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Introduction Parental predisposition and age of onset may be independently associated with 1-year total weight loss (TWL) failure ( Methods This cohort study includes all cases of the German StuDoQ|MBE register (2015–2019) with data on parental predisposition, obesity onset, and at least 1-year follow up after primary MBS procedures (n = 14,404). We provide descriptive statistics of the cohort in terms of the main outcome and 1-year TWL failure, and provide characteristics of surgery type subgroups. Finally, we provide a multivariate logistic regression model of 1-year TWL failure. Results 58.8% and 45.7% of patients reported maternal and paternal predisposition for obesity, respectively. Average onset of obesity was 15.5 years and duration of disease 28.3 years prior to MBS. SG is the most frequently performed procedure (47.2%) followed by RYGB (39.7%) and OAGB (13.1%). Mean 1-year TWL is 32.7 ± 9.3%, and 7.8% (n = 1,119) of patients show TWL failure (p Conclusion The proportions of MBS patients that report on paternal and maternal predisposition for obesity are 45.7% and 58.8% respectively, and average age at onset is 15.5 years. 7.8% of patients do not meet current target criteria of successful response to surgery at 1 year. Early onset, male sex, age at operation, pre-operative BMI, pre-operative weight loss, SG, and T2D are independently associated with weight loss failure. Graphical abstract

Purpose Hiatal hernias with intrathoracic migration of the intestines are serious complications after minimally invasive esophageal resection with gastric sleeve conduit. High recurrence rates have been reported for standard suture hiatoplasties. Additional mesh reinforcement is not generally recommended due to the serious risk of endangering the gastric sleeve. We propose a safe, simple, and effective method to close the hiatal defect with the ligamentum teres. Methods After laparoscopic repositioning the migrated intestines, the ligamentum teres is dissected from the ligamentum falciforme and the anterior abdominal wall. It is then positioned behind the left lobe of the liver and swung toward the hiatal orifice. Across the anterior aspect of the hiatal defect it is semi-circularly fixated with non-absorbable sutures. Care should be taken not to endanger the blood supply of the gastric sleeve. Results We have used this technique for a total of 6 patients with hiatal hernias after hybrid minimally invasive esophageal resection in the elective (n = 4) and emergency setting (n = 2). No intraoperative or postoperative complications have been observed. No recurrence has been reported for 3 patients after 3 months. Conclusion Primary suture hiatoplasties for hiatal hernias after minimally invasive esophageal resection can be technically challenging, and high postoperative recurrence rates are reported. An alternative, safe method is needed to close the hiatal defect. Our promising preliminary experience should stimulate further studies regarding the durability and efficacy of using the ligamentum teres hepatis to cover the hiatal defect.

Background In 2017, the prevalence of obesity (BMI ≥ 30 kg/m2) in Germany was approximately 16%. Obesity increases an individual's risk of developing type 2 diabetes (T2DM) and arterial hypertension; it also increases overall mortality. Consequently, effective treatment is a necessity. Approximately 20 000 bariatric operations are performed in Germany each year. Methods This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane databases and on current German clinical practice guidelines. Results The types of obesity surgery most commonly performed in Germany, Roux-en-Y gastric bypass and sleeve gastrectomy, lead to an excess weight loss of 27-69% ≥ 10 years after the procedure. In obese patients with T2DM, the diabetes remission rate ≥ 10 years after these procedures ranges from 25% to 62%. Adjusted regression analyses of data from large registries have shown that the incidence of malignancies is 33% lower in persons who have undergone obesity surgery compared to control subjects with obesity (unadjusted incidence 5.6 versus 9.0 cases per 1000 person-years). The operation can cause vitamin deficiency, surgical complications, gastroesophageal reflux, and dumping syndrome. Therefore, lifelong follow-up is necessary. Conclusion In view of an increasing number of patients undergoing bariatric surgery, it will probably not be feasible in the future for lifelong follow-up to be provided exclusively in specialized centers.

Background Response to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas. Materials and Methods We performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness. Results DJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham. Conclusion In this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis. Graphical abstract

A large number of significant applications involve numerical solution of stochastic differential equations (SDE's) evolving in Lie groups such as $SO(3)$ . In the engineering literature, the proper formulation of numerical schemes has largely been ignored so that many schemes are flawed, i.e., do not guarantee the solution stays in the Lie group. There is a small mathematics literature but it is not easily accessible. With this in mind, we give a directly accessible derivation of numerical schemes for solving SDE's that do not rely on differential geometry or advanced random process theory. In doing so, we develop some new results. We illustrate the numerical schemes with simulations.

