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1.
Surgeon ; 18(1): 24-30, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31466841

RESUMO

BACKGROUND: The influence of postoperative complications, specifically, pancreatic fistula (PF), on long-term oncologic outcome in patients with pancreatic ductal adenocarcinoma (PDAC) is unclear. METHODS: Prospectively collected data of patients who underwent pancreaticoduodenectomy (PD) for PDAC between 2008 and 2016 were retrospectively reviewed and analyzed. Deaths within 90 days were excluded. Median follow-up time was 22 months for the entire cohort (range 2-102 months). PF was graded as biochemical leak, grade B, or grade C according to the criteria of the International Study Group on Pancreatic Fistula. Postoperative complications were graded according to the Clavien-Dindo classification (CDC). Data on clinical and pathological characteristics as well as on recurrence and survival were collected. RESULTS: Twenty-nine of the 148 identified patients (19%) developed PF, of whom 17 (11.4%) had a PF grade B or C. 29 patients developed a postoperative complication CDC grade 3 or 4. The respective 3-year disease-free survival was 15.5% and 19.2% (P = 0.725), and the 5-year overall survival was 20% and 16% (P = 0.914) in patients with and without PF. On multivariate analysis, the use of adjuvant chemotherapy, lymph node involvement, surgical margin involvement, and tumor grade were associated with patient survival. PF and postoperative complications CDC grade 3 or 4 were not associated with decreased long-term survival, disease-free survival or local recurrence rate. CONCLUSIONS: While acknowledging the limited sample size, no association was seen between PF or postoperative complications and overall or disease-free survival in patients undergoing PD for PDAC.

2.
Front Oncol ; 9: 1267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803630

RESUMO

The peritoneal cavity, especially the omentum, is a common site for gastric cancer metastasis, representing advanced disease stage and poor prognosis. Here, we studied the effects of omental tissue on gastric cancer tumor progression in vitro and in vivo. Utilizing in vitro models, we found that omental tissue secreted factors increased gastric cancer cellular growth (by 30-67%, P < 0.05), motility (>8-fold, P < 0.05), invasiveness (>7-fold, P < 0.05) and chemoresistance to platinum-based chemotherapeutic agents (>1.2-fold for oxaliplatin and >1.6-fold for cisplatin, P < 0.05). Using a robust proteomic approach, we identified numerous molecules secreted into the omental tissue conditioned medium (CM) which may promote gastric cancer cellular aggressiveness (i.e., IL-6, IL-8, MMP9, FN1, and CXCL-5). Next, an in vivo xenograft mouse model showed an increased human gastric adenocarcinoma tumor volume of cells co-cultured with human omental tissue secreted factors; 1.6 ± 0.55 vs. 0.3 ± 0.19 cm3 (P < 0.001), as well as increased angiogenesis. Finally, exosomes were isolated from human omental tissue CM of gastric cancer patients. These exosomes were taken up by gastric cancer cells enhancing their growth (>8-fold, P < 0.01) and invasiveness (>8-fold, P < 0.001). Proteomic analysis of the content of these exosomes identified several established cancer- related proteins (i.e., IL-6, IL-8, ICAM-1, CCl2, and OSM). Taken together, our findings imply that the omentum play an active role in gastric cancer metastasis. The data also describe specific cytokines that are involved in this cross talk, and that omental tissue- derived exosomes may contribute to these unique cellular interactions with gastric cancer cells. Further studies aimed at understanding the biology of gastric cancer intra peritoneal spread are warranted. Hopefully, such data will enable to develop future novel therapeutic strategies for the treatment of metastatic gastric cancer.

3.
Transpl Infect Dis ; 21(6): e13171, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518477

RESUMO

Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for kidney transplantation. After the introduction of ART, several studies have demonstrated comparable patient and graft outcomes between HIV-negative and HIV-positive kidney recipients. The US Congress passed the HIV Organ Policy Equity (HOPE) Act in 2013, which permits research in the area of HIV-positive to HIV-positive transplantation. HIV-infected living donation is also permitted under the HOPE Act. However, there is a concern regarding the safety of kidney donation in an HIV-infected person, given the risk of renal disease associated with HIV infection. We report here the case of successful kidney transplantation from HIV-positive living donor to HIV-positive recipient performed in our center on July 2012. To the best of our knowledge, this is the earliest case done in this medical context to be reported in the literature, therefore, potentially carrying several important messages to the transplantation community. In the present case, the living-donor kidney transplant was performed between a married couple infected with same strain of HIV-1, both on effective ART with efficiently suppressed viral replication and satisfactory pre-transplantation immune status.

