PCNL vs. two staged RIRS for kidney stones greater than 20 mm: systematic review, meta-analysis, and trial sequential analysis.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is considered the gold standard treatment for kidney stones greater than 20 mm. However, retrograde intrarenal surgery (RIRS) may achieve the same stone-free rate with repeated procedures, and potentially fewer complications. This study aimed to compare the efficacy and safety of PCNL and two-staged RIRS. EVIDENCE ACQUISITION: We conducted a systematic search in PubMed, Embase, Scopus, Cochrane, and Web of Science for studies comparing PCNL and RIRS for kidney stones greater than 20mm. The primary outcome is stone-free rate (SFR) of PCNL and RIRS (repeated once if needed). Secondary outcomes were SFR of PCNL versus RIRS (single procedure), operative time, hospital stay, need for auxiliary procedures, and complications. We performed a subgroup analysis for randomized trials, non-randomized trials, and patients with solitary kidney. We performed a trial sequential analysis for the main outcome. EVIDENCE SYNTHESIS: We included 31 articles, with 1987 patients in the PCNL and 1724 patients in RIRS. We confirmed the traditional result that after a single procedure PCNL has a higher SFR. We also found that comparing the SFR of PCNL and RIRS, repeated up to two times if needed, no difference in SFR was observed. Surprisingly, only 26% (CI95 23%-28%) of the patients required a second RIRS. In the trial sequential analysis, the last point of the z-curve was within futility borders. We observed that PCNL has a higher incidence of complications (RR=1.51; CI95 1.24, 1.83; P<0.0001; I2=28%), specifically CD2 (RR=1.82; CI95 1.30, 2.54; P=0.0004; I2=26%) and longer hospital stay (MD 2.57; 2.18, 2.96; P<0.00001; I2-98%). No difference was observed regarding operative time. CONCLUSIONS: RIRS repeated up to two times is equivalent to PCNL in terms of the SFR and may have the same safety.

Cachexia causes time-dependent activation of the inflammasome in the liver.

BACKGROUND: Cachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well-characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight-stable cancer patient. METHODS: Colon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, n = 1) were enrolled in the study, after obtainment of fully informed consent. Eight-week-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 107 cells in 1.0 mL; tumour-bearing [T]; or phosphate-buffered saline-controls [C]). The liver was excised on Days 0 (n = 5), 7 (n = 5) and 14 (n = 5) after tumour cell injection. RESULTS: In rodent cachexia, we found progressively higher numbers of CD68+ myeloid cells in the liver along cancer-cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c-Jun N-terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (P < 0.05). These changes were accompanied by augmented expression of the active interleukin-1ß (IL-1ß) form (P < 0.05 for both circulating and hepatic content). CONCLUSIONS: The results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL-1ß.

Photodynamic Therapy (PDT), Radiofrequency Ablation (RFA) With Biliary Stents in Palliative Treatment of Unresectable Extrahepatic Cholangiocarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: Extrahepatic unresectable cholangiocarcinoma carries a dismal prognosis. In addition to biliary drainage by stent placement; photodynamic therapy (PDT) and radiofrequency ablation (RFA) have been tried to prolong survival. In this meta-analysis, we appraise the current known data on the use of PDT, RFA in the palliative treatment of extrahepatic unresectable cholangiocarcinoma. METHODS: We searched multiple databases from inception through July 2020 to identify studies that reported on PDT and RFA. Pooled rates of survival, stent patency, 30-, 90-day mortality, and adverse events were calculated. Study heterogeneity was assessed using I2% and 95% prediction interval. RESULTS: A total of 55 studies (2146 patients) were included. A total of 1149 patients underwent treatment with PDT (33 studies), 545 with RFA (22 studies), and 452 patients with stent-only strategy. The pooled survival rate with PDT, RFA, and stent-only groups was 11.9 [95% confidence interval (CI): 10.7-13.1] months, 8.1 (95% CI: 6.4-9.9) months, and 6.7 (95% CI: 4.9-8.4) months, respectively. The pooled time of stent patency with PDT, RFA, and stent-only groups was 6.1 (95% CI: 4.2-8) months, 5.5 (95% CI: 4.2-6.7) months, and 4.7 (95% CI: 2.6-6.7) months, respectively. The pooled rate of 30-day mortality with PDT was 3.3% (95% CI: 1.6%-6.7%), with RFA was 7% (95% CI: 4.1%-11.7%) and with stent-only was 4.9% (95% CI: 1.7%-13.1%). The pooled rate of 90-day mortality with PDT was 10.4% (95% CI: 5.4%-19.2%) and with RFA was 16.3% (95% CI: 8.7%-28.6%). CONCLUSION: PDT seemed to demonstrate better overall survival and 30-day mortality rates than RFA and/or stent-only palliation.

Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia.

Background: Cachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1ß and IL-18. Aim: based on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-κB. Results: For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-κB p50, NF-κB p65, IL-1ß. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1ß and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants. Conclusions: The results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.

Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

Human Cachexia Induces Changes in Mitochondria, Autophagy and Apoptosis in the Skeletal Muscle.

Cachexia is a wasting syndrome characterized by the continuous loss of skeletal muscle mass due to imbalance between protein synthesis and degradation, which is related with poor prognosis and compromised quality of life. Dysfunctional mitochondria are associated with lower muscle strength and muscle atrophy in cancer patients, yet poorly described in human cachexia. We herein investigated mitochondrial morphology, autophagy and apoptosis in the skeletal muscle of patients with gastrointestinal cancer-associated cachexia (CC), as compared with a weight-stable cancer group (WSC). CC showed prominent weight loss and increased circulating levels of serum C-reactive protein, lower body mass index and decreased circulating hemoglobin, when compared to WSC. Electron microscopy analysis revealed an increase in intermyofibrillar mitochondrial area in CC, as compared to WSC. Relative gene expression of Fission 1, a protein related to mitochondrial fission, was increased in CC, as compared to WSC. LC3 II, autophagy-related (ATG) 5 and 7 essential proteins for autophagosome formation, presented higher content in the cachectic group. Protein levels of phosphorylated p53 (Ser46), activated caspase 8 (Asp384) and 9 (Asp315) were also increased in the skeletal muscle of CC. Overall, our results demonstrate that human cancer-associated cachexia leads to exacerbated muscle-stress response that may culminate in muscle loss, which is in part due to disruption of mitochondrial morphology, dysfunctional autophagy and increased apoptosis. To the best of our knowledge, this is the first report showing quantitative morphological alterations in skeletal muscle mitochondria in cachectic patients.

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa.

BACKGROUND: Cachexia is a multifactorial and multiorgan syndrome associated with cancer and other chronic diseases and characterized by severe involuntary body weight loss, disrupted metabolism, inflammation, anorexia, fatigue, and diminished quality of life. This syndrome affects around 50% of patients with colon cancer and is directly responsible for the death of at least 20% of all cancer patients. Systemic inflammation has been recently proposed to underline most of cachexia-related symptoms. Nevertheless, the exact mechanisms leading to the initiation of systemic inflammation have not yet been unveiled, as patients bearing the same tumour and disease stage may or may not present cachexia. We hypothesize a role for gut barrier disruption, which may elicit persistent immune activation in the host. To address this hypothesis, we analysed the healthy colon tissue, adjacent to the tumour. METHODS: Blood and rectosigmoid colon samples (20 cm distal to tumour margin) obtained during surgery, from cachectic (CC = 25) or weight stable (WSC = 20) colon cancer patients, who signed the informed consent form, were submitted to morphological (light microscopy), immunological (immunohistochemistry and flow cytometry), and molecular (quantification of inflammatory factors by Luminex® xMAP) analyses. RESULTS: There was no statistical difference in gender and age between groups. The content of plasma interleukin 6 (IL-6) and IL-8 was augmented in cachectic patients relative to those with stable weight (P = 0.047 and P = 0.009, respectively). The number of lymphocytic aggregates/field in the gut mucosa was higher in CC than in WSC (P = 0.019), in addition to those of the lamina propria (LP) eosinophils (P < 0.001) and fibroblasts (P < 0.001). The area occupied by goblet cells in the colon mucosa was decreased in CC (P = 0.016). The M1M2 macrophages percentage was increased in the colon of CC, in relation to WSC (P = 0.042). Protein expression of IL-7, IL-13, and transforming growth factor beta 3 in the colon was significantly increased in CC, compared with WSC (P = 0.02, P = 0.048, and P = 0.048, respectively), and a trend towards a higher content of granulocyte-colony stimulating factor in CC was also observed (P = 0.061). The results suggest an increased recruitment of immune cells to the colonic mucosa in CC, as compared with WSC, in a fashion that resembles repair response following injury, with higher tissue content of IL-13 and transforming growth factor beta 3. CONCLUSIONS: The changes in the intestinal mucosa cellularity, along with modified cytokine expression in cachexia, indicate that gut barrier alterations are associated with the syndrome.

