Small bowel intussusception in adults

Catedra Chirurgie nr.1 “N.Anestiadi”, Laboratorul Chirurgie Hepato-Pancreato-Biliară, USMF „Nicolae Testemițanu”, Chișinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Invaginația se definește ca telescoparea unui segment al tractului digestiv în cel adiacent. Invaginația intestinului subțire (IIS) este o formă de obstrucție intestinală ce se întâlnește foarte rar la adulți. Scopul lucrării: Analiza cazurilor de IIS la adulți. Material și metode: S-a efectuat reviul retrospectiv a 79 pacienți adulți cu tumori ale intestinului subțire pe parcursul anilor 1992 - 2014. Au fost selectați pacienții cu IIS. Rezultate: Au fost selectate 8 (10,1%) cazuri de IIS (F-7, B-1) cu vârsta medie de 41,6±52 ani (95%CI: 29,33–53,92). Simptomele principale au fost: durerea abdominală, grețurile, voma. Laparotomia a relevat invaginație ileo-ileală (n=7), iar întrun caz – jejuno-jejunală (p=0,0101), cauzate de o masă intramurală. După o dezinvaginare atentă se efectuează rezecția intestinului subțire (n=6) și rezecție cuneiformă (n=2) cu anastomoză primară termino-terminală (n=7) și jejunostomie Maydl (n=1). Examenul histologic a relevat: fibrom (vimentin +++; CD117 –, desmin –, actin –, S–100 –) (n=4), adenocarcinom (n=1), tumoră gastrointestinală stromală (c-kit/CD117 +++) (n=1), lipom (n=1) și tumora Vanek (n=1). Concluzii: Invaginația la adulți se manifestă printr-o varietate acută, intermitentă și cronică de simptome, făcând astfel diagnosticarea preoperatorie dificilă. O dezinvaginare atentă poate fi încercată în IIS dacă segmentul implicat este viabil și nu se suspectă malignizarea. Tratamentul constă, de obicei în rezectarea segmentului invaginat.Introduction: Intussusception is defined as telescoping of one segment of the digestive tract into an adjacent one. Small bowel intussusception (SBI) is rare form of intestinal obstruction which occurs infrequently in adults. The aim of study: To analyze the cases of SBI in adults. Material and methods: A retrospective review of 79 adult patients with small-bowel tumors between 1992 – 2014 was conducted. Pts with diagnosis of SBI were selected. Results: There were 8 (10.1%) cases of SBI (F-7, M-1) with mean age 41.6±5.2 years (95%CI: 29.33–53.92). Abdominal pain, nausea, and vomiting were the most common symptoms. Laparotomy revealed ileo–ileal (n=7) and jejuno–jejunal (n=1) intussusception (p=0.0101), caused by an intramural mass. After gentle reduction a small bowel resection (n=6) and wedge resection (n=2) were performed with primary anastomosis – end-to-end (n=7) and Maydl jejunostomy (n=1). Histological examination of the specimen revealed: fibroma (vimentin +++; CD117 –, desmin –, actin –, S–100 –) (n=4), adenocarcinoma (n=1), gastrointestinal stromal tumors (c-kit/CD117 +++) (n=1), lipoma (n=1) and Vanek's tumour (n=1). Conclusions: Adult intussusception presents with a variety of acute, intermittent, and chronic symptoms, thus making its preoperative diagnosis difficult. Gentle reduction can be attempted in SBI if the segment involved is viable or malignancy is not suspected. Treatment usually requires resection of the invaginated bowel segment

Von Recklinghausen's disease associated with gastrointestinal tumors: a case seria