4.
Transplant Proc ; 51(6): 1867-1873, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399171

RESUMO

BACKGROUND: Liver transplantation (LT) and liver resection (LR) are curative treatment options for patients with hepatocellular carcinoma within the Milan criteria. Severe organ shortage dictates the preference for LR. Our aim was to provide an intention-to-treat retrospective comparison of survival between patients who were placed on waiting lists for LT and those who underwent LR. METHODS: The medical records of patients with hepatocellular carcinoma within the Milan criteria treated by LR or listed for LT between 2007 and 2016 were reviewed. We performed intention-to-treat analyses of overall survival and recurrence. RESULTS: There were 54 patients on the waiting list for LT, and 30 of them underwent LR. Thirteen of the 54 patients (24%) were not transplanted because of disease-related mortality or tumor progression. The median waiting time to transplantation was 304 days. The 90-day mortality was higher in transplanted patients (9.8% vs 3.3%, P = .003). Intention-to-treat survival was similar for the LT and LR groups (5-year survival, 47.8% vs 55%, respectively, P = .185). There was a trend toward improved 5-year disease-free survival for listed patients (56.2% vs 26.3% for patients undergoing LR, P = .15). CONCLUSION: Intention-to-treat survival is similar in patients undergoing LR and those on waiting lists for LT. There is a 24% risk to drop from the transplant list. The higher perioperative mortality among patients undergoing LT is balanced by a higher tumor recurrence rate after LR.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Listas de Espera/mortalidade , Adulto , Idoso , Feminino , Humanos , Análise de Intenção de Tratamento , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
5.
Cell ; 178(3): 686-698.e14, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31257031

RESUMO

Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.

6.
J Gastrointest Surg ; 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197692

RESUMO

BACKGROUND: Management of asymptomatic, nonfunctioning small pancreatic neuroendocrine tumors (PNETs) is controversial because of their overall good prognosis, and the morbidity and mortality associated with pancreatic surgery. Our aim was to compare the outcomes of resection with expectant management of patients with small asymptomatic PNETs. METHODS: Retrospective review of patients with nonfunctioning asymptomatic PNETs < 2 cm that underwent resection or expectant management at the Tel-Aviv Medical Center between 2001 and 2018. RESULTS: Forty-four patients with small asymptomatic, biopsy-proven low-grade PNETs with a KI67 proliferative index < 3% were observed for a mean of 52.48 months. Gallium67DOTATOC-PET scan was completed in 32 patients and demonstrated uptake in the pancreatic tumor in 25 (78%). No patient developed systemic metastases. Two patients underwent resection due to tumor growth, and true tumor enlargement was evidenced in final pathology in one of them. Fifty-five patients underwent immediate resection. Significant complications (Clavien-Dindo grade ≥ 3) developed in 10 patients (18%), mostly due to pancreatic leak, and led to one mortality (1.8%). Pathological evaluation revealed lymphovascular invasion in 1 patient, lymph node metastases in none, and a Ki67 index ≥ 3% in 5. No case of tumor recurrence was diagnosed after mean follow-up of 52.8 months. CONCLUSIONS: No patients with asymptomatic low-grade small PNETs treated by expectant management were diagnosed with regional or systemic metastases after a 52.8-month follow-up. Local tumor progression rate was 2.1%. Surgery has excellent long-term outcomes, but it harbors significant morbidity and mortality. Observation can be considered for selected patients with asymptomatic, small, low grade PNETs.