Tumour-derived transforming growth factor-ß signalling contributes to fibrosis in patients with cancer cachexia.

BACKGROUND: Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro-environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro-environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients. METHODS: 74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components. RESULTS: Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte-macrophage colony-stimulating factor, interferon-α, and interleukin (IL)-8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight-stable counterparts. Also, IL-8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of α-smooth muscle actin (P < 0.0001) in tumours of cachectic cancer patients, characterizing fibrosis. In addition, higher transforming growth factor (TGF)-ß1, TGF-ß2, and TGF-ß3 expression (P = 0.003, P = 0.05, and P = 0.047, respectively) was found in the tumour of cachectic patients, parallel to p38 mitogen-activated protein kinase alteration. Hypoxia-inducible factor-1α mRNA content was significantly increased in the tumour of cachectic patients, when compared with weight-stable group (P = 0.005). CONCLUSIONS: Our results demonstrate TGF-ß pathway activation in the tumour in cachexia, through the (non-canonical) mitogen-activated protein kinase pathway. The results show that during cachexia, intratumoural inflammatory response contributes to the onset of fibrosis. Tumour remodelling, probably by TGF-ß-induced transdifferentiation of fibroblasts to myofibroblasts, induces unbalanced inflammatory cytokine profile, angiogenesis, and elevation of extracellular matrix components (EMC). We speculate that these changes may affect tumour aggressiveness and present consequences in peripheral organs.

Pain inhibition through transplantation of fetal neuronal progenitors into the injured spinal cord in rats.

Neuropathic pain after spinal cord injury (SCI) is a complex condition that responds poorly to usual treatments. Cell transplantation represents a promising therapy; nevertheless, the ideal cell type in terms of neurogenic potential and effectiveness against pain remains largely controversial. Here, we evaluated the ability of fetal neural stem cells (fNSC) to relieve chronic pain and, secondarily, their effects on motor recovery. Adult Wistar rats with traumatic SCI were treated, 10 days after injury, with intra-spinal injections of culture medium (sham) or fNSCs extracted from telencephalic vesicles (TV group) or the ventral medulla (VM group) of E/14 embryos. Sensory (von Frey filaments and hot plate) and motor (the Basso, Beattie, Bresnahan locomotor rating scale and inclined plane test) assessments were performed during 8 weeks. Thereafter, spinal cords were processed for immunofluorescence and transplanted cells were quantified by stereology. The results showed improvement of thermal hyperalgesia in the TV and VM groups at 4 and 5 weeks after transplantation, respectively. Moreover, mechanical allodynia improved in both the TV and VM groups at 8 weeks. No significant motor recovery was observed in the TV or VM groups compared with sham. Stereological analyses showed that ~70% of TV and VM cells differentiated into NeuN+ neurons, with a high proportion of enkephalinergic and GABAergic cells in the TV group and enkephalinergic and serotoninergic cells in the VM group. Our study suggests that neuronal precursors from TV and VM, once implanted into the injured spinal cord, maturate into different neuronal subtypes, mainly GABAergic, serotoninergic, and enkephalinergic, and all subtypes alleviate pain, despite no significant motor recovery. The study was approved by the Animal Ethics Committee of the Medical School of the University of São Paulo (protocol number 033/14) on March 4, 2016.

