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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Recidiva Local de Neoplasia , Reoperação , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Hepatectomia/métodos , PrognósticoRESUMO
BACKGROUND: Perihilar cholangiocarcinoma (PHC) is a rare malignancy that arises at the biliary confluence. Achieving a margin-negative resection (R0) is challenging given the anatomic location of tumors and remains the most important prognostic indicator of long-term survival. The objective of this study is to review the impact of intraoperative revision of positive biliary margins in PHC on oncologic outcomes. PATIENTS AND METHODS: Electronic databases were searched from inception to October 2021. Studies comparing three types of patients undergoing resection of PHC with intraoperative frozen section of the proximal and/or distal bile ducts were identified: those who were margin-negative (R0), those with an initially positive margin who had revised negative margins (R1R0), and those with a persistently positive margin with or without revision of a positive margin (R1). The primary outcome was overall survival (OS). Secondary outcomes included risk of postoperative complication. RESULTS: A total of 449 studies were screened. Ten retrospective observational studies reporting on 1955 patients were included. Patients undergoing successful revision of a positive proximal and/or distal bile duct margin (R1R0) had similar OS to those with a primary margin-negative resection (R0) [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.72-1.19, p = 0.56, I2 = 84%], and significantly better OS than patients with a positive final bile duct margin (R1) (HR 0.52, 95% CI 0.34-0.79, p = 0.002, I2 = 0%). There was no increase in the risk of postoperative complications associated with additional resection, although postoperative morbidity was inconsistently reported. CONCLUSIONS: This review supports routine intraoperative biliary margin evaluation during resection of PHC with revision if technically feasible.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/cirurgia , Secções Congeladas , Humanos , Tumor de Klatskin/patologia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Neoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC. METHODS: We reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded. RESULTS: Overall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p < 0.0001). On multivariable analysis, carbohydrate antigen (CA) 19-9 and pathologic treatment responses were predictors of RFS and OS. CONCLUSION: CS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CA-19-9 , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Estudos RetrospectivosRESUMO
Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.
Assuntos
COVID-19 , Falência Hepática Aguda , Transplante de Fígado , Adolescente , Feminino , Humanos , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Pandemias , Reação em Cadeia da Polimerase , SARS-CoV-2RESUMO
BACKGROUND: Institutions training both General Surgery (GS) residents and Hepato-Pancreatico-Biliary (HPB) fellows must strive for adequate case volumes for each trainee cohort. METHODS: Six academic years of graduating ACGME Residency and HPB Fellowship Council case logs (July 2011-June 2017) and institutional administrative faculty billing data were examined at a single high-volume center with a formal HPB Surgical Division with both GS Residency and HPB Surgery Fellowship trainees. RESULTS: During the 6-year period, 7482 operations were performed by HPB faculty (5.5 total full-time equivalent (FTE)) and included 2419 major liver, 375 major biliary, and 1591 major pancreas cases. Residents/fellows performed 1102 (50%)/1101 (50%) of all major liver operations, 165 (49.7%)/163 (50.3%) major biliary operations, and 843 (59.2%)/581 (40.8%) major pancreas operations, with significantly different case mix of pancreas for resident versus fellow, p < 0.0001. The overall relative proportion of total HPB cases performed by residents versus fellows was 53%/47%, respectively, and this was stable over time, with no significant decrease in resident exposure/cases with dedicated HPB fellowship. CONCLUSIONS: Our experience in training both GS residents and HPB fellows with a formal HPB Surgical Division suggests that a high volume HPB Division allows for more than adequate exposure for both groups of trainees.
Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Procedimentos Cirúrgicos do Sistema Digestório , Cirurgia Geral , Internato e Residência , Competência Clínica , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Cirurgia Geral/educação , HumanosRESUMO
BACKGROUND: Surgical portosystemic shunts are rare. We reviewed indications, operative details, and outcomes of patients undergoing surgical portosystemic shunt procedures. METHODS: We retrospectively reviewed clinical data of consecutive patients between 1997 and 2018 from a single institution. Clinical characteristics and outcomes were compared between two groups: patients with portomesenteric venous thrombosis (PMVT) vs those with cirrhosis. Endpoints included 30-day mortality, shunt-related complications, patency, and survival. RESULTS: There were 99 patients, 45 male and 54 female, with a mean age of 46 ± 18 years, enrolled in the study. There were 63 patients (63%) with PMVT and 36 patients (36%) with cirrhosis. Both groups had similar demographics, cardiovascular risk factors, and aneurysm extent, except for more diabetes among those with cirrhosis (p < 0.05). There were no significant differences in procedural metrics and intra-procedure complications between groups, except that patients with PMVT underwent more non-selective shunts than those with cirrhosis (63% vs. 30%, p < 0.001). There were two 30-day deaths (2%), with no difference in mortality and MAEs between groups. On univariate analysis, cholangiopathy and PMVT were associated with graft thrombosis (HR = 9.22, 95% CI 1.22-70.27) while race, smoking, cardiac comorbidity, type of operative shunt, configuration of the shunt, and use of conduit were not (p > 0.05). Patients with PMVT had significantly lower 1-, 5-, and 10-year primary (77%, 71%, and 71% vs. 97%, p = 0.009) and secondary patency (88%, 76%, and 72% vs. 96%, p = 0.027) compared with those with cirrhosis. The 1-, 5-, and 10-year survival rates were 94%, 84%, and 61% for patients with PMVT compared with 88%, 58%, and 26% for those with cirrhosis (non-adjusted HR 0.40, 95% CI 0.19-0.84, p = 0.01, age-adjusted HR 0.51, 95% CI 0.24-1.09, p = 0.08). The survival of patients with PMVT without liver disease trended higher than those with liver disease; however, when adjusted for age, the survival gap narrowed, and the difference was not statistically significant (p = 0.19), survival being lowest for those with PMVT and liver disease. CONCLUSIONS: Surgical portosystemic shunts are safe and effective for symptom relief in selected patients with portal hypertension. The odds of graft thrombosis is 9 times higher in patients with PMVT. Overall survival is similar in patients with PMVT or cirrhosis.
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Hipertensão Portal , Trombose Venosa , Adulto , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Cirúrgica , Estudos RetrospectivosRESUMO
BACKGROUND: The impact of additional resection for positive proximal bile duct margins during hepatic resection of hilar cholangiocarcinoma (HCCA) on survival and disease progression remains unclear. We asked how re-resection of positive proximal bile duct margins affected outcomes. METHODS: Patients undergoing resection between 1993-2017 were reviewed. Both frozen section and final margin status were reviewed. Overall survival was the primary outcome. RESULTS: 153 patients underwent surgical resection for HCCA. Median survival (months) for initial margin negative (M-), margin-positive to margin-negative (M+/M-) and margin-positive to margin-positive (M+/M+) was 45, 33, and 35 months respectively. Nodal metastases increased with margin positivity: 32% with M-, 49% with M+/M- and 63% with M+/M+ (p = 0.016). Local/regional progression more frequently occurred in M+/M- (27.3%) and M+/M+ (33.3%) patients (M+/M- vs. M-: p = 0.41, M+/M+ vs. M-: p = 0.27). Patients receiving postoperative chemotherapy were 33% M-, 46% M+/M- and 63% in M+/M+. Postoperative radiation was used in 13% of M-, 31% of M+/M- and 63% of M+/M+. Most frequent initial recurrences were within the liver and hepaticojejunostomy site. CONCLUSION: Competing risk for systemic disease based on primary characteristics of HCCA outweighs the impact of re-resection to achieve R0 status. Improved survival will likely depend on future regional and systemic therapy.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia/efeitos adversos , Humanos , Tumor de Klatskin/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. STUDY DESIGN: Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. RESULTS: Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001). CONCLUSIONS: Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.