7.
Oncotarget ; 10(27): 2644-2656, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31080555

RESUMO

Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC), representing an advanced disease stage and independently predicting patient survival. Current nodal staging is inadequate preoperatively and even less so postoperatively, and molecular biomarkers are needed to improve prognostication and selection of therapy. Recent data have suggested important roles of miRNAs in PDAC tumorigenesis and progression. The aim of the present study was to identify miRNA expression signature for nodal spread in PDAC patients. Using PDAC human tissue specimens, we identified 39 miRNAs which were differently expressed in LN positive compared to LN negative PDAC samples. Of them, six miRNAs have been reported to play a role in cancer invasion and metastasis. A high versus low six- miRNA signature score was predictive of LN metastasis in the PDAC validation cohort. We demonstrated a similar expression pattern of four out of the six miRNAs in the plasma of PDAC patients. The results of our in-vitro studies revealed that miR-141 and miR-720 are involved in the process of epithelial to mesenchymal-transition in PDAC. These miRNAs significantly inhibited in vitro proliferation, migration and invasion of PDAC cells as evidence by gain- and loss- of function studies, specifically, via ZEB-1 and TWIST1 transcription factors, as well as through the activation of the MAP4K4/JNK signaling pathway.

8.
Genes Immun ; 20(7): 589-598, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30880333

RESUMO

Myeloid derived suppressor cells (MDSCs) play key roles in cancer development. Accumulation of peripheral-blood MDSCs (PB-MDSCs) corresponds to the progression of various cancers, but provides only a crude indicator. We aimed toward identifying changes in the transcriptional profile of PB-MDSCs in response to tumor growth. CT26 colon cancer cells and B16 melanoma cells (106) were inoculated into peritoneal cavities of BALB/c mice and subcutaneously to C57-black mice, respectively. The circulating levels and global transcriptional patterns of PB CD11b+Ly6g+ MDSCs were assessed in control mice, and 4, 8, and 11 days following tumor cell inoculation. Although a significant accumulation of PB-MDSCs was demonstrated only 11 days following tumor induction, a pronounced transcriptional response was identified already on day 4 while the tumor was ~1 mm in size. Further transcriptional changes correlated with different stages of tumor growth. Key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in both cancer models, and a consensus set of 817 genes, involved in myeloid cell recruitment and angiogenesis, was identified. The data suggest that the transcriptional signatures of PB-MDSC may serve as markers for tumor progression, as well as providing potential targets for future therapies.


Assuntos
Antígeno CD11b/genética , Células Supressoras Mieloides/metabolismo , Animais , Antígeno CD11b/análise , Progressão da Doença , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Células Supressoras Mieloides/fisiologia , Neoplasias/imunologia , Transcriptoma/genética
9.
Transpl Int ; 32(7): 730-738, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30793376

RESUMO

Inflammatory bowel diseases (IBD) is a systemic disorder with possible renal involvement, yet data regarding the outcome of kidney transplantation (KT) in those patients, and IBD course post KT, are scarce. In this retrospective analysis, we studied the outcome of 12 IBD kidney recipients (seven Crohn's disease, five ulcerative colitis; primary kidney disease was IgA nephropathy in five, polycystic disease in four), compared to two control groups: matched controls and a cohort of recipients with similar kidney disease. During a follow-up period of 60.1 (11.0-76.6) months (median, interquartile range), estimated 5-year survival was 80.8 vs. 96.8%, with and without IBD, respectively (P = 0.001). Risk of death with a functioning graft was higher with IBD (HR = 1.441, P = 0.048), and with increased age (HR = 1.109, P = 0.05). Late rehospitalization rate was higher in IBD [incidence rate ratio = 1.168, P = 0.030], as well as rate of hospitalization related to infection [1.42, P = 0.037]. All patients that were in remission before KT, remission was maintained. Patients that were transplanted with mild or moderate disease remained stable or improved with Infliximab or Adalimumab treatment. In conclusion, IBD is associated with an increased risk of mortality, hospitalization because of infection and late rehospitalization after KT. Clinical course of IBD is stable after KT.


Assuntos
Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adalimumab/administração & dosagem , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/cirurgia , Hospitalização , Humanos , Imunossupressão , Infliximab/administração & dosagem , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
10.
BMC Nephrol ; 20(1): 30, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704441