Introduction: Lipoedema is characterized as subcutaneous lipohypertrophy in association with soft-tissue pain affecting female patients. Recently, the disease has undergone a paradigm shift departing from historic reiterations of defining lipoedema in terms of classic edema paired with the notion of weight loss-resistant leg volume towards an evidence-based, patient-centered approach. Although lipoedema is strongly associated with obesity, the effect of bariatric surgery on thigh volume and weight loss has not been explored. Material and Methods: In a retrospective cohort study, thigh volume and weight loss of 31 patients with lipoedema were analyzed before and 10–18 and ≥19 months after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Fourteen patients, with distal leg lymphoedema (i.e., with healthy thighs), who had undergone bariatric surgery served as controls. Statistical analysis was performed using a linear mixed-effects model adjusted for patient age and initial BMI. Results: Adjusted initial thigh volume in patients with lipoedema was 23,785.4 mL (95% confidence interval [CI] 22,316.6–25,254.1). Thigh volumes decreased significantly in lipoedema and control patients (baseline vs. 1st follow-up, p < 0.0001 and p = 0.0001; baseline vs. 2nd follow-up, p < 0.0001 and p = 0.0013). Adjusted thigh volume reduction amounted to 33.4 and 37.0% in the lipoedema and control groups at the 1st follow-up, and 30.4 and 34.7% at the 2nd follow-up, respectively (lipoedema vs. control p > 0.999 for both). SG and RYGB led to an equal reduction in leg volume (operation type × time, p = 0.83). Volume reduction was equally effective in obese and superobese patients (weight category × time, p = 0.43). Conclusion: SG and RYGB lead to a significant thigh volume reduction in patients with lipoedema.

Galectin-1 (Gal-1) has been implicated in the progression of chronic lymphocytic leukemia (CLL) but also the development of immunodeficiency, which commonly accompany this malignancy. In this in vitro study, we investigated the effects of Gal-1 inhibition in the sera of immunocompromised CLL patients on immunomodulating properties of dendritic cells (DCs). DCs derived from peripheral blood mononuclear cells were treated with a healthy serum, CLL serum as well as the combination of CLL serum and Gal-1 inhibitor (OTX008). Following the treatment, the expression levels of DC maturation markers (CD80, CD83, CD86 and IDO-1) were determined as well as their cytokine profile and the ability to polarize the immune response in co-cultures with CD4+ T cells. After treatment with CLL serum, an increase in interleukin (IL)-10 production was observed in both DC cultures and co-cultures with CD4+ T cells. OTX008 caused a reduction in IL-10 production as well as IL-2, but no significant alteration in the expression of DC maturation markers or T regulatory cell (Treg) frequency was observed. The results of our study suggest that Gal-1 from CLL serum give rise to a specific IL-10+ CD4+ T cell phenotype, other than Treg, that could mediate immunodeficiency development in CLL patients.

Objective To examine pasireotide’s effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. Material and methods Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. Results Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. Conclusion Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.

Background/Aim. In classical Hodgkin?s lymphoma (cHL) the existing prognostic scoring systems do not include markers that adequately reflect the interaction of malignant Hodgkin and Reed-Sternberg (HRS) cells and tumor environment. The aim of this study was to determine the relationship between serum Galectin-1 (Gal-1) and soluble CD163 (sCD163) and the clinical status of patients with cHL, with special emphasis on the presence of relapse, progression, or resistance to the therapy applied. Methods. The research included 79 patients of whom 63 were patients with cHL, and the control group of 16 healthy volunteers. The study group of 63 patients with cHL included a subgroup of newly diagnosed patients without therapy, newly diagnosed patients with therapy, patients with relapse and progression of the disease and primary refractory patients during 2014 and 2015. Results. Analysis of the levels of sCD163 and Gal-1 within a group of patients suffering from cHL showed that the values of both molecules were higher in relapsed patients and the subgroup with progressive disease comparing to the subgroup of newly diagnosed patients without therapy or patients with therapy onset. Conclusion. Determination of Gal-1 and sCD163 levels is simple and reliable analysis that can contribute to the identification of high-risk patients with cHL and deserves inclusion in current prognostic scoring systems.

Introduction. Timely assessment of severity of acute pancreatitis is needed to avoid severe systemic complications by making optimal therapeutic approach and correct prognosis of the disease. The aim of the study was to establish the role of several inflammatory biomarkers and coagulation parameters in prediction of AP severity, and also to propose a mathematical formula which allows their combined use for the same purpose. Material and Methods. The prospective study included 70 patients with AP. The patients were divided into groups: mild (group I), moderate (group II) and severe AP (group III). All patients were further classified into two groups: group A (mild AP) and group B (moderate and severe AP). Biochemical markers, inflammatory biomarkers and coagulation factors were tested in all patients. Results. Based on the results of Mann-Whitney,s test, it can be concluded that groups A and B are significant different from each other for CRP (p

Summary High risk Hodgkin lymphoma patients may occasionally have borderline characteristics similar to gray zone lymphomas and T-cell/histiocyte rich B cell lymphomas. These entities require different and more aggressive treatment modalities. Aggressive behavior is often associated with disturbances caused by Epstein Barr virus, or immune evasion caused by overexpression of check point inhibitors PDL-1 and PDL-2 coupled with the lack of expression of Class I and II MHC molecules. Galectin-1, TARC, sCD163 and other surrogate markers of immunosuppression in Hodgkin lymphoma may be useful for the assessment of treatment response. The improvements in lymphoma management diminished the importance of prognostic factors unified in the International Prognostic Scoring system, reducing them from 7 to 3 factors that remained relevant. Interim PET analysis is the only method able to identify resistant patients while chemotherapy is ongoing, thus enabling adjustment of treatment according to the treatment response. Efforts for stratification of patients according to disease histology, biology, microenvironment, clinical scoring systems and PET scan are ongoing. Current breakthroughs have set strong background for novel therapies with monoclonal antibodies and check point inhibitors that will result in improvement of management of high risk patients.

