[Multidisciplinary approach to surgical disorders of the pancreas in children]. / Multidisciplinární prístup k chirurgickému onemocnení pankreatu v detském veku.

INTRODUCTION: Surgical diseases of the pancreas in children are not common and may be associated with significant morbidity and potential mortality. A multidisciplinary approach is essential for correct diagnosis, surgical strategy and postoperative as well as follow-up care. METHOD: Retrospective analysis of patients operated on due to a pathological lesion of the pancreas focused on diagnostics, operating procedures, postoperative complications, and long-term results. Between 1991 and 2016, eighty-nine children were treated in our department for a pathologic lesion of the pancreas. 39 of them were boys and 50 were girls. RESULTS: Mean age of the patients was 9.3 years (1 month-18.4 years). Patients were followed from the operation to the age of 19, after which they were referred for follow-up to adult specialists. The indications for surgery were trauma in 34 children, solid pseudopapillary tumor in 23 children, biopsy in 10, hyperinsulinism in 8, chronic pancreatitis in 4, pancreatic cyst in 3, insulinoma in 3, carcinoma in 2, and serous cystadenoma and pancreas divisum in one patient. The most frequent procedures performed on the pancreas were distal pancreatectomy in 35 cases, the duodenum-preserving pancreatic head resection in 23 cases, pseudocystogastroanastomosis in 11 cases, 9095% pancreatic resection in 5 cases, Whipple operation in two cases, Puestow procedure in one case, tumor enucleation in one case, and tumor biopsy for cancer in one case. In 5 patients after major pancreatic injury, ERCP and papillotomy with insertion of a stent into the pancreatic duct was performed. 3 patients died, one after a polytrauma with severe pancreatic injury and two patients with pancreatic cancer. CONCLUSION: Pancreatic surgery in children is not a common operation, and individual as well as institutional experience remains limited. After more than 20 years of experience with pancreatic surgery, we believe that close cooperation with surgeons, pediatric gastroenterologists, radiologists, anesthesiologists, intensivist, pathologists and ERCP specialists is necessary for successful diagnosis and treatment of pancreatic disease in children.Key words: pancreas pancreatic surgery in children duodenum preserving head resection of the pancreas.

[Massive bleeding in portal hypertension endoscopic, surgical or endovascular management?] / Prudké krvácení pri portální hypertenzi endoskopické, chirurgické, nebo intervencní resení?

Upper gastrointestinal bleeding is a serious and potentially life-threatening abdominal emergency. An important diagnostic goal is to determine the cause and localize the bleeding site(s), which is crucial for choosing an appropriate therapy and consequently also for the long-term result. Our case report presents a patient with recurrent upper gastrointestinal bleeding where even repeated endoscopic, surgical and endovascular interventions were not sufficient to determinate the cause of bleeding and to save the patient´s life.Key words: portal hypertension hepatic cirrhosis variceal bleeding ulcerative bleeding.

Photonic coherent state transfer with Hamiltonian dynamics.

We report the observation of near-perfect light wave transfer by emulating quantum state transfer on a lattice with Hamiltonian dynamics, i.e., time-dependent intersite couplings. The structure transferring a single waveguide excitation over 11 sites with a fidelity of 0.93 works for classical light as well as single photons. As our implementation of perfect quantum state transfer uses a photonic setting, we introduce polarization as a new degree of freedom to the transport protocol. We demonstrate rotation operations of up to 40° on polarization during state transfer.

Meal replacement reduces insulin requirement, HbA1c and weight long-term in type 2 diabetes patients with >100 U insulin per day.