RESUMO

BACKGROUND: Only few studies of living kidney donors have included controls that were similarly healthy, including excellent kidney function. METHODS: In this study, we aimed to estimate long term metabolic and renal outcome in a cohort of 211 living donors compared to two control groups: paired-matched controls, and another control group of 2534 healthy individuals with excellent kidney function. RESULTS: Donors presented with higher estimated Glomerular Filtration Rate (eGFR): (97.6 ± 15.2 vs 96.1 ± 12.2 vs 94.5 ± 12.4 ml/min/1.73m2) and lower urine albumin to creatinine ratio (UACR) (4.3 ± 5.9 vs 5.9 ± 6.1 vs 6.1 ± 6.9 mg/g) for donors, matched controls and healthy controls, respectively (p <  0.001). In a mean follow up period of 5.5 for donors, donors presented with positive eGFR slopes during the first 3 years post donation, followed by negative slopes, compared to constantly negative slopes presented in the control group (p <  0.05). The variables related to the slope were being a donor, baseline eGFR, Body Mass Index (BMI) and age but not eGFR on the last day of follow-up or increased delta UACR. There was a significant increase in UACR in donors, as well as a higher rate of albuminuria, associated with a longer time since donation, higher pre-donation UACR and higher pre-donation BMI. Healthy controls had a lower BMI at baseline and gained less weight during the follow up period. Donors and controls had similar incidence of new onset diabetes mellitus and hypertension, as well as similar delta systolic and diastolic blood pressure. Donors were more likely to develop new onset metabolic syndrome, even after adjustment for age, gender and BMI. The higher incidence of metabolic syndrome resulted mainly from increased triglycerides and impaired fasting glucose criteria. However, prevalence of major cardiovascular events was not higher in this group. CONCLUSIONS: Donors are at increased risk to develop features of the metabolic syndrome in addition to the expected mild reduction of GFR and increased urine albumin excretion. Future studies are needed to explore whether addressing those issues will impact post donation morbidity and mortality.


Assuntos
Rim/fisiopatologia , Doadores Vivos , Síndrome Metabólica/etiologia , Nefrectomia/efeitos adversos , Obtenção de Tecidos e Órgãos , Adulto , Albuminúria/etiologia , Glicemia/análise , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Hemoglobina A Glicada/análise , Humanos , Hipertensão/etiologia , Hipertrigliceridemia/etiologia , Transplante de Rim , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Risco , Ganho de Peso
11.
World J Surg Oncol ; 17(1): 26, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704497

RESUMO

BACKGROUND: Reoperation following PD is a surrogate marker for a complex post-operative course and may lead to devastating consequences. We evaluate the indications for early reoperation following PD and analyze its effect on short- and long-term outcome. METHODS: Four hundred and thirty-three patients that underwent PD between August 2006 and June 2016 were retrospectively analyzed. RESULTS: Forty-eight patients (11%; ROp group) underwent 60 reoperations within 60 days from PD. Forty-two patients underwent 1 reoperation, and 6 had up to 6 reoperations. The average time to first reoperation was 10.1 ± 13.4 days. The most common indications were anastomotic leaks (22 operations in 18 patients; 37.5% of ROp), followed by post-pancreatectomy hemorrhage (PPH) (14 reoperations in 12 patients; 25%), and wound complications in 10 (20.8%). Patients with cholangiocarcinoma had the highest reoperation rate (25%) followed by ductal adenocarcinoma (12.3%). Reoperation was associated with increased length of hospital stay and a high post-operative mortality of 18.7%, compared to 2.6% for the non-reoperated group. For those who survived the post-operative period, the overall and disease-free survival were not affected by reoperation. CONCLUSIONS: Early reoperations following PD carries a dramatically increased mortality rate, but has no impact on long-term survival.


Assuntos
Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Reoperação/estatística & dados numéricos , Idoso , Fístula Anastomótica/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/mortalidade , Estudos Retrospectivos
12.
J Surg Oncol ; 119(3): 347-354, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30548552

RESUMO

BACKGROUND AND OBJECTIVES: The impact of resection margins on the outcome of patients with colorectal liver metastasis (CRLM) remains controversial. We evaluated the short and long-term results of R1 resection. METHODS: Between 2006 and 2016, 202 patients underwent liver resection for CRLM. R1 resection was defined as a distance of less than 1 mm between tumor cells and the transection plain. Patient and tumor characteristics, perioperative, and long-term outcomes were assessed. RESULTS: In 161 (79.7%) and 41 (20.3%) patients, an R0 and R1 resections were achieved, respectively. Patients that underwent an R1 resection had higher rates of disease progression while on chemotherapy (12.1% vs 5.5%, P = 0.001), need for second-line chemotherapy (17% vs 6.2%, P < 0.001), increased use of preoperative volume manipulation (14.6% vs 5.5%, P = 0.001), and inferior vena-cava involvement (21.9% vs 8.7%, P < 0.001). These patients had higher rates of major postoperative complications (19.5% vs 6.8%, P < 0.001) and reoperations (7.3% vs 2.4%, P < 0.001). Multivariate analysis demonstrated that R1 resections were not associated with decreased recurrence-free survival or overall survival. CONCLUSIONS: Although R1 resection is associated with worse disease behavior and postoperative complications, the long-term outcome of patients following an R1 resection is non-inferior to those who underwent an R0 resection.