We perform fully resolved simulations of expansion waves propagating into particle beds of varying volume fractions using the discontinuous Galerkin spectral element method. We validate state-of-the-art drag models and predict the final state of the particle bed using isentropic flow relations.

Recently, there has been focus on penalized log-likelihood covariance estimation for sparse inverse covariance (precision) matrices. The penalty is responsible for inducing sparsity, and a very common choice is the convex $l_{1}$ norm. However, the best estimator performance is not always achieved with this penalty. The most natural sparsity promoting “norm” is the nonconvex $l_{0}$ penalty but its lack of convexity has deterred its use in sparse maximum likelihood estimation. In this paper, we consider nonconvex $l_{0}$ penalized log-likelihood inverse covariance estimation and present a novel cyclic descent algorithm for its optimization. Convergence to a local minimizer is proved, which is highly nontrivial, and we demonstrate via simulations the reduced bias and superior quality of the $l_{0}$ penalty as compared to the $l_{1}$ penalty.

Hemophilia A is an inherited disease characterized by deficiency of coagulation factor VIII and bleeding tendency. It is transmitted through the X chromosome. Hemophilia A is characterized by excessive bleeding in various tissues of the body, including soft tissue hematomas and hemarthrosis. In formulating the diagnosis of hemophilia A, in addition to a well-taken medical history and physical examination, laboratory tests should also be carried out and analyzed. Tooth extraction is the most common surgical procedures in patients with hemophilia. Hematological preparation implies the application of a concentrated factor VIH for one to two days prior to the intervention to achieve a desired level of factor VIII needed for the operation. In tooth extraction, this level has to be 50% before and after the tooth extraction for 5 days, with the application of antifibrinolytic agents. In oral surgical interventions the desired level of factor VIII is 50-80% preoperatively, 30-80% for 5 days after surgery, and 30% up to 14 days, also with the use of antifibrinolytic therapy. Patients with hemophilia and inhibitors are prepared for intervention through the application of recombinant FVIIa at the dose of 120mcg/kg, repeated every 2 hours for the period of 7-10 days after the intervention. It is necessary to apply antifibrinolytic agents and local hemostatic measures. Measures of local hemostasis are unavoidable in the case of oral surgical interventions in patients with hemophilia A. Implementation of these procedures in oral surgery has the role of minimizing the possibility of intra- and postoperative bleeding in patients with hemophilia A. For this purpose, the following are mostly used: absorbable suture thread, preparations of collagen, oxycellulose, gelatin, fibrin glue, with topical application of tranexamic or epsilon aminocaproic acid. Conclusion: Close cooperation between hematologists and oral surgeons is essential in order to minimize unwanted complications in patients with hemophilia A.

Follicular lymphoma (FL) is an indolent lymphoma that responds well to rituximab+chemotherapy. We evaluated the prognosis and efficacy of immunochemotherapy in patients with previously untreated, advanced FL.REFLECT 1 is a multicentre, prospective study of 99 patients with previously untreated FL stage III-IV. All patients were treated with rituximab+chemotherapy x 6 cycles, plus 2 cycles of rituximab monotherapy. Clinical assessment was performed at baseline, after completion of the first 6 cycles of therapy and every 3 months from the end of immunochemotherapy to the end of the study period.Eighty-nine out of 99 patients with complete documentation were included. Complete remission (CR) was achieved in 61.6%, partial remission (PR) in 11.6% and progressive disease (PD) in 24.4% of the patients. Time to progression (TTP) and overall survival (OS) after the 1st, 2nd and 3rd year were 89.9, 72.7, 57.8%, and 94.2, 92,6 and 92.6%, respectively. The probability of achieving CR was significantly lower in the high risk group according to Follicular Lymphoma Prognostic Index (FLIPI) score. Expression of CD43 antigen had a significant impact on the probability of 2-year TTP and OS, and ECOG performance status had a significant impact on OS.Treatment with rituximab plus chemotherapy is effective in advanced stages of FL. Significant prognostic factors are FLIPI score for induction therapy outcome, CD43 antigen expression for OS and TTP and ECOG performance status for OS.

Graphical models are well established in providing meaningful conditional probability descriptions of complex multivariable interactions. In the Gaussian case, the conditional independencies between different variables correspond to zero entries in the precision (inverse covariance) matrix. Hence, there has been much recent interest in sparse precision matrix estimation in areas such as statistics, machine learning, computer vision, pattern recognition, and signal processing. A popular estimation method involves optimizing a penalized log-likelihood problem. The penalty is responsible for inducing sparsity and a common choice is the convex l1 norm. Even though the l0 penalty is the natural choice guaranteeing maximum sparsity, it has been avoided due to lack of convexity. As a result, in this paper we bridge the gap between these two penalties and propose the non-concave lq penalized log-likelihood problem for sparse precision matrix estimation where 0 ≤ q

