Artigos e Materiais de Revistas Científicas - FM/MGT

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.

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PRECLINICAL MODELS OF LIVER CÂNCER
(2023) GALVÃO, Flávio Henrique Ferreira; TRALDI, Maria Clara Camargo; ARAÚJO, Renata Sandres Souza; STEFANO, Jose Tadeu; D’ALBUQUERQUE, Luiz Augusto Carneiro; OLIVEIRA, Claudia P
ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.
IMPACT OF HELICOBACTER PYLORI ON EARLY POSTOPERATIVE COMPLICATIONS AFTER SLEEVE GASTRECTOMY: A SYSTEMATIC REVIEW AND META-ANALYSIS
(2023) DANTAS, Anna Carolina Batista; JAYME, Vitoria Ramos; FILARDI, Kaique Flavio Xavier Cardoso; PAJECKI, Denis; SANTO, Marco Aurelio
The impact of Helicobacter pylori (HP) on postoperative outcomes after sleeve gastrectomy (SG) is still controversial. A systematic review and meta-analysis were performed to compare the incidence of early complications after SG between HP-positive and HP-negative patients. Eight retrospective comparative studies were included, comprising 4,877 individuals. The prevalence of HP infection in gastric resected specimens ranged from 7.77 to 43.20%. There were no statistically significant differences between groups for overall complications (OR 1.46; 95%CI 0.95-2.23; p=0.08), bleeding (OR 1.35; 95%CI 0.70-2.60; p=0.38), and leak (OR 1.74; 95%CI 0.80-3.81; p=0.17) rates. The need for routine screening and treatment of HP infection before SG remains ambiguous.
CONSTIPATION SCORING SYSTEM VALIDATED FOR THE PORTUGUESE LANGUAGE (ÍNDICE DE GRAVIDADE DA CONSTIPAÇÃO INTESTINAL): IS IT RELIABLE IN ASSESSING THE SEVERITY OF INTESTINAL CHRONIC CONSTIPATION IN OUR POPULATION?
(2023) FROEHNER JUNIOR, Ilario; JORGE, Jose Marcio Neves; MARQUES, Carlos Frederico Sparapan; SANTOS, Vera Lucia Conceicao de Gouveia; JUKEMURA, Jose
BACKGROUND: There is a lack of valid and specific tools to measure chronic constipation severity in Brazil. AIMS: To validate the Constipation Scoring System for Brazilian spoken Portuguese. METHODS: Translation, cultural adaptation, and validation itself (reliability and convergent and divergent validation). Translation: definitive version from the original version's translation and evaluation by specialists. Cultural adaptation: score content analysis of the definitive version, as an interview to patients. Interobserver reliability: application by two researchers on the same day. Intraobserver reliability: same researcher at different times, in a 7-day interval. Divergent validation: non-constipated volunteers. Convergent validation: two groups, good response to clinical treatment and refractory to treatment. RESULTS: Cultural adaptation: 81 patients, 89% female, with mean age of 55 and seven years of schooling, and overall content validity index was 96.5%. Inter and intraobserver reliability analysis: 60 patients, 86.7% female, mean age of 56 and six years of schooling, and the respective intraclass correlation coefficients were 0.991 and 0.987, p<0.001. Divergent validation: 40 volunteers, 25 male, mean age of 49 years, and the mean global score was 2. Convergent validation of patients with good response to clinical treatment: 47 patients, 39 female, mean age of 60 and six years of schooling, and the pre- and post-treatment scores were 19 and 8, respectively (p<0.001). Convergent validation of refractory to clinical treatment patients: 75 patients, 70 female, mean age of 53 and seven years of schooling, and the global average score was 22. CONCLUSIONS: The Constipation Scoring System (indice de Gravidade da Constipacao Intestinal) validated for the Brazilian population is a reliable instrument for measuring the severity of intestinal chronic constipation.
LAPAROSCOPIC RIGHT AND LEFT COLECTOMY: WHICH PROVIDES BETTER POSTOPERATIVE RESULTS FOR ONCOLOGY PATIENTS?