Assuntos
Neoplasias Colorretais/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Margens de Excisão , Complicações Pós-Operatórias/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
14.
Eur J Surg Oncol ; 44(10): 1619-1623, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30146251

RESUMO

OBJECTIVE: To assess clinical and pathologic efficacy of neoadjuvant FOLFIRINOX for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS: Patients receiving neoadjuvant FOLFIRINOX for LAPC and BRPC treated between 2014 and 2017 were identified. Post-treatment patients achieving resectability were referred for surgery, whereas unresectable patients continued chemotherapy. Clinical and pathological data were retrospectively compared with control group consisting of 47 consecutive patients with BRPC undergoing pancreatic and portal vein resection between 2008 and 2017. RESULTS: Thirty LAPC and 23 BRPC patients were identified. Reasons for unresectability included disease progression (70%), locally unresectable disease (18%), and poor performance status (11%). Three patients (10%) with LAPC, and 20 (87%) with BRPC underwent curative surgery. Compared with control group, perioperative complication rate (4.3% versus 28.9%, p = 0.016), and pancreatic fistula rate (0 versus 14.8%, p = 0.08) were lower. Peripancreatic fat invasion (52.2% vs 97.8%, p = 0.001), lymph node involvement (22% vs 54.3%, p = 0.01), and surgical margin involvement (0 vs 17.4%, p = 0.04) were higher in the control group. Median survival was 34.3 months in BRPC patients operated after FOLFIRINOX and 26.1 months in the control group (p = 0.07). Three patients (13%) with complete pathological response are disease-free after mean follow-up of 19 months. CONCLUSIONS: Whereas neoadjuvant FOLFIRINOX rarely achieves resectability in patients with LAPC (10%), most BRPC undergo resection (87%). Neoadjuvant FOLFIRINOX leads to complete pathological response in 13% of cases, tumor downstaging, and a trend towards improved survival compared with patients undergoing up-front surgery.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Antineoplásicos/uso terapêutico , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/patologia , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Fluoruracila/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Irinotecano , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Invasividade Neoplásica , Estadiamento de Neoplasias , Compostos Organometálicos/efeitos adversos , Oxaliplatina , Pancreatectomia , Ductos Pancreáticos , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Veia Porta/cirurgia , Complicações Pós-Operatórias/etiologia , Taxa de Sobrevida
15.
Clin Transplant ; 32(3): e13187, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29314293

RESUMO

BACKGROUND: The utilization of extended criteria liver allografts (ECD) shortens time to transplantation. OBJECTIVE: To characterize the effect of liver allograft fibrosis on graft and patient survival after liver transplantation (LT), with particular attention to fibrosis progression. METHODS: Retrospective database search of donor and recipient liver allograft histology of liver transplants performed between 2007 and 2011. Donor and patient characteristics were analyzed. RESULTS: One hundred and one patients underwent LT with donor liver allografts with early-stage fibrosis (stage 1 fibrosis and stage 2 fibrosis). The level of liver fibrosis did not progress in 40% of the patients tested, and there was a regression of fibrosis in 30%. At a median follow-up of 71 months, of 101 patients transplanted with fibrotic livers, 63 patients (63%) were alive with functioning initial grafts, six patients (6%) were retransplanted, and 35 patients expired. The graft survival rates were 82% and 69% at 1 and 5 years, respectively. Graft survival differences were not found to be statistically significant between the degrees of liver allograft fibrosis: 5-year graft survival (73% for stage 1 fibrosis and 62% for stage 2 fibrosis, P = .24). The entire fibrosis group was further compared with a control group of 208 consecutive primary liver transplant patients with allografts having no fibrosis. The 5-year graft survival was not significantly different between the groups (69% for the fibrosis group vs 75% for the nonfibrosis group, P = .19). Survival was also not statistically different between the groups (5-year survival of 73% for the fibrosis group vs 79% for the nonfibrosis group, P = .2). In patients with HCV, graft survival differences were not found to be statistically significant with the use of early-stage fibrotic livers: 5-year graft survival of 60% for fibrosis group vs 70% for the nonfibrosis group, P = .22). CONCLUSION: This study demonstrates that allografts with early-stage fibrosis achieve acceptable long-term survival after liver transplantation. Given these preliminary results, the use of organs with early-stage fibrosis warrants further studies at a larger scale to validate these results.