Catedra Chirurgie 1 „Nicolae Anestiadi”, Laboratorul Chirurgie Hepato-Pancreato-Biliară, USMF „NicolaeTestemiţanu”, Secţia Chirurgie Toraco-abdominală, Institutul Oncologic, Chişinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Boala von Recklinghausen (VR) reprezintă una dintre cele mai frecvente afecţiuni cu transmitere autozomaldominantă cu penetranţă mare a genotipurilor și expresivitate variabilă, cauzată de mutaţia genei supresiei tumorale NF1. Mutaţia acestei gene duce la pierderea funcției supresoare tumorale, care la rândul său, determină dezvoltarea tumorilor benigne și maligne. Tabloul clinic se caracterizează prin prezenţa neurofibromatozelor multiple, afectării pielii (pete pigmentare „cafe au lait”), pistruilor și hamartromelor în iris (noduli Lisch). În 25% cazuri se observă manifestări gastrointestinale, cel mai frecvent – tumori stromale gastrointestinale (GIST). Cazuri clinice: Se prezintă trei cazuri (bărbaţi, n=3) cu vârste cuprinse între 40-65 ani cu tumori gastro-intestinale asociate cu boala VR. Cazul # 1: Bărbat de 65 ani se prezintă cu durere violentă abdominală şi pierdere în greutate cu GIST multiple de stomac (CD117++, Ki-67 24,7%). S-a intervenit cu o rezecţie subtotală a stomacului. Cazul # 2: Pacientul de 40 ani a fost internat în spital cu semne clinice de perforaţie a intestinului cu hemoragie intraluminală. Intraoperator au fost depistate tumori stromale gastrointestinale (GIST) a jejunului (CD117++), s-a efectuat rezecția de intestin cu anastomoză termino-terminală. Peste 8 ani – reoperat din cauza ocluziei intestinale. Cazul # 3: Pacientul de 52 ani cu multiple GIST a jejunului (CD117+++, CD34+++) în asociere cu tumoare neuroendocrină a papilei mici a duodenului (NSE+, Cromogranina A+), manifestate prin ocluzie intestinală înaltă a fost tratat prin rezecţie pancreatoduodenală (procedeul Kausch-Whipple). Concluzii: Boala von Recklinghausen reprezintă o afecţiune ereditară cu transmitere autozomal-dominantă, care duce la dezvoltarea tumorilor benigne și maligne. În cele mai frecvente cazuri tumorile stromale gastrointestinale apar spontan, însă pacienţii cu boala VR au un risc crescut pentru dezvoltarea acestor tumori. Diagnosticul precoce a manifestărilor abdominale ale acestei afecţiuni este necesar pentru un tratament adecvat şi evitarea complicaţiilor organice severe legate de prezenţa tumorilor.Introduction: The von Recklinghausen's (VR) disease is one of the most common autosomal dominant disorders with almost complete penetration and with variable expression, caused by mutations in the NF1 tumor suppressor gene. The mutation of this gene leads to the loss of tumor suppressor function, which in turn causes the development of benign and malignant tumors. Clinical diagnostic features are multiple neurofibromas, „cafe au lait”, skin fold freckles, and iris hamartomas (Lisch nodules). In 25% of the cases gastrointestinal manifestations are found, most often gastrointestinal stromal tumors (GIST). Clinical cases: We describe three males aged 40-65 years with gastrointestinal tumors associated with VR disease. Case # 1: 65 years old patient presented a severe abdominal pain and weight loss with multiple GIST of the stomach (CD117++, Ki-67 27.4%). It was practiced subtotal gastrectomy. Case # 2: 40 years old patient was hospitalized with clinical signs of intestinal perforation and intraluminal bleeding. Intraoperatively were found GIST of jejunum (CD117++). It was performed resection with end-to-end anastomosis. After 8 years he was reoperated for intestinal obstruction. Case # 3: 52 years old patient with multiple jejunal GIST (CD117+++, CD34+++) and neuroendocrine tumor (NSE+, Cromogranina A+) of the minor duodenal papilla, manifested with proximal intestinal obstruction and resolved by pancreatoduodenectomy (Kausch-Whipple procedure). Conclusions: The von Recklinghausen's disease is an autosomal dominant genetic disorder that leads to the development of benign and malignant tumors. In the most cases gastrointestinal stromal tumors appear spontaneously, but the patients with VR disease have some higher risk for developing of these tumors. Early diagnosis of abdominal manifestations of this disease is necessary for appropriate treatment and prevention of severe organic complications related to tumor

ANALYTICAL STUDY OF THE STATIC THERMOMECHANICAL STRESSES OF THE ASSEMBLIES WITH OPTIONAL RING FLANGES. ROTATION OF THE FLANGE RING AROUND THE CIRCUMFERENCE OF CENTERS FOR BOLT HOLES

This paper addresses the evaluation of thermal and mechanical stresses that occur in assemblies with flat ring flanges, of optional type. The flange rings are fixed by welding to the wall of the cylindrical body of the vessel, with a constant thickness along its length. Regarding of the above, the compatibility of the deformations of the component elements (radial displacements and rotations) is approached. A linear algebraic system is formed in which both external loads (pressure, temperature) and connecting loads (bending unit moments and unit forces) are present. The present analysis discusses the quantitative, cumulative effect of the deformed gasket and the stiffness of the curved/bent screws on the tightness of the system. The methodology is flexible by introducing selection factors so that the mentioned influences can be easily separated

