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1.
Hepatology ; 77(5): 1527-1539, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36646670

RESUMO

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Síndrome Metabólica , Humanos , Hepatectomia/métodos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
2.
Ann Surg ; 278(5): e1041-e1047, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36994755

RESUMO

OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Falência Hepática , Neoplasias Hepáticas , Síndrome Metabólica , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Ascite/complicações , Ascite/cirurgia , Síndrome Metabólica/complicações , Síndrome Metabólica/cirurgia , Hepatectomia , Pontuação de Propensão , Falência Hepática/cirurgia , Tempo de Internação , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia
3.
Ann Surg Oncol ; 30(7): 4417-4428, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37020094

RESUMO

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.


Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Fluoruracila , Leucovorina/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Paclitaxel , Estudos Multicêntricos como Assunto
4.
Am J Physiol Lung Cell Mol Physiol ; 317(1): L141-L154, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042083

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia that mainly affects the elderly. Several reports have demonstrated that aging is involved in the underlying pathogenic mechanisms of IPF. α-Klotho (KL) has been well characterized as an "age-suppressing" hormone and can provide protection against cellular senescence and oxidative stress. In this study, KL levels were assessed in human plasma and primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF-FB) and in lung tissue from mice exposed to bleomycin, which showed significant downregulation when compared with controls. Conversely, transgenic mice overexpressing KL were protected against bleomycin-induced lung fibrosis. Treatment of human lung fibroblasts with recombinant KL alone was not sufficient to inhibit transforming growth factor-ß (TGF-ß)-induced collagen deposition and inflammatory marker expression. Interestingly, fibroblast growth factor 23 (FGF23), a proinflammatory circulating protein for which KL is a coreceptor, was upregulated in IPF and bleomycin lungs. To our surprise, FGF23 and KL coadministration led to a significant reduction in fibrosis and inflammation in IPF-FB; FGF23 administration alone or in combination with KL stimulated KL upregulation. We conclude that in IPF downregulation of KL may contribute to fibrosis and inflammation and FGF23 may act as a compensatory antifibrotic and anti-inflammatory mediator via inhibition of TGF-ß signaling. Upon restoration of KL levels, the combination of FGF23 and KL leads to resolution of inflammation and fibrosis. Altogether, these data provide novel insight into the FGF23/KL axis and its antifibrotic/anti-inflammatory properties, which opens new avenues for potential therapies in aging-related diseases like IPF.


Assuntos
Lesão Pulmonar Aguda/patologia , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica , Glucuronidase/genética , Fibrose Pulmonar Idiopática/genética , Transdução de Sinais/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/imunologia , Idoso , Animais , Bleomicina/administração & dosagem , Estudos de Casos e Controles , Colágeno/antagonistas & inibidores , Colágeno/genética , Colágeno/metabolismo , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Glucuronidase/metabolismo , Glucuronidase/farmacologia , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Testes de Função Renal , Proteínas Klotho , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Cultura Primária de Células , Testes de Função Respiratória , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/farmacologia
5.
J Surg Oncol ; 120(2): 262-269, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31093997

RESUMO

BACKGROUND AND OBJECTIVES: Unlike pancreatic head tumors, little is known about the biological significance of radiographic vessel involvement with pancreatic body/tail adenocarcinoma. We hypothesized radiographic splenic vessel involvement may be an adverse prognostic factor. METHODS: All distal pancreatectomies performed for resectable pancreatic adenocarcinoma between 2000 and 2016 were reviewed and clinicopatholgic data were collected, retrospectively. Preoperative computed tomography imaging was re-reviewed and splenic vessel involvement was graded as none, abutment, encasement, or occlusion. RESULTS: Among a total of 71 patients, splenic artery or vein encasement/occlusion was present in 41% (29 of 71) of patients, each. There were no significant differences in tumor size or grade, margin positivity, and perineural or lymphovascular invasion. However, splenic artery encasement/occlusion (P = 0.001) and splenic vein encasement/occlusion (P = 0.038) both correlated with lymph node positivity. Splenic artery encasement was associated with a reduced median overall survival (20 vs 30 months, P = 0.033). Multivariate analysis also showed that splenic artery encasement was an independent risk factor of worse survival (hazard ratio, 2.246; 95% confidence interval, 1.118-4.513; P = 0.023). CONCLUSION: Patients with cancer of the body or tail of the pancreas presenting with radiographic encasement of the splenic artery, but not the splenic vein, have a poorer prognosis and perhaps should be considered for neoadjuvant therapy before an attempt at curative resection.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Baço/irrigação sanguínea , Idoso , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Masculino , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Baço/diagnóstico por imagem , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Eur Respir J ; 52(1)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29748308