Assuntos
Cirrose Hepática/fisiopatologia , Hepatopatias/mortalidade , Transplante de Fígado/mortalidade , Doadores de Tecidos , Aloenxertos , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Hepatopatias/patologia , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
PLoS One ; 12(6): e0179862, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28632775

RESUMO

Pancreatic cancer is a common cause of cancer-related mortality. Omental spread is frequent and usually represents an ominous event, leading to patient death. Omental metastasis has been studied in ovarian cancer, but data on its role in pancreatic cancer are relatively scarce and the molecular biology of this process has yet to be explored. We prepared tissue explants from human omental fat, and used conditioned medium from the explants for various in vitro and in vivo experiments designed to evaluate pancreatic cancer development, growth, and survival. Mass spectrometry identified the fat secretome, and mRNA array identified specific fat-induced molecular alternations in tumor cells. Omental fat increased pancreatic cancer cellular growth, migration, invasion, and chemoresistance. We identified diverse potential molecules secreted by the omentum, which are associated with various pro-tumorigenic biological processes. Our mRNA array identified specific omental-induced molecular alternations that are associated with cancer progression and metastasis. Omental fat increased the expression of transcription factors, mRNA of extracellular matrix proteins, and adhesion molecules. In support with our in vitro data, in vivo experiments demonstrated an increased pancreatic cancer tumor growth rate of PANC-1 cells co-cultured for 24 hours with human omental fat conditioned medium. Our results provide novel data on the role of omental tissue in omental metastases of pancreatic cancer. They imply that omental fat secreted factors induce cellular reprogramming of pancreatic cancer cells, resulting in increased tumor aggressiveness. Understanding the mechanisms of omental metastases may enable us to discover new potential targets for therapy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Omento/citologia , Neoplasias Pancreáticas/patologia , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Antimetabólitos Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Meios de Cultivo Condicionados/análise , Meios de Cultivo Condicionados/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/toxicidade , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Espectrometria de Massas em Tandem , Transplante Heterólogo
18.
Mol Cancer Res ; 14(12): 1254-1265, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27621268

RESUMO

Previous data demonstrated that high retroperitoneal visceral fat content increases retroperitoneal soft-tissue sarcoma (RSTS) local recurrence and patients' mortality. Most RSTS tumors initiate and recur within visceral fat. The objective of the current study was to evaluate potential paracrine effects of visceral fat on RSTS. A xenograft model was used to evaluate in vivo effects of human visceral fat on STS growth. Tissue explants were prepared from visceral fat, and their conditioned medium (CM) was utilized for various in vitro experiments designed to evaluate growth, survival, migration, and invasion of STS and endothelial cells. Visceral fat-secreted protumorigenic factors were identified by mass spectrometry. The in vivo experiments demonstrated a significant increase in STS tumor growth rate when SK-LMS-1 leiomyosarcoma cells were colocalized with human visceral fat compared with subcutaneous injection of cancer cells only. The in vitro model demonstrated that visceral fat CM increased STS cellular growth and reduced doxorubicin-induced apoptosis. Visceral fat also enhanced STS cellular migration and invasion. In addition, visceral fat CM significantly increased endothelial cell tube formation, suggesting its role as a proangiogenic factor in the STS tumor microenvironment (TME). Using a robust proteomic approach, liquid chromatography and tandem mass spectrometry resolved various molecules within the visceral fat CM, of which a subset was associated with protumorigenic biologic processes. These results suggest that visceral fat directly interacts with STS cells by secreting specific adipokines into the TME, thus augmenting STS tumor cell proliferation and invasiveness. Fat-induced STS molecular deregulations should be studied to identify new potential prognostic and therapeutic targets. IMPLICATIONS: Visceral fat induces protumorigenic effects, in STS, through various secreted factors that should be investigated to improve our understanding of adipose-cancer cell interactions. Mol Cancer Res; 14(12); 1254-65. ©2016 AACR.