Assuntos
Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Complexas Mistas/cirurgia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Complexas Mistas/mortalidade , Neoplasias Complexas Mistas/patologia , Estudos Retrospectivos , Carga TumoralRESUMO
Since the establishment of the Milan criteria, liver transplantation (LT) has been identified as an optimal therapy for selected patients with early stage, unresectable hepatocellular carcinoma (HCC) complicating cirrhosis, although a major limitation is the critical shortage of available deceased donor liver allografts. This review focuses on the evolution of liver allocation for HCC in the United States and what the most recent revisions to the allocation system mean for patients with HCC.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Obtenção de Tecidos e Órgãos , Listas de Espera/mortalidade , Humanos , Doadores Vivos , Política OrganizacionalRESUMO
BACKGROUND: Spleen preservation during distal pancreatectomy (SpDP) can be accomplished by a variety of surgical approaches, but the impact on spleen function is unknown. This study aimed to compare spleen volume, function and complications between patients who underwent vessel sparing (VSDP) vs. vessel ligating (Warshaw, WDP) SpDP. METHODS: All patients who underwent SpDP at the Toronto General Hospital from 2006 to 2015 were included. Primary outcomes were pre- and post-operative spleen volumes and contrast enhancement on CT, hematologic parameters, and spleen-related complications. RESULTS: 82 patients underwent SpDP with median follow up of 20.4 months. Splenic volumes were able to be calculated on 44 patients (VSDP n = 8, WDP n = 36). There was no difference between WDP and VSDP in operative duration, blood loss, hospital length of stay, or Clavien-Dindo ≥3 complication rate. Spleen volumes did not differ from baseline in either group. On postoperative imaging more WDP patients had areas of splenic hypoperfusion (p = 0.032). These differences resolved by 3 months after surgery, there were no instances of long term infectious or bleeding complications related to poor splenic function or gastric varices. CONCLUSION: Both WDP and VSDP achieve splenic preservation. Neither technique resulted in clinically apparent spleen related complications. There is no difference in splenic volume and function in the short/long term.
Assuntos
Varizes Esofágicas e Gástricas , Laparoscopia , Neoplasias Pancreáticas , Humanos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Baço/diagnóstico por imagem , Baço/cirurgiaRESUMO
BACKGROUND: Resection margin status has been recognized as an independent prognostic factor on overall survival in pancreatic cancer patients undergoing surgical resection. However, its impact after neoadjuvant treatment remains uncertain. METHODS: We analyzed 305 patients with resectable or borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatoduodenectomy at 3 tertiary referral centers between 2010 and 2017. Positive resection margin was defined as 1 or more cancer cells at any margin. Overall survival was measured from the date of surgery until death or last follow-up. RESULTS: One hundred and seventy-eight patients received neoadjuvant chemotherapy and 127 received neoadjuvant chemoradiotherapy. The median overall survival was 29.8 months. The 1-, 3-, and 5-year overall survival rates were 79.2%, 44.0%, and 23.5%, respectively. Negative margin was achieved in 275 (90.2%) patients. Negative margin resection patients had a significantly longer overall survival than positive resection margin patients (31.3 vs 16.3 months, P < .001). In univariate analyses, overall survival was associated with age, margin status, histologic grade, ypT, number of positive lymph nodes, perineural invasion, treatment effect, postoperative carbohydrate antigen 19-9, and adjuvant therapy. Positive margin resection, poorly differentiated carcinoma, treatment effect score of 3, postoperative carbohydrate antigen 19-9 of 37 U/mL or higher, and lack of adjuvant therapy were predictive of poor overall survival in multivariate Cox regression analysis. CONCLUSION: Margin status was an independent predictor of overall survival in patients treated with neoadjuvant therapy and pancreatoduodenectomy, supporting the use of a negative margin resection as a surrogate of adequate oncological resection in this setting. Our findings may also have significant implications for patient stratification in future randomized trials.
