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INTRODUCTION: Infective endocarditis(IE) has a low incidence, but it remains a serious disease with high mortality rates. Only 5 % of these patients will develop a splenic abscess, and the number of patients that have IE and a splenic abscess requiring surgery is low. The current guidelines recommend that splenectomy should be performed prior to valve replacement, but there is no strong evidence to support this statement and no evidence to clearly endorse the order in which the surgical interventions should be performed. The objective of this review and case series is to establish the proper treatment strategy, to assess the adequate order of the surgical interventions and to clarify the role of percutaneous drainage in the management of these patients. MATERIAL AND METHODS: All patients with infective endocarditis and splenic abscess who underwent surgery in our institution, between January 2008 and December 2020 were included in this study, excluding patients which had cardiac device related endocarditis. Literature review on the matter included a number of 30 studies which were selected from the PubMed database. RESULTS: Assessing the literature and case series no reinfection was reported for simultaneously performing splenectomy(S) and valvular surgery(VS) nor for VS followed by S. CONCLUSION: Percutaneous drainage of the splenic abscesses is a feasible solution as definitive therapy in high-risk patients or as bridge therapy. Additional studies are needed, even though they are difficult to conduct, therefore a national/international infectious endocarditis register may be of use to clarify these challenges.
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Background: Splenectomy has been performed for various indications from haematological diseases to benign cysts and tumours, and for splenic traumatic injuries. However, there has been a steady decline in splenectomies in the last 20 years. The aim of this study is to establish the reasons behind this decline in splenectomy and to analyse them based on indication, type of splenectomy, and manner of approach (open, laparoscopic or robotic). Material and Methods: This is a retrospective study of a single centre experience of all the splenectomies, both total and partial, performed in the Department of General Surgery of Fundeni Clinical Institute (Bucharest) between 2002 and 2023. Only surgeries for primary splenic diseases were selected, splenic resections as part of other major operations were not included. Results: Between 2002 and 2023, 876 splenectomies were performed in the Department of General Surgery of Fundeni Clinical Institute (Bucharest). Most splenectomies (n=245) were performed for immune thrombocytopenic purpura (ITP), followed by benign tumours and cysts (n=136), lymphoma (n=119), hypersplenism due to cirrhosis (n=107) and microspherocytosis (n=95). Other indications included myelodysplastic syndrome (n=39), trauma (n=35), thalassemia (n=22), leukaemia (n=18) and also there were 60 splenectomies that were performed for hypersplenism of unknown cause. There were 795 total splenectomies (TS) and 81 partial splenectomies (PS). There was a decline in the number of splenectomies both TS and PS for all these indications, most notably in the case of ITP, microspherocytosis and hypersplenism due to cirrhosis with no splenectomies performed for these indications since 2020. Conclusion: With the development of new lines of treatment, advances in interventional radiology and in surgery with the spleen parenchyma sparing options, the need for total splenectomy has been greatly reduced which is reflected in the decline in the number of splenectomies performed in the last 20 years in our clinic.
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Laparoscopia , Procedimentos Cirúrgicos Robóticos , Esplenectomia , Esplenopatias , Humanos , Esplenectomia/métodos , Esplenectomia/estatística & dados numéricos , Estudos Retrospectivos , Laparoscopia/métodos , Romênia/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Esplenopatias/cirurgia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/cirurgia , Idoso , Linfoma/cirurgia , Hiperesplenismo/cirurgia , Hiperesplenismo/etiologia , Talassemia/cirurgia , Cistos/cirurgiaRESUMO
Background: Bearing in mind that the open procedure is already validated by multiple studies, the article aims to prove that pelvic exenteration performed in a minimally invasive fashion might offer better survival and to potentially identify prognostic factors for the outcome of these patients. Material and Methods: Data regarding past and present classifications and surgical indications are presented. Patient data were collected retrospectively. Results: The most frequent diseases treated with pelvic exenteration, in terms of the hystological type, were gynecological malignancy and squamous cell carcinoma. Recurrent pelvic disease was found in 68.2% of patients. R0 resection was achieved in 72.7% of patients in the MI group, and in 73.7% of patients in the OP group. Peri-operative morbidity was reported to be 56.6% for open surgery, and 18.1% for minimally invasive. Average DFS was 20.15 months, ranging from 1.5 to 70.3 months, while the OS was calculated to be 38.1 months (0.33 1508) up until November 2023. Conclusion: Pelvic exenteration is a continuously improving surgical procedure, open approach being favored to minimally invasive one. On the other hand, hospitalization and morbidity are reduced when choosing the latter. R0 and lymph node status are important predictors for overall survival, as well as major early postoperative complications. All in all, pelvic exenteration is still a promising surgical procedure to extend cancer patients lives.
