even less common in the case of ovarian germ cell tumors. The pathogenesis of GTS is not completely understood and diagnosis can only be made with certainty after complete pathologic examination. Although histologically benign, GTS may present an enveloping growth with aggressive local expansion, which can be related to substantial morbidity and mortality. Surgery is the only recommended treatment and early recognition of this syndrome is essential as it offers hope for curative resection and avoids the use of ineffective chemotherapy. The authors present a brief review of the literature, along with the case report of a 37-year-old woman presenting GTS with liver involvement who was successfully treated by debulking surgery followed by major liver resection. This report demonstrates that complete surgical resection results in excellent disease control. More importantly, it highlights that clinicians need to be aware of the possible development of GTS when monitoring their patients with non-seminomatous germ cell tumors. These patients require coordinated care between oncologist, gynecologists, and general surgeons to obtain the best possible outcomes.

Evaluation of retinal nerve fiber layer thickness measured by optical coherence tomography in Moroccan patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by focal inflammatory infiltrates, demyelinating lesions and axonal injury. The purpose of the study was to evaluate the retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in Moroccan patients with MS and to assess the relationship between RNFL thickness and disease duration, Expanded Disability Status Scale (EDSS) score, visual acuity and automated visual field indices. MATERIALS AND METHODS: Thirty-one patients with definite MS and thirty-one disease-free controls were enrolled in the study. After neurologic consultation, ophthalmologic examination including visual acuity, automated visual field testing and OCT were performed. RESULTS: Significant differences between both groups were observed in OCT parameters (total, temporal and macular ganglion cell layer) with lower thickness in the MS group. In patients without a history of optic neuritis, there were statistically significant inverse correlations between total RNFL thickness and disease duration, neurologic disability evaluated by the EDSS, logMAR visual acuity and automated visual field indices. CONCLUSIONS: OCT seems to be a reproducible test to detect axonal loss of ganglion cells in MS. Further and larger longitudinal prospective studies would be valuable to assess the evolution over time of the RNFL measurements in Moroccan MS patients.

Assessment of an extended dataset of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption.

Dermal absorption is a key parameter in non-dietary human safety assessments for agrochemicals. Conservative default values and other criteria in the EFSA guidance have substantially increased generation of product-specific in vitro data and in some cases, in vivo data. Therefore, data from 190 GLP- and OECD guideline-compliant human in vitro dermal absorption studies were published, suggesting EFSA defaults and criteria should be revised (Aggarwal et al., 2014). This follow-up article presents data from an additional 171 studies and also the combined dataset. Collectively, the data provide consistent and compelling evidence for revision of EFSA's guidance. This assessment covers 152 agrochemicals, 19 formulation types and representative ranges of spray concentrations. The analysis used EFSA's worst-case dermal absorption definition (i.e., an entire skin residue, except for surface layers of stratum corneum, is absorbed). It confirmed previously proposed default values of 6% for liquid and 2% for solid concentrates, irrespective of active substance loading, and 30% for all spray dilutions, irrespective of formulation type. For concentrates, absorption from solvent-based formulations provided reliable read-across for other formulation types, as did water-based products for solid concentrates. The combined dataset confirmed that absorption does not increase linearly beyond a 5-fold increase in dilution. Finally, despite using EFSA's worst-case definition for absorption, a rationale for routinely excluding the entire stratum corneum residue, and ideally the entire epidermal residue in in vitro studies, is presented.

Assessment of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption.

Dermal absorption is an integral part of non-dietary human safety risk assessments for agrochemicals. Typically, dermal absorption data for agrochemical active substances are generated from the undiluted formulation concentrate and its spray dilutions. European Food Safety Authority (EFSA) guidance, which combines highly conservative default values, very limited opportunities for read-across from existing data and other overly conservative conclusions, was the driver for this assessment. To investigate the reliability of the EFSA guidance, a homogeneous data-set of 190 GLP and OECD guideline compliant in vitro human skin studies, chosen to match the test method preferred by EU data requirements, was evaluated. These studies represented a wide range of active substances, formulation types, and concentrations. In alignment with EFSA guidance on human exposure assessment, a conservative estimate of absorption (95th percentile) was chosen to define defaults, which were also based on the EFSA worst-case assumption that all material in skin, excluding the first two tape strips, is absorbed. The analysis supports dermal absorption defaults of 6% for liquid concentrates, 2% for solid concentrates, and 30% for all spray dilutions, irrespective of the active substance concentration. Relatively high dermal absorption values for organic solvent-based formulations, compared to water-based or solid concentrates, support their use as worst-case surrogate data for read-across to other formulation types. The current review also shows that dermal absorption of sprays does not increase linearly with increasing dilution, and provides a novel, science-based option for extrapolation from existing data.

RhoD participates in the regulation of cell-cycle progression and centrosome duplication.