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Margens de Excisão , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Pancreaticoduodenectomia , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate technical success, efficacy and safety of portomesenteric venous (PMV) intervention for PMV stenosis or occlusion following nontransplant hepatobiliary or pancreatic (HPB) surgery. MATERIALS AND METHODS: A retrospective review identified 42 patients (mean age 60 y) with PMV stenosis (n = 33; 79%) or occlusion (n = 9; 21%) who underwent attempted PMV intervention following HPB surgery between June 1, 2011, and April 1, 2018. Main outcomes were technical success, primary patency rates, and complications. Technical success was compared by venous pathology and primary PMV patency based on anticoagulation status after the procedure using Fisher exact test. Rates of primary patency by stent group were estimated using Kaplan-Meier method. RESULTS: Technical success was 91% (n = 38/42) and significantly higher in patients with stenosis (n = 33/33; 100%) vs occlusion (n = 5/9; 56%) (P = .001). Primary presenting symptom resolved in 28 (87%) patients, including 6 (100%) patients with gastrointestinal bleeding. At mean imaging follow-up of 8.6 months ± 8.8, primary stent patency was 76%. There was no significant difference in primary stent patency based on anticoagulation status after the procedure (P = .48). There were 2 (4.8%) periprocedural complications. CONCLUSIONS: Portomesenteric venoplasty and stent placement following nontransplant HPB surgery is safe with a high rate of technical success if performed before chronic occlusion.
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Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Endovasculares , Isquemia Mesentérica/terapia , Oclusão Vascular Mesentérica/terapia , Veias Mesentéricas , Veia Porta , Trombectomia , Trombose Venosa/terapia , Adulto , Idoso , Anticoagulantes/administração & dosagem , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Constrição Patológica , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Hepatectomia/efeitos adversos , Humanos , Masculino , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/etiologia , Isquemia Mesentérica/fisiopatologia , Oclusão Vascular Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/etiologia , Oclusão Vascular Mesentérica/fisiopatologia , Veias Mesentéricas/diagnóstico por imagem , Veias Mesentéricas/fisiopatologia , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Stents , Trombectomia/efeitos adversos , Trombectomia/instrumentação , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Trombose Venosa/fisiopatologia , Adulto JovemRESUMO
Pancreatic surgery with en bloc venous resection and reconstruction is becoming increasingly common in the current era of expanding neoadjuvant oncologic therapies and advanced surgical techniques for patients with more anatomically complex tumors. However, patients who have alterations in their venous outflow are at increased risk for postoperative portomesenteric venous stenosis and/or thrombosis. Cross-sectional imaging for postoperative surveillance, including multiphase CT or MRI, is critical for recognizing portomesenteric venous complications and thus implementing early intervention and preventing complications related to portomesenteric venous hypertension. Hypertension-related complications include ascites, variceal or gastrointestinal bleeding, postprandial abdominal pain, intestinal edema, protein-losing enteropathy, malabsorptive diarrhea, and splenomegaly. Percutaneous transhepatic, transsplenic, and transjugular portomesenteric interventions, including venoplasty, stent placement, and thrombectomy or thrombolysis, are safe and effective options for restoring patency to the portomesenteric venous system. Preintervention CT or MRI and diagnostic catheter venography are important for procedural planning, while postintervention CT or MRI surveillance is critical for detecting recurrent stenosis or thrombosis, or de novo portomesenteric venous disease. Online supplemental material is available for this article. ©RSNA, 2020.
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Veias Mesentéricas/cirurgia , Neoplasias Pancreáticas/cirurgia , Sistema Porta/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Vasculares , HumanosRESUMO
Laparoscopic liver surgery for secondary liver cancer is increasing. The most common indications are colorectal cancer liver metastases followed by adenocarcinoma metastases from other solid organs, such as breast, pancreatic neuroendocrine, and other gastrointestinal tract cancers. This article provides a comprehensive review of crucial concepts when managing secondary liver cancer minimally invasively, a summary of the up-to-date literature, and a discussion of the development of the application of this technique over time.