RESUMO

Circulating levels of fibroblast growth factor (FGF)23 are associated with systemic inflammation and increased mortality in chronic kidney disease. α-Klotho, a co-receptor for FGF23, is downregulated in chronic obstructive pulmonary disease (COPD). However, whether FGF23 and Klotho-mediated FGF receptor (FGFR) activation delineates a pathophysiological mechanism in COPD remains unclear. We hypothesised that FGF23 can potentiate airway inflammation via Klotho-independent FGFR4 activation.FGF23 and its effect were studied using plasma and transbronchial biopsies from COPD and control patients, and primary human bronchial epithelial cells isolated from COPD patients as well as a murine COPD model.Plasma FGF23 levels were significantly elevated in COPD patients. Exposure of airway epithelial cells to cigarette smoke and FGF23 led to a significant increase in interleukin-1ß release via Klotho-independent FGFR4-mediated activation of phospholipase Cγ/nuclear factor of activated T-cells signalling. In addition, Klotho knockout mice developed COPD and showed airway inflammation and elevated FGFR4 expression in their lungs, whereas overexpression of Klotho led to an attenuation of airway inflammation.Cigarette smoke induces airway inflammation by downregulation of Klotho and activation of FGFR4 in the airway epithelium in COPD. Inhibition of FGF23 or FGFR4 might serve as a novel anti-inflammatory strategy in COPD.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/metabolismo , Pulmão/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Adulto , Idoso , Animais , Células Epiteliais/metabolismo , Feminino , Fator de Crescimento de Fibroblastos 23 , Glucuronidase/genética , Humanos , Inflamação/patologia , Proteínas Klotho , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumaça/efeitos adversos
8.
J Surg Oncol ; 117(8): 1655-1663, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29761510

RESUMO

BACKGROUND AND OBJECTIVES: Although race and socioeconomic status have been shown to affect outcomes in pancreatic ductal adenocarcinoma (PDAC), the impact of rural residence on the delivery of adjuvant therapy (AT) has not been studied. METHODS: Patients with resected PDAC were identified using the National Cancer Database (NCDB). Individuals were classified as living in a metro area, urban/rural adjacent to a metro area (URA), and urban/rural remote (URR) area. Multivariate logistic regression was used to assess geographic inhabitance as a predictor of receiving AT. RESULTS: A total of 32 521 individuals who underwent pancreatectomy for PDAC were identified. Univariate analysis demonstrated individuals in URR areas were less likely to receive adjuvant chemotherapy (ACT) than those living in URA or metro areas (55.3% vs 55.6% vs 58.8%, P = 0.011). However on multivariate analysis URR inhabitance was no longer a predictor of ACT (OR = 0.911 P = 0.125) or ART (OR = 0.953 P = 0.462). Cox proportional hazard modeling demonstrated URR inhabitance remained independently associated with poor OS (HR 1.076; 95% CI [1.008, 1.149], P < 0.029). CONCLUSIONS: URR inhabitance does not impact access to AT, however it is independently associated with a decreased OS. Attention must be focused on optimizing oncologic care to patients with disparate access to healthcare.


