Publications by authors named "Marcelo Linhares"

87 Publications

The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats.

Mol Psychiatry 2021 Jul 27. Epub 2021 Jul 27.

Graduate Program in Neuroscience, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.

We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (n = 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (n = 29). The microinfusion of ERK1/2 inhibitor (FR180204, n = 8-13/group) or MEK inhibitor (U0126, n = 8-9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (n = 9-11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear. HIGHLIGHTS: The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy. The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats. ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.
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http://dx.doi.org/10.1038/s41380-021-01203-0DOI Listing
July 2021

The prognostic significance of serum aspartate transaminase and gamma-glutamyl transferase in liver deceased donors.

Transpl Int 2021 Nov 14;34(11):2247-2256. Epub 2021 Sep 14.

AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Villejuif, France.

The impact of aspartate transaminases (AST) and gamma-glutamyl transferase (GGT) in serum of deceased donors on outcomes after liver transplantation (LT) is unclear. This study aimed to explore the relationship between donor highest AST value or first donor GGT value and graft survival. All consecutive patients who underwent a primary LT in a single center with available donor AST (N = 1253) and GGT value (N = 1152) were included. There was no significant association between donor AST and 90-day graft survival. We found a moderate association between GGT and 90-day graft survival. We found a significant interaction with a donor history of alcohol abuse (HAA). The risk of graft loss was associated with AST and GGT in donors with an HAA but remains unchanged in donors without HAA. There was no difference in graft survival according to donor AST or GGT with a cutoff ≥95th percentile (475 UI/l for AST and 170 UI/l for GGT). However, graft survival was significantly decreased when donors combined GGT ≥ 170 UI/l and HAA (61% at one year). Hepatic grafts from donors with high AST or high GGT but without alcohol history and no additional risk factors can be transplanted in low-risk recipient.
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http://dx.doi.org/10.1111/tri.13978DOI Listing
November 2021

Brazilian-Portuguese Validation Assessment of the for Patients After Laparoendoscopic Cholecystectomy.

J Laparoendosc Adv Surg Tech A 2021 Jan 15. Epub 2021 Jan 15.

Division of Gastroenterology, Escola Paulista de Medicina, Federal University of Sao Paulo, Sao Paulo, Brazil.

Cholelithiasis is currently one of the most common diagnosis in Brazil. The aim of this study was to validate the Gastrointestinal Quality of Life Index (GIQLI) as a quality-of-life (QoL) assessment among the Brazilian population with syntomatic gallstone. The questionnaire was translated and culturally adapted after the linguistic validation process determined by the international methodology. Sixty-three patients who underwent laparoscopic cholecystectomy responded to the GIQLI-Brazil and Short-Form Health Survey (SF-36) instruments. For the evaluation of reproducibility, 30 patients responded to GIQLI-Brazil two more times after 2 and 4 weeks. After the University of São Paulo Ethics Commitee Board approval (UNIFESP/CEP: 1270/2019), the study was carryed out between May 2019 and February 2020 at the Gastroenterology outpatient clinic of Hospital São Paulo-Federal University of São Paulo (UNIFESP). Cronbach's alpha, the calculation of the intraclass correlation coefficient (ICC), and Spearman's correlation were used to assess the validity and reproducibility of the instrument translated into Portuguese, and to measure correlation between the domains of the GIQLI-Brazil and SF-36 ( < .05). Seven questions were modified during the process of translation and cultural adaptation. The Brazilian version of the instrument presented a Cronbach's alpha of 0.89, and excellent reproducibility through the ICC, with the following variation between domains: meteorism (ICC = 0.918;  < .001) and gastrointestinal function (lower tract) (ICC = 0.956;  < .001). The dimensions of the GIQLI-Brazil and SF-36 demonstrated a significant correlation ( < .001), except between the domains: functional aspects of the SF-36 and gastrointestinal function (lower tract) of the GIQLI-Brazil ( = 0.211). The GIQLI was translated and validated for Portuguese-Brazil and can be used to assess the QoL of adult patients with gastrointestinal diseases and/or disorders.
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http://dx.doi.org/10.1089/lap.2020.0921DOI Listing
January 2021

AMPAr GluA1 Phosphorylation at Serine 845 in Limbic System Is Associated with Cardiac Autonomic Tone.

Mol Neurobiol 2021 Apr 6;58(4):1859-1870. Epub 2021 Jan 6.

Center for Applied Neuroscience, University Hospital (HU), UFSC, Florianopolis, SC, Brazil.