FULL-THICKNESS ENDOSCOPIC GASTRIC RESECTION USING A STAPLER AND GASTROSTOMY: A FEASIBILITY STUDY.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is currently the most frequently performed bariatric procedure in Turkey. The goal of weight reduction surgery is not only to decrease excess weight, but also to improve obesity related comorbidities and quality of life (QoL). AIM: To evaluate the impact of LSG on patient quality of life, weight loss, and comorbidities associated with morbid obesity according to the updated BAROS criteria. METHODS: Eleven hundred thirty-eight adult patients were undergone to LSG by our bariatric surgery team between January 2013 and January 2016. A questionnaire (The Bariatric Analysis and Reporting Outcome System - BAROS) was published on social media. The data on postoperative complications were collected from hospital database. RESULTS: Number of respondants was 562 (49.4%). Six of 1138 patients(0.5%) had leakage. All patients who had leakage were respondants. The overall complication rate was 7.7%. After a mean period of 7.4±5.3 months(1-30), mean excess weight loss was 71.3±27.1% (10.2-155.4). The respondants reported 772 comorbidities. Of these, 162 (30%) were improved, and 420 (54.4%) were resolved. The mean scores for QoL were significantly increased after LSG (range, p<0.05 to <0.001). Of the 562 patients, 26 (4.6%) were classified as failures; 86 (15.3%) fair; 196 (34.9%) good; 144 (25.6%) very good, and 110 (19.6%) excellent results according to the updated BAROS scoring system. CONCLUSION: LSG is a highly effective bariatric procedure in the manner of weight control, improvement in comorbidities and increasing of QoL in short- and mid-term.

Ex vivos models to teaching therapeutic endoscopic ultrasound (T-EUS).

BACKGROUND: Endoscopic ultrasound training has a learning curve greater than the other endoscopic therapeutic techniques. One of the preclinical teaching methods is the use of ex vivo porcine models. AIM: To describe five ex vivo porcine models for training in therapeutic echoendoscopic procedures. MATERIALS AND METHODS: Using porcine digestive tract containing esophagus, stomach, duodenum, spleen, liver and gallbladder, five models for therapeutic echoendoscopy training were described. With other segments of the porcine pieces (such as the bladder, spleen segment and omentum segment) and with easily accessible materials (such as grape and ultrasound gel), lesions were simulated to be treated. These models were applied in the Hands on course at the IRCAD (Institut de recherche contre les cancers de l'appareil digestif) Barretos of 2017. Endoscopic equipment and instruments are the same as those used in clinical practice. RESULT: The models are easily reproducible and do not require exchange during the hands on course period. Endoscopic and echographic imaging and tactile sensitivity are similar to the real one. CONCLUSION: The models described in this study demonstrated to be realistic, easy to reproduce and allow repetition during the same session. However, comparative studies are necessary to verify the real impact on teaching.