Assuntos
Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante/estatística & dados numéricos , Pancreatectomia , Radioterapia Adjuvante/estatística & dados numéricos , População Rural , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Fatores Etários , Idoso , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Bases de Dados Factuais , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde , Humanos , Masculino , Margens de Excisão , Medicaid , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Grupos Raciais , Tempo para o Tratamento , Estados Unidos/epidemiologia
9.
Gastrointest Endosc ; 82(3): 460-8.e2, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25851162

RESUMO

BACKGROUND: Data on endoscopic stenting of malignant gastric outlet obstruction (GOO) are based on studies predominantly involving patients with pancreatic adenocarcinoma. OBJECTIVE: To compare survival and clinical outcome after stent placement for GOO due to pancreatic cancer compared with nonpancreatic cancer. DESIGN: Retrospective study. SETTING: Single tertiary hospital. PATIENTS: A total of 292 patients with malignant GOO. INTERVENTION: Stent placement. MAIN OUTCOME MEASUREMENTS: Post-stent placement survival and clinical outcome. RESULTS: In 196 patients with pancreatic cancer and 96 with nonpancreatic cancer, median post-stent placement survival was similar (2.7 months in pancreatic cancer vs 2.4 months in nonpancreatic cancer). Overall survival was shorter in patients with pancreatic cancer (13.7 vs 17.1 months; P = .004). Clinical success rates at 2 months (71% vs 91%) and reintervention rates (30% vs 23%) were comparable. Post-stent placement chemotherapy and the absence of distant metastasis were associated with better post-stent placement survival in both groups (pancreatic cancer: chemotherapy vs no chemotherapy, 5.4 vs 1.5 months, P < .0001; metastasis vs no metastasis, 1.8 vs 4.6, P = .005; nonpancreatic cancer: chemotherapy vs no chemotherapy, 9.2 vs 1.8, P = .001; metastasis vs no metastasis, 2.1 vs 6.1, P = .009). LIMITATIONS: Retrospective study. CONCLUSIONS: In this large series of patients undergoing stent placement for malignant GOO in North America, we observed no difference in post-stent placement survival despite better overall survival in patients with nonpancreatic cancer. GOO is a marker for poor survival in malignancy, regardless of the type. Chemotherapy and the absence of distant metastasis were associated with better post-stent placement survival in both groups.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Neoplasias Duodenais/cirurgia , Duodeno/cirurgia , Obstrução da Saída Gástrica/cirurgia , Neoplasias Pancreáticas/cirurgia , Stents , Neoplasias Gástricas/cirurgia , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Idoso , Ampola Hepatopancreática , Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/complicações , Colangiocarcinoma/complicações , Estudos de Coortes , Neoplasias do Ducto Colédoco/complicações , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Duodenais/complicações , Endoscopia do Sistema Digestório , Feminino , Obstrução da Saída Gástrica/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Taxa de Sobrevida , Resultado do Tratamento
10.
Ann Surg Oncol ; 21(6): 1927-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24370905