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Carcinoma de Células Escamosas , Exenteração Pélvica , Humanos , Exenteração Pélvica/métodos , Feminino , Estudos Retrospectivos , Resultado do Tratamento , Masculino , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto , Recidiva Local de Neoplasia/cirurgia , Romênia/epidemiologia , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/mortalidade , Intervalo Livre de Doença , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
Background: Nowadays the question persists whether to choose the endoscopic or surgical method as the first treatment of choice for achalasia. Another debate topic is about the differences between the outcomes of the two approaches of minimally invasive surgical treatment and their feasibility. Material and Methods: This retrospective observational study included 193 patients with achalasia treated between 2008 and 2021. The patients were divided into 2 groups (A and B): 152 with minimally invasive heller myotomy (HM), and 41 with pneumatic dilation (PD). Patients surgically treated were then subdivided into robotic group (RG) and laparoscopic group (LG). Results: The recurrence rate was significantly higher in PD group (Ã?2 = 16.81, DF = 1, p 0.0001), with a success rate of 63,4%, comparing with 92,7% in HM group. No significant difference was obtained between the 2 groups concerning symptom relief on patients successfully treated. The success rate was comparable between the robotic and laparoscopic groups (p = 1). Significant difference was obtained in length of hospital stay between the 2 groups, with a mean of 4.78 +-1.59 days in the RG and, respectively, 5.52 +-2.1 days in the LG (t = 2.40, DF = 124.34, p = 0.0177). Postprocedural esophagitis rates were higher in patients with no fundoplication (6 out of 37 - 16.2%) and in patients treated with pneumatic dilation (4 out of 26 - 15.4%) than in patients with fundoplication (4 out of 46 - 8.5%). Conclusion: The present study indicates that surgery may be a better choice in fit patients for the treatment of achalasia. The procedure has a better success rate, even if the long-term outcomes are comparable in patients successfully treated. The success rate and long-term results were comparable between laparoscopy and robotic surgery.
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Acalasia Esofágica , Esofagoplastia , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Acalasia Esofágica/cirurgia , Resultado do TratamentoRESUMO
Introduction: Currently, surgeons deal with an older patient cohort, confronting new challenges brought by the raised life expectancy. This population is unrepresented in surgical trials; therefore, the optimal therapy is still a matter of debate. The efficacy of open versus minimal invasive management of colorectal cancer (CRC) in an elderly cohort is not clearly established. The current study assesses the minimal invasive approach in elderly patients undergoing colorectal surgery. Material and Methods: The General Surgery Department database was inquired between 2012 and 2015 using the following filters: age â?¥ 65 and rectal or colon adenocarcinoma. After applying the exclusion criteria, 975 cases were obtained: 842 underwent open surgery (OS) and 133 underwent minimal invasive surgery (MIS). A propensity score matching was performed to reduce patient selection bias. Results: After the propensity score matching, the MIS group had a shorter postoperative hospital stay than the OS group (p = 0.025). From the preoperative variables, the presence of chronic lung disease was significantly higher in the OS group (p = 0.039). The presence of chronic lung disease positively associates with the Clavien-Dindo classification (p 0.001) and with the number of days from surgery to discharge (p = 0.028). Conclusion: The chronological age alone should not be a limit to MIS granting that it showed no inferiority to the OS in terms of postoperative morbidity, correlating with lower postoperative stay in the elderly. Further prospective studies are needed to assess the outcome of MIS in elderly population.