The central autonomic network, which is connected to the limbic system structures including the amygdala (AMY) and anterior hippocampus (aHIP), regulates the sympathetic and parasympathetic modulation of visceromotor, neuroendocrine, pain, and behavior manifestations during stress responses. Heart rate variability (HRV) is useful to estimate the cardiac autonomic tone. The levels of phosphorylation on the Ser831 and Ser845 sites of the GluA1 subunit of the AMPAr (P-GluA1-Ser845 and P-GluA1-Ser831) are useful markers of synaptic plasticity. The relation between synaptic plasticity in the human limbic system structures and autonomic regulation in humans is unknown. This study investigated the association between HRV and neurochemistry biomarkers of synaptic plasticity in AMY and aHIP. HRV indices were obtained from the resting state electrocardiogram of patients with drug-resistant mesial temporal lobe epilepsy (MTLE, n = 18) and the levels of P-GluA1-Ser845 and P-GluA1-Ser831 in the AMY and aHIP resected during the epilepsy surgery. A backward stepwise multiple linear regression models were used to analyze the association between HRV and synaptic plasticity biomarkers controlling for imbalances in the distribution of sociodemographic, clinical, neuroimaging, and neurosurgical variables. P-GluA1-Ser845 levels in AMY show a negative association (p < 0.05) with the 3 investigated parasympathetic autonomic HRV indices (SDNN, rMSSD, and HF) predicting 24 to 40% of their variation. The final multiple linear regression models include disease duration and levels of P-GluA1-Ser845 and predict 24 to 56% of cardiac autonomic tone variation (p < 0.01). P-GluA1-Ser845 levels in AMY and aHIP are negatively associated with the resting HRV in MTLE-HS indicating that increased synaptic efficiency in amygdala is associated with a parasympathetic cardiac autonomic tone impairment. The results suggest that specific changes in synaptic plasticity may be involved in the brain-heart axis regulation by the limbic system.
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http://dx.doi.org/10.1007/s12035-020-02272-yDOI Listing
April 2021

BRAZILIAN CONSENSUS ON INCIDENTAL GALLBLADDER CARCINOMA.

Arq Bras Cir Dig 2020 Jul;33(1):e1496

Department of Gastrointestinal Surgery, AC Camargo Cancer Center, São Paulo, Brazil.

Background: Incidental gallbladder cancer is defined as a cancer discovered by histological examination after cholecystectomy. It is a potentially curable disease. However, some questions related to their management remain controversial and a defined strategy is associated with better prognosis.

Aim: To develop the first evidence-based consensus for management of patients with incidental gallbladder cancer in Brazil.

Methods: Sixteen questions were selected, and 36 Brazilian and International members were included to the answer them. The statements were based on current evident literature. The final report was sent to the members of the panel for agreement assessment.

Results: Intraoperative evaluation of the specimen, use of retrieval bags and routine histopathology is recommended. Complete preoperative evaluation is necessary and the reoperation should be performed once final staging is available. Evaluation of the cystic duct margin and routine 16b1 lymph node biopsy is recommended. Chemotherapy should be considered and chemoradiation therapy if microscopically positive surgical margins. Port site should be resected exceptionally. Staging laparoscopy before reoperation is recommended, but minimally invasive radical approach only in specialized minimally invasive hepatopancreatobiliary centers. The extent of liver resection is acceptable if R0 resection is achieved. Standard lymph node dissection is required for T2 tumors and above, but common bile duct resection is not recommended routinely.

Conclusions: It was possible to prepare safe recommendations as guidance for incidental gallbladder carcinoma, addressing the most frequent topics of everyday work of digestive and general surgeons.
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http://dx.doi.org/10.1590/0102-672020190001e1496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357549PMC
July 2020

Decision making process in simultaneous laparoscopic resection of colorectal cancer and liver metastases. Review of literature.

Acta Cir Bras 2020 22;35(3):e202000308. Epub 2020 May 22.

MD, Research Institute against Cancer of the Digestive System, Strasbourg, France. Manuscript writing, critical revision.

Purpose: The benefits of laparoscopic approaches to treat colorectal cancer (CRC) and colorectal liver metastases (CRLM) separately are well established. However, there is no consensus about the optimal timing to approach the primary tumor and CRLM, whether simultaneously or staged. The objective of this review with practical reports is to discuss technical aspects required for patient selection to perform simultaneous laparoscopic approaches for CRC and CRLM.

Methods: Literature review of oncological factors associated with patient selection for surgical treatment of CRLM and the use of laparoscopy in those cases, and report of technical aspects for simultaneous CRC and CRLM approaches.

Results: Simultaneous laparoscopic resection has been successful in many series of selected patients, although it seems to be safer to perform minor and major liver resection with non-extended colorectal resections, and to avoid two high-risk procedures at the same time.

Conclusions: Simultaneous CRC and CRLM resections seem to be safe when patients are carefully selected, also considering the risk of recurrence concerning oncologic outcomes. The pre-planning of simultaneous resection is mandatory to plan trocar positioning, procedure sequencing, and patient position.
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http://dx.doi.org/10.1590/s0102-865020200030000008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251979PMC
June 2020

Late Conversion to Sirolimus or Everolimus After Pancreas Transplant.

Transplant Proc 2020 Jun 22;52(5):1376-1379. Epub 2020 Mar 22.

Nephrology Division, Federal University of São Paulo/Hospital do Rim e Hipertensão, São Paulo, SP, Brazil. Electronic address:

Background: Pancreas transplant is an effective treatment for insulin-dependent diabetic individuals with end-stage renal disease, yet immunosuppression-associated adverse events may adversely affect patient and graft survival. The aim of the study was to document whether mammalian target of rapamycin inhibitors (mTORi) are safe and effective as a second-line drug after pancreas transplant.

