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1.
BMC Surg ; 19(1): 18, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717719

RESUMO

BACKGROUND: Although the effect of the recent Greek economic crisis and austerity on the population's health and the health system effectiveness have been discussed a lot recently, data on common surgical conditions affecting large part of the population are missing. Using inguinal hernia as a model we investigated possible changes of citizens' attitude regarding the time of referral, the perioperative details and the intraoperative findings of the emergency hernioplasties. METHODS: The present retrospective study was conducted by a Department of Surgery in a tertiary public hospital of the Greek capital. We reviewed the records of all hernioplasties performed during two 5-year periods: 2005-2009 and 2012-2016, i.e. before and during the crisis focusing on the emergency ones (either incarcerated or strangulated). RESULTS: An equal number of hernioplasties was performed in both periods. During the crisis however, an emergency hernioplasty was significantly more probable (HR 1.269, 95% CI 1.108-1.1454, p = 0.001), at a younger age (p = 0.04), mainly in patients younger than 75 years old (p = 0.0013). More patients presented with intestinal ischemia (7 vs 18, p = 0.002), requiring longer hospitalization (5.2 vs 9.6 days, p = 0.04), with higher cost (560 ± 262.4€ vs 2125 ± 1180.8€ p < 0.001). In contrast the percentage of patients with intestinal resection, their hospitalization length and treatment-cost remained unchanged. During the crisis there was a non-significant increase of emergency patients requiring ICU postoperatively (0 vs 4, p = 0.07) and a non-significant 60% increase of emergency operations in migrants/refugees population (3.5% vs 5.8%, p = 0.28). Epidural anesthesia was significantly more frequent during the crisis. CONCLUSION: During the crisis: (i) the emergency hernioplasties increased significantly, (ii) more patients (exclusively Greek) presented with intestinal ischemia requiring longer hospitalization and higher treatment cost, (iii) the mean age of the urgently treated patients decreased significantly (iv) regional (epidural) anesthesia was more frequent. Although a direct causal relation could not be proven by the present study most observations can be explained by an increase of the patients who delayed the elective treatment of their hernia, and by a redistribution of the surgical workload towards big central hospitals. This can be prevented by adequately supporting the small district hospitals.


Assuntos
Atitude Frente a Saúde , Hérnia Inguinal/epidemiologia , Hérnia Inguinal/cirurgia , Herniorrafia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Recessão Econômica/estatística & dados numéricos , Emergências/economia , Emergências/epidemiologia , Feminino , Grécia/epidemiologia , Custos de Cuidados de Saúde , Hérnia Inguinal/economia , Hérnia Inguinal/psicologia , Herniorrafia/economia , Herniorrafia/psicologia , Hospitais Públicos/economia , Hospitais Públicos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
BMC Cancer ; 18(1): 1202, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509242

RESUMO

BACKGROUND: The incidence of colorectal cancer (CRC) is expected to increase by 80% in year 2035. Even though advantages in treatment of CRC have being made over the last decades, the outcome remains poor. Recently, several inflammatory markers including pretreatment neutrophil to lymphocyte ratio (NLR), have being used as prognostic factors, since host inflammatory response to cancer is believed to determine disease progression. The aim of this study is to evaluate the prognostic significance of pretreatment NLR, in terms of overall survival (OS), 5-year survival, disease-free survival (DFS) and recurrence, in CRC patients who underwent curative resection. METHODS: We retrospectively reviewed 296 patients, who were submitted to elective surgery as first therapeutic option in curative intent, between January 2010 and December 2015. Pretreatment NLR, as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS, 5-year survival, DFS and recurrence. RESULTS: The cutoff point of NLR was calculated with Kaplan-Meier curves and log-rank test to 4.7. Univariate and multivariate analyses disclosed elevated NLR as a significant dismal prognostic factor for DFS (HR 1.88; 95% CI 1.01-3.52; p = 0.048), 5-year survival (HR 2.14; 95% CI 1.12-4.10; p = 0.021) and OS (HR 2.11; 95% CI 1.11-4.03; p = 0.023). In a subgroup analysis, in patients with stage II CRC, NLR > 4.7 was a stronger poor predictor for DFS (HR 2.76; 95% CI 1.07-7.13; p = 0.036), 5-year survival (HR 3.84; 95% CI 1.39-10.63; p = 0.01) and OS (HR 3.62; 95% CI 1.33-4.82; p = 0.012). After adjusting stage for gender, age, location of the primary tumor, differentiation, as well as the presence of perineural, vascular, and lymphovascular invasion, the significance of NLR > 4.7 became more prominent for DFS (HR 2.85; 95% CI 1.21-6.73; p = 0.0176), 5-year survival (HR 4.06; 95% CI 1.66-9.93; p = 0.002) and OS (HR 4.07; 95% CI 1.69-9.91; p = 0.002) in stage II patients. CONCLUSION: Pretreatment NLR > 4.7 is a poor prognostic factor for DFS, 5-year survival and OS in CRC patients undergoing curative resection. The dismal prognostic effect of NRL is magnified in Stage II CRC patients.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Linfócitos/metabolismo , Neutrófilos/metabolismo , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos
3.
J BUON ; 23(5): 1210-1215, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30512250