BACKGROUND: Despite high insulin doses, good glycaemic control is often lacking in type 2 diabetes patients and new therapeutic options are needed. METHODS: In a proof of principle study, an energy-restricted, protein-rich meal replacement (PRMR) was examined as a means of reducing insulin requirement, HbA1C and body weight. Obese type 2 diabetes patients (n = 22) with >100 U insulin per day replaced, in week 1, the three main meals with 50 g of PRMR (Almased-Vitalkost) each (= 4903 kJ day(-1) ). In weeks 2-4, breakfast and dinner were replaced, and, in weeks 5-12, only dinner was replaced. Clinical parameters were determined at baseline, and after 4, 8 and 12 weeks, as well as after 1.5 years of follow-up. The Wilcoxon signed-rank test was used for the intention-to-treat analysis and the Mann-Whitney U-test for subgroup analyses. RESULTS: The 12-week-programme was completed by 15 participants (68%). After 1 week, the mean insulin dose was reduced from 147 (75) U to 91 (55) U day(-1) (P = 0.0001), and to 65 (32) U (P < 0.0001) after 12 weeks of study. Over a period of 12 weeks, HbA1c decreased from 8.8% (1.4%) to 8.1% (1.6%) (P = 0.048) and weight decreased from 118.0 (19.7) kg to 107.4 (19.2) kg (P < 0.0001). Moreover, body mass index, waist and hip circumference, fasting blood glucose, triglycerides and high-density lipoprotein cholesterol improved significantly. After 1.5 years, insulin requirement and weight remained significantly lower than baseline. Participants who continued PRMR further reduced their HbA1c, weight and insulin dose. Two patients were able to stop insulin therapy altogether. CONCLUSIONS: Energy-restricted PRMR was effective in reducing insulin requirement of type 2 diabetes patients with intensified insulin therapy accompanied by a reduction of HbA1c, weight and other cardiometabolic risk factors. With the continuous use of PRMR, glycaemic control might be improved in the long term.

Einstein-Podolsky-Rosen spatial entanglement in ordered and anderson photonic lattices.

We demonstrate quantum walks of a photon pair in a spatially extended Einstein-Podolsky-Rosen state coupled into an on-chip multiport photonic lattice. By varying the degree of entanglement we observe Anderson localization for pairs in a separable state and Anderson colocalization for pairs in an Einstein-Podolsky-Rosen entangled state. In the former case, each photon localizes independently, while in the latter neither photon localizes, but the pair colocalizes--revealing unexpected survival of the spatial correlations through strong disorder.

Negative coupling between defects in waveguide arrays.

We report on the experimental demonstration of negative coupling constants between defect guides in a waveguide lattice. We find that coupling can only be negative if the defects are negative and an odd number of lattice sites is between the defect guides.

Optical analogues for massless dirac particles and conical diffraction in one dimension.

We demonstrate that light propagating in an appropriately designed lattice can exhibit dynamics akin to that expected from massless relativistic particles as governed by the one-dimensional Dirac equation. This is accomplished by employing a waveguide array with alternating positive and negative effective coupling coefficients, having a band structure with two intersecting minibands. Through this approach optical analogues of massless particle-antiparticle pairs are experimentally realized. One-dimensional conical diffraction is also observed for the first time in this work.

Microbial sulfate reduction and organic sulfur formation in sinking marine particles.

Climate change is driving an expansion of marine oxygen-deficient zones, which may alter the global cycles of carbon, sulfur, nitrogen, and trace metals. Currently, however, we lack a full mechanistic understanding of how oxygen deficiency affects organic carbon cycling and burial. Here, we show that cryptic microbial sulfate reduction occurs in sinking particles from the eastern tropical North Pacific oxygen-deficient zone and that some microbially produced sulfide reacts rapidly to form organic sulfur that is resistant to acid hydrolysis. Particle-hosted sulfurization could enhance carbon preservation in sediments underlying oxygen-deficient water columns and serve as a stabilizing feedback between expanding anoxic zones and atmospheric carbon dioxide. A similar mechanism may help explain more-extreme instances of organic carbon preservation associated with marine anoxia in Earth history.

Wave localization at the boundary of disordered photonic lattices.

We report on the experimental observation of reduced light-energy transport and disorder-induced localization close to a boundary of a truncated 1D disordered photonic lattice. Our observations uncover that a higher level of disorder near the boundary is required to obtain similar localization than in the bulk.