Recently, there has been a lot of focus on penalized least squares problems for noisy sparse signal estimation. The penalty induces sparsity and a very common choice has been the convex l1 norm. However, to improve sparsity and reduce the biases associated with the l1 norm, one must move to non-convex penalties such as the lq norm . In this paper we present a novel cyclic descent algorithm for optimizing the resulting lq penalized least squares problem. Optimality conditions for this problem are derived and competing ones clarified. Coordinate-wise convergence as well as convergence to a local minimizer of the algorithm, which is highly non-trivial, is proved and we illustrate with simulations comparing the signal reconstruction quality with three penalty functions: l0, l1 and lq with 0

Background: The study was done to compare treatment and long‐term outcomes of neoadjuvant chemoradiation (neoCRT) and perioperative chemotherapy (periCTX) in patients with surgically treated esophageal adenocarcinoma. Methods: An analysis of 105 patients with esophageal adenocarcinoma undergoing neoCRT (n ¼58) or periCTX (n ¼47) and esophagectomy between 2000 and 2012 was carried out. Results: The overall median survival was 5.97 years. Postoperative morbidity and in‐hospital mortality occurred in 74%/7% of the patients the neoCRT group and in 53%/0% of the patients in the periCTX group (P ¼0.03/P ¼0.08). Total or subtotal histological tumor response after neoadjuvant treatment and esophagectomy was found in 59% after neoCRT and 30% after periCTX (P

Immunochemotherapy used in the treatment of non-Hodgkin diffuse large B-cell lymphoma (DLBCL) modifies the course of disease and has a positive effect on overall survival (OS). The purpose of this study was to verify the existence of the important Myd 88 mutation and other immunohistochemical factors on disease prognosis in patients with DLBCL in southeast Serbia.Immunohistochemical expression of CD10, Bcl- 2, Bcl-6, Ki-67 and MUM 1 was performed using paraffin blocks of DLBCL. Molecular-genetic study of MyD88 L265P gene polymorphism was done by isolation of genomic DNA from paraffin embedded tissue by means of polymerase chain reaction (PCR).Immunochemotherapy (rituximab+CHOP/R-CHOP) significantly improved the overall survival (OS) of patients with DLBCL compared with patients treated with CHOP alone (p0.0001). OS in the R-CHOP group was longest in patients with International Prognostic Index (IPI) 2 score (p=0.012) and IPI 4 score (p=0.024). Patients with Bcl-2 +, and MUM 1+ benefited from R-CHOP and their expression had no effect on OS. Analysis of restriction fragment length on the genomic DNA showed a homozygous normal TT genotype.Addition of rituximab to CHOP standard protocol improved the OS rate in patients with DLBCL and altered the character and significance of previously recognized prognostic factors. IPI score in the immunochemotherapy era could not reveal possible predictive factors of poor prognosis which would help identify a high-risk subgroup of newly diagnosed DLBCL. In the patient population from Southeast Serbia pathological signaling pathway achieved by Myd 88 L265 mutation was not responsible for the development of DLBCL.

Rank minimization problems, which consist of finding a matrix of minimum rank subject to linear constraints, have been proposed in many areas of engineering and science. A specific problem is the matrix completion problem in which a low rank data matrix can be recovered from incomplete samples of its entries by solving a rank penalized least squares problem. The rank penalty is in fact the l0 “norm” of the matrix singular values. A recent convex relaxation of this penalty is the commonly used l1 norm of the matrix singular values. In this paper, we bridge the gap between these two penalties and propose the lq, 0

Pancreatic pseudocyst is a complication of pancreatic trauma. We describe improved nonoperative treatment of patient with posttraumatic pancreatic pseudocyst with somatostatin analogue. A 9-year-old girl was admitted to our hospital after blunt abdominal trauma with handlebar. Three weeks after abdominal trauma, pancreatic pseudocyst developed. Nonoperative treatment of posttraumatic pancreatic pseudocyst (the largest dimensions 70 × 55 × 65 mm) with somatostatin analogue, octreotide acetate, was applied for the next 52 days. The patient was followed up for 24 months after the discontinuation of octreotide and there were no recurrence of pancreatic pseudocyst. Somatostatin analogue could be usefull in the nonoperative treatment of posttraumatic pancreatic pseudocysts in children.

Visceral leishmaniosis (VL) has emerged as an important opportunistic parasitosis associated with human immunodeficiency virus (HIV) infection. The aim of this paper is to report the first case of Leishmania/HIV coinfection in a patient from Niš (Southeastern Serbia). Microscopical examination of Giemsa-stained bone marrow (BM) smears show the presence of Leishmania spp. amastigotes based on their morphological characteristics. In spite of the parasitological finding, the serological test applied gave negative results. Molecular analyses confirmed the infection and allowed us to identify the leishmania species as Leishmania infantum (100% identity). VL/HIV coinfection has important clinical, diagnostic and epidemiological implications. In fact, the failure of serological tests is expected in this condition, and the application of molecular diagnostics to the blood may offer, apart from an easy and non-invasive diagnostic opportunity, the possibility of warning about the risk of possible nosocomial infections. [Projekat Ministarstva nauke Republike Srbije, br. 41018 and br. 175034]

Laparoscopic sleeve gastrectomy (LSG) has been described as the first step of a two-step laparoscopic Roux-en-Y gastric bypass (LRYGB) or biliopancreatic diversion with duodenal switch (BPD-DS) in extremely obese patients. It has also been used as an independent bariatric procedure. Recently a banded sleeve gastrectomy using human dermis was published. Gastric sleeve dilatation is one of the unfavorable postoperative courses that may limit weight loss. Our technique of a banded sleeve gastrectomy using the GaBP Ring Autolock(TM) System to calibrate the sleeve and prevent distal sleeve dilatation is described in this article.