Methodology: An observational single-center study was performed in a cohort of 490 simultaneous pancreas-kidney transplant and 45 pancreas-after-kidney transplant individuals after conversion to mTORi (n = 13) owing to adverse events of either tacrolimus or mycophenolate.

Results: mTORi conversion was performed 11.5 ± 10.1 (range, 1-28) months after pancreas transplant, mainly owing to cytomegalovirus infection and gastrointestinal intolerance. We frequently observed clinical complications after mTORi conversion, yet creatinine, eGFR, proteinuria, fasting plasma glucose, HbA1c, and C-peptide remained stable throughout the study (mean follow-up 8.2 ± 5, range 1-17) years, as did the lipid profile (P > .05). However, graft loss occurred in almost 20% of patients owing to chronic alterations.

Limitations: The small number of patients and a single-center cohort were limitations of the study.

Conclusions: Late mTORi conversion is a safe and effective approach when tacrolimus or mycophenolate-mediated adverse events occur after pancreas transplant.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.028DOI Listing
June 2020

The role of minimally invasive hepatectomy for hilar and intrahepatic cholangiocarcinoma: A systematic review of the literature.

J Surg Oncol 2020 Apr 4;121(5):863-872. Epub 2020 Jan 4.

Escola Paulista de Medicina-Universidade Federal de São Paulo, São Paulo, Brazil.

Despite the fact laparoscopic liver resections (LLR) for cholangiocarcinoma is still limited, this systematic review addressed surgical and oncological outcomes of LLR to treat both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA). Five comparative and 20 noncomparative studies were found. Regarding iCCA, LLR had lower blood loss and less need for Pringle maneuver. However, open liver resections (OLR) were performed more for major hepatectomies, with better lymphadenectomy rates and higher number of harvested lymph nodes. High heterogeneity and selection bias were suggested for iCCA studies.
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http://dx.doi.org/10.1002/jso.25821DOI Listing
April 2020

LIVER RESECTION FOR NON-ORIENTAL HEPATOLITHIASIS.

Arq Bras Cir Dig 2019 20;32(4):e1463. Epub 2019 Dec 20.

Department of Gastrointestinal Surgery, Santa Casa de Porto Alegre, RS, Brazil.

Background: Primary intrahepatic lithiasis is defined when the stones are formed in the liver and associated with local dilatation and biliary stricture. Liver resection is the ideal procedure.

Aim: To evaluate the results of liver resection in the treatment of non-oriental intrahepatic lithiasis.

Methods: Fifty-one patients with symptomatic benign non-oriental hepatolithiasis underwent surgical resection in six institutions in Brazil. Demography data, clinical symptoms, classification, diagnosis, management and postoperative course were analyzed.

Results: Of the 51 patients, 28 were male (54.9%), with a mean age of 49.3 years. History of cholangitis was observed in 15 (29.4%). The types of intrahepatic lithiasis were type I in 39 (76.5%) and type IIb in 12 (23.5%), with additional type Ea in six (11.8%). Liver function test were normal in 42 patients (82.4%). Segmental atrophy was observed in 12 (23.5%). Treatments included left lateral sectionectomy in 24 (47.1%), left hepatectomy in 14 (27.5%) and right hepatectomy in eight (15.7%), with associated hepaticojejunostomy in four (7.8%). Laparoscopic liver resection was performed in eight (15.7%). Postoperative complications were observed in 20 (39.2%) with no mortality.

Conclusion: Liver resection in patients with hepatolithiasis is the ideal procedure as it removes stones, stricture, atrophic parenchyma, and minimizes the risk of cholangiocarcinoma.
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http://dx.doi.org/10.1590/0102-672020190001e1463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918752PMC
March 2020

The quality of life in type I diabetic patients with end-stage kidney disease before and after simultaneous pancreas-kidney transplantation: a single-center prospective study.

Transpl Int 2020 03 23;33(3):330-339. Epub 2019 Dec 23.

Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, Sao Paulo, Brazil.

Simultaneous pancreas-kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end-stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life-Short-Form Health Survey (KDQOL-SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (<1, 1-3, and >3 years). Mean KDQOL-SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients' stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL.
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http://dx.doi.org/10.1111/tri.13562DOI Listing
March 2020

Predictors of Pain Recurrence After Lumbar Facet Joint Injections.

Front Neurosci 2019 20;13:958. Epub 2019 Sep 20.

Center for Applied Neuroscience (CeNAp), University Hospital (HU), Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.

Introduction: Facet joint injections (FJIs) of anesthetic and corticosteroids are useful for the diagnosis and treatment of low back pain (LBP). In the current study, we evaluated the efficacy of FJI on LBP treatment and the predictive variables of pain recurrence after FJI.