(2023) PINTO, Rodrigo Ambar; SOARES, Diego Fernandes Maia; GERBASI, Lucas; NAHAS, Caio Sergio Rizkallah; MARQUES, Carlos Frederico Sparapan; BUSTAMANTE-LOPES, Leonardo Alfonso; CAMARGO, Mariane Gouvea Monteiro de; NAHAS, Sergio Carlos
BACKGROUND: The laparoscopic approach considerably reduced the morbidity of colorectal surgery when compared to the open approach. Among its benefits, we can highlight less intraoperative bleeding, early oral intake, lower rates of surgical site infection, incisional hernia, and postoperative pain, and earlier hospital discharge. AIMS: To compare the perioperative morbidity of right versus left colectomy for cancer and the quality of laparoscopic oncologic resection. METHODS: Retrospective analysis of patients submitted to laparoscopic right and left colctomy between 2006 and 2016. Postoperative complications were classified using the Clavien-Dindo scale, 30 days after surgery. RESULTS: A total of 293 patients were analyzed, 97 right colectomies (33.1%) and 196 left colectomies (66.9%). The averageage was 62.8 years. The groups were comparable in terms of age, comorbidities, body mass index, and the American Society of Anesthesiology (ASA) classification. Preoperative transfusion was higher in the right colectomy group (5.1% versus 0.4%, p=0.004, p<0.05). Overall, 233 patients (79.5%) had no complications. Complications found were grade I and II in 62 patients (21.1%) and grade III to V in 37 (12.6%). Twenty-three patients (7.8%) underwent reoperation. The comparison between left and right colectomy was not statistically different for operative time, conversion, reoperation, severe postoperative complications, and length of stay. The anastomotic leak rate was comparable in both groups(5.6% versus 2.1%, p=0.232, p>0.05). The oncological results were similar in both surgeries. In multiple logistic regression, ASA statistically influenced the worst results (>= III; p=0.029, p<0.05). CONCLUSIONS: The surgical and oncological results of laparoscopic right and left colectomies are similar, making this the preferred approach for both procedures.
Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)
(2023) MOREIRA, Rodrigo Oliveira; VALERIO, Cynthia Melissa; VILLELA-NOGUEIRA, Cristiane Alves; CERCATO, Cintia; GERCHMAN, Fernando; LOTTENBERG, Ana Maria Pita; GODOY-MATAS, Amelio Fernando; OLIVEIRA, Ricardo de Andrade; MELLO, Carlos Eduardo Brandao; ALVARES-DA-SILVA, Mario Reis; LEITE, Nathalie Carvalho; COTRIM, Helma Pinchemel; PARISI, Edison Roberto; SILVA, Giovanni Faria; MIRANDA, Paulo Augusto Carvalho; HALPERN, Bruno; OLIVEIRA, Claudia Pinto
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.
Comparing three-dimensional endorectal ultrasound and magnification chromoendoscopy for early rectal neoplasia invasion depth assessment
(2024) PINTO, Rodrigo Ambar; KAWAGUTI, Fabio Shiguehissa; KIMURA, Cintia Mayumi Sakurai; CORREA NETO, Isaac Jose Felippe; NAHAS, Caio Sergio Rizkallah; MARQUES, Carlos Frederico Sparapan; BUSTAMANTE-LOPEZ, Leonardo Alfonso; RIBEIRO-JR, Ulysses; MALUF-FILHO, Fauze; NAHAS, Sergio Carlos
IntroductionAccurate assessment of invasion depth of early rectal neoplasms is essential for optimal therapy. We aimed to compare three-dimensional endorectal ultrasound (3D-ERUS) with magnification chromoendoscopy (MCE) regarding their accuracy in assessing parietal invasion depth (T).MethodsPatients with middle and distal rectum neoplasms were prospectively included. Two providers blinded to each other's assessment performed 3D-ERUS and MCE, respectively. The T stage assessed through ERUS was compared to the MCE evaluation. The results were compared to the surgical specimen anatomopathological report. Sensitivity, specificity, accuracy, positive (PPV), and negative (NPV) predictive values were calculated for the T stage and for the final therapy (local excision or radical surgery).ResultsIn 8 years, 70 patients were enrolled, and all underwent both exams. MCE and ERUS showed an accuracy of 94.3% and 85.7%, sensitivity of 83.7 and 93.3%, specificity of 96.4 and 83.6%, PPV of 86.7 and 60.9%, and NPV of 96.4 and 97.9%, respectively. Kappa for T stage assessed through ERUS was 0.64 and 0.83 for MCE.ConclusionMCE and 3D-ERUS had good diagnostic performance, but the endoscopic method had higher accuracy. Both methods reliably assessed lesion extension, circumferential involvement, and distance from the anal verge.
Self-expandable metallic stent-induced esophagorespiratory fistulas in patients with advanced esophageal cancer
(2023) JOSINO, Iatagan R.; MARTINS, Bruno C.; MACHADO, Andressa A.; LIMA, Gustavo R. de A.; CORDERO, Martin A. C.; POMBO, Amanda A. M.; SALLUM, Rubens A. A.; JR, Ulysses Ribeiro; BARON, Todd H.; MALUF-FILHO, Fauze
Background/Aims: Self-expandable metallic stents (SEMSs) are widely adopted for the palliation of dysphagia in patients with malignant esophageal strictures. An important adverse event is the development of SEMS-induced esophagorespiratory fistulas (SEMSERFs). This study aimed to assess the risk factors related to the development of SEMS-ERF after SEMS placement in patients with esophageal cancer. Methods: This retrospective study was performed at the Instituto do Cancer do Estado de Sao Paulo. All patients with malignant esophageal strictures who underwent esophageal SEMS placement between 2009 and 2019 were included in the study. Results: Of the 335 patients, 37 (11.0%) developed SEMS-ERF, with a median time of 129 days after SEMS placement. Stent flare of 28 mm (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.15-5.51; p=0.02) and post-stent chemotherapy (HR, 2.0; 95% CI, 1.01- 4.00; p=0.05) were associated with an increased risk of developing SEMS-ERF, while lower-third tumors were a protective factor (HR, 0.5; 95% CI, 0.26-0.85; p=0.01). No difference was observed in overall survival. Conclusions: The incidence of SEMS-ERFs was 11%, with a median time of 129 days after SEMS placement. Post-stent chemotherapy and a 28 mm stent flare were associated with a higher risk of SEMS-ERF.