The banded Roux-en-Y gastric bypass can be used as a primary or revisionary bariatric procedure. This article describes the operation technique including materials, size and placement of the banding and gives an overview con cerning evolution and indications of the operation. A video of a primary banded Roux-en-Y gastric bypass is presented.

Background and purpose: Spinal lesions with marked destruction are common site of morbidity in patients with multiple myeloma causing serious clinical symptoms. The aim of the study was to evaluate the therapeutic benefit of percutaneous vertebroplasty (PVP) in treating vertebral body lesions in patients suffering from multiple myeloma. Materials and methods: Twenty nine patients (55 vertebral bodies) were treated after complete diagnostic evaluation, preparation and obtaining informed consent. Needle position and acrylic material injection was performed under fluoroscopic guidance. Results: Average visual analogue score dropped from 7.8 before to 2.3 after the intervention. Soft tissue leak was present at 9 treated levels, small epidural cement collection at 5, venous leak at 4 and intradiscal leak at 3 levels without any clinically manifest complications. The effects of PVP were stable in all of the patients at 12 months follow-up. Subjective outcome scores collected through follow-up showed improvement of +1.45 in pain, + 1.15 in ambulation and + 1.23 in medication use. There were recurrence of back pain in 9 patients at non-treated levels due to the new lesions. Conclusion: In our series, PVP of painful lesions caused by multiple myeloma provides immediate and long-term pain relief. The procedure is safe and, despite of the present leakage of cement, may be performed on outpatients basis.

Background/Aim. Prostatic intraepithelial high grade neoplasia (PINHG) is accepted as preneoplastic lesion in prostatic carcinoma. One of the fundamental events in early oncogenesis is the disruption of proliferative activity. One of the numerous regulatory proteins is Ki-67 expressed in all proliferating cells. Index Ki-67 is considered to have prognostic significance. The aim of the study was to compare the level of proliferation in hyperplastic epithelium, prostatic carcinoma (Gleason score > 6) and PINHG. Methods. Micromorphological examination was done in 85 patients. Pathohistological analysis was performed on standard histologic specimens with the estimation of Gleason score and the presence of PINHG in its surroundings. Nuclear proliferative activity was analyzed immunohistochemically in 19 cases, using a monoclonal anti-Ki-67 antibody. Results. PINHG was found in prostatic carcinoma surrounding in 30% of the patients. In hyperplastic epithelia Ki-67 proliferative activity was 1,08, in PINHG 2,25 (p < 0,05), while in prostatic cancer, Ki-67 index was 17,64. Proliferative activity in prostatic carcinoma was significantly higher than in PINHG (p < 0,001) and hyperplasia (p < 0,001). Conclusion. This study confirmed that high grade PIN lesion predominately appears in the surrounding of poor or moderately differentiated prostate carcinoma, and that it represents progressive disorder of proliferation in preneoplastic and neoplastic prostatic epithelium. .

Background/Aim. Autoimmune atrophic fundic gastritis induces the pernicious anemia (PA), as well as the changes in both epithelium and endocrine cells of gastric mucosa. The most important complications are: achlorhydria, hypergastrinemia, gastric cancer and enterochromaffin-like ( ECL) carcinoid. The aim of this study was to examine ECL carcinoid histogenesis in A-gastritis associated with PA. Methods. During the period from 2000?2006, 65 patients with PA and 30 patients of the control group were examined. Histopathological examination was done in endoscopical biopsies of gastric mucosa fixed in 10% formaldehyde. Paraffin sections were stained with classic hematoxylin-eosin (HE); histochemical AB-PAS (pH 2.5), cytochemical argyrophilic Servier-Munger?s and immunocytochemical PAP methods for G cell identification and chromogranin A antibodies - specific marker for neuroendocrine ECL cells. Both G and ECL cells were counted per 20 fields, of surface 0.0245312 mm2 by a field. Basal gastrin serum levels were also examined by using radioimmunoassay (RIA) method. The obtained results were statisticaly calculated by using Student?s t test. Results. Marked antral G cell hyperplasia associated with corporal ECL hyperplasia was found. ECL cell hyperplasia was of simplex, linear, adenomatoid type to the pattern of intramucous ECL cell carcinoid. An average number of G cells was statistically significant in the patients with PA as compared to the control group (p < 0.05) as well as an average number of ECL cells. Conclusion. We concluded that antral G cell hyperplasia accompanied by gastrinemia induces ECL hyperplasia and ECL corporal carcinoid in A-gastritis and that their histogenesis develops trough simple, linear and adenomatoide hyperplasia. .