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Adenocarcinoma , Neoplasias do Colo , Laparoscopia , Pneumopatias , Humanos , Idoso , Resultado do Tratamento , Neoplasias do Colo/cirurgia , Pontuação de Propensão , Adenocarcinoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Pneumopatias/cirurgia , Estudos Retrospectivos , Tempo de InternaçãoRESUMO
The development and progression of colorectal cancer (CRC) have been associated with inflammation processes that involve the overactivation of the NF-κB signalling pathway. The characterization of the NF-κB expression profile in CRC is an important topic since the suppression of NF-κB represents a potential therapeutic approach. In this study, we assessed the expression levels of 84 NF-κB-related genes in paired tumoral (T) and peritumoral (PT) tissues from 18 CRC patients and 18 normal colonic mucosae, and the expression levels of three miRNAs targeting the most dysregulated genes revealed by the case-control analysis. Comparing the gene expression profile of T and controls, 60 genes were dysregulated. The comparison of T and PT revealed 17 dysregulated genes in the tumoral tissues, with IL1B, CXCL8, IL1A, and CSF2 being the most upregulated. Notably, through a bioinformatics analysis, the differential gene expression of 11 out of the 17 genes was validated on a larger cohort of 308 CRC patients compared with 41 controls. Moreover, a decrease in the levels of RELA, NOD1, CASP8, BCL2L1, ELK1, and IKBKB was identified in poorly differentiated tumours compared to moderately differentiated tumours. The analysis of the three miRNAs targeting IL1B, CXCL8, IL1A, and CSF2 showed that miR-182-5p was upregulated in T compared with PT, whereas miR-10b-5p was downregulated in T compared with PT and control tissues. Our results may contribute to the design of new experimental therapeutic strategies based on endogenous molecules, such as miRNAs, to target the genetic key players of the NF- κB pathway.
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Neoplasias Colorretais , MicroRNAs , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/patologiaRESUMO
OBJECTIVE: To assess metabolic dysfunctions and steatohepatosis after standard and local pancreatic resections for benign and premalignant neoplasms. SUMMARY OF BACKGROUND DATA: Duodenopancreatectomy, hemipancreatectomy, and parenchyma-sparing, limited pancreatic resections are currently in use for nonmalignant tumors. METHODS: Medline, Embase, and Cochrane libraries were searched for studies reporting measured data of metabolic functions following PD, pancreatic left resection (PLR), duodenum-sparing pancreatic head resection (DPPHR), pancreatic middle segment resection (PMSR), and tumor enucleation (TEN). Forty cohort studies comprising data of 2729 patients were eligible. RESULTS: PD for benign tumor was associated in 46 of 327 patients (14.1%) with postoperative new onset of diabetes mellitus (pNODM) and in 109 of 243 patients (44.9%) with postoperative new onset of pancreatic exocrine insufficiency measured after a mean follow-up of 32âmonths. The meta-analysis displayed pNODM following PD in 32 of 204 patients (15.7%) and in 10 of 200 patients (5%) after DPPHR [P < 0.01; OR: 0.33; (95%-CI: 0.15-0.22)]. PEI was found in 77 of 174 patients following PD (44.3%) and in 7 of 104 patients (6.7%) following DPPHR (P < 0.01;OR: 0.15; 95%-CI: 0.07-0.32). pNODM following PLR was reported in 107 of 459 patients (23.3%) and following PMSR 23 of 412 patients (5.6%) (P < 0.01; OR: 0.20; 95%-CI: 0.12-0.32). Postoperative new onset of pancreatic exocrine insufficiency was found in 17% following PLR and in 8% following PMSR (P < 0.01). pNODM following PPPD and tumor enucleation was observed in 19.7% and 5.7% (P < 0.03) of patients, respectively. Following PD/PPPD, 145 of 608 patients (23.8%) developed a nonalcoholic fatty liver disease after a mean follow-up of 30.4âmonths. Steatohepatosis following DPPHR developed in 2 of 66 (3%) significantly lower than following PPPD (P < 0.01). CONCLUSION: Standard pancreatic resections for benign tumor carry a considerable high risk for a new onset of diabetes, pancreatic exocrine insufficiency and following PD for steatohepatosis. Parenchyma-sparing, local resections are associated with low grade metabolic dysfunctions.