RESUMO

The Dutch D1D2 Trial revealed a noncompliance rate of 51% in gastric cancer patients who should have undergone a D2 dissection, while it disclosed that the D2 lymph node dissection group of patients exhibited a higher 15-year overall survival (OS) rate, lower rates of local and regional recurrence, lower rates of liver metastases and lower cancer-related death rates compared to the D1 group, implying that the surgical technique per se may influence outcomes. On the other hand, the predominant up-regulation of invasive and metastatic genes in the Western tumor libraries, the differences in the criteria used for gastric cancer diagnosis in the East and the steady fnding that the Asian ethnicity is a favorable prognostic factor for patients with gastric cancer treated in the US, have been proposed as possible explanations for the differences observed in the gastric cancer outcome between the East and the West. Moreover, literature addresses that gastric cancers in the East are mainly diagnosed at younger ages, they are of intestinal type, located distally, diagnosed at an early stage of disease, while gastric cancers in the West are mainly affecting elderly patients with comorbidities, they are of diffuse type, located proximally, and diagnosed at an advanced stage of disease. Future discoveries in genetics and molecular biology may clarify the characteristics of each tumor, while future achievements in imaging modalities and biological or target therapies may establish "personalized" therapies. Until that time, all efforts for improving our surgical techniques and optimizing the perioperative care are mandatory.


Assuntos
Gastrectomia/mortalidade , Neoplasias Gástricas/classificação , Neoplasias Gástricas/mortalidade , Humanos , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
4.
J BUON ; 23(5): 1350-1361, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30570858

RESUMO

PURPOSE: To retrospectively evaluate the short-term and the long-term oncological outcome between two groups of patients who had undergone either high or low ligation of inferior mesenteric vessels (IMV) in rectal cancer surgery. METHODS: Between January 2009 and December 2014, 120 patients with rectosigmoid and rectal adenocarcinoma were operated with curative intent as first therapeutic option. Patients were divided in two groups depending on the level of the inferior mesenteric artery (IMA) ligation. High ligation was defined as the division of the IMA less than 2cm from the aorta followed by the ligation of the inferior mesenteric vein at its origin from the lower border of the pancreas (n=76), while low ligation was defined as the division of IMA immediately distal to the origin of the left colic artery (n=44). RESULTS: The median follow up was 51 months. Univariate analyses disclosed that low ligation was related to a higher postoperative complications rate, mainly related to the higher rate of urinary dysfunction but it was also related to a favorable 5-year overall survival (OS) rate. However, multivariate analyses among factors which might influence the short- and long-term outcomes did not disclose the level of ligation as a factor influencing the postoperative course, the recurrence, the disease free survival (DFS) and the 1-, 3- and 5-year OS rates. CONCLUSIONS: The present study disclosed no differences in surgical, histological, short-term and long-term oncological outcomes between patients treated with either high or low ligation of IMA.