Brazilian Landscape of Hepatocellular Carcinoma
(2023) FONSECA, Leonardo G.; CHEN, Andre T. C.; OLIVEIRA, Irai S. de; CHAGAS, Aline L.; KRUGER, Jaime A. P.; CARRILHO, Flair J.
The incidence of hepatocellular carcinoma (HCC) is expected to increase in the coming years, and strategies to mitigate the burden of this disease are needed in different regions. Geographic variations in epidemiology and risk factors, such as viral hepatitis and metabolic disease, pose challenges in adopting programs for early detection programs and management of patients with HCC. Brazil, like other countries, has high economic and social inequality, with heterogeneous access to health care. Viral hepatitis is themain risk factor but there is growing awareness of fatty liver disease. Risk factor monitoring and screening programs are unmet priorities because patients are often diagnosed at later stages. Advances in the management of patients with HCC have been made in recent years, including new tools for selecting patients for liver transplantation, sophisticated surgical techniques, and new systemic agents. High-volume academic centers often achieve favorable results through the adoption and application of established treatments, but this is not a reality in most regions of Brazil, because of disparities in wealth and resources. As HCC management requires a coordinated and multidisciplinary team, the role of local referral centers in decentralizing access to treatments and promoting health education in different regions should be encouraged and supported.
Practice variation in anastomotic leak after esophagectomy: Unravelling differences in failure to rescue
(2023) UBELS, Sander; MATTHEE, Eric; VERSTEGEN, Moniek; KLARENBEEK, Bastiaan; BOUWENSE, Stefan; HENEGOUWEN, Mark I. van Berge; DAAMS, Freek; DEKKER, Jan Willem T.; DET, Marc J. van; ESSER, Stijn van; GRIFFITHS, Ewen A.; HAVEMAN, Jan Willem; NIEUWENHUIJZEN, Grard; SIERSEMA, Peter D.; WIJNHOVEN, Bas; HANNINK, Gerjon; WORKUM, Frans van; ROSMAN, Camiel; HEISTERKAMP, Joos; POLAT, Fatih; SCHOUTEN, Jeroen; SINGH, Pritam
Introduction: Failure to rescue (FTR) is an important outcome measure after esophagectomy and reflects mortality after postoperative complications. Differences in FTR have been associated with hospital resection volume. However, insight into how centers manage complications and achieve their outcomes is lacking. Anastomotic leak (AL) is a main contributor to FTR. This study aimed to assess differences in FTR after AL between centers, and to identify factors that explain these differences.Methods: TENTACLE -Esophagus is a multicenter, retrospective cohort study, which included 1509 patients with AL after esophagectomy. Differences in FTR were assessed between low-volume (<20 re-sections), middle-volume (20-60 resections) and high-volume centers (>= 60 resections). Mediation analysis was performed using logistic regression, including possible mediators for FTR: case-mix, hos -pital resources, leak severity and treatment. Results: FTR after AL was 11.7%. After adjustment for confounders, FTR was lower in high-volume vs. low-volume (OR 0.44, 95%CI 0.2-0.8), but not versus middle-volume centers (OR 0.67, 95%CI 0.5-1.0). After mediation analysis, differences in FTR were found to be explained by lower leak severity, lower secondary ICU readmission rate and higher availability of therapeutic modalities in high-volume centers. No statistically significant direct effect of hospital volume was found: high-volume vs. low-volume 0.86 (95%CI 0.4-1.7), high-volume vs. middle-volume OR 0.86 (95%CI 0.5-1.4).Conclusion: Lower FTR in high-volume compared with low-volume centers was explained by lower leak severity, less secondary ICU readmissions and higher availability of therapeutic modalities. To reduce FTR after AL, future studies should investigate effective strategies to reduce leak severity and prevent sec-ondary ICU readmission.(c) 2023 The Authors.