RESUMO

BACKGROUND: En bloc resection of the superior mesenteric vein (SMV), portal vein (PV), and/or splenic vein (SV) with concomitant venous reconstruction is required in 11-65 % of cases of locally advanced pancreatic cancer.1 Early retropancreatic dissection of the superior mesenteric artery (SMA) from behind the pancreatic head utilizing an 'artery first' approach has been reported to be an efficient and safe approach to pancreaticoduodenectomy when SMA involvement is suspected.2 Additionally, this technique has been shown to reduce blood loss and result in shorter PV clamp times.3 While there are multiple variations to 'artery first' resection,4 this video will illustrate the critical steps of using the 'posterior approach' in patients with locally advanced pancreatic cancer. This approach has the benefit of early identification of a replaced right hepatic artery, but may be difficult in obese patients or those with extensive peripancreatic inflammation. These difficulties may be overcome by utilizing an 'inferior supracolic (anterior) approach', but this necessitates early division of the pancreatic neck and stomach.5 METHODS: Select video clips were compiled from several pancreatoduodenectomies to demonstrate this technique. A variety of bipolar devices were utilized for dissection depending on surgeon preference. All patients were diagnosed with locally advanced pancreatic cancer by Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology (AHPBA/SSO) consensus criteria, confirmed by biopsy, and completed neoadjuvant chemotherapy. Patients were restaged by pancreas protocol computed tomography scan at the end of chemotherapy and offered local resection if the tumor did not progress and they were medically fit. No Institutional Review Board approval was required. RESULTS: The operation begins by dividing the attachment of the transverse mesocolon to the right perinephric area and extending this down to the white line of Toldt, followed by a wide Kocher maneuver. The lateral attachments to the pancreatic head are then divided, thereby exposing the left renal vein. The lesser sac is entered directly over the uncinate, allowing for a full visceral rotation of the pancreatic head, and further facilitating exposure of the left renal vein. In the setting of malignancy, the SMA may now be palpated posterior to the pancreatic head and/or neck to confirm it is free of tumor. If tumor is invading the SMA, the pancreaticoduodenectomy is aborted prior to performing any gastrointestinal or pancreatic transections. If the SMA is free, the dissection is then carried on to the inferior aspect of the pancreatic neck. Here the SMV (jejunal and ileal branches), middle colic vein, and the gastroepiploic vein are identified and the latter is ligated and transected. Following this, dissection of the portal structures (hepatic arteries, gastroduodenal artery, common bile duct, and PV) is performed. The jejunum is then divided, the ligament of Treitz is taken down, and the jejunum is then mobilized to the patient's right side. This allows for clear visualization of the pancreatic head/uncinate/SMV relationship. At this point, proximal and distal control of the PV, SMV, and SV should be obtained using vessel loops or umbilical tape. The dissection then proceeds laterally along the SMA border (posterior to the pancreatic head). This is often facilitated by use of a bipolar sealing device due to a rich lymphovascular network. Once the lateral border of the SMA is clearly exposed, dissection along its longitudinal axis is performed utilizing the jejunum for traction. Following this dissection, larger vessels such as the inferior pancreaticoduodenal artery can be more readily identified and ligated to fully mobilize the pancreatic head. After the head is completely separated from the SMA, the neck is divided. This leaves the specimen attached solely by the PV and SMV, which greatly facilitates venous resection and reconstruction when necessary. CONCLUSION: The 'artery first' approach has been shown to be safe and feasible in pancreatic resections. This technique should be considered whenever tumor is thought to involve the SMV and/or PVs as a means to facilitate safe venous resection and reconstruction while preserving sound oncologic principles.


Assuntos
Dissecação/métodos , Artéria Mesentérica Superior/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Humanos
11.
Ann Surg Oncol ; 21(5): 1530-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24473642

RESUMO

BACKGROUND: The optimum approach to neoadjuvant therapy for patients with borderline resectable pancreatic cancer is undefined. Herein we report the outcomes of an extended neoadjuvant chemotherapy regimen in patients presenting with borderline resectable adenocarcinoma of the pancreatic head. METHODS: Patients identified as having borderline resectable pancreatic head cancer by American Hepato-Pancreato-Biliary Association/Society of Surgical Oncology consensus criteria from 2008 to 2012 were tracked in a prospectively maintained registry. Included patients were initiated on a 24-week course of neoadjuvant chemotherapy. Medically fit patients who completed neoadjuvant treatment without radiographic progression were offered resection with curative intent. Clinicopathologic variables and surgical outcomes were collected retrospectively and analyzed. RESULTS: Sixty-four patients with borderline resectable pancreatic cancer started neoadjuvant therapy. Thirty-nine (61 %) met resection criteria and underwent operative exploration with curative intent, and 31 (48 %) were resected. Of the resected patients, 18 (58 %) had positive lymph nodes, 15 (48 %) required en-bloc venous resection, 27 (87 %) had a R0 resection, and 3 (10 %) had a complete pathologic response. There were no postoperative deaths at 90 days, 16 % of patients had a severe complication, and the 30-day readmission rate was 10 %. The median overall survival of all 64 patients was 23.6 months, whereas that of unresectable patients was 15.4 months. Twenty-five of the resected patients (81 %) are still alive at a median follow-up of 21.6 months. CONCLUSIONS: Extended neoadjuvant chemotherapy is well tolerated by patients with borderline resectable pancreatic head adenocarcinoma, selects a subset of patients for curative surgery with low perioperative morbidity, and is associated with favorable survival.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Período Pós-Operatório , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
12.
J Surg Res ; 189(1): 57-67, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24650457

