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1.
Isr Med Assoc J ; 22(1): 53-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927807

RESUMO

BACKGROUND: Primary retroperitoneal neoplasms (PRN) arise from diverse retroperitoneal tissues. Soft tissue sarcomas (STS) comprise the majority and are well studied. Other non-sarcomatous PRN are very rare and less familiar. OBJECTIVES: To evaluate the clinicopathologic and radiologic features of non-sarcomatous PRN, as well as the outcome of complete tumor resection (TR). METHODS: Retrospective data were collected on consecutive patients (June 2006 to January 2015) who underwent resection of retroperitoneal lesions at our department. Final pathology of non-sarcomatous PRN was included. RESULTS: The study population included 36 patients (26% with PRN). PRN were neurogenic (17%), fat-containing (3%), and cystic (6%). The preoperative diagnosis was correct in only 28%. All patients underwent TR via laparotomy (72%) or laparoscopy (28%), for mean operative time of 120 ± 46 minutes. En bloc organ resection was performed in 11%. Complete TR was achieved in 97%. Intra-operative spillage occurred in 8%. Intra-operative, 90-day postoperative complications, and mortality rates were 11%, 36%, and 0%, respectively. The mean length of stay was 6.5 ± 5.5 days. The median overall survival was 53 ± 4.9 months. CONCLUSIONS: Familiarity with radiologic characteristics of PRN is important for appropriate management. Counter to STS, other PRN are mostly benign and have an indolent course. Radical surgery is not required, as complete TR confers good prognosis. Expectant management is reserved for small, asymptomatic, benign neoplasms.


Assuntos
Neoplasias Retroperitoneais/diagnóstico , Idoso , Feminino , Ganglioneuroma/diagnóstico , Ganglioneuroma/diagnóstico por imagem , Ganglioneuroma/patologia , Ganglioneuroma/cirurgia , Humanos , Lipoma/diagnóstico , Lipoma/diagnóstico por imagem , Lipoma/patologia , Lipoma/cirurgia , Masculino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Neurilemoma/cirurgia , Neurofibroma/diagnóstico , Neurofibroma/diagnóstico por imagem , Neurofibroma/patologia , Neurofibroma/cirurgia , Paraganglioma/diagnóstico , Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Paraganglioma/cirurgia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
2.
Int J Cancer ; 146(1): 115-122, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211411

RESUMO

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5-hydroxymethylcytosine (5-hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5-hmC quantification methods. Here we present and validate a fluorescence-based platform for high-throughput and cost-effective quantification of global genomic 5-hmC levels. We utilized the assay to characterize cancerous tissues based on their 5-hmC content, and observed a pronounced reduction in 5-hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof-of-concept data for treatment of familial adenomatous polyposis.


Assuntos
5-Metilcitosina/análogos & derivados , Biomarcadores Tumorais/metabolismo , Epigênese Genética , Ensaios de Triagem em Larga Escala/métodos , Neoplasias/genética , 5-Metilcitosina/metabolismo , Animais , Análise Custo-Benefício , Fluorescência , Ensaios de Triagem em Larga Escala/economia , Humanos , Camundongos , Neoplasias/classificação , Estudo de Prova de Conceito
3.
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.

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.
Surgeon ; 2019 Aug 26.
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.

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.
Indian J Surg Oncol ; 10(Suppl 1): 19-23, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30886488

RESUMO

The treatment of peritoneal surface malignancies, either primary or secondary (peritoneal metastasis), has evolved over the past two decades. A nihilistic approach of incurable "carcinomatosis" is changing into treatment of peritoneal metastasis with curative intent. The aim of the present study is to review the current practice, past history, and future of peritoneal surface oncology in Israel. A systematic review of all patients treated in institutions performing cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies. Each center provided the following data: start year, number of total cases, number of cases performed in 2017, and the method used (open vs. closed technique). Between 1990 and 2018, there were 1462 patients treated by CRS/HIPEC in Israel by eight different surgical groups in six medical centers. Currently, there are seven surgical groups in six medical centers routinely performing CRS/HIPEC. The annual rate of CRS/HIPEC was 171 cases in 2017 with a range of (4-69 cases/center). This is the first step of establishing an Israeli Peritoneal Surface Oncology Group that will have joined database and perform clinical trials in this challenging field of surgical oncology.