We have previously identified a Rho protein, RhoD, which localizes to the plasma membrane and the early endocytic compartment. Here, we show that a GTPase-deficient mutant of RhoD, RhoDG26V, causes hyperplasia and perturbed differentiation of the epidermis, when targeted to the skin of transgenic mice. In vitro, gain-of-function and loss-of-function approaches revealed that RhoD is involved in the regulation of G1/S-phase progression and causes overduplication of centrosomes. Centriole overduplication assays in aphidicolin-arrested p53-deficient U2OS cells, in which the cell and the centrosome cycles are uncoupled, revealed that the effects of RhoD and its mutants on centrosome duplication and cell cycle are independent. Enhancement of G1/S-phase progression was mediated via Diaph1, a novel effector of RhoD, which we have identified using a two-hybrid screen. These results indicate that RhoD participates in the regulation of cell-cycle progression and centrosome duplication.

Identification of a gene variant in the master regulator of lipid metabolism SREBP-1 in a family with a novel form of severe combined hypolipidemia.

OBJECTIVE: Alterations of lipid metabolism play a pivotal role in the development of atherosclerosis and its complications, today's major mortality risks. The predominant regulators controlling cholesterol- and fatty acids synthesis in liver are the sterol regulatory element-binding proteins (SREBPs), a family of transcription factors that were formerly identified as cholesterol sensor for LDLR gene expression. Variation of gene structure in these genes might therefore indicate a predisposition to develop complications like myocardial infarction and stroke. METHODS: We investigated 190 unrelated German subjects, including 69 subjects with LDL-cholesterol <55mg/dl, for mutations in SREBP genes SREBF-1 and SREBF-2 by direct sequencing. The impact on SREBP functionality was analyzed by protein biochemical analyses, promoter reporter gene assays and gene expression studies. RESULTS: A missense mutation in SREBF-1 (c.332 C>T; P111L) was identified in a subject with LDL-cholesterol <5mg/dl. Examination of the subject's family confirmed the mutation in two of three siblings. Detailed clinical evaluation of these subjects disclose a novel form of primary combined hypolipidemia only in SREBP-1a P111L carriers, characterized by low levels of apoB and apoA1, low triglyceride, LDL-cholesterol and HDL-cholesterol levels. Functional analyses indicated that the mutation abolishes phosphorylation of SREBP-1. As a consequence transcriptional activation of classical target genes, i.e. LDLR, HMG-CoAR, FAS, ABCA1, but also MTTP, was dramatically reduced. CONCLUSIONS: Phosphorylation of SREBP-1, the master regulator of genes for central rate limiting enzymes of cholesterol and lipid metabolism, appears to be a biological principle with clinical implications.

[Pseudotumoral gallbladder tuberculosis]. / Tuberculose pseudotumorale de la vésicule biliaire.

Gallblader tuberculosis is uncommon and may mimic a neoplasia. We report a 55-year-old man who presented with fever and abdominal pain compatible with cholecystitis. Abdominal ultrasound and computed tomographic scan showed a tumoral aspect of the bottom of the gallbladder and invasion of adjacent liver. Diagnosis of pseudo-tumoral gallbladder tuberculosis was obtained with the histologic examination of surgical sampling. Disease course was uneventful with appropriate antituberculous therapy.

[Desmoid tumors of the abdominal wall: three cases]. / Les tumeurs desmoïdes de la paroi abdominale. A propos de trois cas.

Desmoids tumors are rare. They often develop from the fascia and muscles of the abdominal wall. They are considered as benign, but endowed with local aggressiveness. Treatment is primarily surgical. Complete resection with large safety margins and sometimes complex reconstruction is necessary to reduce the risk of local reccurrence. WE report three cases of histology proven desmoids tumors of the abdominal wall treated between 2000 and 2007. Etiologic factors, diagnosis, surgical management and adjuvant therapy in case of incomplete resection or reccurrence are discussed.

Cardiotoxicity of 5-fluorouracil.

Cardiac side effects of the cytostatic agent 5-fluorouracil (5-FU) have an incidence of 1.2-7.6%. Potentially, arrhythmias, myocardial infarction and sudden cardiac death could occur. Life-threatening cardiotoxicity is rarely observed with a frequency <1%. Cardiotoxicity of 5-FU seems to differ from well known effects of other cytostatics, e.g., anthracyclines. Myocardial ischemia was suggested as potential mechanism due to occasionally observed ECG alterations during 5-FU administration. Experimental studies revealed potential mechanisms of cardiotoxicity ranging from direct toxic effects on vascular endothelium involving endothelial NO synthase leading to coronary spasms and endothelium independent vasoconstriction via protein kinase C. In addition, rheological side effects have to be considered. Coronary artery disease is judged to increase the risk of cardiac side effects. Despite lack of prospective trials, verapamil type calcium antagonists as well as nitrates seem to be useful for treatment of 5-FU induced coronary spasms. In addition, modification of the cytostatic regimen has to be considered in patients who had been symptomatic. It could be assumed that 5-FU toxicity is reversible in the majority of cases when acute complications, e.g., arrhythmias, are resolved.

Unsaturated fatty acids isolated from human lipoproteins activate protein phosphatase type 2Cbeta and induce apoptosis in endothelial cells.