RESUMO

BACKGROUND: Radio frequency ablation (RFA) and hepatic resection (HR) provide similar survival for early stage hepatocellular carcinoma (ES-HCC). Although RFA has a higher recurrence rate, HR is associated with an increased risk of complications and death. When multiple treatments are available, patients should be enabled to direct their preferred therapy. Yet there is lack of knowledge on patients' preferences for the treatment of ES-HCC. The objective of this study was to assess treatment preferences between HR and RFA for ES-HCC. METHODS: A cohort of 75 cirrhotic adults was educated about the natural history of HCC, treatment options, and the risks and the benefits of HR and RFA. Probability trade-off interviews were used to elicit participants' preferences between the two treatments and strength of their decisions. RESULTS: RFA was preferred by 70% of participants (P = 0.001) who identified the risk of perioperative morbidity and mortality of HR as the main reasons for their decision. Participants changed their minds if HR could provide better 5 (≥15%) and 3-y disease-free survival (≥10%) when compared with RFA. Their preference also changed when RFA had a median ≥8% risk for complications, ≥5% for mortality, ≥8% for nonradical therapy, and ≥5% for tumor seeding. CONCLUSIONS: Informed cirrhotic patients prefer RFA for the treatment of ES-HCC. Participants who preferred RFA were more concerned about the risks of perioperative morbidity and mortality of HR than long-term cancer outcomes. Patients' values and attitudes toward risks and benefits for the treatment of ES-HCC should be explicitly elicited and included in multidisciplinary treatment decisions.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Preferência do Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Tomada de Decisões , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Adulto Jovem
13.
Am J Surg ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38641448

RESUMO

BACKGROUND: Pancreaticoduodenectomy has been the standard of care for managing duodenal neoplasms, but recent studies show similar overall and disease-specific survival after pancreas-preserving duodenectomy (PPrD) with potentially less morbidity. METHODS: Retrospective cohort of all adult (age >18) patients who underwent PPrD with curative intent of a neoplasm in or invading into the duodenum at our institution from 2011 to 2022 (n â€‹= â€‹29), excluding tumors involving the Ampulla of Vater or the pancreas. Statistical analyses were performed using STATA. RESULTS: R0 resection was achieved in 93 â€‹% patients. Ten (34.4 â€‹%) experienced postoperative complications (13.7 â€‹% within Clavien-Dindo III-V). PPrD patients had lower rates of pancreatic leak, delayed gastric emptying, and deep surgical site infection. CONCLUSIONS: In this case series, we demonstrate PPrD is safe and effective, with a high rate of complete resection and lower complication rate than that seen in pancreaticoduodenectomy.