Diagnostic efficacy of ERCP in cholestatic infants and neonates--a retrospective study on a large series.

BACKGROUND AND STUDY AIMS: Cholestatic jaundice in infants is a serious condition, requiring timely and accurate diagnostic evaluation. Our aim was to determine the safety and diagnostic efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of cholestatic liver disease in neonates and infants. PATIENTS AND METHODS: ERCP procedures in cholestatic infants performed in our endoscopy unit between December 1998 and March 2008 were reviewed retrospectively (n = 104 children, 48 boys, 56 girls; mean age 7 weeks, range 3 - 25 weeks; mean weight 4.05 kg, range 1.5 - 4.8 kg). Endoscopic findings were compared with final diagnoses. Statistical analysis was performed and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of ERCP were calculated both separately for each diagnosis and on aggregate. RESULTS: Cannulation of the papilla was successful in 95 of 104 patients (success rate 91.3 %). Biliary atresia of any type was found in 51 children (53.7 %), with a sensitivity of 86 %, a specificity of 94 %, a PPV of 96 %, and a NPV of 100 %. Choledochal cysts were found in seven children (7.4 %), with a sensitivity of 100 %, a specificity of 90 %, PPV of 86 %, and NPV of 100 %. Biliary stones were found in seven patients (7.4 %). Other structural pathology was found in six patients, and no abnormality was seen in 24 patients. No severe complications occurred during or after ERCP. CONCLUSIONS: ERCP in cholestatic infants, when performed in an expert center, is a safe and reliable procedure that can detect biliary tract abnormalities (e. g. biliary atresia, bile duct stones or choledochal cysts) with high sensitivity and specificity. Laparotomies can be prevented in infants by demonstrating normal patency of the biliary tract by ERCP or by magnetic resonance cholangiography if improvements in this technique are made.

Adiabatic transfer of light via a continuum in optical waveguides.

The optical analog of the stimulated Raman adiabatic passage via a continuum is experimentally demonstrated for photonic tunneling in femtosecond laser written waveguides. The results clearly show that the mechanism of light transfer relies on destructive interference and on the existence of a photonic dark state.

Nonlinearity-induced broadening of resonances in dynamically modulated couplers.

We report the observation of nonlinearity-induced broadening of resonances in dynamically modulated directional couplers. When the refractive index of the guiding channels in the coupler is harmonically modulated along the propagation direction and is out-of-phase in two channels, coupling can be completely inhibited at resonant modulation frequencies. We observe that nonlinearity broadens such resonances and that localization can be achieved even in detuned systems at power levels well below those required in unmodulated couplers.

Observation of two-dimensional superlattice solitons.

We observe experimentally two-dimensional solitons in superlattices comprising alternating deep and shallow waveguides fabricated via the femtosecond-laser direct writing technique. We find that the symmetry of linear diffraction patterns as well as soliton shapes and threshold powers largely differ for excitations centered on deep and shallow sites. Thus, bulk and surface solitons centered on deep waveguides require much lower powers than their counterparts on shallow sites.

[Diagnostics and treatment of organic hyperinsulinism--experience in 105 cases]. / Diagnostika a lécba organického hyperinzulinismu--zkusenosti u 105 pacientu.

BACKGROUND: Organic hyperinsulinism causes hypoglycaemia manifesting mainly in the fasting state. We summarize our experience with diagnosis and treatment of 105 patients with organic hyperinsulinism. METHODS AND RESULTS: The diagnosis was confirmed in all patients by spontaneous hypoglycemia and neuroglycopenic symptoms, both developed during fasting test. Endoscopic ultrasonography was the most reliable method for the insulinoma localization (77% of insulinomas confirmed by surgery in the same location within the pancreas), less positive results were obtained by digital subtraction angiography (29%) and still less was found by computed tomography (18%). The localization remains unclear in about 20-25% of insulinomas despite of combined different exploring techniques. Surgical removal of insulinoma by enucleation is the best way of treatment, in some cases laparoscopic removal is a method of choice. From total number of 95 surgically treated patients the successful removal of insulinoma was performed in 84 patients (88%) and another 3 had histopathology diagnosis of micronodular polyadenomatosis. CONCLUSIONS: Insulinoma was not found during surgery and subsequent thorough histopathology investigation of the whole resecate in 8 patients which have to be treated like other non-surgically treated patients by diazoxide together with diabetic diet.