Assuntos
Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , HumanosRESUMO
BACKGROUND: /Objective. To determine the outcomes of a non-operative management approach for sporadic, small, non-functional pancreatic neuroendocrine tumours. METHODS: A retrospective chart review of patients with non-functional pancreatic neuroendocrine tumours initially managed non-operatively at a single institution was performed. Patients were identified through a search of radiologic reports, and individuals with ≥2 cross-sectional imaging studies performed >6 months apart from Jan. 1, 2000 to Dec. 31, 2013 were included. Data on tumour size, radiologic characteristics at diagnosis, interval radiologic growth, and surgical outcomes were recorded. RESULTS: Over the thirteen-year study period, 95 patients met inclusion criteria and were followed radiologically for a median of 36 months (18-69 months). Median initial tumour size on first imaging was 14.0â¯mm (IQR 10-19â¯mm). Median overall tumour growth rate was 0.03â¯mm/month (IQR: 0.00-0.14â¯mm/month). There was no significant relationship between initial tumour size and growth rate for tumours ≤ 2â¯cm or for lesions between 2 and 4â¯cm. Thirteen (14%) patients initially managed non-operatively underwent resection during the follow-up period. Reasons for surgery included interval tumour growth, patient anxiety or preference, or diagnostic uncertainty. Median time to surgery was 14 months (IQR 8-19 months). No patients progressed beyond resectability or developed metastatic disease during the observation period. CONCLUSION: For patients with sporadic, small, non-functional pancreatic neuroendocrine tumours, radiologic surveillance appears to be a safe initial approach to management.
Assuntos
Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The Hippo pathway effector, Yes-associated protein (YAP), is a transcriptional coactivator implicated in cholangiocarcinoma (CCA) pathogenesis. YAP is known to be regulated by a serine/threonine kinase relay module (MST1/2-LATS1/2) culminating in phosphorylation of YAP at Serine 127 and cytoplasmic sequestration. However, YAP also undergoes tyrosine phosphorylation, and the role of tyrosine phosphorylation in YAP regulation remains unclear. Herein, YAP regulation by tyrosine phosphorylation was examined in human and mouse CCA cells, as well as patient-derived xenograft (PDX) models. YAP was phosphorylated on tyrosine 357 (Y357) in CCA cell lines and PDX models. SRC family kinase (SFK) inhibition with dasatinib resulted in loss of YAPY357 phosphorylation, promoted its translocation from the nucleus to the cytoplasm, and reduced YAP target gene expression, including cell lines expressing a LATS1/2-resistant YAP mutant in which all serine residues were mutated to alanine. Consistent with these observations, precluding YAPY357 phosphorylation by site-directed mutagenesis (YAPY357F) excluded YAP from the nucleus. Targeted siRNA experiments identified LCK as the SFK that most potently mediated YAPY357 phosphorylation. Likewise, inducible CRISPR/Cas9-targeted LCK deletion decreased YAPY357 phosphorylation and its nuclear localization. The importance of LCK in CCA biology was demonstrated by clinical observations suggesting LCK expression levels were associated with early tumor recurrence following resection of CCA. Finally, dasatinib displayed therapeutic efficacy in PDX models. Mol Cancer Res; 16(10); 1556-67. ©2018 AACR.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Colangiocarcinoma/tratamento farmacológico , Dasatinibe/administração & dosagem , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Citoplasma/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição , Tirosina/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAP , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/genéticaRESUMO