VARIANTS FOR EVALUATING THE RIGIDITY OF FLAT RING FLANGES

This paper describes an analytical way of comparative evaluation of the stiffnesses developed in assemblies with flat ring flanges, of optional type, welded to the cylindrical body of a pressure vessel. Based on the theory of the compatibility of deformations (radial displacements and rotations), the mathematical expressions necessary for the evaluation of the unitary radial bending moments and the unitary shearing forces of connection are established. With their help, the values of the rotation angles of the rings can be calculated and compared with the admissible ones. The present analysis considers the quantitative effect of the deformed gasket and the stiffness of the curved/bent screws on the tightness of the system. The methodology is flexible by introducing some selection factors, so that the mentioned influences can be easily separated and compared

VARIANTS FOR EVALUATING THE RIGIDITY OF FLAT RING FLANGES

This paper describes an analytical way of comparative evaluation of the stiffnesses developed in assemblies with flat ring flanges, of optional type, welded to the cylindrical body of a pressure vessel. Based on the theory of the compatibility of deformations (radial displacements and rotations), the mathematical expressions necessary for the evaluation of the unitary radial bending moments and the unitary shearing forces of connection are established. With their help, the values of the rotation angles of the rings can be calculated and compared with the admissible ones. The present analysis considers the quantitative effect of the deformed gasket and the stiffness of the curved/bent screws on the tightness of the system. The methodology is flexible by introducing some selection factors, so that the mentioned influences can be easily separated and compared

Combined miRNA and SERS urine liquid biopsy for the point-of-care diagnosis and molecular stratification of bladder cancer

Background: Bladder cancer (BC) has the highest per-patient cost of all cancer types. Hence, we aim to develop a non-invasive, point-of-care tool for the diagnostic and molecular stratification of patients with BC based on combined microRNAs (miRNAs) and surface-enhanced Raman spectroscopy (SERS) profiling of urine. Methods: Next-generation sequencing of the whole miRNome and SERS profiling were performed on urine samples collected from 15 patients with BC and 16 control subjects (CTRLs). A retrospective cohort (BC = 66 and CTRL = 50) and RT-qPCR were used to confirm the selected differently expressed miRNAs. Diagnostic accuracy was assessed using machine learning algorithms (logistic regression, naive Bayes, and random forest), which were trained to discriminate between BC and CTRL, using as input either miRNAs, SERS, or both. The molecular stratification of BC based on miRNA and SERS profiling was performed to discriminate between high-grade and low-grade tumors and between luminal and basal types. Results: Combining SERS data with three differentially expressed miRNAs (miR-34a-5p, miR-205-3p, miR-210-3p) yielded an Area Under the Curve (AUC) of 0.92 +/- 0.06 in discriminating between BC and CTRL, an accuracy which was superior either to miRNAs (AUC = 0.84 +/- 0.03) or SERS data (AUC = 0.84 +/- 0.05) individually. When evaluating the classification accuracy for luminal and basal BC, the combination of miRNAs and SERS profiling averaged an AUC of 0.95 +/- 0.03 across the three machine learning algorithms, again better than miRNA (AUC = 0.89 +/- 0.04) or SERS (AUC = 0.92 +/- 0.05) individually, although SERS alone performed better in terms of classification accuracy. Conclusion: miRNA profiling synergizes with SERS profiling for point-of-care diagnostic and molecular stratification of BC. By combining the two liquid biopsy methods, a clinically relevant tool that can aid BC patients is envisaged

Associations between eating speed, diet quality, adiposity, and cardiometabolic risk factors

Objective: To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children. Study design: A cross-sectional study in 1371 preschool age children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the β-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile. Results: Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (β, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (β, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (β, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (β, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (β, −0.5 points; 95% CI, −0.9 to −0.1 points). Conclusions: Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

Combining search space diagnostics and optimisation

Stochastic optimisers such as Evolutionary Algorithms outperform random search due to their ability to exploit gradients in the search landscape, formed by the algorithm's search operators in combination with the objective function. Research into the suitability of algorithmic approaches to problems bas been made more tangible by the direct study and characterisation of the underlying fitness landscapes. Authors have devised metrics, such as the autocorrelation length, to help define these landscapes. In this work, we contribute the Predictive Diagnostic Optimisation method, a new local-search based algorithm which provides knowledge about the search space while it searches for the global optimum of a problem. It is a contribution to a less researched area which may be named Diagnostic Optimisation