PALLIATIVE GASTRECTOMY VERSUS GASTRIC BYPASS FOR SYMPTOMATIC CLINICAL STAGE IV GASTRIC CANCER: A PROPENSITY SCORE MATCHING ANALYSIS
(2023) PINTO, Sterphany Ohana Soares Azevedo; PEREIRA, Marina Alessandra; JR, Ulysses Ribeiro; D'ALBUQUERQUE, Luiz Augusto Carneiro; RAMOS, Marcus Fernando Kodama Pertille
BACKGROUND: Patients with clinical stage IV gastric cancer may require palliative procedures to manage complications such as obstruction. However, there is no consensus on whether performing palliative gastrectomy compared to gastric bypass brings benefits in terms of survival. AIMS: To compare the overall survival of patients with distal obstructive gastric cancer undergoing palliative surgical treatment, using propensity score matching analysis. METHODS: Patients who underwent palliative bypass surgery (gastrojejunostomy or partitioning) and resection between the years 2009 and 2023 were retrospectively selected. Initial and postoperative clinicopathological variables were collected. RESULTS: 150 patients were initially included. The derived group (n=91) presented more locally invasive disease (p<0.01), greater degree of obstruction (p<0.01), and worse clinical status (p<0.01), while the resected ones (n= 59) presented more distant metastasis (p<0.01). After matching, 35 patients remained in each group. There was no difference in the incidence of postoperative complications, but the derived group had higher 90-day mortality (p<0.01). Overall survival was 16.9 and 4.5 months for the resected and derived groups, respectively (p<0.01). After multivariate analysis, hypoalbuminemia (hazard ratio - HR=2.02, 95% confidence interval - 95%CI 1.17-3.48; p=0.01), absence of adjuvant chemotherapy (HR=5.97; 95%CI 3.03-11.7; p<0.01), and gastric bypass (HR=3,28; 95%CI 1.8-5.95; p<0.01) were associated with worse survival. CONCLUSIONS: Palliative gastrectomy was associated with greater survival and lower postoperative morbidity compared to gastric bypass. This may be due to better local control of the disease, with lower risks of complications and better effectiveness of chemotherapy.
Prevalence and significance of antimitochondrial antibodies in autoimmune hepatitis (AIH): Results from a large multicentre study of the International AIH Group
(2023) GATSELIS, Nikolaos K.; ZACHOU, Kalliopi; LOZA, Aldo J. Montano; CANCADO, Eduardo Luiz Rachid; ARINAGA-HINO, Teruko; MURATORI, Paolo; EFE, Cumali; FLOREANI, Annarosa; INVERNIZZI, Pietro; TAKAHASHI, Athushi; TAKAKI, Akinobu; BERETTA-PICCOLI, Benedetta Terziroli; HOEK, Bart van; LYTVYAK, Ellina; GUEDES, Laura Vilar; PURNAK, Tugrul; CAZZAGON, Nora; LYGOURA, Vasiliki; ARVANITI, Pinelopi; RIGOPOULOU, Eirini I.; MURATORI, Luigi; DALEKOS, George N.
Background & Aims: Antimitochondrial antibodies (AMA) are specific markers for the diagnosis of primary biliary cholangitis (PBC) but can also be found occasionally in patients with autoimmune hepatitis (AIH). The present large multicentre cohort study assessed the prevalence and significance of AMA in AIH-patients. Methods: 123 AMA-positive AIH-patients were investigated and compared with 711 age-matched AMA-negative AIH-patients and 69 patients with AIH/PBC variant. Results: AMA prevalence in AIH-patients was 5.1% (range: 1.2%-11.8%). AMA-positivity was associated with female sex (p = 0.031) in AMA-positive AIH-patients but not with liver biochemistry, bile duct injury on liver biopsy, disease severity at baseline and response to treatment compared to AMA-negative AIH-patients. Comparing AMA-positive AIH-patients to those with AIH/PBC variant, there was no difference in disease severity. Regarding liver histology, AIH/PBC variant patients were characterized by the presence of at least one feature of bile duct damage (p<0.001). Response to immunosuppressive treatment was similar among groups. From AMA-positive AIH patients only those with evidence of non-specific bile duct injury had higher risk to progress to cirrhosis (HR=4.314, 95%CI: 2.348-7.928; p<0.001). During follow-up, AMA-positive AIH-patients had higher risk to develop histological bile duct injury (HR 4.654, 95%CI 1.829-11.840; p = 0.001). Conclusions: AMA presence is relatively common among AIH-patients, but their clinical significance seems important only when they co-exist with non-specific bile duct injury at the histological level. Therefore, a careful evaluation of liver biopsy seems of utmost importance in these patients.