Significant attention has been given to minimizing a penalized least squares criterion for estimating sparse solutions to large linear systems of equations. The penalty induces sparsity and the natural choice is the so-called l 0 norm. In this paper we develop a Momentumized Iterative Shrinkage Thresholding (MIST) algorithm for minimizing the resulting non-convex criterion and prove its convergence to a local minimizer. Simulations on large data sets show superior performance of the proposed method to other methods.

Quantification of protein expression based on immunohistochemistry (IHC) is an important step in clinical diagnoses and translational tissue-based research. Manual scoring systems are used in order to evaluate protein expression based on staining intensities and distribution patterns. However, visual scoring remains an inherently subjective approach. The aim of our study was to explore whether digital image analysis proves to be an alternative or even superior tool to quantify expression of membrane-bound proteins. We analyzed five membrane-binding biomarkers (HER2, EGFR, pEGFR, β-catenin, and E-cadherin) and performed IHC on tumor tissue microarrays from 153 esophageal adenocarcinomas patients from a single center study. The tissue cores were scored visually applying an established routine scoring system as well as by using digital image analysis obtaining a continuous spectrum of average staining intensity. Subsequently, we compared both assessments by survival analysis as an end point. There were no significant correlations with patient survival using visual scoring of β-catenin, E-cadherin, pEGFR, or HER2. In contrast, the results for digital image analysis approach indicated that there were significant associations with disease-free survival for β-catenin, E-cadherin, pEGFR, and HER2 (P = 0.0125, P = 0.0014, P = 0.0299, and P = 0.0096, respectively). For EGFR, there was a greater association with patient survival when digital image analysis was used compared to when visual scoring was (visual: P = 0.0045, image analysis: P < 0.0001). The results of this study indicated that digital image analysis was superior to visual scoring. Digital image analysis is more sensitive and, therefore, better able to detect biological differences within the tissues with greater accuracy. This increased sensitivity improves the quality of quantification.

The novel technology of tissue microarray (TMA) allows rapid and cost-effective analysis of hundreds of markers on the same set of specimens. Limited amounts of tissue that could be analyzed and the problem of tissue heterogeneity are the major drawbacks of the TMA technique for immunohistochemical characterization of lymphomas. These problems do not outweigh the enormous advantages of TMA, namely the cost- and time-saving, and the mostly homogeneous results of immunohistochemistry. In Non Hodgkin's lymphomas (NHL), TMA detection of Oct1 and Oct2 immunoglobulin transcription factors and their coactivator BOB1 showed particularly useful in distinguishing T-cell-rich B-cell lymphomas from classical Hodgkin's disease, nodular lymphocyte predominant Hodgkin's lymphoma and plasmablastic lymphomas. Outcome prediction for subtypes of diffuse large B-cell lymphomas, using a TMA panel with CD10, Bcl-6 and MUM1, was comparable to results of cDNA microarray analysis. Detection of p53 tumor suppressor gene and Ki-67 proliferation antigen is important for the prognosis of many NHL subtypes. In spite of their heterogeneity in expression, TMA showed 90 and 92% concordance rate, with conventional tissue sections for p53 and Ki-67 respectively, and that could be sufficient for routine practice. There is no doubt that the widespread use of TMAs will become an integral part of daily practice in research and routine clinical laboratories.

BACKGROUND: The novel technology of tissue microarray (TMA) allows rapid and cost-effective analysis of hundreds of markers on the same set of specimens. Limited amount of tissue that could be analyzed and problem of tissue heterogeneity, are the major drawbacks of TMA technique for immunohistochemical characterization of lymphomas. METHODS: In this paper 65 cases of lymphomas were analyzed using TMA with following panel of antibodies: BOB1, Oct2, Bcl2, Bcl6, CD20, CD21, CD23, CD3, CD5, CD10, CD43, CD79a, CD138, Cyclin D1, Ki67, MUM1, Pax5, p53. RESULTS: In 14 patients with diffuse large B-cell lymphoma (DLBCL), 5 were classified as germinative center and 3 as non-germinative center cases according to the Bcl6, CD10, and MUM1 positivity. Other 2 patients were identified as T cell rich B cell lymphoma based on morphology and Oct2 and BOB1 positivity of pleomorphic B lymphocytes. DLBCL with Bcl6+ immunophenotype had better overall survival than Bcl6- cases. All cases of classic mantle cell lymphoma had significantly lower Ki-67 proliferation index than blastoid subtypes. There were 14 cases of chronic lymphocytic leukemia/small cell lymphocytic lymphoma, 6 cases with follicular lymphoma, 5 cases of marginal zone lymphoma, and 7 cases of lymphoplazmacitoid lymphoma. In the indolent lymphoma group, survival of patients with p53+/- was poorer comparing to p53- group. CONCLUSION: We conclude that TMA technique is a valuable method in diagnosis and prognosis of lymphomas, which are considered very heterogeneous group of hematological neoplasms.

