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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.
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
4.
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.

5.
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.

6.
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
7.
FASEB J ; 33(5): 5967-5978, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30730772

RESUMO

Liver regeneration depends on sequential activation of pathways and cells involving the remaining organ in recovery of mass. Proliferation of parenchyma is dependent on angiogenesis. Understanding liver regeneration-associated neovascularization may be useful for development of clinical interventions. Myeloid-derived suppressor cells (MDSCs) promote tumor angiogenesis and play a role in developmental processes that necessitate rapid vascularization. We therefore hypothesized that the MDSCs could play a role in liver regeneration. Following partial hepatectomy, MDSCs were enriched within regenerating livers, and their depletion led to increased liver injury and postoperative mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte hypertrophy and proliferation, and aberrant liver function. Gene expression profiling of regenerating liver-derived MDSCs demonstrated a large-scale transcriptional response involving key pathways related to angiogenesis. Functionally, enhanced reactive oxygen species production and angiogenic capacities of regenerating liver-derived MDSCs were confirmed. A comparative analysis revealed that the transcriptional response of MDSCs during liver regeneration resembled that of peripheral blood MDSCs during progression of abdominal tumors, suggesting a common MDSC gene expression profile promoting angiogenesis. In summary, our study shows that MDSCs contribute to early stages of liver regeneration possibly by exerting proangiogenic functions using a unique transcriptional program.-Nachmany, I., Bogoch, Y., Sivan, A., Amar, O., Bondar, E., Zohar, N., Yakubovsky, O., Fainaru, O., Klausner, J. M., Pencovich, N. CD11b+Ly6G+ myeloid-derived suppressor cells promote liver regeneration in a murine model of major hepatectomy.

8.
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
9.
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
11.
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
12.
Surg Obes Relat Dis ; 14(2): 181-185, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29198751

RESUMO

BACKGROUND: Diabetes and other obesity-related diseases are a worldwide pandemic that transcends geographic borders as well as socioeconomic levels. Currently, it is well known that medical treatment alone is insufficient to ensure adequate and sustainable weight loss and co-morbidity resolution. It has been well proven that bariatric surgery can produce almost immediate resolution of diabetes and other co-morbidities as well as long-term weight loss. OBJECTIVES: Here, we present our experience with the one anastomosis gastric bypass (OAGB) in terms of weight loss and diabetes resolution with 1 year of follow-up. SETTING: Large, metropolitan, tertiary, university hospital. METHODS: A retrospective analysis of all patients who underwent OAGB between March 2015 and March 2016 was performed. Patient demographic characteristics, co-morbidities, operative and postoperative data, as well as first year outcomes were collected and analyzed. RESULTS: There were 407 patients who underwent OAGB (254 females, average age 41.8 ± 12.05 yr, body mass index = 41.7 ± 5.77 kg/m2). Of patients, 102 (25.1%) had diabetes with average glycosylated hemoglobin of 8.64 ± 1.94 g%, 93 (22.8%) had hypertension, 123 (28.8%) had hyperlipidemia, and 35 patients (8.6%) had obstructive sleep apnea. The average length of hospital stay was 2.2 ± .84 days (range, 2-10 d). The average excess weight loss 1 year after surgery was 88.9 ± 27.3. After 1 year, follow-up data were available for more than 85% of the study's general population. Of 102 diabetic patients, only 8 (7.8%) were still considered diabetic and taking antidiabetic medication, with an average glycosylated hemoglobin of 5.4 ± 0.6. CONCLUSIONS: OAGB may be performed safely and with promising efficacy as both a primary and a revisional bariatric surgery, and it offers excellent resolution of diabetes.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/epidemiologia , Derivação Gástrica/métodos , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Adulto , Anastomose Cirúrgica/métodos , Índice de Massa Corporal , Estudos de Coortes , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Seguimentos , Hospitais Universitários , Humanos , Israel , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/diagnóstico , Cuidados Pós-Operatórios/métodos , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Resultado do Tratamento , Perda de Peso/fisiologia
14.
Int J Colorectal Dis ; 32(11): 1577-1582, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28879552