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Diabetes Mellitus/etiologia , Insuficiência Pancreática Exócrina/etiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Humanos , Pâncreas/cirurgia , Pancreatectomia/métodos , Pancreaticoduodenectomia/métodos , Complicações Pós-OperatóriasRESUMO
BACKGROUND Surges of critically ill patients can overwhelm hospitals during pandemic waves and disrupt essential surgical activity. This study aimed to determine whether hospital mortality increased during the COVID-19 pandemic and during pandemic waves. MATERIAL AND METHODS This was a retrospective analysis of a prospective, observational, epidemiological database. All patients who underwent surgery from January 1 to December 31, 2020, were included in the analysis. The setting was a large Eastern European Surgical Center referral center of liver transplant and liver surgery, a major center of abdominal surgery. RESULTS A total of 1078 patients were analyzed, and this number corresponded to a reduction of surgical activity by 30% during the year 2020 compared with 2019. Despite an increase in surgery complexity during the pandemic, perioperative mortality was not different, and this was maintained during the pandemic wave. The pandemic (OR 1.45 [0.65-3.22], P=0.365) and the wave period (OR 0.897 [0.4-2], P=0.79) were not associated with hospital mortality in univariate analysis. In the multivariate model analysis, only the American Society of Anesthesiology (ASA) score (OR 5.815 [2.9-11.67], P<0.0001), emergency surgery (OR 5.066 [2.24-11.48], P<0.0001), and need for surgical reintervention (OR 5.195 [1.78-15.16], P=0.003) were associated with hospital mortality. CONCLUSIONS Despite considerable challenges, in this large retrospective cohort, perioperative mortality was similar to that of pre-pandemic practice. Efforts should be made to optimize personnel issues, while maintaining COVID-19-free surgical pathways, to adequately address patients' surgical needs during the following waves of the pandemic.
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COVID-19 , Pandemias , Humanos , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: The mechanisms that induce immunodeficiency after splenectomy remain unknown. The aim of this study was to measure the cytokine releasing capacity of the whole blood as an expression of the innate immunity after total (TS) and subtotal/partial splenectomy (S/PS) in order to assess the impact of splenectomy on the individual cytokine reactivity. METHODS: We prospectively collected blood before (D0) and at multiple time points after splenectomy (7 days - D7, 30 days - D30, 90 days - D90, 180 days - D180, and 360 days - D360) and measured the cytokines releasing capacity of IL-6, TNF-alpha and IL-10 from whole blood under LPS stimulation which we normalized to the monocytes number. RESULTS: When analyzing all splenectomies at D0, D7 and D30, normalized ΔTNF-alpha significantly dropped after splenectomy (p = .0038) and normalized ΔIL-6 and ΔIL-10 did not significantly change. More specifically, normalized ΔTNF-alpha dropped after TS (p = .0568) and significantly increased after S/PS (p = .0388). Open surgery induced a decrease in normalized ΔTNF-alpha (p = .0970), whereas minimally invasive (MI) surgery significantly increased the normalized ΔTNF-alpha releasing capacity (p = .0178). The cytokine levels were heterogenous between pathologies at D0, and ΔIL-6 dropped mainly in cirrhotic patients after splenectomy (all underwent TS), ΔTNF-alpha dropped in immune thrombocytopenic purpura patients (all underwent TS), but increased in spherocytosis (91% underwent S/PS) after splenectomy. CONCLUSIONS: Splenectomy induces a decrease of the pro-inflammatory cytokine TNF-alpha and if splenic parenchyma is spared and the surgery is performed MI, this change is hindered.