9.
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
10.
Pancreas ; 48(3): 367-373, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30768574

RESUMO

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as desmoplasia. We aimed to study desmoplasia in PDAC lymph node (LN) metastases. METHODS: We evaluated LNs from 66 patients with PDAC and LN metastases. We used immunohistochemistry and real-time polymerase chain reaction to phenotype the desmoplastic response. RESULTS: Desmoplasia was identified in 57% of patients with LN metastases (Des+). Cancer-associated fibroblasts (CAFs) in Des+ expressed α-smooth muscle actin and collagen 11A1. The latter expression was present only in CAFs but not in LN stroma or in LN metastases without desmoplasia (Des-). Desmoplasia was associated with upregulation of transforming growth factor ß messenger RNA. Whereas numbers of CD8+ in tumor vicinity were not different between Des+ and Des- patients (78 [standard deviation {SD}, 57] vs 92 [SD, 52], P = 0.48, respectively), the numbers of GATA-3+ cells, a marker of T-helper 2 immune response was significantly increased (3.7 [SD, 6.3] for Des+ vs 1.3 [SD, 2.7] for Des-, P < 0.05). CONCLUSIONS: Lymph node desmoplasia is associated with CAF pattern activation and Th2 infiltration. Therapeutic modulation of desmoplasia may be relevant in the metastatic phase and influence antitumor immune response.


Assuntos
Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Células Th2/patologia , Idoso , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Proliferação de Células , Colágeno Tipo XI/genética , Colágeno Tipo XI/metabolismo , Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Células Th2/metabolismo
11.
Clin Cancer Res ; 25(8): 2664-2671, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30723141

RESUMO

PURPOSE: The role of surgery for first relapse locally recurrent retroperitoneal sarcoma (RPS-LR1) is uncertain. We report outcomes of the largest RPS-LR1 series and propose a new prognostic nomogram. EXPERIMENTAL DESIGN: Patients with consecutive RPS-LR1 without distant metastases who underwent resection at 22 centers (2002-2011) were included. Endpoints were disease-free and overall survival (DFS, OS) and crude-cumulative-incidence (CCI) of local/distant recurrence from second surgery. Nomograms predicting DFS and OS from second surgery were developed and validated (calibration plots); discrimination was assessed (Harrell C index). RESULTS: Of 684 patients identified, full prognostic variable data were available for 602. Initial surgery for primary RPS was performed at our institutions in 188 patients (31%) and elsewhere in 414 (69%). At a median follow-up of 119 months [Interquartile range (IQR), 80-169] from initial surgery and 75 months (IQR 50-105) from second surgery, 6-year DFS and OS were 19.2% [95% confidence interval (CI), 16.0-23.0%] and 54.1% (95% CI, 49.8-58.8%), respectively. Recurrence patterns and survival probability were histology-specific, with liposarcoma subtypes having the highest 6-year CCI of second local recurrence (LR, 60.2%-70.9%) and leiomyosarcoma (LMS) having higher 6-year CCI of distant metastasis (DM, 36.3%). Nomograms included age at second surgery, multifocality, grade, completeness of second surgery, histology, chemotherapy/radiotherapy at first surgery, and number of organs resected at first surgery. OS and DFS nomograms showed good calibration and discriminative ability (C index 0.70 and 0.67, respectively). CONCLUSIONS: We developed nomograms to predict DFS and OS for patients undergoing RPS-LR1 resection. Nomograms provide individualized, disease-relevant estimations of survival for RPS-LR1 patients and assist in clinical decisions.