EUS-guided Choledochoduodenostomy Versus Hepaticogastrostomy: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative in cases of endoscopic retrograde cholangiopancreatography (ERCP) failure. Two types of EUS-BD methods for achieving biliary drainage when ERCP fails are choledochoduodenostomy (CDS) or hepaticogastrostomy (HGS). However, there is no consensus if one approach is better than the other. Therefore, we conducted a systematic review and meta-analysis to evaluate these 2 main EUS-BD methods. METHODS: We searched MEDLINE, Embase, Scopus, Cochrane database, LILACS from inception through April 8, 2017, using the following search terms in various combinations: biliary drainage, biliary stent, transluminal biliary drainage, choledochoduodenostomy, hepaticogastrostomy, endoscopic ultrasound-guided biliary drainage. We selected studies comparing CDS and HGS in patients with malignant biliary obstruction with ERCP failure. Pooled odds ratio (OR) were calculated for technical success, clinical success, and adverse events and difference of means calculated for duration of procedure and survival after procedure. RESULTS: A total of 10 studies with 434 patients were included in the meta-analysis: 208 underwent biliary drainage via HGS and the remaining 226 via CDS. The technical success for CDS and HGS was 94.1% and 93.7%, respectively, pooled OR=0.96 [95% confidence interval (CI)=0.39-2.33, I=0%]. Clinical success was 88.5% in CDS and 84.5% in HGS, pooled OR=0.76 (95% CI=0.42-1.35, I=17%). There was no difference for adverse events OR=0.97 (95% CI=0.60-1.56), I=37%. CDS was about 2 minutes faster with a pooled difference in means of was -2.69 (95% CI=-4.44 to -0.95). CONCLUSION: EUS-CDS and EUS-HGS have equal efficacy and safety, and are both associated with a very high technical and clinical success. The choice of approach may be selected based on patient anatomy.

Full-thickness endoscopic gastric resection using a stapler and gastrostomy: a feasibility study / Ressecção gástrica parcial endoscópica utilizando a combinação de grampeador e gastrostomia: estudo de viabilidade

ABSTRACT Background: Laparoscopic sleeve gastrectomy (LSG) is currently the most frequently performed bariatric procedure in Turkey. The goal of weight reduction surgery is not only to decrease excess weight, but also to improve obesity related comorbidities and quality of life (QoL). Aim: To evaluate the impact of LSG on patient quality of life, weight loss, and comorbidities associated with morbid obesity according to the updated BAROS criteria. Methods: Eleven hundred thirty-eight adult patients were undergone to LSG by our bariatric surgery team between January 2013 and January 2016. A questionnaire (The Bariatric Analysis and Reporting Outcome System - BAROS) was published on social media. The data on postoperative complications were collected from hospital database. Results: Number of respondants was 562 (49.4%). Six of 1138 patients(0.5%) had leakage. All patients who had leakage were respondants. The overall complication rate was 7.7%. After a mean period of 7.4±5.3 months(1-30), mean excess weight loss was 71.3±27.1% (10.2-155.4). The respondants reported 772 comorbidities. Of these, 162 (30%) were improved, and 420 (54.4%) were resolved. The mean scores for QoL were significantly increased after LSG (range, p<0.05 to <0.001). Of the 562 patients, 26 (4.6%) were classified as failures; 86 (15.3%) fair; 196 (34.9%) good; 144 (25.6%) very good, and 110 (19.6%) excellent results according to the updated BAROS scoring system. Conclusion: LSG is a highly effective bariatric procedure in the manner of weight control, improvement in comorbidities and increasing of QoL in short- and mid-term.

RESUMO Racional: A gastrectomia vertical laparoscópica (LSG) é atualmente o procedimento bariátrico mais frequentemente realizado na Turquia. O objetivo da operação de redução de peso não é apenas diminuir o excesso de peso, mas também melhorar as comorbidades e a qualidade de vida relacionadas à obesidade (QoL). Objetivo: Avaliar o impacto do LSG na qualidade de vida dos pacientes, perda de peso e comorbidades associadas à obesidade mórbida de acordo com os critérios BAROS atualizados. Métodos: Estudo não-randomizado de intervenção comportamental e de saúde pública. Um total de 1138 pacientes adultos foram submetidos a LSG entre janeiro de 2013 e janeiro de 2016. Um questionário (The Bariatric Analysis and Reporting Outcome System - BAROS foi utilizado. Os dados sobre complicações pós-operatórias foram coletados do banco de dados hospitalar. Resultados: Responderam ao questionário 562 (49,4%) pacientes. Seis de 1138 pacientes (0,5%) tiveram deiscência e todos estes responderam a pesquisa. A taxa geral de complicações foi de 7,7%. Após período médio de 7,4±5,3 meses (1-30), a perda média de excesso de peso foi de 71,3±27,1% (10,2-155,4). Os questionados relataram 772 comorbidades. Destes, 162 (30,0%) foram melhorados e 420 (54,4%) foram resolvidos.Os escores médios de QoL foram significativamente aumentados após LSG (p<0,05 a <0,001). Dentre os resultados dos 562 pacientes, 26 (4,6%) foram classificadas como falhas; 86 (15,3%) regular; 196 (34,9%) bom;144 (25,6%) muito bom; e 110 (19,6%) excelente de acordo com para o sistema de pontuação BAROS atualizado. Conclusão: O LSG é procedimento bariátrico altamente efetivo para controle de peso, melhora nas comorbidades e aumento da QoL em curto e meio prazos.