Assuntos
Laparoscopia/mortalidade , Artéria Mesentérica Inferior/cirurgia , Complicações Pós-Operatórias , Neoplasias Retais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Ligadura , Masculino , Artéria Mesentérica Inferior/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
5.
J Surg Res ; 208: 121-131, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27993199

RESUMO

BACKGROUND: The role of hepatic hemodynamic modulation in the development of "small-for-size" syndrome (SFSS) after extended hepatectomy (EH) or living-donor liver transplantation is still controversial. We have designed an experimental study to investigate the effect of hemodynamic parameters of the liver circulation on the development of SFSS after EH in a porcine model. METHODS: Eighteen pigs were randomly divided into two groups: group A has received EH (75%-80%) without splenectomy, and group B with EH and simultaneous splenectomy was carried out. Portal hemodynamics, liver function tests, histologic findings, injury and survival rates were compared between groups A and B. RESULTS: The 7-d survival rate in the splenectomy group was significantly improved compared with group A (88.9% versus 44.4%, P < 0.05). Portal vein pressure, portal vein flow, and liver function tests in the splenectomy group were significantly lower than in group A immediately after splenectomy and postoperatively until the day of sacrifice. Histologic findings in group A clearly illustrate severe inflammation, bridging necrosis, ischemic cholangitis, and severe congestion, while in group B there were less serious histologic changes. CONCLUSIONS: Our experimental study indicates that perioperative portal modulation can successfully prevent the manifestation of SFSS after EH. Therefore, by focusing on "flow" rather than on "size," researchers may understand better the pathophysiology of this syndrome.


Assuntos
Hepatectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Esplenectomia , Animais , Hemodinâmica , Fígado/patologia , Testes de Função Hepática , Regeneração Hepática , Transplante de Fígado , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/prevenção & controle , Distribuição Aleatória , Suínos
6.
J BUON ; 22(5): 1137-1143, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29135094

RESUMO

PURPOSE: The contradictory long-term results following D2 lymphadenectomy have revealed the necessity for a more tailored lymphadenectomy in cases of gastric cancer. Among the patients who had undergone a modified D2 lymphadenectomy for gastric cancer, we further analyzed the subgroup in which histologically and immunohistochemically solitary lymph node metastases were detected. Classifying the primary tumors as towards to the lesser and towards to the grater curvature, we propose possible routes of lymphatic spread and possible clinical implications. METHOD: Between January 2007 and December 2016, 212 patients suffering from gastric adenocarcinoma underwent a modified D2 lymphadenectomy. Solitary lymph node metastases were detected by histology in 14 patients (7 skip metastases) and by immunohistochemistry in an additional 10 patients (5 skip micrometastases). RESULTS: The incidence of the histologically detected solitary lymph node metastases was 6.6% for the whole cohort, increasing to 11.3% with the use of immunohistochemistry. The incidence of the histologically detected skip solitary lymph node metastases was 3.3% for the whole cohort, increasing to 5.7% with the use of immunohistochemistry. Tumors of the lower and middle third of the stomach were equally drained both to the level I and II lymph node stations. However, tumors towards the lesser curvature were mainly drained in the level II lymph node stations (12 out of 19; 63%), while tumors towards the greater curvature were all drained in the level I lymph node stations (5 out of 5; 100%). CONCLUSION: Primary gastric tumors towards the lesser curvature should be treated by a modified D2 lymphadenctomy. However, for tumors towards the greater curvature, a D1(+) lymphadenectomy always including the no. 7 & 9 lymph node stations complex, might be enough.