Propensity-score Matched and Coarsened-exact Matched Analysis Comparing Robotic and Laparoscopic Major Hepatectomies: An International Multicenter Study of 4822 Cases
(2023) LIU, Qu; ZHANG, Wanguang; ZHAO, Joseph J.; SYN, Nicholas L.; CIPRIANI, Federica; ALZOUBI, Mohammad; AGHAYAN, Davit L.; SIOW, Tiing-Foong; LIM, Chetana; SCATTON, Olivier; HERMAN, Paulo; COELHO, Fabricio Ferreira; V, Marco Marino; MAZZAFERRO, Vincenzo; CHIOW, Adrian K. H.; SUCANDY, Iswanto; IVANECZ, Arpad; CHOI, Sung-Hoon; LEE, Jae Hoon; PRIETO, Mikel; VIVARELLI, Marco; GIULIANTE, Felice; VALLE, Bernardo Dalla; RUZZENENTE, Andrea; YONG, Chee-Chien; CHEN, Zewei; YIN, Mengqiu; FONDEVILA, Constantino; EFANOV, Mikhail; MORISE, Zenichi; BENEDETTO, Fabrizio Di; BRUSTIA, Raffaele; VALLE, Raffaele Dalla; BOGGI, Ugo; GELLER, David; BELLI, Andrea; MEMEO, Riccardo; GRUTTADAURIA, Salvatore; MEJIA, Alejandro; PARK, James O.; ROTELLAR, Fernando; CHOI, Gi-Hong; ROBLES-CAMPOS, Ricardo; WANG, Xiaoying; SUTCLIFFE, Robert P.; SCHMELZLE, Moritz; PRATSCHKE, Johann; TANG, Chung-Ngai; CHONG, Charing C. N.; LEE, Kit-Fai; MEURS, Juul; D'HONDT, Mathieu; MONDEN, Kazuteru; LOPEZ-BEN, Santiago; KINGHAM, Thomas Peter; FERRERO, Alessandro; ETTORRE, Giuseppe Maria; SANDRI, Giovanni Battista Levi; SALEH, Mansour; CHERQUI, Daniel; ZHENG, Junhao; LIANG, Xiao; MAZZOTTA, Alessandro; SOUBRANE, Olivier; WAKABAYASHI, Go; I, Roberto Troisi; CHEUNG, Tan-To; KATO, Yutaro; SUGIOKA, Atsushi; D'SILVA, Mizelle; HAN, Ho-Seong; Phan Phuoc Nghia; Tran Cong Duy Long; EDWIN, Bjorn; FUKS, David; CHEN, Kuo-Hsin; HILAL, Mohammad Abu; ALDRIGHETTI, Luca; LIU, Rong; GOH, Brian K. P.
Objective: To compare the outcomes between robotic major hepatectomy (R-MH) and laparoscopic major hepatectomy (L-MH). Background: Robotic techniques may overcome the limitations of laparoscopic liver resection. However, it is unknown whether R-MH is superior to L-MH. Methods: This is a post hoc analysis of a multicenter database of patients undergoing R-MH or L-MH at 59 international centers from 2008 to 2021. Data on patient demographics, center experience volume, perioperative outcomes, and tumor characteristics were collected and analyzed. Both 1:1 propensity-score matched (PSM) and coarsened-exact matched (CEM) analyses were performed to minimize selection bias between both groups Results: A total of 4822 cases met the study criteria, of which 892 underwent R-MH and 3930 underwent L-MH. Both 1:1 PSM (841 R-MH vs. 841 L-MH) and CEM (237 R-MH vs. 356 L-MH) were performed. R-MH was associated with significantly less blood loss {PSM:200.0 [interquartile range (IQR):100.0, 450.0] vs 300.0 (IQR:150.0, 500.0) mL; P = 0.012; CEM:170.0 (IQR: 90.0, 400.0) vs 200.0 (IQR:100.0, 400.0) mL; P = 0.006}, lower rates of Pringle maneuver application (PSM: 47.1% vs 63.0%; P < 0.001; CEM: 54.0% vs 65.0%; P = 0.007) and open conversion (PSM: 5.1% vs 11.9%; P < 0.001; CEM: 5.5% vs 10.4%, P = 0.04) compared with L-MH. On subset analysis of 1273 patients with cirrhosis, R-MH was associated with a lower postoperative morbidity rate (PSM: 19.5% vs 29.9%; P = 0.02; CEM 10.4% vs 25.5%; P = 0.02) and shorter postoperative stay [PSM: 6.9 (IQR: 5.0, 9.0) days vs 8.0 (IQR: 6.0 11.3) days; P < 0.001; CEM 7.0 (IQR: 5.0, 9.0) days vs 7.0 (IQR: 6.0, 10.0) days; P = 0.047]. Conclusions: This international multicenter study demonstrated that R-MH was comparable to L-MH in safety and was associated with reduced blood loss, lower rates of Pringle maneuver application, and conversion to open surgery.
Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases
(2023) CHEUNG, Tan-To; LIU, Rong; CIPRIANI, Federica; WANG, Xiaoying; EFANOV, Mikhail; FUKS, David; CHOI, Gi-Hong; SYN, Nicholas L.; CHONG, Charing C. N.; BENEDETTO, Fabrizio Di; ROBLES-CAMPOS, Ricardo; MAZZAFERRO, Vincenzo; ROTELLAR, Fernando; LOPEZ-BEN, Santiago; PARK, James O.; MEJIA, Alejandro; SUCANDY, Iswanto; CHIOW, Adrian K. H.; MARINO, Marco V.; GASTACA, Mikel; LEE, Jae Hoon; KINGHAM, T. Peter; D'HONDT, Mathieu; CHOI, Sung Hoon; SUTCLIFFE, Robert P.; HAN, Ho-Seong; TANG, Chung-Ngai; PRATSCHKE, Johann; TROISI, Roberto I.; WAKABAYASHI, Go; CHERQUI, Daniel; GIULIANTE, Felice; AGHAYAN, Davit L.; EDWIN, Bjorn; SCATTON, Olivier; SUGIOKA, Atsushi; Tran Cong Duy Long; FONDEVILA, Constantino; HILAL, Mohammad Abu; RUZZENENTE, Andrea; FERRERO, Alessandro; HERMAN, Paulo; CHEN, Kuo-Hsin; ALDRIGHETTI, Luca; GOH, Brian K. P.