Activity of serine/threonine protein phosphatase type 2C is known to be stimulated by certain unsaturated fatty acids and this enzyme dephosphorylates Bad, thus acting on apoptosis. This prompted us to investigate endothelial cell death. Here, we present evidence for the presence of protein phosphatase type 2Cbeta (PP2Cbeta) in human umbilical vein endothelial cells (HUVECs) and report on colocalization of PP2Cbeta and Bad in the cytosol of endothelial cells. Lipophilic compounds that stimulated PP2Cbeta activity in vitro were found to induce cell death of HUVECs. Lipoproteins did neither influence PP2Cbeta activity nor affect cell behaviour. Lipoproteins treated with the lipoprotein lipase, however, stimulated the activity of PP2Cbeta at least 10-fold concomitantly triggering cell death. Analytical methods revealed that both effects - stimulation of PP2Cbeta and apoptosis - were caused by free fatty acids liberated from VLDL, LDL and HDL with oleic acid and linoleic acid as major constituents. The results provide novel insights in endothelial apoptosis and suggest that PP2Cbeta participates in the development and progress of atherosclerosis.

Increased production of HDL ApoA-I in homozygous familial defective ApoB-100.

Familial defective apolipoprotein (apo) B-100 (FDB) is a frequent cause of hypercholesterolemia. Hypercholesterolemia in homozygous FDB is less severe than in homozygotes for familial hypercholesterolemia. Recently, we showed decreased low density lipoprotein (LDL) apoB-100 fractional catabolism and decreased production of LDL due to an enhanced removal of apoE-containing precursors in a patient with homozygous FDB. The effects of defective apoB-100 on high density lipoprotein (HDL) metabolism are unknown. We studied HDL apoA-I metabolism in this FDB patient and in 6 control subjects by using (2)H(3)-L-leucine as a tracer. ApoA-I levels were normal in all study subjects. However, the fractional catabolic rate and the production rate of apoA-I were increased, by 79% and 70%, respectively, in FDB; the fractional catabolic rate of apoA-I in FDB was 0.34 day(-1) compared with 0.19+/-0.03 day(-1) in normal controls. The production rate of apoA-I in FDB was 18.4 mg. kg(-1). d(-1) compared with 10.8+/-2.3 mg. kg(-1). d(-1) in controls. Thus, we have shown for the first time that defective apoB-100 may influence HDL kinetics. The increase in total HDL turnover might enhance reverse cholesterol transport and could contribute to the seemingly benign clinical course of FDB compared with that of familial hypercholesterolemia.

Strategies to optimize CAD prevention in modern cardiology. The "Marburg CAD Prevention Project".

In recent years we identified numerous cardiovascular risk factors and had been able to reduce cardiovascular events by a variety of different interventions. There is no question that we can improve the course of coronary artery disease (CAD) in patients with a high-risk profile by modifying these factors. Despite this knowledge, many patients with known CAD or myocardial infarction are not treated for secondary prevention as recommended by well established guidelines (http:¿www.chd-taskforce.com). In order to improve secondary prevention in our patients we started a project, the so called "Marburg CAD Prevention Project". By this we combine our computer data base of the CAD preventional routine laboratory with the computer program CARDDAS. Individual risk factors and the angiographic findings were analyzed. Patients as well as local physicians were informed on the need to treat the important risk factors. This approach ensures that at least all of our patients with documented CAD receive the appropriate preventional recommendations and treatment.

HDL steady state levels are not affected, but HDL apoA-I turnover is enhanced by Lifibrol in patients with hypercholesterolemia and mixed hyperlipidemia.

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol) is a new hypocholesterolemic drug effectively reducing total cholesterol, LDL cholesterol, and apolipoprotein (apo) B in experimental animals and in humans. In contrast to fibrates and HMG-CoA reductase inhibitors the cholesterol and triglyceride lowering effect of Lifibrol is not accompanied by increases in HDL cholesterol and apoA-I levels. We examined the impact of Lifibrol on the metabolism of HDL apoA-I in patients with hyperlipoproteinemia, using endogenous labeling with stable isotopes. Kinetic studies were performed in five male hypercholesterolemic individuals (type IIa), before and on treatment with 450 mg of Lifibrol daily for 4 weeks and in five male individuals suffering from mixed hyperlipidemia (type IIb), before and on therapy, for 12 weeks. Lifibrol reduced total cholesterol by 14% (P=0.02) and LDL cholesterol by 16% (P=0. 014) in all patients, and decreased triglycerides by 34% in type IIb patients. During Lifibrol therapy, HDL cholesterol and ApoA-I concentrations did not change. Tracer kinetics revealed that the fractional catabolic rate (FCR) of HDL apoA-I increased by 22% (P=0. 013). This increase in the apoA-I FCR was accompanied by a 23% increase in HDL apoA-I production rate (P=0.006). We conclude that Lifibrol, although not changing HDL steady state concentrations, enhances the turnover of apoA-I containing HDL particles.