BACKGROUND: Despite guidelines recommending restrictive red blood cell transfusion (RBCT) strategies, perioperative transfusion practices still vary significantly. To understand the underlying mechanisms that lead to gaps in practice, we sought to assess the attitudes of surgeons regarding the perioperative management of anemia and use of RBCT in patients having gastrointestinal surgery. METHODS: We conducted a self-administered Web-based survey of general surgery staff and residents, in a network of eight academic institutions at the University of Toronto. We developed a questionnaire using a systematic approach of items generation and reduction. We tested face and content validity and test-retest reliability. We administered the survey via emails, with planned reminders. RESULTS: Total response rate was 48.1 % (62/125). Half (51.0 %) of respondents stated that they were unlikely to conduct a preoperative anemia work-up. About 54.0 % reported ordering preoperative oral iron supplementation for anemia. Most respondents indicated using a 70 g/L hemoglobin trigger (92.0 %) for transfusion. Factors increasing thresholds above 70 g/L included cardiac comorbidity (58.0 %), acute cardiac disease (94.0 %), symptomatic anemia (68.0 %), and suspected bleeding (58.0 %). With those factors, the transfusion threshold often increased above 90 g/L. Respondents perceived RBCTs to increase the postoperative morbidity (62 %), but not to impact the mortality (48 %) and cancer recurrence (52 %). Institutional protocols (68.0 %), blood conservation clinics (44.0 %), and clinical practice guidelines (84.0 %) were believed to encourage restrictive use of RBCTs. CONCLUSION: Self-reported perioperative transfusion practices for GI surgery are heterogeneous. Few respondents investigated preoperative anemia. Stated use of RBCT indications varied from recommendations in published guidelines for patients with symptomatic anemia. Establishing team consensus and implementing local blood management guidelines appear necessary to improve uptake of evidence-based recommendations.
Assuntos
Anemia/terapia , Procedimentos Cirúrgicos do Sistema Digestório , Transfusão de Eritrócitos , Cirurgia Geral , Padrões de Prática Médica , Anemia/sangue , Atitude do Pessoal de Saúde , Hemoglobinas/metabolismo , Humanos , Internato e Residência , Corpo Clínico Hospitalar , Período Perioperatório , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Perioperative anemia is common, yet detrimental, in surgical patients. However, red blood cell transfusions (RBCTs) used to treat anemia are associated with significant postoperative risks and worse oncologic outcomes. Perioperative iron has been suggested to mitigate perioperative anemia. This meta-analysis examined the impact of perioperative iron compared to no intervention on the need for RBCT in gastrointestinal surgery. We systematically searched Medline, Embase, Web of Science, Cochrane Central, and Scopus to identify relevant randomized controlled trials (RCTs) and nonrandomized studies (NRSs). We excluded studies investigating autologous RBCT or erythropoietin. Two independent reviewers selected the studies, extracted data, and assessed the risk of bias using the Cochrane tool and Newcastle-Ottawa scale. Primary outcomes were proportion of patients getting allogeneic RBCT and number of transfused patient. Secondary outcomes were hemoglobin change, 30-day postoperative morbidity and mortality, length of stay, and oncologic outcomes. A meta-analysis using random effects models was performed. The review was registered in PROSPERO (CRD42013004805). From 883 citations, we included 2 RCTs and 2 NRSs (n = 325 patients), all pertaining to colorectal cancer surgery. Randomized controlled trials were at high risk for bias and underpowered. One RCT and 1 NRS using preoperative oral iron reported a decreased proportion of patients needing RBCT. One RCT on preoperative intravenous iron and 1 NRS on postoperative PO iron did not observe a difference. Only 1 study revealed a difference in number of transfused patients. One RCT reported significantly increased postintervention hemoglobin. Among 3 studies reporting length of stay, none observed a difference. Other secondary outcomes were not reported. Meta-analysis revealed a trend toward fewer patients requiring RBCT with iron supplementation (risk ratio, 0.66 [0.42, 1.02]), but no benefit on the number of RBCT per patient (weighted mean difference, -0.91 [-1.61, -0.18]). Although preliminary evidence suggests that it may be a promising strategy, there is insufficient evidence to support the routine use of perioperative iron to decrease the need for RBCT in colorectal cancer surgery. Well-designed RCTs focusing on the need for RBCT and including long-term outcomes are warranted.