Methods: We included and followed prospectively forty-three consecutive patients with chronic LBP treated with FJI. Clinical assessments were carried out at a baseline 1 week before FJIs and after a 6-month follow-up visit using the visual analog scale (VAS) for pain, Oswestry Disability Index (ODI) for disability-specific measure and MacNab criteria for global effectiveness, and compared through analysis using paired-samples "" tests. Multiple cox-regression analysis was used to identify the presurgical variables independently associated with pain recurrence anytime during the follow-up. In addition to the demographic, clinical, and surgical data, we also analyzed psychometric scales: Pain Catastrophizing Scale (PCS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI).

Results: After a 6-month follow-up, thirty-two patients (74.4%) showed a clinically significant reduction of pain and twenty-seven (62.8%) reported a clinically significant improvement of disability. Presurgical catastrophizing (PCS score ≥ 5, adjusted HR 4.4, CI 95% 1.7-11.3, = 0.002) and smoking (Adjusted HR 12.5, CI 95% 1.1-138.9, = 0.04) remains associated with pain recurrence.

Conclusion: FJI reduces LBP and disability of patients with unresponsive LBP. Pain-related cognitive and behavioral factors determined by pain catastrophizing and smoking were independently associated with pain recurrence after lumbar FJI. The results support the need of a multidisciplinary approach for presurgical evaluation of patients with chronic pain.
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http://dx.doi.org/10.3389/fnins.2019.00958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763569PMC
September 2019

Comparative study of four different types of intraperitoneal mesh prostheses in rats.

Acta Cir Bras 2019 Sep 12;34(7):e201900703. Epub 2019 Sep 12.

PhD, Full Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Design of the study; acquisition, analysis and interpretation of data; critical revision; final approval.

Purpose: To compare four types of mesh regarding visceral adhesions, inflammatory response and incorporation.

Methods: Sixty Wistar rats were divided into four groups, with different meshes implanted intraperitoneally: polytetrafluoroethylene (ePTFE group); polypropylene with polydioxanone and oxidized cellulose (PCD); polypropylene (PM) and polypropylene with silicone (PMS). The variables analyzed were: area covered by adhesions, incorporation of the mesh and inflammatory reaction (evaluated histologically and by COX2 immunochemistry).

Results: The PMS group had the lowest adhesion area (63.1%) and grade 1 adhesions. The ePTFE and PM groups presented almost the total area of their surface covered by adherences (99.8% and 97.7% respectively) The group ePTFE had the highest percentage of area without incorporation (42%; p <0.001) with no difference between the other meshes. The PMS group had the best incorporation rate. And the histological analysis revealed that the inflammation scores were significantly different.

Conclusions: The PM mesh had higher density of adherences, larger area of adherences, adherences to organs and percentage of incorporation. ePTFE had the higher area of adherences and lower incorporation. The PMS mesh performed best in the inflammation score, had a higher incorporation and lower area of adherences, and it was considered the best type of mesh.
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http://dx.doi.org/10.1590/s0102-865020190070000003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746566PMC
September 2019

Difficulties in activities of daily living are associated with stigma in patients with Parkinson's disease who are candidates for deep brain stimulation.

Braz J Psychiatry 2020 Apr 5;42(2):190-194. Epub 2019 Aug 5.

Faculdade de Medicina, Universidade do Porto, Porto, Portugal.

Objective: Parkinson's disease (PD) is often accompanied by stigma, which could contribute to a worse prognosis. The objective of this study is to identify the variables associated with stigma in PD patients who are candidates for deep brain stimulation (DBS).

Methods: We investigated sociodemographic and clinical variables associated with stigma in a sample of 54 PD patients indicated for DBS. The independent variables were motor symptoms assessed by the Movement Disorder Society-sponsored revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS III), depressive symptoms measured by the Hospital Anxiety and Depression Scale, age, disease duration and the presence of a general medical condition. The Mobility, Activities of daily living and Emotional well-being domains of the 39-item Parkinson's Disease Questionnaire (PDQ-39) were also investigated as independent variables, and the Stigma domain of the PDQ-39 scale was considered the outcome variable.

Results: After multiple linear regression analysis, activities of daily living remained associated with the Stigma domain (B = 0.42 [95%CI 0.003-0.83], p = 0.048). The full model accounted for 15% of the variance in the Stigma domain (p = 0.03).

Conclusions: Although causal assumptions are not appropriate for cross-sectional studies, the results suggest that ADL difficulties could contribute to greater stigma in PD patients with refractory motor symptoms who are candidates for DBS.
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http://dx.doi.org/10.1590/1516-4446-2018-0333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115448PMC
April 2020

Simultaneous pancreas-kidney transplantation and the impact of postoperative complications on hospitalization cost.

Rev Col Bras Cir 2019 Mar 7;46(1):e2096. Epub 2019 Mar 7.

Universidade Federal de São Paulo, Disciplina de Gastroenterologia Cirúrgica, São Paulo, SP, Brasil.

Objective: considering simultaneous pancreas-kidney transplantation cases, to evaluate the financial impact of postoperative complications on hospitalization cost.

Methods: a retrospective study of hospitalization data from patients consecutively submitted to simultaneous pancreas-kidney transplantation (SPKT), from January 2008 to December 2014, at Kidney Hospital/Oswaldo Ramos Foundation (Sao Paulo, Brazil). The main studied variables were reoperation, graft pancreatectomy, death, postoperative complications (surgical, infectious, clinical, and immunological ones), and hospitalization financial data for transplantation.