12.
Obes Surg ; 29(1): 215-220, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30294768

RESUMO

BACKGROUND: It is not uncommon to encounter patients seeking a third, fourth, or even fifth bariatric procedure. With higher expected complication rates and questionable patient benefit, the indication for multiple revisions is still in doubt. To evaluate the perioperative and post-operative outcomes of patients undergoing gastric bypass after two previous bariatric surgeries or more. METHODS: We identified all patients that underwent gastric bypass following at least 2 previous bariatric surgeries. We looked at patient demographics, previous bariatric surgeries, pre-operative body mass index (BMI) and obesity-related co-morbidities, perioperative complications, length of stay (LOS), re-admissions and re-operations, percentage of excess weight loss, and resolution or improvement in comorbidities. RESULTS: Forty-two patients met the inclusion criteria, the majority being females (31, 73.8%). Average age was 45.6 years (range 27-62), average weight and BMI was 116 kg (range 75-175 kg) and 41.1 kg/m2 (range 25.6-58.7 kg/m2), respectively. Thirty-two patients had two previous bariatric surgeries (73.8%), and 10 patients had 3 former bariatric surgeries (23.8%), and for one patient, this was the fifth bariatric procedure (2.4%). Mean LOS was 10 days (range 2-56 days). Eight patients (19%) needed re-admission and 5 (11.9%) needed re-operation. At a median follow up of 48 months (range 7-99 months), the average BMI was 34.5 kg/m2 (range 23.7-55.1 kg/m2) reflecting an excess BMI loss of 43.3%. CONCLUSIONS: Gastric bypass as a third or more bariatric procedure is effective yet associated with high complication rates, re-admissions, and re-operations.


Assuntos
Derivação Gástrica , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação/métodos , Adulto , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/estatística & dados numéricos , Índice de Massa Corporal , Estudos de Coortes , Comorbidade , Feminino , Derivação Gástrica/métodos , Derivação Gástrica/estatística & dados numéricos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Perda de Peso/fisiologia
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.
Ann Surg Oncol ; 25(2): 475-481, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29124488

RESUMO

BACKGROUND: Although lymph node (LN) metastases is considered a grave prognostic sign in pancreatic ductal adenocarcinoma (PDAC), patients with positive lymph nodes (PLN) constitute a heterogeneous group. Our purpose was to identify morphological and immune parameters in the primary tumor and in PLN of resected PDAC patients, which could further stratify these patients to different subgroups. METHODS: We retrospectively evaluated histological and immunohistochemical characteristics of 66 patients with PDAC who were operated at our institution. These were subsequently correlated to clinical outcome. RESULTS: Mean patient age and number of LN harvested was 65.5 ± 10.3 and 12.3 ± 6.5 years, respectively. Tumor size (T stage) and perineural invasion had no effect on clinical outcome. High-grade tumor was associated with decreased survival [overall survival (OS) = 19.6 ± 2.7 months for poorly differentiated PDAC vs. 31.2 ± 4 for well and moderately differentiated, p = 0.03]. Patients with ≥ 8 PLN had significantly worse outcome (OS = 7.3 ± 0.8 months for PLN ≥ 8 vs. OS = 30.1 ± 3.2 months for PLN < 8, p < 0.0001). T helper (Th) 1 immune response was measured both by its effector cells (CD8+) and expression of its main transcription factor, T-bet. CD8+ high patients had significantly increased OS compared with CD8+ low (OS = 36.8 ± 5.3 months for CD8 + high vs. OS = 24.3 ± 3.5 for CD8 + low, p = 0.03) Similarly, Th1 predominant immune response measured by T-bet expression was associated with improved OS compared with non-Th1 (OS = 32.8 ± 3.2 vs. OS = 19.5 ± 2.9, p < 0.0001). CONCLUSIONS: Our data indicate an association between Th1-type immune response and increased survival. Future research is needed to exploit Th1 immune response as a biological marker for immunotherapy.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/mortalidade , Linfonodos/imunologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Pancreáticas/mortalidade , Células Th1/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
16.
Obes Surg ; 28(2): 364-368, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28891022