14.
JHEP Rep ; 6(7): 101075, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961853

RESUMO

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

15.
Surg Endosc ; 25(8): 2516-21, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21359898

RESUMO

BACKGROUND: This study sought to know the opinions of general surgeons registered in the state of Connecticut about their use of laparoscopic lysis of adhesions (LLA) to manage adhesive small bowel obstruction (SBO) compared with open lysis of adhesions (OLA) in terms of safety, contraindications, and outcomes. METHODS: A questionnaire was designed to gather the opinions of general surgeons registered in Connecticut on this topic. The questionnaire was administered electronically and through the mail. RESULTS: Of the 205 general surgeons to whom the questionnaire was sent, 87 completed it (42% response). The respondents were evenly distributed throughout Connecticut. Of these respondents, 9% were university teaching hospital faculty, 55% were community teaching hospital based, and 36% were community nonteaching hospital based. The answers to the questions were expressed as percentages and differences between groups tested using Fisher's exact test, with the significance level set at a P value less than 0.05. According to their self-reports, 60% of the respondents used LLA in their practice, with 38% of this group using LLA for less than 15% of their adhesive SBO cases. Compared with surgeons out of training less than 15 years, a greater number of surgeons out of training more than 15 years considered LLA to be safer (P = 0.03) and to have better outcomes (P = 0.04) than OLA. More surgeons in academic/teaching settings considered LLA to be safe than did surgeons in nonacademic/nonteaching settings (P = 0.04), and more members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)/Society of Laparoendoscopic Surgeons (SLS) considered LLA to be safe than nonmembers (P = 0.001). CONCLUSIONS: Many surgeons do not perform LLA for reasons that differ from those in the surgical literature, which supports LLA. Surgeons recently trained or with membership in minimally invasive surgery (MIS) societies are more likely to use LLA. These data suggest that recent training and interest or membership in MIS associations influence surgeons' choice for LLA. This survey demonstrated that an opportunity exists to improve patient outcomes with education about the merits of LLA in the state of Connecticut.


Assuntos
Obstrução Intestinal/cirurgia , Laparoscopia , Laparotomia , Padrões de Prática Médica , Connecticut , Feminino , Humanos , Enteropatias/complicações , Enteropatias/cirurgia , Obstrução Intestinal/etiologia , Intestino Delgado , Masculino , Inquéritos e Questionários , Aderências Teciduais/complicações , Aderências Teciduais/cirurgia
16.
Am Surg ; 76(7): 687-91, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20698371

RESUMO

We compared patients with small bowel obstruction (SBO) admitted through the emergency department to the surgical service (SS) with those admitted to the medical service (MS) with respect to outcomes and healthcare cost. We conducted a retrospective analysis of our SBO database comparing 482 patients admitted to SS and 153 patients admitted to MS at a single institution over a 5-year period (January 2003 to December 2007). Study outcomes included length of hospital stay (LOS), time to surgery (TTS), hospital charges, incidence of bowel resection, and mortality. Both groups were comparable for age, gender, and race. The SS group had a shorter LOS (6.1 vs. 7.5 days; P = 0.01), less hospital charges ($29,549 vs. $35,789; P = 0.06), shorter TTS (log rank comparison; P = 0.006), and less mortality (eight [1.66%] vs. six [3.92]; P = 0.11). The SS group had more bowel resections (13.1 vs. 5.2%; P = 0.007). Coronary artery disease (CAD), acute renal failure (ARF), admission to SS, and female gender were significant predictors of bowel resection. CAD and ARF were significant predictors of mortality. Two hundred forty-four patients required operative intervention (surgery operative subgroup [SOS] 210 [43.6%], medicine operative subgroup [MOS] 34 [22.2%]). SOS and MOS were comparable for gender and race. SOS had shorter LOS (9.1 vs. 12.3 days; P = 0.02), less hospital charges ($46,258 vs. $62,778, P = 0.05), and less mortality (eight [3.81%] vs. four [11.76%]; P = 0.07). Bowel resection was comparable (SOS 30% vs. MOS 23%; P = 0.44). CAD and congestive heart failure (CHF) were significant predictors of bowel resection, whereas CAD was the only significant predictor of mortality in this subgroup. We recommend that patients with SBO be admitted to SS because this might translate to shorter LOS, earlier operative intervention, and reduced healthcare use direct cost. Bowel resection and death are more likely to occur in patients with comorbidities like CHF, CAD, diabetes mellitus, and ARF.