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Laparoscopia , Esplenectomia , Humanos , Interleucina-10 , Interleucina-6 , Lipopolissacarídeos , Fator de Necrose Tumoral alfaRESUMO
Background and objectives: Gastric cancer (GC) is often diagnosed in the metastatic stage. Palliative systemic therapy is still considered the gold standard, even for patients with resectable oligometastatic disease. The aim of the current study is to assess the potential benefit of up-front gastric and liver resection in patients with synchronous resectable liver-only metastases from GC (LMGC) in a Western population. Materials and Methods: All patients with GC and synchronous LMGC who underwent gastric resection with or without simultaneous resection of LMs between January 1997 and December 2016 were selected from the institutional records. Those with T4b primary tumors or with unresectable or more than three LMs were excluded from the analysis. All patients who underwent emergency surgery for hemorrhagic shock or gastric perforation were also excluded. Results: Out of 28 patients fulfilling the inclusion criteria, 16 underwent simultaneous gastric and liver resection (SR group), while 12 underwent palliative gastric resection (GR group). The median overall survival (OS) of the entire cohort was of 18.81 months, with 1-, 3- and 5-year OS rates of 71.4%, 17.9% and 14.3%, respectively. The 1-, 3- and 5-year OS rates in SR group (75%, 31.3% and 25%, respectively) were significantly higher than those achieved in GR group (66.7%, 0% and 0%, respectively; p = 0.004). Multivariate analysis of the entire cohort revealed that the only independent prognostic factor associated with better OS was liver resection (HR = 3.954, 95% CI: 1.542-10.139; p = 0.004). Conclusions: In a Western cohort, simultaneous resection of GC and LMGC significantly improved OS compared to patients who underwent palliative gastric resection.
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Carcinoma , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Gastrectomia , Estudos RetrospectivosRESUMO
Background and Objectives: GISTs are the most frequent type of mesenchymal neoplasm of the digestive tract. The prognosis is mainly determined by tumor dimensions, mitotic rate and location, but other less well-documented factors can influence evolution and survival. The immune microenvironment and checkpoint molecule expression were proven to impact the prognosis in different types of cancer. The aim of this study was to determine PD-L1 expression in GISTs and to evaluate the level of intratumoral immune infiltration in relation to prognostic variables and survival. Materials and Methods: Sixty-five GISTs diagnosed in the same institution between 2015 and 2018 were immunohistochemically tested for PD-L1 and evaluated using CPS. Immune cells were emphasized, with CD3, CD4, CD8, CD20 and CD68 antibodies and quantified. All data were processed using statistical tools. Results: The median age was 61 years (range, 28-78) and 36 patients (55.4%) were males. The location of the tumors was predominantly gastric (46%), followed by the small bowel (17%) and colorectal (6%). In addition, 11% were EGISTs and 20% were secondary tumors (11% metastases and 9% local recurrences). PD-L1 had a variable expression in tumor and inflammatory cells, with a CPS ranging from 0 to 100. Moreover, 64.6% of cases were PD-L1 positive with no significant differences among categories of variables, such as the age and the sex of the patient, tumor location, the primary or secondary character of the tumor, dimensions, mitotic rate, the risk of disease progression and tumor cell type. Immune cells had a variable distribution throughout the tumors. CD3+ lymphocytes were the most frequent type. CD20+ cells were identified in a larger number in tumors ≤5 cm (p = 0.038). PD-L1-positive tumors had a higher number of immune cells, particularly CD3+, CD20+ and CD68+, in comparison to PD-L1-negative ones (p = 0.032, p = 0.051, p = 0.008). Epithelioid and mixed cell-type tumors had a higher number of CD68+ cells. Survival was not influenced by PD-L1 expression; instead, it was decreased in multifocal tumors (p = 0.0001) and in cases with Ki67 ≥ 50% (p = 0.008). Conclusions: PD-L1-positive expression and the presence of different immune cell types, in variable quantities, can contribute to a better understanding of the complex interactions between tumor cells and the microenvironment, with a possible therapeutic role in GISTs.