RESUMO

BACKGROUND: Sleeve gastrectomy (SG) is gaining popularity and has become the procedure of choice for many bariatric surgeons. Long-term weight loss failure is not uncommon. The preferred revisional procedure for these patients is still under debate. OBJECTIVE: The objective of this study was to assess the safety and efficacy of laparoscopic gastric bypass as a revisional surgery for sleeve gastrectomy patients with weight loss failure. SETTING: The study was done at a bariatric surgery center in a university hospital. METHODS: We reviewed our prospectively collected database and identified all patients who underwent conversion of a sleeve gastrectomy to a gastric bypass for weight loss failure. Data on patient demographics, baseline characteristics, and outcomes of bariatric surgery were retrieved. RESULTS: Twenty-three patients with a mean body mass index (BMI) of 41.6 kg/m2 (range 34.1-50.1 kg/m2) underwent conversion to a gastric bypass. Four patients underwent a gastric band prior to the sleeve gastrectomy, and two patients underwent a re-sleeve gastrectomy prior to conversion to a gastric bypass. At a mean follow-up of 24 months (range 9-46 months), the average body mass index (BMI) decreased to 33.8 kg/m2 and the excess body mass index loss (EBMIL) was 42.6%. Diabetes, hypertension, dyslipidemia, and obstructive sleep apnea resolved or improved in 44.4, 45.5, 50, and 50% of the patients, respectively. Three patients developed early postop complications (13%), while late complications occurred in four patients (17%). CONCLUSION: Converting a sleeve gastrectomy to a gastric bypass for weight loss failure is safe, yet weight loss benefit is limited.


Assuntos
Gastrectomia/métodos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Reoperação/métodos , Adulto , Índice de Massa Corporal , Feminino , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Reoperação/efeitos adversos , Estudos Retrospectivos , Falha de Tratamento , Perda de Peso/fisiologia
17.
Surg Endosc ; 32(2): 963-970, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28779247

RESUMO

BACKGROUND: Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging. METHODS: Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R). RESULTS: The optimal liposomal ICG loading dose was 20%, for the different liposomes' sizes tested (30, 60, 100 nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60 nm, which yielded a U/R of 5.2 ± 1.7 (p < 0.001 vs. free ICG). The optimal ICG dose was 8 mg/kg (U/R = 2.1 ± 0.4, p < 0.05 vs. 4 mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10 min after injection and persisting for at least 90 min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection. CONCLUSIONS: Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments.


Assuntos
Corantes Fluorescentes/administração & dosagem , Verde de Indocianina/administração & dosagem , Imagem Óptica/métodos , Ureter/diagnóstico por imagem , Animais , Feminino , Lipossomos , Masculino , Camundongos , Espectroscopia de Luz Próxima ao Infravermelho , Suínos
18.
Surg Obes Relat Dis ; 13(10): 1753-1759, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28918992

RESUMO

BACKGROUND: Morbidly obese patients undergoing bariatric surgery are at risk for developing venous thromboembolic events. Data regarding the appropriate dosing strategy in this special population is limited. OBJECTIVE: To evaluate 2 different dosing regimens of enoxaparin in a prospective cohort of patients undergoing laparoscopic sleeve gastrectomy. SETTING: University hospital, Israel METHODS: The study cohort consisted of 54 patients divided into 2 groups. Group I received 40 mg enoxaparin every 24 hours, and group II received 60 mg enoxaparin every 24 hours. Anti-factor Xa (FXa) levels from each patient were obtained 3 to 4 hours after administration of the third dose of enoxaparin. Levels between .2 and 0.5 U/mL were considered appropriate. Five additional patients were selected as controls. RESULTS: There were 31 patients in group I and 23 patients in group II. There was a statistically significant difference between anti-FXa levels achieved in each group: .247 U/mL in group I (range, .15-.39) versus .346 U/mL (range, .24-.8) in group II. Both groups achieved mean anti-FXa levels in the range designated appropriate with a high proportion of patients achieving appropriate levels (group I: 80.6%; group II: 91.3%). Univariate analyses found that total weight and sex were significantly correlated with anti-FXa levels. However, a multivariate analysis including enoxaparin dose found that only enoxaparin dose remained significantly correlated with anti-FXa levels. CONCLUSION: In the absence of sufficient data regarding clinical efficacy and safety of different dosing regimens both dosing regimens studied are reasonable choices for venous thromboembolic events prophylaxis after bariatric surgery.


Assuntos
Cirurgia Bariátrica/métodos , Enoxaparina/administração & dosagem , Fibrinolíticos/administração & dosagem , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Esquema de Medicação , Inibidores do Fator Xa/metabolismo , Feminino , Gastrectomia/métodos , Humanos , Masculino , Obesidade Mórbida/sangue , Estudos Prospectivos , Tromboembolia Venosa/prevenção & controle
19.
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
20.
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
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