Lipases and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer.

BACKGROUND: Cancer cachexia is a multifactorial metabolic syndrome characterized by marked loss of adipose tissue and skeletal muscle. Fat loss from adipose tissue in cancer cachexia is partly the result of increased lipolysis. Despite the growing amount of studies focused on elucidating the mechanisms through which lipolysis-related proteins regulate the lipolytic process, there are scarce data concerning that profile in the adipose tissue of cancer cachectic patients. Considering its fundamental importance, it was our main purpose to characterize the expression of the lipolysis-related proteins in the white adipose tissue of cachectic cancer patients. METHODS: Patients from the University Hospital were divided into three groups: control, cancer cachexia (CC), and weight-stable cancer patients (WSC). To gain greater insight into adipose tissue wasting during cancer cachexia progression, we have also analyzed an experimental model of cachexia (Walker 256 carcinosarcoma). Animals were divided into: control, intermediate cachexia (IC) and terminal cachexia (TC). Subcutaneous white adipose tissue of patients and epidydimal white adipose tissue of animals were investigated regarding molecular aspects by determining the protein content and gene expression of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), perilipin 1, leptin, adiponectin, visfatin, and tumour necrosis factor alpha (TNF-alpha). RESULTS: We found augmented lipolysis in CC associated with increased HSL expression, as well as upregulation of ATGL expression and reduction in perilipin 1 content. In IC, there was an imbalance in the secretion of pro- and anti-inflammatory factors. The alterations at the end-stage of cachexia were even more profound, and there was a reduction in the expression of almost all proteins analyzed in the animals. CONCLUSIONS: Our findings show that cachexia induces important morphological, molecular, and humoral alterations in the white adipose tissue, which are specific to the stage of the syndrome.

Perforated Meckel's diverticulum.

We report a patient with diffuse peritonitis due to perforation of Meckel's diverticulum. This patient was referred to the operating room and underwent bowel resection segment encompassing the area of the diverticulum and terminoterminal primary enteroanastomosis on two levels with good evolution. The diverticulum complications are often related to the presence of ectopic mucosa, specially the gastric and pancreatic type. Since preoperative diagnosis is difficult and infrequent, in most cases this anomaly is confirmed only during surgery. Surgical resection of the affected intestinal segment is the mainstay of treatment in both diverticula diagnosed incidentally, as the complicated by inflammation, bleeding, obstruction or perforation. We conclude that in cases of acute abdomen punctured, the diagnosis of Meckel's diverticulum should be considered.

Perforated Meckel's diverticulum: una entidad inusual / Divertículo de Meckel perforado

We report a patient with diffuse peritonitis due to perforation of Meckel's diverticulum. This patient was referred to the operating room and underwent bowel resection segment encompassing the area of the diverticulum and terminoterminal primary enteroanastomosis on two levels with good evolution. The diverticulum complications are often related to the presence of ectopic mucosa, especially the gastric and pancreatic type. Since preoperative diagnosis is difficult and infrequent, in most cases this anomaly is confirmed only during surgery. Surgical resection of the affected intestinal segment is the mainstay of treatment in both diverticula diagnosed incidentally, as the complicated by inflammation, bleeding, obstruction or perforation. We conclude that in cases of acute abdomen punctured, the diagnosis of Meckel's diverticulum should be considered.