[Treatment of hemosuccus pancreaticus by bilateral embolization of gastric arteries]. / Lécba hemosuccus pancreaticus embolizací obou gastrických tepen.

BACKGROUND: Arosion of peripancreatic arteries in acute or chronic pancreatitis is a rare cause of bleeding into gastrointestinal tract--hemosuccus pancreaticus. Aim of the paper is to show the diagnostic and therapeutic options in this serious clinical stage. METHODS AND RESULTS: We report a case of a patient with chronic pancreatitis who developed acute bleeding into the gastrointestinal tract due to the perforation of a pseudoaneurysm into pancreatic pseudocyst in the area of the pancreatic body. The diagnosis of hemosuccus pancreaticus, established by endoscopy and postcontrast CT examination, was confirmed by angiography. We stopped the acute bleeding from pseudoaneurysm, unusually well supplied by both gastric arteries by embolization of both arteries with metallic coils. CONCLUSIONS: Angiography plays an irreplaceable role in patients with hemosuccus pancreaticus. Our case demonstrates bleeding from pseudoaneurysm supplied by both gastric arteries, whose embolization produced an immediate hemostasis and improvment the patient's condition.

Molecular genetic analysis of volatile-anesthetic action.

The mechanism(s) and site(s) of action of volatile inhaled anesthetics are unknown in spite of the clinical use of these agents for more than 150 years. In the present study, the model eukaryote Saccharomyces cerevisiae was used to investigate the action of anesthetic agents because of its powerful molecular genetics. It was found that growth of yeast cells is inhibited by the five common volatile anesthetics tested (isoflurane, halothane, enflurane, sevoflurane, and methoxyflurane). Growth inhibition by the agents is relatively rapid and reversible. The potency of these compounds as yeast growth inhibitors directly correlates with their lipophilicity as is predicted by the Meyer-Overton relationship, which directly correlates anesthetic potency of agents and their lipophilicity. The effects of isoflurane on yeast cells were characterized in the most detail. Yeast cells survive at least 48 h in a concentration of isoflurane that inhibits colony formation. Mutants resistant to the growth-inhibitory effects of isoflurane are readily selected. The gene identified by one of these mutations, zzz4-1, has been cloned and characterized. The predicted ZZZ4 gene product has extensive homology to phospholipase A2-activating protein, a GO effector protein of mice. Both zzz4-1 and a deletion of ZZZ4 confer resistance to all five of the agents tested, suggesting that signal transduction may be involved in the response of these cells to volatile anesthetics.

Ubiquitin metabolism affects cellular response to volatile anesthetics in yeast.

To investigate the mechanism of action of volatile anesthetics, we are studying mutants of the yeast Saccharomyces cerevisiae that have altered sensitivity to isoflurane, a widely used clinical anesthetic. Several lines of evidence from these studies implicate a role for ubiquitin metabolism in cellular response to volatile anesthetics: (i) mutations in the ZZZ1 gene render cells resistant to isoflurane, and the ZZZ1 gene is identical to BUL1 (binds ubiquitin ligase), which appears to be involved in the ubiquitination pathway; (ii) ZZZ4, which we previously found is involved in anesthetic response, is identical to the DOA1/UFD3 gene, which was identified based on altered degradation of ubiquitinated proteins; (iii) analysis of zzz1Delta zzz4Delta double mutants suggests that these genes encode products involved in the same pathway for anesthetic response since the double mutant is no more resistant to anesthetic than either of the single mutant parents; (iv) ubiquitin ligase (MDP1/RSP5) mutants are altered in their response to isoflurane; and (v) mutants with decreased proteasome activity are resistant to isoflurane. The ZZZ1 and MDP1/RSP5 gene products appear to play important roles in determining effective anesthetic dose in yeast since increased levels of either gene increases isoflurane sensitivity whereas decreased activity decreases sensitivity. Like zzz4 strains, zzz1 mutants are resistant to all five volatile anesthetics tested, suggesting there are similarities in the mechanisms of action of a variety of volatile anesthetics in yeast and that ubiquitin metabolism affects response to all the agents examined.