Results: the sample was composed of 179 transplanted patients. The characteristics of donors and recipients were similar in patients with and without complications. In data analysis, 58.7% of the patients presented some postoperative complication, 21.8% required reoperation, 12.3% demanded graft pancreatectomy, and 8.4% died. The need for reoperation or graft pancreatectomy increased hospitalization cost by 53.3% and 78.57%, respectively. The presence of postoperative complications significantly increased hospitalization cost. However, the presence of death, internal hernia, acute myocardial infarction, stroke, and pancreatic graft dysfunction did not present statistical significance in hospitalization cost (in average US$ 18,516.02).

Conclusion: considering patients who underwent SPKT, postoperative complications, reoperation, and graft pancreatectomy, as well as surgical, infectious, clinical, and immunological complications, significantly increased the mean cost of hospitalization. However, death, internal hernia, acute myocardial infarction, stroke, and pancreatic graft dysfunction did not statistically interfere in hospitalization cost.
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http://dx.doi.org/10.1590/0100-6991e-20192096DOI Listing
March 2019

Pushing the limits of liver surgery for colorectal liver metastases: Current state and future directions.

World J Gastrointest Surg 2019 Feb;11(2):34-40

Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo SP 04023-062, Brazil.

Liver surgery for the treatment of colorectal liver metastases is the standard treatment in a dynamic surgical field with many variables that should be considered in a curative intent scenario. Hepatectomy for colorectal liver metastases has undergone constant changes over the last 30 years, including indications until the need for rescue procedures of recurrent and advanced diseases as well as minimally invasive surgery. These advancements in liver surgery have not only resulted from overall improvements in the surgical field but have also resulted from a better understanding of the biological behavior of the disease, liver regeneration, and homeostasis during and after surgery. Improvements in anesthesiology, intensive care medicine, radiology, and surgical devices have correlated with further advancements of hepatectomies. Moreover, changes are still forthcoming, and both fields of augmented reality and artificial intelligence will likely have future contributions in this field in regard to both diagnoses and the planning of procedures. The aim of this editorial is to emphasize several aspects that have contributed to the paradigm shifts in colorectal liver metastases surgery over the last three decades as well as to discuss the factors concerning patient selection and the technical aspects of liver surgery. Finally, this editorial will highlight the promising new features of this surgery for diagnoses and treatments in this field.
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http://dx.doi.org/10.4240/wjgs.v11.i2.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397797PMC
February 2019

Determinants for Meaningful Clinical Improvement of Pain and Health-Related Quality of Life After Spinal Cord Stimulation for Chronic Intractable Pain.

Neuromodulation 2019 Apr 10;22(3):280-289. Epub 2018 Dec 10.

Center for Applied Neuroscience (CeNAp), University Hospital (HU), Federal University of Santa Catarina State (UFSC), Florianópolis, SC, Brazil.

Objectives: Previous studies demonstrated significant improvement in mean pain scores and quality of life (QOL) scales in patients with chronic pain who underwent spinal cord stimulation (SCS). However, the number of individuals who experience relevant improvements in QOL, termed the meaningful clinical improvement (MCI), is not known. The present study investigated changes in pain measurements based on MCI after SCS.

Materials And Methods: Thirty-four patients with chronic intractable pain completed scales of pain (visual analogue scale [VAS]), QOL (SF-36), and psychological dimensions during a 22-month follow-up period (mean). Patient-centered MCI of the VAS and SF-36 domain scores were determined based on the MacNab criteria of surgical global effectiveness. Independent presurgical predictors for MCI in the VAS and SF-36 domains were analyzed using multiple binary logistic regression.

Results: There was significant improvement of pain and QOL after the SCS (p < 0.00001). Twenty-three patients (67.6%) reached an MCI of pain, and 16 (47.7%)-23 (67.7%) reported an MCI of QOL. Predictors of MCI included ≥80% paresthesia coverage of the painful area, lower levels of anxiety and catastrophizing symptoms, shorter pain duration, female gender and no use of opioids before surgery. MCI of pain and QOL was observed in 50%-70% of patients with chronic pain after SCS.

Conclusions: The identification of determinants for MCI is a challenge to improve the accuracy of prognostic models in SCS for patients with chronic pain. Our results, if confirmed in other populations with a larger sample size, have implications for patients with chronic pain who are candidates for SCS treatment.
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http://dx.doi.org/10.1111/ner.12891DOI Listing
April 2019

Amygdala levels of the GluA1 subunit of glutamate receptors and its phosphorylation state at serine 845 in the anterior hippocampus are biomarkers of ictal fear but not anxiety.

Mol Psychiatry 2020 03 7;25(3):655-665. Epub 2018 Jun 7.

Center for Applied Neuroscience, University Hospital, UFSC, Florianópolis, SC, Brazil.