Se describe el caso de un paciente con peritonitis difusa debido a la perforación de un divertículo de Meckel. Este paciente fue llevado a la sala de operaciones y fue sometido a resección del segmento intestinal incluyendo el área del divertículo y enteroanastomosis primaria termino-terminal en dos niveles, con buena evolución. Las complicaciones del divertículo a menudo están relacionadas con la presencia de mucosa ectópica especialmente del tipo gástrica y pancreática. Dado que el diagnóstico preoperatorio es difícil y poco frecuente, en la mayoría de los casos esta anomalía se confirma únicamente durante la intervención quirúrgica. La resección quirúrgica del segmento intestinal afectado es el pilar del tratamiento, tanto en los divertículos hechos con diagnóstico en forma casual, como el complicado por la inflamación, sangrado, obstrucción o perforación. Llegamos a la conclusión de que en los casos de abdomen agudo perforados el diagnóstico de divertículo de Meckel debe ser considerado.

Comparative anatomical analysis of the transcallosal-transchoroidal and transcallosal-transforniceal-transchoroidal approaches to the third ventricle.

OBJECTIVE Access to the third ventricle is a veritable challenge to neurosurgeons. In this context, anatomical and morphometric studies are useful for establishing the limitations and advantages of a particular surgical approach. The transchoroidal approach is versatile and provides adequate exposure of the middle and posterior regions of the third ventricle. However, the fornix column limits the exposure of the anterior region of the third ventricle. There is evidence that the unilateral section of the fornix column has little effect on cognitive function. This study compared the anatomical exposure afforded by the transforniceal-transchoroidal approach with that of the transchoroidal approach. In addition, a morphometric evaluation of structures that are relevant to and common in the 2 approaches was performed. METHODS The anatomical exposure provided by the transcallosal-transchoroidal and transcallosal-transforniceal-transchoroidal approaches was compared in 8 fresh cadavers, using a neuronavigation system. The working area, microsurgical exposure area, and angular exposure on the longitudinal and transversal planes of 2 anatomical targets (tuber cinereum and cerebral aqueduct) were compared. Additionally, the thickness of the right frontal lobe parenchyma, thickness of the corpus callosum trunk, and longitudinal diameter of the interventricular foramen were measured. The values obtained were submitted to statistical analysis using the Wilcoxon test. RESULTS In the quantitative evaluation, compared with the transchoroidal approach, the transforniceal-transchoroidal approach provided a greater mean working area (transforniceal-transchoroidal 150 ± 11 mm2; transchoroidal 121 ± 8 mm2; p < 0.05), larger mean microsurgical exposure area (transforniceal-transchoroidal 101 ± 9 mm2; transchoroidal 80 ± 5 mm2; p < 0.05), larger mean angular exposure area on the longitudinal plane for the tuber cinereum (transforniceal-transchoroidal 71° ± 7°; transchoroidal 64° ± 6°; p < 0.05), and larger mean angular exposure area on the longitudinal plane for the cerebral aqueduct (transforniceal-transchoroidal 62° ± 6°; transchoroidal 55° ± 5°; p < 0.05). No differences were observed in angular exposure along the transverse axis for either anatomical target (tuber cinereum and cerebral aqueduct; p > 0.05). The mean thickness of the right frontal lobe parenchyma was 35 ± 3 mm, the mean thickness of the corpus callosum trunk was 10 ± 1 mm, and the mean longitudinal diameter of the interventricular foramen was 4.6 ± 0.4 mm. In the qualitative assessment, it was noted that the transforniceal-transchoroidal approach led to greater exposure of the third ventricle anterior region structures. There was no difference between approaches in the exposure of the structures of the middle and posterior region. CONCLUSIONS The transforniceal-transchoroidal approach provides greater surgical exposure of the third ventricle anterior region than that offered by the transchoroidal approach. In the population studied, morphometric analysis established mean values for anatomical structures common to both approaches.