Assuntos
Excisão de Linfonodo/métodos , Metástase Linfática/patologia , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia
7.
J BUON ; 21(6): 1403-1409, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28039700

RESUMO

PURPOSE: After liver transplantation with a small-for-size liver graft or after extensive hepatectomy for liver malignancies or other non malignant conditions with an insufficient liver volume, the survival of patients depends on liver regeneration. This study was carried out in order to create a new porcine model for the study of small-for-size syndrome (SFSS) after extensive hepatectomy. METHODS: In the present study we used 23 domestic Landrace pigs weighing 28.3±3 kg and aged 19-21 weeks. We describe our detailed surgical procedure for 75% partial hepatectomy a in porcine model, using the saline-coupled bipolar sealing device (Aquamantys®) for hepatectomy. RESULTS: The Aquamantis 2.3 bipolar sealer was connected to the Aquamantis generator and was adjusted to produce 150 watts at a medium flow rate of 20 ml/min. The device temperature was programmed to remain at approximately 100° C and, as a consequence, it produced a tissue ablation without charring. The mean operating time was 153.8 min and the mean blood loss 81.9 ml. The estimated residual liver weight (ERL) was 177 g, whereas the mean proportion of ERL was 24.5%. There was no perioperative mortality. CONCLUSIONS: A large animal model, such as pig, is extremely useful in order to reproduce and understand the SFSS. Our simple technique for successful resection of 75% of the liver in pigs, using the Aquamantys system, achieves effective and safe liver parenchymal transection with significant decrease of intraoperative blood loss and can provide useful information for researchers.


Assuntos
Eletrocoagulação/instrumentação , Hepatectomia/instrumentação , Fígado/cirurgia , Animais , Perda Sanguínea Cirúrgica , Eletrocoagulação/efeitos adversos , Desenho de Equipamento , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Fígado/patologia , Regeneração Hepática , Modelos Animais , Duração da Cirurgia , Sus scrofa , Fatores de Tempo
8.
Hepatobiliary Pancreat Dis Int ; 14(1): 69-74, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25655293

RESUMO

BACKGROUND: Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The application of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency ablation-assisted liver resection. METHODS: A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resection was performed. Intraoperative blood loss, need for transfusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all evaluated. RESULTS: Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 mL, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients (8.3%). The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients (32.4%) with postoperative complications. There is no mortality within 30 days after surgery. CONCLUSIONS: Radiofrequency ablation-assisted liver resection permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Ablação por Cateter/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Idoso , Perda Sanguínea Cirúrgica/mortalidade , Transfusão de Sangue , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
Am J Case Rep ; 24: e939862, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37812585

RESUMO

BACKGROUND Desmoid tumors are a fibroblastic proliferation of soft tissues, with an extreme inclination for local dissemination and recurrence. Surgical excision is the usual treatment choice, with data regarding pharmaceutical treatment being scarce. CASE REPORT A 74-year-old female patient was admitted to "Laikon" General Hospital of Athens, Greece presenting with acute kidney injury secondary to diarrhea. The ultrasound, CT, and abdominal MRI performed showed a 12×6×10 cm tumorous liver lesion. Biopsy of the lesion revealed loosely organized, mesenchymal tissue with spindle cells, and myxoid stroma. Immunochemistry was positive for SMA and b-catenin. Right hemicolectomy was performed with tumor-free surgical margins (R0 resection) and tamoxifen was initiated. Six months after the last MRI (3 months after the use of tamoxifen), a follow-up MRI was performed. The tumor had increased to 14.2×11×12.3 cm, and at the next follow-up it had grown to 20.3×19 cm maximal dimensions; no new metastases were found. The patient received sorafenib and pazopanib. Our patient had PFS with sorafenib for more than 2 years and remained in a good performance status (ECOG 1). For Pazopanid, the median PFS for this treatment option was 6.5 months. CONCLUSIONS The results were good and show a promising method for the treatment of this rare but severe malignancy.