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Antígeno B7-H1 , Tumores do Estroma Gastrointestinal , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Microambiente TumoralRESUMO
Oncological surgery is constantly evolving. Recommendations and guidelines are updated periodically in light of new research. Since surgery is a key step in the treatment of cervical cancer in Romania and considering the new findings, this study aims to assess the new guideline recommendations and the surgical treatment options available. The paradigm shift that took place in 2018 left the question: does minimally invasive surgery still play a role in the treatment of cervical cancer? K ouml;hler surgical technique seems to address some of the issues raised by the minimally invasive surgery with good results. H ouml;ckel proposes total mesometrial excision to decrease the risk of recurrence. This study presents 3 cases of cervical cancer patients with stages ranging from IB1 to IIIB that had undergone total mesometrial excision and vaginal cuff closure using the laparoscopic approach to minimize the risk of local recurrence. The case series presented showed that it is feasible and safe to merge these techniques. Further prospective studies are needed in order to assess the risk and benefits of these techniques.
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Neoplasias do Colo do Útero , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Prospectivos , Romênia , Resultado do Tratamento , Neoplasias do Colo do Útero/cirurgiaRESUMO
Introduction: Acute pancreatitis (AP) represents a major burden for the medical system, associating important morbidity and mortality rates. This paper is focused on debatable aspects of the management of biliary AP, namely indications, timing and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) on the hand and, on the other hand, same-admission cholecystectomy as a preventive measure for recurrent disease. Material and methods: This is a retrospective study including 108 patients with biliary AP in whom ERCP was performed, treated in the Clinical Emergency Hospital of Bucharest between 2016 and 2020. According to the urgency of the ERCP, we divided the patients into two groups: urgent versus delayed ERCP. Results: Urgent ERCP was performed in 52 patients, while delayed ERCP was performed in 56 patients; the hospital stay was higher in the urgent group than in the delayed group (10 days vs 8 days, p = 0.299) with no difference in morbidity rates. The mean time between ERCP and surgery was 5 days, without significant difference between the groups. The laparoscopic approach was the preferred method, with a conversion rate of 7%. Conclusion: ERCP with stone extraction followed by same-admission laparoscopic cholecystectomy is a safe therapeutic option, that prevents recurrent pancreatitis. The timing of the procedures remains debatable, further prospective studies being needed to achieve statistical significance.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatite , Doença Aguda , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomia , Humanos , Pancreatite/etiologia , Pancreatite/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic. METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients. RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients. CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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Instabilidade Cromossômica , Neoplasias Colorretais/genética , Neoplasias Experimentais/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/genética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aurora Quinase B/metabolismo , Azoximetano/toxicidade , Carcinogênese/genética , Linhagem Celular Tumoral , Colo/citologia , Colo/patologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Análise Citogenética , Dextranos/toxicidade , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Transgênicos , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Organoides , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/genéticaRESUMO
OBJECTIVES: The present study compares abdominoperineal resection (APR) performed by minimally invasive and open approach, regarding preoperative selection criteria, intraoperative and early postoperative aspects, in choosing the suitable technique performed by surgical teams with experience in both open and minimally invasive surgery (MIS). Methods: This is a retrospective study, conducted between 2008-2020. Two hundred thirty-three patients with APR performed for low rectal or anal cancer were included. The cohort was divided into two groups, depending on the surgical approach used: Minimally Invasive Surgery (laparoscopic and robotic procedures) and Open Surgery (OS). The perioperative characteristics were analyzed in order to identify the optimal approach and a possible selection criteria. Results: We identified a high percentage of patients with a history of abdominal surgery in the open group (p = .0002). Intraoperative blood loss was significantly higher in the open group (p= .02), with an increased number of simultaneous resections (p = .041). The early postoperative outcome was marked by significantly lower morbidity in the MIS group (p = .005), with mortality recorded only in the open group (3 cases), in patients that associated severe comorbidities. The hystopathological results identified a significant number of patients with stage T2 in the MIS group (p= .037). Conclusions: Minimally invasive surgery provides a major advantage to APR, by avoiding an additional incision, the specimen being extracted through the perineal wound. The success of MIS APR seems to be assured by a good preoperative selection of the patients, alongside with experienced surgical teams in both open and minimally invasive rectal resections. The lack of conversion identified in robotic APR confirm the technical superiority over laparoscopic approach.