Background: The use of laparoscopic (LLR) and robotic liver resections (RLR) has been safely performed in many institutions for liver tumours. A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours >= 10 cm. Methods: This was a retrospective review of 971 patients who underwent LLR and RLR for huge (>= 10 cm) tumors at 42 international centers between 2002-2020. Results: One hundred RLR and 699 LLR which met study criteria were included. The comparison between the 2 approaches for patients with huge tumors were performed using 1: 3 propensity- score matching (PSM) (73 vs. 219). Before PSM, LLR was associated with significantly increased frequency of previous abdominal surgery, malignant pathology, liver cirrhosis and increased median blood. After PSM, RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time (242 vs. 290 min, P=0.286), transfusion rate rate (19.2% vs. 16.9%, P=0.652), median blood loss (200 vs. 300 mL, P=0.694), open conversion rate (8.2% vs. 11.0%, P=0.519), morbidity (28.8% vs. 21.9%, P=0.221), major morbidity (4.1% vs. 9.6%, P=0.152), mortality and postoperative length of stay (6 vs. 6 days, P=0.435). Conclusions: RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes. There was no significant difference in perioperative outcomes after RLR or LLR.
Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease
(2024) MICHALCZUK, Matheus Truccolo; LONGO, Larisse; KEINGESKI, Melina Belen; BASSO, Bruno de Souza; GUERREIRO, Gabriel Tayguara Silveira; FERRARI, Jessica T.; VARGAS, Jose Eduardo; OLIVEIRA, Claudia P.; URIBE-CRUZ, Carolina; CERSKI, Carlos Thadeu Schmidt; FILIPPI-CHIELA, Eduardo; ALVARES-DA-SILVA, Mario Reis
BACKGROUND Prevalence of hepatocellular carcinoma (HCC) is increasing, especially in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). AIM To investigate rifaximin (RIF) effects on epigenetic/autophagy markers in animals. METHODS Adult Sprague-Dawley rats were randomly assigned (n = 8, each) and treated from 5-16 wk: Control [standard diet, water plus gavage with vehicle (Veh)], HCC [high-fat choline deficient diet (HFCD), diethylnitrosamine (DEN) in drinking water and Veh gavage], and RIF [HFCD, DEN and RIF (50 mg/kg/d) gavage]. Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained. RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis, and cirrhosis, but three RIF-group did not develop HCC. Comparing animals who developed HCC with those who did not, miR-122, miR-34a, tubulin alpha-1c (Tuba-1c), metalloproteinases-2 (Mmp2), and metalloproteinases-9 (Mmp9) were significantly higher in the HCC-group. The opposite occurred with Becn1, coactivator associated arginine methyltransferase-1 (Carm1), enhancer of zeste homolog-2 (Ezh2), autophagy-related factor LC3A/B (Map1 Lc3b), and p62/sequestosome-1 (p62/SQSTM1)-protein. Comparing with controls, Map1 Lc3b, Becn1 and Ezh2 were lower in HCC and RIF-groups (P < 0.05). Carm1 was lower in HCC compared to RIF (P < 0.05). Hepatic expression of Mmp9 was higher in HCC in relation to the control; the opposite was observed for p62/Sqstm1 (P < 0.05). Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control (P = 0.024). There was no difference among groups for Tuba-1c, Aldolase-B, alpha-fetoprotein, and Mmp2 (P > 0.05). miR-122 was higher in HCC, and miR-34a in RIF compared to controls (P < 0.05). miR-26b was lower in HCC compared to RIF, and the inverse was observed for miR-224 (P < 0.05). There was no difference among groups regarding miR-33a, miR-143, miR-155, miR-375 and miR-21 (P > 0.05). CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.