Assuntos
Fibromatose Agressiva , Neoplasias Hepáticas , Feminino , Humanos , Idoso , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/cirurgia , Sorafenibe , Tamoxifeno , Neoplasias Hepáticas/diagnóstico por imagem
10.
BMC Cancer ; 12: 264, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-22892134

RESUMO

BACKGROUND: Palliative surgery followed by postoperative chemotherapy is a challenging approach in the treatment of stage IV gastric cancer yet patients must be carefully selected on the basis of likely clinical benefit. METHODS: The records of 218 patients with histological diagnosis of gastric adenocarcinoma who underwent palliative surgery followed by postoperative chemotherapy were retrospectively reviewed. Twelve potential prognostic variables including tumour DNA index and serum IgG anti- Helicobacter pylori (HP) antibodies were evaluated for their influence on overall survival by multivariate analysis. RESULTS: The median survival was 13.25 months [95% Confidence Interval (CI) 12.00, 14.50]. Three factors were found to have an independent effect on survival: performance status (PS) [PS 60-70 vs. 90-100 Hazard Ratio (HR) 1.676; CI 1.171-2.398, p = 0.005], liver metastases (HR 1.745; CI 1.318-2.310, p < 0.001), and DNA Index as assessed by Image cytometry (2.2-3.6 vs. >3.6 HR 3.059; CI 2.185-4.283, p < 0.001 and <2.2 vs. >3.6 HR; 4.207 CI 2.751-6.433 <0.001). HP infection had no statistically significant effect on survival by either univariate or multivariate analysis. CONCLUSION: Poor pre-treatment PS, the presence of liver metastasis and high DNA Index were identified factors associated with adverse survival outcome in patients with Stage IV gastric cancer treated with palliative gastrectomy and postoperative chemotherapy. HP infection had no influence on survival of these patients.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adenocarcinoma/etiologia , Idoso , Infecções por Helicobacter/complicações , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ploidias , Prognóstico , Neoplasias Gástricas/etiologia
11.
World J Surg Oncol ; 9: 6, 2011 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-21266030

RESUMO

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported. We report a 31 years-old female MEN1-patient, in whom hyperplasia of the parathyroid glands, prolactinoma, non functioning pancreatic endocrine carcinoma and functioning bilateral adrenal carcinomas were diagnosed. Interestingly, a not previously described in the literature data, novel germline mutation (p.E45V) in exon 2 of MEN1 gene, was detected. The association of exon 2 mutation of the MEN1 gene with bilateral adrenal carcinomas in MEN1 syndrome, should be further investigated.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Mutação em Linhagem Germinativa/genética , Neoplasia Endócrina Múltipla Tipo 1/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adulto , Éxons/genética , Feminino , Humanos , Neoplasia Endócrina Múltipla Tipo 1/patologia , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Prognóstico
12.
J BUON ; 25(5): 2160-2170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33277831

RESUMO

PURPOSE: To investigate the expressions of caspase-3 and survivin in colorectal cancer patients and their possible associations with clinicopathological parameters and the oncological outcome. METHODS: Between January 2008 and December 2011, 85 patients with sporadic colorectal cancer were submitted to colectomy with curative intent. Postoperatively, all patients were followed every three months up to the 36th month. Immunohistochemical detection of the apoptosis-related proteins was carried out on 4-µm-thick deparaffinized sections from all primary tumors. Univariate and multivariate analyses were performed by using the R software for Windows, version 3.3.2. RESULTS: Setting the cut-off point for caspase-3 positivity at 5%, 48% of the patients were characterized as caspase-3(+). Caspase-3 positivity was not found related either to any clinicopathological parameter or to the oncological outcome. Choosing simple survivin positivity as the cut-off point for its expression, 78% of the patients were considered as survivin(+). Survivin inexpression predisposed to poorly differentiated tumors of advanced T stage. However, neither a dismal nor a favorable prognostic role for survivin expression or inexpression was disclosed. By dividing all enrolled patients in four different groups, a trend for worse 3-year overall survival rate in the caspase-3(-)/survivin(-) subgroup of patients was noticed (p=0.067). CONCLUSION: Caspase-3 expression was unrelated to the oncological outcome in colorectal cancer patients. The proposed favorable prognostic role for survivin inexpression was not confirmed. On the contrary, survivin(-) tumors were mainly of poor differentiation and advanced T stage. An inverse relationship between caspase-3 and survivin expressions was also not confirmed. Future studies focusing on specific survivin isoforms expression or inexpression may give answers on apoptotic-antiapoptotic interactions on cancer cell death.