Assuntos
Adipócitos/citologia , Adipocinas/metabolismo , Leiomiossarcoma/patologia , Proteômica/métodos , Neoplasias Retroperitoneais/patologia , Adipócitos/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Cromatografia Líquida , Meios de Cultivo Condicionados/farmacologia , Humanos , Leiomiossarcoma/metabolismo , Camundongos , Neoplasias Experimentais , Comunicação Parácrina , Neoplasias Retroperitoneais/metabolismo , Espectrometria de Massas em Tandem , Técnicas de Cultura de Tecidos , Microambiente Tumoral
19.
Clin Transplant ; 30(9): 1010-5, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27291067

RESUMO

BACKGROUND: Living donor liver transplantation is a viable option to increase access to transplantation and techniques to limit the operative incision is one way to increase donation by decreasing donor morbidity. We describe our experience with a limited upper midline incision (UMI) for living donor right hepatectomy. STUDY DESIGN: Prospective data were collected on 58 consecutive living liver donors who underwent right hepatectomy via a UMI. RESULTS: Donor median age was 32 years, with median body mass index of 24.6. The mean incision length was 11.7 cm. Ten liver grafts included middle hepatic vein. The mean graft volume by preoperative imaging was 940 cc. The mean operative time was 407 minutes; cellsaver was utilized in 35 patients with median of 1 unit. Mean peak aspartate transaminase (AST) and alanine transaminase (ALT) were 492 and 469, and peak bilirubin and international normalized ratio (INR) were 3.3 and 1.8. The average length of stay was 6 days. There were 10 Clavien grade I and 11 Clavien grade II complications. Three patients developed an incisional hernia requiring surgical repair. CONCLUSION: Living liver donor hepatectomy can be safely performed through a UMI. This approach consolidates the steps of liver mobilization, hilar dissection, and parenchymal transection in a single-exposure technique, with incision comparable to the laparoscopic-assisted modality.


Assuntos
Hepatectomia/métodos , Laparotomia/métodos , Transplante de Fígado/métodos , Fígado/cirurgia , Doadores Vivos , Coleta de Tecidos e Órgãos/métodos , Adulto , Feminino , Humanos , Laparoscopia/métodos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
20.
J Laparoendosc Adv Surg Tech A ; 26(6): 470-4, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27149307

RESUMO

BACKGROUND: Although laparoscopic distal pancreatectomy (LDP) is gradually recognized as a safe and effective alternative to open distal pancreatectomy (ODP), it is not yet widely accepted. OBJECTIVE: We describe our experience, with emphasis on the learning curve of LDP. METHODS: Patients who underwent distal pancreatectomy (DP) between January 2011 and August 2014 were included. Operative and postoperative parameters, as well as pathology reports were evaluated. RESULTS: Thirty-nine and 41 patients underwent LDP and ODP, respectively. The mean age and gender distribution were comparable between groups. In six patients (15.4%), a conversion to open surgery was indicated. Operating time and intraoperative blood transfusion rates were comparable between groups. One patient of the LDP group died postoperatively. Postoperative complications were comparable with similar Dindo-Clavien (DC) score. Length of stay (LOS) was shorter following LDP (8.15 ± 4.68 versus 11.3 ± 6.3 days, P = .014). Patients selected to have LDP had larger lesions compared to those who underwent ODP (4.59 ± 4.23 versus 3 ± 2.52 cm, respectively, P = .048). R0 resection rates between the groups were comparable (92.3% in LDP versus 97.5% in ODP) as well as lymph node (LN) harvest (6.4 ± 6.4 LN in LDP versus 7.6 ± 6.6 LN in ODP). Following the 17th patient, LDP operative time decreased by more than 35 minutes, no conversions were done, no blood transfusion was needed, and the LOS was shortened by over 2 days. CONCLUSIONS: Short learning curve, shorter LOS, and satisfactory short-term oncological outcome place LDP as an attractive alternative for selected patients requiring DP.


Assuntos
Laparoscopia , Curva de Aprendizado , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Adolescente , Adulto , Idoso , Criança , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
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