Impact of Liver Cirrhosis, Severity of Cirrhosis, and Portal Hypertension on the Difficulty and Outcomes of Laparoscopic and Robotic Major Liver Resections for Primary Liver Malignancies
(2024) CIPRIANI, Federica; ALDRIGHETTI, Luca; RATTI, Francesca; WU, Andrew G. R.; KABIR, Tousif; SCATTON, Olivier; LIM, Chetana; ZHANG, Wanguang; SIJBERDEN, Jasper; AGHAYAN, Davit L.; SIOW, Tiing-Foong; DOKMAK, Safi; COELHO, Fabricio Ferreira; HERMAN, Paulo; MARINO, Marco V.; MAZZAFERRO, Vincenzo; CHIOW, Adrian K. H.; SUCANDY, Iswanto; IVANECZ, Arpad; CHOI, Sung-Hoon; LEE, Jae Hoon; GASTACA, Mikel; VIVARELLI, Marco; GIULIANTE, Felice; RUZZENENTE, Andrea; YONG, Chee-Chien; YIN, Mengqiu; FONDEVILA, Constantino; EFANOV, Mikhail; MORISE, Zenichi; BENEDETTO, Fabrizio Di; BRUSTIA, Raffaele; VALLE, Raffaele Dalla; BOGGI, Ugo; GELLER, David; BELLI, Andrea; MEMEO, Riccardo; GRUTTADAURIA, Salvatore; MEJIA, Alejandro; PARK, James O.; ROTELLAR, Fernando; CHOI, Gi-Hong; ROBLES-CAMPOS, Ricardo; WANG, Xiaoying; SUTCLIFFE, Robert P.; PRATSCHKE, Johann; LAI, Eric C. H.; CHONG, Charing C. N.; D'HONDT, Mathieu; MONDEN, Kazuteru; LOPEZ-BEN, Santiago; KINGHAM, T. Peter; FERRERO, Alessandro; ETTORRE, Giuseppe Maria; CHERQUI, Daniel; LIANG, Xiao; SOUBRANE, Olivier; WAKABAYASHI, Go; TROISI, Roberto I.; CHEUNG, Tan-To; KATO, Yutaro; SUGIOKA, Atsushi; HAN, Ho-Seong; Tran Cong duy Long; LIU, Qu; LIU, Rong; EDWIN, Bjorn; FUKS, David; CHEN, Kuo-Hsin; HILAL, Mohammad Abu; GOH, Brian K. P.
BackgroundMinimally invasive liver resections (MILR) offer potential benefits such as reduced blood loss and morbidity compared with open liver resections. Several studies have suggested that the impact of cirrhosis differs according to the extent and complexity of resection. Our aim was to investigate the impact of cirrhosis on the difficulty and outcomes of MILR, focusing on major hepatectomies.MethodsA total of 2534 patients undergoing minimally invasive major hepatectomies (MIMH) for primary malignancies across 58 centers worldwide were retrospectively reviewed. Propensity score (PSM) and coarsened exact matching (CEM) were used to compare patients with and without cirrhosis.ResultsA total of 1353 patients (53%) had no cirrhosis, 1065 (42%) had Child-Pugh A and 116 (4%) had Child-Pugh B cirrhosis. Matched comparison between non-cirrhotics vs Child-Pugh A cirrhosis demonstrated comparable blood loss. However, after PSM, postoperative morbidity and length of hospitalization was significantly greater in Child-Pugh A cirrhosis, but these were not statistically significant with CEM. Comparison between Child-Pugh A and Child-Pugh B cirrhosis demonstrated the latter had significantly higher transfusion rates and longer hospitalization after PSM, but not after CEM. Comparison of patients with cirrhosis of all grades with and without portal hypertension demonstrated no significant difference in all major perioperative outcomes after PSM and CEM.ConclusionsThe presence and severity of cirrhosis affected the difficulty and impacted the outcomes of MIMH, resulting in higher blood transfusion rates, increased postoperative morbidity, and longer hospitalization in patients with more advanced cirrhosis. As such, future difficulty scoring systems for MIMH should incorporate liver cirrhosis and its severity as variables.
Impact of baseline abnormal liver enzymes in the outcome of COVID-19 infection
(2023) FARIAS, Joao Pedro; CODES, Liana; VINHAES, Diana; AMORIM, Ana Paula; D'OLIVEIRA, Ricardo Cruz; FARIAS, Alberto Queiroz; BITTENCOURT, Paulo Lisboa
Background: Little is known about the significance of liver function tests (LFT) abnormalities in COVID-19 and their impact on disease outcomes. The aims of the study were to evaluate abnormalities of LFT in patients with COVID-19 and their impact on disease severity, mortality, and correlation with leukocyte markers of inflammation. Methods: All patients with COVID-19 admitted to the emergency department (ED) of a single reference center were retrospectively evaluated. Data were collected using an electronic medical database covering the following variables: demographics, baseline complete blood count (CBC) and ratios, neutrophillymphocyte (NLR) and monocyte-lymphocyte ratios (MLR), systemic immune-inflammation index (SII), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Disease severity was defined by the presence of organ failure (OF) or requirement for intensive care unit (ICU) support. Mortality was considered as patient death during hospitalization. Results: A total of 1,539 subjects (799 women, mean age 57 +/- 18 years) with COVID-19 were evaluated. Abnormal AST and/or ALT were seen in 50% of them, with a frequency and magnitude that significantly correlated with leukocyte count and ratios. Both LFT were significantly associated with requirement for hospital and ICU admission and mortality. High AST levels were significantly associated with the presence, number, and types of OFs and in-hospital length of stay (LOS). Elevated ALT was also significantly associated with the aforementioned variables, with the exception of OFs presence, circulatory failure and LOS. Conclusions: LFT abnormalities are frequently seen in COVID-19 patients, reflect SARS-CoV-2 associated inflammation and may predict adverse outcomes. LFT may be useful to aid decision-making in the ED for hospital admission or scheduled outpatient reevaluation.