Ribosomal DNA replication fork barrier and HOT1 recombination hot spot: shared sequences but independent activities.

In the ribosomal DNA of Saccharomyces cerevisiae, sequences in the nontranscribed spacer 3' of the 35S ribosomal RNA gene are important to the polar arrest of replication forks at a site called the replication fork barrier (RFB) and also to the cis-acting, mitotic hyperrecombination site called HOT1. We have found that the RFB and HOT1 activity share some but not all of their essential sequences. Many of the mutations that reduce HOT1 recombination also decrease or eliminate fork arrest at one of two closely spaced RFB sites, RFB1 and RFB2. A simple model for the juxtaposition of RFB and HOT1 sequences is that the breakage of strands in replication forks arrested at RFB stimulates recombination. Contrary to this model, we show here that HOT1-stimulated recombination does not require the arrest of forks at the RFB. Therefore, while HOT1 activity is independent of replication fork arrest, HOT1 and RFB require some common sequences, suggesting the existence of a common trans-acting factor(s).

Surgical management of major pancreatic injury in children.

INTRODUCTION: Major or complicated pancreatic trauma in children is uncommon and management strategies remain controversial. The aim of this study was to evaluate our experience with both early and delayed surgery in these pediatric cases. METHODS: We carried out a retrospective analysis of data of pediatric patients with major or complicated pancreatic injury operated on between January 1994 and December 2005 in our pediatric trauma center. RESULTS: Thirteen children (9 boys and 4 girls) with a mean age of 8.5 years (range 3 - 16 years) were operated for major or complicated pancreatic injury. The extent of injury was: grade II (major contusion without duct injury or tissue loss) in 4 children; grade III (distal transection) in 5 children and grade IV injury (proximal transection) in four patients. Pseudocyst developed in 8 children: 4 with grade II injury, 2 with grade III injury and 2 with grade IV injury (one with abdominal pseudocyst and one with an abdominal and a mediastinal pseudocyst). Early diagnosis and operation was achieved in 5 cases, while delayed diagnosis and operation occurred in 8. Three children underwent cystogastrostomy; 6 had a spleen-sparing distal pancreatectomy and 4 had resection with Roux-en-Y jejunostomy drainage. Endoscopic retrograde cholangiopancreaticography (ERCP) was the most useful diagnostic tool in assessing ductal injury. There were no deaths or long-term morbidity in our group of patients. CONCLUSIONS: Our results support the view that early operation is important in ductal pancreatic injury. We recommend transferring children with a suspected ductal injury to a tertiary center with experience in both pediatric ERCP and pancreatic surgery.

A gene with specific and global effects on recombination of sequences from tandemly repeated genes in Saccharomyces cerevisiae.

The preservation of sequence homogeneity and copy number of tandemly repeated genes may require specific mechanisms or regulation of recombination. We have identified mutations that specifically affect recombination among natural repetitions in the yeast Saccharomyces cerevisiae. The rrm3 mutation stimulates mitotic recombination in the naturally occurring tandem repeats of the rDNA and copper chelatin (CUP1) genes. This mutation does not affect recombination of several other types of repeated genes tested including Ty elements, mating type information and duplications created by transformation. In addition to stimulating exchange among the multiple CUP1 repeats at their natural chromosomal location, rrm3 also increases recombination of a duplication of CUP1 units present at his4. This suggests that the RRM3 gene may encode a sequence-specific factor that contributes to a global suppression of mitotic exchange in sequences that can be maintained as tandem arrays.