Assuntos
Preços Hospitalares/estatística & dados numéricos , Obstrução Intestinal/economia , Obstrução Intestinal/cirurgia , Intestino Delgado , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricos , Idoso , Comorbidade , Feminino , Humanos , Incidência , Obstrução Intestinal/mortalidade , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
17.
Front Oncol ; 10: 1112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850319

RESUMO

Background: Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC. Patients and Methods: A meta-analysis of individual participant data (IPD) on GEM-NAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data. Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1-25.2). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9-31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3-18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4-18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3-34.2) vs. 16.2 months (95% CI 7·9-24.5) in the R1 group (p = 0·001). Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve survival and R0 resection in BR-PDAC. Also, GEM-NAT may result in a good palliative option in non-resected patients because of progressive disease after neoadjuvant treatment. Results from randomized controlled trials (RCTs) are awaited to validate these findings.

18.
Surg Oncol Clin N Am ; 28(4): 539-572, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31472905

RESUMO

The accurate diagnosis of a liver mass can usually be established with a thorough history, examination, laboratory inquiry, and imaging. The necessity of a liver biopsy to determine the nature of a liver mass is rarely necessary. Contrast-enhanced computed tomography and magnetic resonance are the standard of care for diagnosing liver lesions and high-quality imaging should be performed before performing a biopsy. This article discusses current consensus guidelines for imaging of liver masses, as well as masses found on surveillance imaging. The ability to accurately characterize lesions requires proper use and understanding of the technology and expert interpretation.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética/normas , Tomografia Computadorizada por Raios X/normas , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Prognóstico , Tomografia Computadorizada por Raios X/métodos
19.
JPEN J Parenter Enteral Nutr ; 32(2): 190-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18407913

RESUMO

Emodin is a commonly used traditional herbal treatment in China, including use for pancreatic malignancy. In this study, the potential for emodin to inhibit pancreatic cancer cell proliferation was examined using 4 human pancreatic adenocarcinoma cell lines: Mia Paca-2, BxPC-3, Panc-1, and L3.6pl. WST-1 proliferation, propidium iodide flow cytometry cell cycle analysis, and poly-ADP-ribose polymerase (PARP) Western blot analysis were performed. Forty-eight-hour treatment with 50 muM emodin inhibited proliferation in Mia Paca-2 cells by 42%, BxPc-3 by 38%, L3.6pl by 56%, and Panc-1 by 18% (all P < .01). In three-fourths of the cell lines, emodin treatment resulted in an increase (from 4.7% to 22%) in the cell population number in apoptosis when measured by flow cytometric analysis. Mia Paca-2 revealed a significant PARP cleavage product when compared with control. These feasibility experiments provide initial evidence that emodin exerts an antiproliferative effect, likely through apoptosis induction-related mechanism(s), that is reproducible in various human pancreatic cancer cell lines.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Emodina/farmacologia , Pâncreas/citologia , Inibidores de Proteínas Quinases/farmacologia , Adenocarcinoma/tratamento farmacológico , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Rheum/química , Resultado do Tratamento
20.
Am Surg ; 73(11): 1133-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18092648

RESUMO

The abdominal cocoon is a rare disease that is characterized by total or partial encasement of the small bowel by a thick and fibrotic membrane. After an increased number of case reports, the characteristic age group and sex distribution of abdominal cocoon have changed. Although the etiology is unknown, congenital malformation is implicated as the causative factor in the two patients in this report. Although preoperative diagnosis is a matter of challenge and usually made at laparotomy, our experience suggests that computed tomographic evidence of clustered small bowel loops encased by a thin membrane-like sac is a characteristic preoperative finding in patients with abdominal cocoon. Surgical removal of the membrane and adhesions is the most appropriate choice of therapy.


Assuntos
Obstrução Intestinal/etiologia , Doenças Peritoneais/complicações , Peritônio/patologia , Adulto , Diagnóstico Diferencial , Fibrose/complicações , Fibrose/patologia , Fibrose/cirurgia , Humanos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/cirurgia , Laparotomia , Masculino , Pessoa de Meia-Idade , Doenças Peritoneais/diagnóstico , Peritônio/diagnóstico por imagem , Peritônio/cirurgia , Tomografia Computadorizada por Raios X
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