TUMOR MARKERS EXPRESSION LEVELS IN GASTRIC CANCER PATIENT'S PERIPHERAL BLOOD BY RT-PCR ASSESSMENT
(2023) KAWAKAMI, Gabriel da Silva; PEREIRA, Marina Alessandra; KUBRUSLY, Marcia Saldanha; CARRASCO, Alexis German Murillo; RAMOS, Marcus Fernando Kodama Pertille; JR, Ulysses Ribeiro
BACKGROUND: Hematological recurrence is the second most frequent cause of failure in the treatment of gastric cancer. The detection of circulating tumor markers in peripheral blood by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method may be a useful tool to predict recurrence and determine the patient's prognosis. However, no consensus has been reached regarding the association between the tumor markers level in peripheral blood and its impact on patient survival. AIMS: To evaluate the expression of the circulating tumor markers CK20 and MUC1 in peripheral blood samples from patients with gastric cancer by qRT-PCR, and to verify the association of their expression levels with clinicopathological characteristics and survival. METHODS: A total of 31 patients with gastric adenocarcinoma were prospectively included in this study. CK20 and MUC1 expression levels were analyzed from peripheral blood by the qRT-PCR technique. RESULTS: There was no statistically significant (p>0.05) association between CK20 expression levels and clinical, pathological, and surgical features. Higher MUC1 expression levels were associated with female patients (p=0.01). There was a correlation between both gene levels (R=0.81, p<0.001), and CK20 level and tumor size (R=0.39, p=0.034). CONCLUSIONS: CK20 and MUC1 expression levels could be assessed by qRT-PCR from total peripheral blood samples of patients with gastric cancer. CK20 levels were correlated to MUC1 levels as well as to tumor size. There was no difference in disease-free survival and overall survival regarding both genetic markers expression in this series
Gastrointestinal genetic reprogramming of vitamin A metabolic pathways in response of Roux-en-Y gastric bypass
(2024) SAMPAIO, Priscilla; WAITZBERG, Dan Linetzky; MACHADO, Natasha Mendonca; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle C.; FERREIRA, Beatriz A. M.; MARQUES, Mariane; BARCELOS, Samira; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; HEYMSFIELD, Steven B.; CORREA-GIANNELLA, Maria Lucia; PASSADORE, Mariana Doce; SALA, Priscila
Roux-en-Y gastric bypass (RYGB) is one of the most performed bariatric surgical techniques. However, RYGB commonly results, as side effects, in nutritional deficiencies. This study aimed to examine changes in the expression of vitamin A pathway encoding genes in the gastrointestinal tract (GI) and to evaluate the potential mechanisms associated with hypovitaminosis A after RYGB. Intestinal biopsies were obtained through double-balloon endoscopy in 20 women with obesity (age 46.9 +/- 6.2 years; body mass index [BMI] 46.5 +/- 5.3 kg/m(2) [mean +/- SD]) before and three months after RYGB (BMI, 38.2 +/- 4.2 kg/m(2)). Intestinal mucosal gene microarray analyses were performed in samples using a Human GeneChip 1.0 ST array (Affymetrix). Vitamin A intake was assessed from 7-day food records and serum retinot levels were evaluated by electrochemiluminescence immunoassay. Our results showed the following genes with significant downregulation (p <= 0.05): LIPF (-0.60), NPC1L1 (-0.71), BCO1 (-0.45), and RBP4 (-0.13) in duodenum: CD36 (-0.33), and ISX (-0.43) in jejunum and BCO1 (-0.29) in ileum. No significant changes in vitamin A intake were found (784 +/- 694 retinal equivalents [RE] pre-operative vs. 809 +/- 753 RE post-operative [mean +/- SD]). Although patients were routinely supplemented with 3500 international units IU/day (equivalent to 1050 mu gRE/day) of oral retinal palm itate, serum concentrations were lower in the post-operative when compared to pre-operative period (0.35 +/- 0.14 mu g/L vs. 0.52 +/- 0.33 mu g/L respectively - P=0.07), both within the normal range. After RYGB, the simultaneous change in expression of GI genes, may impair carotenoid metabolism in the enterocytes, formation of nascent chylomicrons and transport of retinol, resulting in lower availability of vitamin A.
Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
(2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
(2022) GRANJA, S. C.; LONGATTO-FILHO, A.; CAMPOS, P. B. De; OLIVEIRA, C. P.; STEFANO, J. T.; MARTINS-FILHO, S. N.; CHAGAS, A. L.; HERMAN, P.; D'ALBUQUERQUE, L. C.; ALVARES-DA-SILVA, M. Reis; CARRILHO, F. J.; BALTAZAR, F.; ALVES, V. A. F.
Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.

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