Fear is a conscious state caused by exposure to real or imagined threats that trigger stress responses that affect the body and brain, particularly limbic structures. A sub-group of patients with mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) have seizures with fear, which is called ictal fear (IF), due to epileptic activity within the brain defensive survival circuit structures. Synaptic transmission efficacy can be bi-directionally modified through potentiation (long-term potentiation (LTP)) or depression (long-term depression (LTD)) as well as the phosphorylation state of Ser831 and Ser845 sites at the GluA1 subunit of the glutamate AMPA receptors, which has been characterized as a critical event for this synaptic plasticity. In this study, GluA1 levels and the phosphorylation at Ser845 and Ser831 in the amygdala (AMY), anterior hippocampus (aHIP) and middle gyrus of temporal neocortex (CX) were determined with western blots and compared between MTLE-HS patients who were showing (n = 06) or not showing (n = 25) IF. Patients with IF had an 11% decrease of AMY levels of the GluA1 subunit (p = 0.05) and a 21.5% decrease of aHIP levels of P-GluA1-Ser845 (p = 0.009) compared to patients not showing IF. The observed associations were not related to imbalances in the distribution of other concomitant types of aura, demographic, clinical or neurosurgical variables. The lower levels of P-GluA1-Ser845 in the aHIP of patients with IF were not related to changes in the levels of the serine/threonine-protein phosphatase PP1-alpha catalytic subunit or protein kinase A activation. Taken together, the GluA1 subunit levels in AMY and P-GluA1-Ser845 levels in the aHIP show an overall accuracy of 89.3% (specificity 95.5% and sensitivity 66.7%) to predict the presence of IF. AMY levels of the GluA1 subunit and aHIP levels of P-GluA1-Ser845 were not associated with the psychiatric diagnosis and symptoms of patients. Taken together with previous findings in MTLE-HS patients with IF who were evaluated by stereotactic implanted depth electrodes, we speculate our findings are consistent with the hypothesis that AMY is not a centre of fear but together with other sub-cortical and cortical structures integrates the defensive circuit that detect and respond to threats. This is the first report to address neuroplasticity features in human limbic structures connected to the defensive survival circuits, which has implications for the comprehension of highly prevalent psychiatric disorders and symptoms.
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http://dx.doi.org/10.1038/s41380-018-0084-7DOI Listing
March 2020

Evaluation of high-grade astrocytoma recurrence patterns after radiotherapy in the era of temozolomide: A single institution experience.

Rep Pract Oncol Radiother 2018 May-Jun;23(3):154-160. Epub 2018 Mar 17.

Research Institue & College Pequeno Príncipe, Av. Iguaçu, 333, Rebouças, CEP: 80230-020, Curitiba, PR, Brazil.

Aim: Evaluating the recurrence patterns of high-grade astrocytomas in patients who were treated with radiotherapy (RT) plus temozolomide (TMZ).

Background: The current literature suggests that reducing the margins added to the CTV does not significantly change the risk of recurrence and overall survival; thus, we decided to analyze our data and to examine the possibility of changing the adopted margins.

Materials And Methods: From February 2008 till September 2013, 55 patients were treated for high-grade astrocytomas, 20 patients who had been confirmed to have recurrence were selected for the present study. Post-operative MRI was superimposed on the planning CT images in order to correlate the anatomical structures with the treatment targets. Recurrences were defined according to the Response Assessment Criteria for Glioblastoma. The mean margins of the PTV and PTV were 1.2 cm and 1.4 cm, respectively. The analysis of the percentage of the recurrence volume (Vol) within the 100% isodose surface was based on the following criteria: (I) Central: >95% of the Vol; (II) In-field: 81-95% of the Vol; (III) Marginal: 20-80% of the Vol; and (IV) Outside: <20% of the Vol.

Results: Of the 20 patients, 13 presented with central recurrences, 3 with in-field recurrences, 2 with marginal recurrences and 2 with outside recurrences. Therefore, the lower Vol within 100% of the prescribed dose was considered in the classification.

Conclusions: Of the selected patients, 80% had ≥81-95% of the Vol within 100% of the prescribed dose and predominantly had central or in-field recurrences. These results are comparable with those from the literature.
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http://dx.doi.org/10.1016/j.rpor.2018.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948418PMC
March 2018

Neuropsychological functioning and brain energetics of drug resistant mesial temporal lobe epilepsy patients.

Epilepsy Res 2017 12 12;138:26-31. Epub 2017 Oct 12.

Centro de Neurociências Aplicadas, Hospital Universitário (HU), Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil; Centro de Epilepsia do Estado de Santa Catarina, CEPESC, HU, UFSC, Florianópolis, SC, Brazil; Serviço de Neurologia, Departamento de Clínica Médica, HU, UFSC, Florianópolis, SC, Brazil. Electronic address:

Interictal hypometabolism is commonly measured by 18-fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) in the temporal lobe of patients with mesial temporal lobe epilepsy (MTLE-HS). Left temporal lobe interictal FDG-PET hypometabolism has been associated with verbal memory impairment, while right temporal lobe FDG-PET hypometabolism is associated with nonverbal memory impairment. The biochemical mechanisms involved in these findings remain unknown. In comparison to healthy controls (n=21), surgically treated patients with MTLE-HS (n=32, left side=17) had significant lower scores in the Rey Auditory Verbal Learning Test (RAVLT retention and delayed), Logical Memory II (LMII), Boston Naming test (BNT), Letter Fluency and Category Fluency. We investigated whether enzymatic activities of the mitochondrial enzymes Complex I (C I), Complex II (C II), Complex IV (C IV) and Succinate Dehydrogenase (SDH) from the resected samples of the middle temporal neocortex (mTCx), amygdala (AMY) and hippocampus (HIP) were associated with performance in the RAVLT, LMII, BNT and fluency tests of our patients. After controlling for the side of hippocampus sclerosis, years of education, disease duration, antiepileptic treatment and seizure outcome after surgery, no independent associations were observed between the cognitive test scores and the analyzed mitochondrial enzymatic activities (p>0.37). Results indicate that memory and language impairment observed in MTLE-HS patients are not strongly associated with the levels of mitochondrial CI, CII, SDH and C IV enzymatic activities in the temporal lobe structures ipsilateral to the HS lesion.
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http://dx.doi.org/10.1016/j.eplepsyres.2017.10.009DOI Listing
December 2017

Use of fibrinogen and thrombin sponge in pediatric split liver transplantation.

Acta Cir Bras 2017 Aug;32(8):673-679

PhD, Associate Professor, Division of Pediatric Surgery, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study, analysis and interpretation of data, final approval of the version to be published.

Purpose:: To analyze the use of this sponge in pediatric patients undergoing split-liver transplantation.

Methods:: Retrospective study, including 35 pediatric patients undergoing split-liver transplantation, divided into two groups according to the use of the sponge: 18 patients in Group A (no sponge) and 17 in Group B (with sponge).

Results: : The characteristics of recipients and donors were similar. We observed greater number of reoperation due to bleeding in the wound area in Group A (10 patients - 55.5%) than in Group B (3 patients - 17.6%); p = 0.035. The median volume of red blood cells transfused in Group A was significantly higher (73.4 ± 102.38 mL/kg) than that in Group B (35.1 ± 41.67 mL/kg); p = 0.048. Regarding bile leak there was no statistical difference.

Conclusion:: The use of the human fibrinogen and thrombin sponge, required lower volume of red blood cell transfusion and presented lower reoperation rates due to bleeding in the wound area.
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http://dx.doi.org/10.1590/s0102-865020170080000009DOI Listing
August 2017

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery.

Epilepsy Behav 2017 10 1;75:218-224. Epub 2017 Sep 1.

Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil; Serviço de Neurologia, Departamento de Clínica Médica, HU-UFSC, Florianópolis, SC, Brazil; Centro de Epilepsia de Santa Catarina (CEPESC), HU-UFSC, Florianópolis, SC, Brazil. Electronic address:

Purpose: The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests.

Methods: Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline.

Key Findings: Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function.

Significance: Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE.
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http://dx.doi.org/10.1016/j.yebeh.2017.08.012DOI Listing
October 2017

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?

Acta Cir Bras 2017 Jul;32(7):515-522

PhD, Associate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; drafting the article; final approval of the version to be published.

Purpose: : To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy.

Methods: : Forty rats were subjected to 70% hepatectomy and then ~106 mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted.

Results: : No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05).

Conclusions: : Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.
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http://dx.doi.org/10.1590/s0102-865020170070000002DOI Listing
July 2017

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.

Epilepsia 2017 05 23;58(5):755-763. Epub 2017 Mar 23.

Center for Applied Neurosciences (CeNAp), University Hospital (HU), Federal University of Santa Catarina State (UFSC), Florianópolis, Santa Catarina, Brazil.

Objectives: To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients.

Methods: Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS.

Results: The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity.

Significance: These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.
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http://dx.doi.org/10.1111/epi.13721DOI Listing
May 2017

PEDIATRIC LIVER TRANSPLANTATION WITH EX-SITU LIVER TRANSECTION AND THE APPLICATION OF THE HUMAN FIBRINOGEN AND THROMBIN SPONGE IN THE WOUND AREA.

Arq Bras Cir Dig 2016 Nov-Dec;29(4):236-239

Department of Surgical Gastroenterology and Liver Transplantation.

Background: Surgical strategy to increase the number of liver transplants in the pediatric population is the ex-situ liver transection (reduction or split). However, it is associated with complications such as hemorrhage and leaks. The human fibrinogen and thrombin sponge is useful for improving hemostasis in liver surgery.

Aim: Compare pediatric liver transplants with ex-situ liver transection (reduction or split) with or without the human fibrinogen and thrombin sponge.

Methods: Was performed a prospective analysis of 21 patients submitted to liver transplantation with ex-situ liver transection with the application of the human fibrinogen and thrombin sponge in the wound area (group A) and retrospective analysis of 59 patients without the sponge (group B).

Results: The characteristics of recipients and donors were similar. There were fewer reoperations due to bleeding in the wound area in group A (14.2%) compared to group B (41.7%, p=0.029). There was no difference in relation to the biliary leak (group A: 17.6%, group B: 5.1%, p=0.14).