RESUMO

PURPOSE: Hartmann's procedure is commonly practiced in emergent cases with the restoration of bowel continuity planned at a second stage. This study assessed the rate of restorations following Hartmann's procedure and evaluated factors affecting decision-making. METHODS: Data on patient demographics, comorbidities, causes for Hartmann's procedure, reversal rate, and complications were collected in a multicenter retrospective cohort study of patients who underwent Hartmann's procedure in five medical centers. RESULTS: Six hundred forty patients underwent Hartmann's procedure for diverticular disease (36.1%), obstructing malignancy (31.8%), benign obstruction (5%), and other reasons (23.1%). Overall, 260 (40.6%) patients underwent subsequent restoration of bowel continuity. One hundred twenty-one (46.5%) patients had post-reversal complications, with an average Clavien-Dindo score of 1.4 and a mortality rate of 0.77%. Decision to avoid reversal was mostly related to comorbidities (49.7%) and metastatic disease (21.6%). Factors associated with the decision to restore bowel continuity included male gender (P = 0.02), patient age (62.3 years in Hartmann's reversal patients vs 73.5 years in non-reversal patients; P < 0.0001), number of comorbidities (1.1 vs 1.58; P < 0.001), average Charlson score (1.93 vs 3.44; P < 0.001), and a neoplastic etiology (P < 0.0001). A sub-analysis excluding all patients who died in the 30 days following Hartmann's procedure showed similar factors associated with ostomy closure. CONCLUSION: Many patients do not have restoration of bowel continuity after undergoing Hartmann's procedure. Hartmann's reversal is associated with a significant postoperative morbidity. Surgeons and patients should be aware of the possibility that the colostomy might become permanent.


Assuntos
Anastomose Cirúrgica , Colo Sigmoide/cirurgia , Doenças do Colo/cirurgia , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Reconstrutivos , Reto/cirurgia , Reoperação , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Estudos de Coortes , Colectomia/efeitos adversos , Colectomia/métodos , Colo Sigmoide/patologia , Colo Sigmoide/fisiopatologia , Colostomia/efeitos adversos , Colostomia/métodos , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Procedimentos Cirúrgicos Reconstrutivos/estatística & dados numéricos , Reoperação/efeitos adversos , Reoperação/métodos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
15.
Surg Obes Relat Dis ; 13(10): 1658-1663, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28843985

RESUMO

OBJECTIVE: Although the laparoscopic sleeve gastrectomy (SG) is increasingly performed for morbid obesity, gastric bypass is still considered by many to be the gold standard procedure for obese diabetic patients. The aim of this study was to assess the long-term results of SG in morbidly obese patients with type 2 diabetes. METHODS: Diabetic patients who underwent SG at a single center between 2009 and 2011 were included. Outcomes assessed included postoperative complications, weight loss, and resolution or improvement in co-morbidities with an emphasis on diabetes, including glycated hemoglobin (HbA1C) and medication status. RESULTS: Fifty-one diabetic patients underwent SG, 35 females and 16 males, with a collective mean age of 49 years and a mean body mass index of 43.2 kg/m2. On average, patients had had diabetes for 5.4 ± 7.3 years before surgery. Mean HbA1C and fasting glucose levels were 7.9 ± 1.6% and 166.9 ± 63 mg/dL, respectively. Eleven patients (22%) were insulin dependent at the time of surgery. Average body mass index at a mean follow-up of 5 years after surgery was 34.4 ± 5.8 kg/m2, with an average HbA1C of 6.6 ± 1% and an average fasting glucose of 123 ± 60 mg/dL. Only 3 patients remained insulin dependent. CONCLUSION: SG offers retainable weight loss results, accompanied by longstanding resolution or improvement of diabetes. Prospective, randomized controlled studies are warranted to better compare long-term outcomes between SG and gastric bypass.


Assuntos
Cirurgia Bariátrica/métodos , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Adulto , Cirurgia Bariátrica/estatística & dados numéricos , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Gastrectomia/estatística & dados numéricos , Hemoglobina A Glicada/metabolismo , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Laparoscopia/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Reoperação/métodos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Perda de Peso/fisiologia
16.
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
17.
Tumour Biol ; 39(4): 1010428317698357, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28443460