An innovative ex-vivo model for rapid change of the papilla for teaching advanced endoscopic retrograde cholangiopancreatography procedures / Modelo ex-vivo inovador de troca rápida da papila para o ensino de procedimentos avançados na colangiopancreatografia endoscópica retrógrada

ABSTRACT Background: Models for endoscopic retrograde cholangiopancreatography training allow practice with an expert feedback and without risks. A method to rapidly exchange the papilla can be time saving and accelerate the learning curve. Aim: To demonstrate a newly method of rapid exchange papilla in ex-vivo models to teach retrograde cholangiopancreatography advanced procedures. Methods: A new model of ex-vivo papilla was developed in order to resemble live conditions of procedures as cannulation, papilotomy or fistula-papilotomy, papiloplasty, biliary dilatation, plastic and metallic stentings. Results: The ex-vivo model of papilla rapid exchange is feasible and imitates with realism conditions of retrograde cholangiopancreatography procedures. Conclusion: This model allows an innovative method of advanced endoscopic training.

RESUMO Racional: Nas últimas décadas os simuladores de colangiopancreatografia retrógrada tiveram grande evolução. Atualmente dispõem-se de vários métodos para realizar o treinamento minimizando os riscos de complicações e tornando a curva de aprendizagem muito rápida. Objetivo: Demonstrar uma variação dos modelos ex-vivos desenvolvidos para o treinamento avançado em colangiopancreatografia retrograda. Método: Foi criado um modelo ex-vivo simulando fatores e condições reais para o treinamento avançado de colangiopancreatografia retrograda como canulação, papilotomia, fistulotomia, papiloplastia e uso de próteses plásticas e metálicas. Resultados: Esse modelo ex-vivo, com a possibilidade de troca rápida da papila, mostrou-se viável e no treinamento simula condições muito próximas às reais. Conclusão: Neste modelo há grande inovação para o treinamento de novos endoscopistas em procedimento avançados na colangiopancreatografia retrógrada.

Recurrent acute pancreatitis caused by pancreatic biliary maljunction due to long common channel / Pancreatitis aguda recurrente causada por deficiente unión pancreático-biliar debido a un colédoco largo

The pancreatic biliary maljunction is a rare anomaly that affects mainly females, defined as an anatomical maljunction of the pancreatic duct and the biliary duct confluence, and may be a rare cause of recurrent acute pancreatitis. In order to early diagnosis and prompt treatment, ERCP has an important role in it

La Malformación de la unión biliopancreática es una afección rara y ocurre más en mujeres jóvenes. Es una causa de pancreatitis aguda de causa no conocida. CPRE es una herramienta eficiente para el diagnóstico y también para ser de la terapéutica

A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems.

The avoidance response is present in pathological anxiety and interferes with normal daily functions. The aim of this article is to shed light on performance markers of active avoidance (AA) using two different rat strains, Sprague-Dawley (SD) and Wistar. Specifically, good and poor performers were evaluated regarding anxiety traits exhibited in the elevated plus maze (EPM) and corticosterone levels and motor activity in the open field test. In addition, the plasma levels of Interleukin-6 (IL-6), Interleukin-1Beta (IL-1beta), Nerve Growth Factor Beta (NGF-beta), Tumor Necrosis Factor-Alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were compared in the good and poor performers to better understand the role of the immunologic system in aversive learning. Behavioral criteria were employed to identify subpopulations of SD and Wistar rats based on their behavioral scores during a two-way AA test. The animals were tested for anxiety-like behavior in the EPM and motor activity in the open-field test. Plasma corticosterone levels were measured at the end of the avoidance test. Cytokine levels of IL-6, IL-1beta, NGF-beta, TNF-alpha, and CINC-1 were measured in the plasma of the Wistar rats. Sixty-six percent of the Wistar rats and 35% of the SD rats exhibited a poor performance. This feature was associated with a decrease in anxiety-like behavior in the EPM. The poor and good performers exhibited lower levels of corticosterone compared with the control animals, which suggests that training alters corticosterone levels, thereby leading to hypocortisolism, independent of the performance. The CINC-1 levels were increased in the poor performers, which reinforces the role of immunologic system activation in learning deficits. Our study provides a better understanding of the complex interactions that underlie neuroimmune consequences and their implications for performance.