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Laparoscopia , Protectomia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Hereditary spherocytosis (HS) is a common inherited disease affecting the erythrocyte membrane. Total splenectomy (TS) is effective in reducing hemolysis and decreasing the need of transfusions, but total removal of the spleen represents a potential risk factor for infectious and non-infectious complications. On the other hand, subtotal splenectomy (STS) could be an alternative therapy for HS. The aim of this study is to establish which surgical approach has the best outcome in HS. METHODS: All patients (n = 63) receiving splenectomy for HS between 2002 and 2016 from one institution were retrospectively reviewed. Hemoglobin and reticulocytes levels during preoperative and postoperative follow-up periods were compared. Additionally, a meta-analysis was performed analyzing data regarding hemoglobin and reticulocytes levels from several available studies. RESULT: At 1-year follow-up, our clinical data showed that mean hemoglobin levels increased after TS from (mean ± SD) 9.77 ± 1.82 to 11.88 ± 2.08 g/dl, while after STS from 8.98 ± 1.66 to 11.87 ± 1.38 g/dl. At 3-year and 5-year follow-up after TS, we observed an increase from 9.77 ± 1.82 to 13.59 ± 2.03 and 13.46 ± 1.64 g/dl, respectively. At 3-year and 5-year follow-up after STS in our cohort, we observed an increase from 8.98 ± 1.66 to 13.21 ± 1.95 and 13.68 ± 1.65 g/dl, respectively. The meta-analysis (for a follow-up period of 1 year) showed that the hemoglobin levels increased with 2.61 g/dl (95% CI 2.15-3.08 g/dl; p < 0.001) after TS, and with 1.67 g/dl (95% CI 1.25-2.10 g/dl; p < 0.001) after STS. CONCLUSION: We conclude that subtotal and minimally invasive splenectomy could be considered as the first line of treatment in severe HS cases, especially in children.
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Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Esferocitose Hereditária/cirurgia , Esplenectomia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esferocitose Hereditária/sangue , Adulto JovemRESUMO
Gastrointestinal stromal tumors (GISTs) are rare neoplasms, colorectal location being met in less than 5% of cases. Knowledge about this site related particularities are limited. The aim of this study is to present our experience with colorectal GISTs between 2005 and 2018 from the clinical, morphological, and immunohistochemical perspectives, with emphasis on prognostic factors. From a total of 203 gastrointestinal stromal tumors registered, 12 were colorectal (6%). The number of colonic tumors surpassed that of the rectum (9 : 3) and on the right side were registered more cases than on the left side (6/3). 9 were primary tumors and 3 were recurrences. Men and women were represented equally and the age range was between 22 and 76. Tumor dimensions varied between 0.5 and 14 cm. Microscopically, spindle cell type was dominant. Mitotic rate was variable between 1 and 115/50HPFs. Accordingly, for primary tumors progression risks were assigned (low risk: 2 cases, intermediate risk: 3 cases and high risk: 4 cases). All GISTs were CD117 and DOG1 positive. Four of the patients died of the disease.