Conclusion: There was a lower number of reoperations due to bleeding of the wound area of ​​the hepatic graft when the human fibrinogen and thrombin sponge were used.
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http://dx.doi.org/10.1590/0102-6720201600040006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225862PMC
March 2017

BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES.

Arq Bras Cir Dig 2016 Jul-Sep;29(3):173-179

Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.
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http://dx.doi.org/10.1590/0102-6720201600030011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074669PMC
March 2017

Variables associated with physical health-related quality of life in Parkinson's disease patients presenting for deep brain stimulation.

Neurol Sci 2016 Nov 25;37(11):1831-1837. Epub 2016 Jul 25.

Centro de Ciências da Saúde (CCS), Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.

Deep brain stimulation (DBS) benefits Parkinson's disease (PD) patient's quality of life specially in domains as mobility, activities of daily living (ADL) and bodily discomfort (BD), but little is known about the variables associated with these HRQOL domains in patients presenting for DBS. The objective is to evaluate variables associated with of HRQOL in a Brazilian sample of PD patients presenting for DBS treatment, specifically in the domains related with motor symptoms. In a cross-sectional study of 59 PD patients evaluated at outpatient Unit for Movement Disorders, multiple linear regression analysis was performed to identify independent variables associated with mobility, ADL and BD domains of the 39-item Parkinson's disease questionnaire (PDQ-39). UPDRS III "on" scores, duration of the disease, age, presence of comorbidities and anxiety and depressive symptoms quantified by hospital anxiety and depression scale (HADS), were the independent variables. In our results, HADS scores were independently associated to mobility domain: β coefficient 1.36 (95 % CI 0.55-2.15) and BD domain: β coefficient 1.57 (95 % CI 0.67-2.48). UPDRS III "on" scores were independently associated to mobility domain: 0.42 (95 % CI 0.03-0.81). The model of each multiple linear regression analysis explains 25 % of the mobility domain variability (p < 0.01) and 24 % of the BD domain variability (p < 0.01). Psychiatric symptoms were at least as relevant to quality of life as motor symptoms in PD patients presenting for DBS treatment. The effect of treating these psychiatric symptoms on patients' HRQOL deserves further investigation.
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http://dx.doi.org/10.1007/s10072-016-2681-zDOI Listing
November 2016

SOLID PSEUDOPAPILLARY NEOPLASM OF THE PANCREAS.

Arq Bras Cir Dig 2016 Apr-Jun;29(2):93-6

Surgical Gastroenterology Division, Department of Surgery, School of Medicine, Federal University of São Paulo (EPM/UNIFESP).

Background: The solid pseudopapillary neoplasm is a rare tumor of the pancreas. However, it´s etiology still maintain discussions.

Aim: To analyze it´s clinical data, diagnosis and treatment.

Methods: A retrospective study of medical records of all patients treated from January 1997 until July 2015.

Results: Were identified 17 cases. Most patients were women (94.11%) and the average age was 32.88 years. The main complaint was abdominal mass (47.05%). The most frequent location was in the body/tail of the pancreas (72.22%) and the most frequently performed surgery was distal pancreatectomy with splenectomy (64.70%). No patient had metastases at diagnosis. Conservative surgery for pancreatic parenchyma was performed in only three cases. The rate of complications in the postoperative period was 35.29% and the main complication was pancreatic fistula (29.41%). No patient underwent adjuvant treatment.

Conclusions: The treatment is surgical and the most common clinical presentation is abdominal mass. Distal pancreatectomy with splenectomy was the most frequently performed surgery for its treatment.
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http://dx.doi.org/10.1590/0102-6720201600020007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944743PMC
March 2017

Prevalence of trigeminal neuralgia: A systematic review.

J Am Dent Assoc 2016 07 24;147(7):570-576.e2. Epub 2016 Mar 24.

Background: The aim of this systematic review was to answer the focused question, "What are the prevalence and the epidemiological characteristics of trigeminal neuralgia in the general population?"

Types Of Studies Reviewed: This systematic review included observational population-based studies reporting the prevalence of trigeminal neuralgia (TN). The authors developed specific search strategies for LILACS, PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar. The authors evaluated the methodological quality of the included studies using criteria from the Agency for Healthcare Research and Quality.

Results: Among 728 studies, the authors selected only 3 for inclusion. Two studies were classified as having low risk of bias and 1 as having moderate risk. The sample size ranged from 1,838 to 13,541 adults. This review identified a higher prevalence of TN in women, ranging from 0.03% (95% confidence interval [CI], 0.01-0.08) to 0.3% (95% CI, 0.16-0.55). The maxillary and mandibular branches of the trigeminal nerve were the most affected. The proportion between women and men who had TN was 3 to 1, and those in the age bracket between 37 and 67 years were the most affected.

Conclusions And Practical Implications: The authors of this review identified a higher prevalence of TN in women older than 40 years that usually affected the maxillary and mandibular branches. Further research is required to validate the prevalence of TN in a well-structured, population-based study without a convenience sample.
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http://dx.doi.org/10.1016/j.adaj.2016.02.014DOI Listing
July 2016
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