RESUMO

Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern. Overexpression of RUNX1 led to diminished tumor growth in nude and severe combined immunodeficiency mouse xenograft tumor model. At the molecular level, RUNX1 occupied thousands of genomic regions and regulated the expression of hundreds of target genes, both directly and indirectly. RUNX1 occupied genomic regions that corresponded to genes that were shown to play a role in brain tumor progression and angiogenesis and upon overexpression led to a substantial down-regulation of their expression level. When overexpressed in U87 glioblastoma multiforme cells, RUNX1 down-regulated key pathways in glioblastoma multiforme progression including epithelial to mesenchymal transition, MTORC1 signaling, hypoxia-induced signaling, and TNFa signaling via NFkB. Moreover, master regulators of the glioblastoma multiforme mesenchymal phenotype including CEBPb, ZNF238, and FOSL2 were directly regulated by RUNX1. The data suggest a central role for RUNX1 as master regulator of gene expression in the U87 glioblastoma multiforme cell line and mark RUNX1 as a potential target for novel future therapies for glioblastoma multiforme.


Assuntos
Proliferação de Células/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Transição Epitelial-Mesenquimal/genética , Glioblastoma/genética , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Subunidade alfa 2 de Fator de Ligação ao Core/biossíntese , Antígeno 2 Relacionado a Fos/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , Camundongos , Proteínas Repressoras/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Obes Surg ; 27(5): 1266-1270, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27885536

RESUMO

BACKGROUND: Although considered a common bariatric procedure, laparoscopic adjustable gastric banding (LAGB) is associated with high rates of weight loss failure and long-term complications. PURPOSE: The purpose of this study was to re-assess the safety and outcome of conversion of failed LAGB to laparoscopic sleeve gastrectomy (LSG). MATERIALS AND METHODS: One hundred and nine patients underwent conversion from LAGB to LSG (78 females, mean age 43 ± 11.3 years, mean BMI 42.4 ± 7.4 kg/m2). Patient demographics, obesity-related co-morbidities, BMI before and after the procedure, post-operative complications, and length of hospital stay were documented. RESULTS: All cases were completed laproscopically, with 88% (n = 96) performed in a single stage. Fourteen patients developed early post-operative complications (12.8%), including two leaks and three post-operative bleeding. There were no mortalities in this series. Average BMI at least 1-year following surgery was 33 ± 5.3 kg/m2 (excess weight loss (EWL) = 53.7%). CONCLUSIONS: Our data suggests that conversion of failed LAGB to LSG is both safe and effective. Randomized controlled studies comparing conversion of a failed LAGB to sleeve gastrectomy versus other bariatric operations are necessary to clarify the optimal conversion procedure.


Assuntos
Remoção de Dispositivo , Gastrectomia , Gastroplastia , Obesidade/cirurgia , Adulto , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Perda de Peso
19.
Surgery ; 161(4): 920-929, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28027817

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography-induced perforation (EP) is a rare but severe complication. We describe the risk factors, management, and outcome of ERCP-induced perforations in a tertiary center. METHODS: This is a case-control study. All EP cases between March 2004 and February 2015 were compared to a control group without perforation. Data on patients, procedures, presentation, perforation type, radiologic findings, management, and outcome were assessed. RESULTS: Of 6,934 endoscopic retrograde cholangiopancreatographies, 37 patients (0.53%) had EP. Independent risk factors included failure of cannulation, a procedure described as "difficult," performing a precut and resection of a periampullary adenoma. Perforation was diagnosed during the procedure in 7 patients (19%). Median interval for diagnosis was 11 hours (range: 0-201 hours), with 84% diagnosed within 30 hours. The periampullary region was the most common EP site (51%). Twenty-nine patients (78%) were managed conservatively and 8 (22%) were operated. Three patients failed conservative management and required delayed operation. Failure of conservative management had a detrimental effect on morbidity and duration of stay. All patients who required operative intervention had perforation of either the duodenal free wall or the periampullary region. CONCLUSION: Clear risk factors can be used to raise suspicion of EP. Early diagnosis and management are critical for better outcome. This is especially important when operative intervention is indicated. Nonetheless, the majority of patients may be managed conservatively.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Tratamento Conservador/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Duodeno/lesões , Doença Iatrogênica , Perfuração Intestinal/terapia , Fatores Etários , Idoso , Estudos de Casos e Controles , Colangiopancreatografia Retrógrada Endoscópica/métodos , Feminino , Humanos , Incidência , Perfuração Intestinal/etiologia , Israel , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Taxa de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
20.
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
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