Recently, major attention has been given to penalized log-likelihood estimators for sparse precision (inverse covariance) matrices. The penalty is responsible for inducing sparsity, and a very common choice is the convexl1 norm. However, it is not always the case that the best estimator is achieved with this penalty. So, to improve sparsity and reduce biases associated with thel1 norm, one must move to non-convex penalties such as thelq (0 q < 1). In this paper we introduce the resulting non-concave lq penalized log-likelihood problem, and derive the corresponding optimality conditions. A novel cyclic descent algorithm is presented for penalized log-likelihood optimization, and we show how the derived conditions can be used to reduce algorithm computation. We illustrate by comparing reconstruction quality over the range 0 q 1 for several experiments.

Acquired factor VIII (FVIII) inhibitor causes a rare but lifethreatening form of bleeding disorder, owing to the formation of autoantibodies against FVIII. Treatment modalities include the use of immunosuppressive drugs, such as cyclophosphamide and corticosteroids, plasmapheresis, and i.v. immunoglobulin. The case of a 67-year-old patient with acquired FVIII inhibitor and psoriasis presented us with a serious bleeding complication. Bleeding reacted poorly to therapy with corticosteroids and cyclophosphamide. Treatment with cyclosporin, however, resulted in a prompt and complete response. The lack of side effects and the relatively quick response suggest that cyclosporin A should be tried as a frontline treatment for patients with acquired FVIII inhibitor.

Introduction In bariatric surgery, still new surgical techniques are developed. On the one hand, the Roux-en-Y gastric bypass (RYGB) is one of the most common procedures used. However, many patients experience dumping syndrome or pain due to bile reflux. On the other hand, revisions after gastric banding are frequent and may be technically challenging. Aim To create a new bariatric procedure counterbalancing the drawbacks of conventional RYGB, also suitable as a redo option after gastric banding. Material and methods To diminish the complication rate and pathophysiological disadvantages in reoperations after gastric banding, we primarily combined a gastric plication (GP) with a single anastomosis duodeno-ileal omega switch (DIOS), bypassing 2/3 of the total bowel length. Further on, in patients with lower body mass index we combined a GP or LSG and laparoscopic sleeve gastrectomy with a duodeno-jejunal omega switch (DJOS), performing an end-to side anastomosis after 1/3 of the total bowel length. Results The DIOS and DJOS techniques restrict food intake and bypass the duodenum and part (DJOS) or the whole (DIOS) jejunum. Restriction is achieved either through gastric plicature or conventional sleeve gastrectomy. Conclusions Similar bariatric and metabolic effects to proximal RYGB are expected in the case of DJOS, or to a conventional duodenal switch when performing a DIOS procedure. Performing a gastric plicature will reduce the risk of gastric leak when revising patients after failed gastric banding.

Introduction. Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. Case report. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Conclusion. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications. [Projekat Ministarstva nauke Republike Srbije, br. 175092]

Early pain relief in patients with acute nontraumatic abdominal pain in emergency departments has been discussed for years. Some randomized trials have addressed this issue but conclusive data are lacking. In this study, we assessed the current treatment practice in German hospitals in order to evaluate the necessity of a further clinical trial. An online survey containing 27 questions was sent to general and visceral surgeons at attending level using a mailing list provided by the Professional Board of German Surgeons (BDC) using a standard interview software. The questionnaire collected demographic data, current treatment policies about frequency of early analgesia, types of pain medication, and opinions about their use and effects. Four hundred ninety-five completed questionnaires were returned. Many surgeons were cautious about early analgesia in the emergency department. Forty-five percent of the surgeons would provide analgesia prior to diagnosis to the majority of patients. Within the departments, differing opinions existed regarding the analgesic treatment (41 %). Thirty-two percent of all the respondents knew about a false diagnosis after early analgesia. There was heterogeneity in the estimation of the impact of pain medication on masking of clinical symptoms. A randomized controlled trial would be supported by the majority of respondents. As influencing factors for withdrawing early analgesia, we found the examiner being over 40 years of age (p

To analyze our experience in patients with duodenal gastrointestinal stromal tumors (GIST) and review the appropriate surgical approach.We retrospectively reviewed the medical records of all patients with duodenal GIST surgically treated at our medical institution between 2002 and 2011. Patient files, operative reports, radiological charts and pathology were analyzed. For surgical therapy open and laparoscopic wedge resections and segmental resections were performed for limited resection (LR). For extended resection pancreatoduodenectomy was performed. Age, gender, clinical symptoms of the tumor, anatomical localization, tumor size, mitotic count, type of resection resectional status, neoadjuvant therapy, adjuvant therapy, risk classification and follow-up details were investigated in this retrospective study.Nine patients (5 males/4 females) with a median age of 58 years were surgically treated. The median follow-up period was 45 mo (range 6-111 mo). The initial symptom in 6 of 9 patients was gastrointestinal bleeding (67%). Tumors were found in all four parts of the duodenum, but were predominantly located in the first and second part of the duodenum with each 3 of 9 patients (33%). Two patients received neoadjuvant medical treatment with 400 mg imatinib per day for 12 wk before resection. In one patient, the GIST resection was done by pancreatoduodenectomy. The 8 LRs included a segmental resection of pars 4 of the duodenum, 5 wedge resections with primary closure and a wedge resection with luminal closure by Roux-Y duodeno-jejunostomy. One of these LRs was done minimally invasive; seven were done in open fashion. The median diameter of the tumors was 54 mm (14-110 mm). Using the Fletcher classification scheme, 3/9 (33%) tumors had high risk, 1/9 (11%) had intermediate risk, 4/9 (44%) had low risk, and 1/9 (11%) had very low risk for aggressive behaviour. Seven resections showed microscopically negative transsection margins (R0), two showed positive margins (R1). No patient developed local recurrence during follow-up. The one patient who underwent pancreatoduodenectomy died due to progressive disease with hepatic metastasis but without evidence of local recurrence. Another patient died in complete remission due to cardiac disease. Seven of the nine patients are alive disease-free.In patients with duodenal GIST, limited surgical resection with microscopically negative margins, but also with microscopically positive margins, lead to very good local and systemic disease-free survival.