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Neoplasias do Colo , Tumores do Estroma Gastrointestinal , Neoplasias Retais , Adulto , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit , Adulto JovemRESUMO
Introduction: Laparoscopic techniques have been increasingly adopted in the field of General Surgery in the last decades. The main disadvantages of laparoscopy are related to limited degrees of freedom of instruments and poor ergonomics, which are associated with a steep learning curve. Robotic surgery overcomes most of the technical limitations of laparoscopic surgery and has the potential to expand the indications of minimal access surgery (MAS) in procedures that are difficult to perform using laparoscopy. Methods: Patients who underwent MAS resections of gastric gastrointestinal stromal tumours (GIST) between January 2002 and October 2018 in a single Surgical Department were retrospectively analysed. Demographic data as well as the following characteristics were recorded for each patient: age, sex, symptoms, tumour location and size, type of surgical procedure, intraoperative blood loss, operative time, length of hospital stay, histopathological assessment of resection margins, and incidence of perioperative complications. Results: The mean patient age was 58 (range, 27-81 years). Most lesions were found on the great curvature (7) and in the distal stomach or antrum (7), respectively. Twenty patients underwent laparoscopic resection, while five patients had robotic resection of gastric GISTs. Surgical laparoscopic treatment consisted of antrectomy (n=4) and wedge gastrectomy (n=16). In all robotic cases a wedge gastrectomy was performed. One patient was converted to open surgery due to adhesions from previous operation. The mean operative time was 130 minutes (range, 70-210 minutes).The mean tumour size was 3.8 cm (range, 2-7 cm). There were no complications except one case that required reoperation for postoperative bleeding. There were no mortalities. Conclusion: The MAS approach of gastric GISTs is safe and effective and it is associated with low morbidity. Therefore, it should constitute the first option in patients with small tumours and favourable locations. The only limiting factor for the widespread use of MAS resections for gastric GISTs is surgeon expertise in this challenging technique.
Assuntos
Gastrectomia/métodos , Tumores do Estroma Gastrointestinal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Adulto , Idoso , Idoso de 80 Anos ou mais , Competência Clínica , Gastrectomia/normas , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non-infectious complications, with unknown mechanisms. In order to explore the role of the non-coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR-223 was overexpressed immediately and late after splenectomy, while miR-146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR-16, miR-93, miR-26a and miR-26b were overexpressed only late after splenectomy, suggesting similarities with sepsis. We also explored the non-coding (nc)RNome of circulating peripheral blood leucocytes by performing a ncRNA full genome profiling. We observed a reorganization of the ncRNoma after splenectomy, characterized by up-regulation of miRNAs and down-regulation of transcribed pyknons (T-PYKs). Pathway analysis revealed that deregulated miRNAs control pathways involved in immunity, cancer and endothelial growth. We checked the expression of the ncRNAs in 15 immune cell types from healthy donors and observed that plasma miRNAs, cellular miRNAs and T-PYKs have a cell-specific expression pattern and are abundant in different types of immune cells. These findings suggest that the ncRNAs potentially regulate the immune changes observed after splenectomy.
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RNA não Traduzido/genética , Esplenectomia , Estudos de Coortes , Regulação para Baixo/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Leucócitos/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , RNA não Traduzido/metabolismo , Reprodutibilidade dos Testes , Transcrição Gênica , Transcriptoma/genética , Regulação para Cima/genéticaRESUMO
Minimally invasive colorectal surgery showed multiple advantages in terms of morbidity, surgeons applied this approach to Hartmann reversal considering improving the reversal rate and postoperative outcome. The database from Fundeni Clinical Institute, General Surgery Department, was analyzed, selecting the laparoscopic Hartmann reversals. Nine cases were reported with a median age of 63 years, mean BMI 29 and three of them with prior open Hartmann surgery. The average operative time was 223 minutes, without any case necessitating ileostomy diversion. No anastomotic leakage was reported. The laparoscopic approach seems to be an attainable alternative in the reversal of Hartmann procedure, considering the experience of the surgical team and the patient's characteristics. Further studies are needed in order to confirm its superiority on larger case series.