Introduction. Patients with severe traumatic brain injury are at a risk of developing ventilator-associated pneumonia. The aim of this study was to describe the incidence, etiology, risk factors for development of ventilator- associated pneumonia and outcome in patients with severe traumatic brain injury. Material and Methods. A retrospective study was done in 72 patients with severe traumatic brain injury, who required mechanical ventilation for more than 48 hours. Results. Ventilator-associated pneumonia was found in 31 of 72 (43.06%) patients with severe traumatic brain injury. The risk factors for ventilator-associated pneumonia were: prolonged mechanical ventilation (12.42 vs 4.34 days, p

AIM: To investigate the influence of remote ischemic preconditioning (RIPC) on anastomotic integrity. METHODS: Sixty male Wistar rats were randomized to six groups. The control group (n = 10) had an end-to-end ileal anastomosis without RIPC. The preconditioned groups (n = 34) varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis (n = 9). On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosal ischemic injury were collected. The data are given as median (range). RESULTS: On postoperative day 4, median bursting pressure was 124 mmHg (60-146 mmHg) in the control group. The experimental groups did not show a statistically significant difference (P > 0.05). Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION: RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning.

In order to establish less invasive therapies for treatment of excess bodyweight and obesity, a device that is placed endoscopically has been developed that mimics some of the anatomical and enteroendocrine effects of bariatric surgery. The EndoBarrier system (GI Dynamics, Lexington, Massachusetts, USA) is a duodenal–jejunal bypass liner (DJBL) that consists of a 60-cm long, impermeable fluoropolymer sleeve, which is fixed in the duodenal bulb by a nitinol anchor with barbs [1]. Initial clinical studies have revealed consistent efficacy and safety, with adverse effects described as moderate or mild [1–5]. In this case report a duodenal perforation associated with DJBL and its minimally invasive treatment were described. A 49-year-old man received a DJBL. After 4 weeks the patient presented to the emergency department with an acute abdomen. Radiologic imaging revealed free air in the abdomen suggestive of intestinal perforation (●" Fig.1). We decided to approach this complication by a combined endoscopic and laparoscopic procedure (●" Video1). The DJBL was removed endoscopically and thiswas followed by laparoscopic closure of the perforation in the duodenal bulb using a running suture with self-retraining suture material (VLoc; Covidien, Dublin, Ireland; ●" Fig.2). The patient was discharged from hospital 9 days after the surgery. This case demonstrates a serious complication of a DJBL, which was successfully treated by an interdisciplinary team of surgeons and endoscopists. Duodenal perforation is a life-threatening event with overall mortality of approximately 8%, higher in patients with accompanying risk factors [6]. The recently introduced over-the-scope clip (OTSC; Ovesco Endoscopy, Tubingen, Germany) is another option for endoscopic treatment of duodenal perforation [7]. Hereby we strongly recommend the use of minimally invasive treatment in such circumstances to preserve the options for subsequent minimally invasive metabolic surgery and reduce the perioperative risks for the patients [8]. However, if duodenal ulceration or perforation starts to be seen more frequently, the anchorage system of this device will need to be re-evaluated and revised to permit possible implantation proximal to the pylorus.

AIM: To assess the effects of bile and pancreatic juice on structural and mechanical resistance of extracellular matrices (ECMs) in vitro. METHODS: Small-intestinal submucosa (SIS), porcine dermal matrix (PDM), porcine pericardial matrix (PPM) and bovine pericardial matrix (BPM) were incubated in human bile and pancreatic juice in vitro. ECMs were examined by macroscopic observation, scanning electron microscopy (SEM) and testing of mechanical resistance. RESULTS: PDM dissolved within 4 d after exposure to bile or pancreatic juice. SIS, PPM and PDM retained their integrity for > 60 d when incubated in either digestive juice. The effect of bile was found to be far more detrimental to mechanical stability than pancreatic juice in all tested materials. In SIS, the loss of mechanical stability after incubation in either of the digestive secretions was less distinct than in PPM and BPM [mFmax 4.01/14.27 N (SIS) vs 2.08/5.23 N (PPM) vs 1.48/7.89 N (BPM)]. In SIS, the extent of structural damage revealed by SEM was more evident in bile than in pancreatic juice. In PPM and BPM, structural damage was comparable in both media. CONCLUSION: PDM is less suitable for support of gastrointestinal healing. Besides SIS, PPM and BPM should also be evaluated experimentally for gastrointestinal indications.