Assuntos
Caspase 3/biossíntese , Neoplasias Colorretais/metabolismo , Proteínas de Drosophila/biossíntese , Survivina/biossíntese , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Caspase 3/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas de Drosophila/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Survivina/genética
13.
Clin Exp Metastasis ; 37(1): 13-30, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578655

RESUMO

More than 2 decades ago, the discovery of osteoprotegerin (OPG) as inhibitor of the receptor of activator of nuclear factor Kb (RANK) ligand (RANKL) revolutionized our understanding of bone biology and oncology. Besides acting as decoy receptor for RANKL, OPG acts as decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). OPG, RANKL, and TRAIL are ubiquitously expressed, stimulating per se pivotal signaling cascades implicated in cancer. In the context of cancer cell-bone cell interactions, cancer cells skew the OPG/RANKL/RANK (RANKL cognate receptor) balance towards bone destruction and tumor growth through favoring the RANKL/RANK interface, circumventing OPG. Numerous preclinical and clinical studies demonstrate the dual role of OPG in cancer: antitumor and tumor-promoting. OPG potentially conveys an antitumor signal through inhibiting the tumor-promoting RANKL signaling-both the osteoclast-dependent and the osteoclast-independent-and the tumor-promoting TRAIL signaling. On the other hand, the presumed tumor-promoting functions of OPG are: (i) abrogation of TRAIL-induced apoptosis of cancer cells; (ii) abrogation of RANKL-induced antitumor immunity; and (iii) stimulation of oncogenic and prometastatic signaling cascades downstream of the interaction of OPG with diverse proteins. The present review dissects the role of OPG in bone oncology. It presents the available preclinical and clinical data sustaining the dual role of OPG in cancer and focuses on the imbalanced RANKL/RANK/OPG interplay in the landmark "vicious cycle" of skeletal metastatic disease, osteosarcoma, and multiple myeloma. Finally, current challenges and future perspectives in exploiting OPG signaling in bone oncology therapeutics are discussed.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Imunoconjugados/uso terapêutico , Osteoprotegerina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Osso e Ossos/citologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imunoconjugados/farmacologia , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteólise/tratamento farmacológico , Osteoprotegerina/uso terapêutico , Ligante RANK/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
14.
J BUON ; 25(3): 1482-1489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32862594

RESUMO

PURPOSE: Replication Protein A (RPA) consists of three subunits (RPA1, RPA2 and RPA3) essential for all major DNA metabolic pathways. Although RPA seems to be a promising therapeutic target, its role in human cancers has not been fully elucidated. This is the first study investigating the expression of all the three RPA subunits in a series of 74 resected gastric carcinomas and analyzing the possible correlations with clinicopathologic parameters (histological type, grade, lymphovascular invasion, lymph node status and disease stage), Ki-67 proliferative index, Topoisomerase IIa expression and patients' survival. METHODS: Immunohistochemistry using monoclonal antibodies. Univariate and multivariate statistical analysis. RESULTS: All the three subunits showed widespread nuclear expressions in gastric carcinomas with significant associations among their expressions. RPA2 demonstrated higher expression levels in low grade carcinomas and a gradual significant decrease from N0 to N3 and from stage I to stage IV carcinomas. All the three subunits were statistical significantly more abundant in lymph node negative and earlier stage (stage I & II) gastric carcinomas. No associations were established among RPAs and the proliferative marker Ki-67. In patients with positive lymph nodes and advanced tumor stage, RPA1 expression seemed to predict a better overall survival implying a probable predictive role. CONCLUSIONS: The widespread expression of RPA(1-3) suggests one or more roles in gastric cancer. Their presence in earlier stage tumors probably offers an opportunity for early targeted therapy. Their probable predictive value in node positive and advanced stage tumors needs further investigation with respect to specific chemotherapeutic treatments.


Assuntos
Proteína de Replicação A/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Am J Clin Oncol ; 43(5): 305-310, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32343515

RESUMO

OBJECTIVES: Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC. METHODS: This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m, oxaliplatin 80 mg/m on day 1, CP 1000 mg/m twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate. RESULTS: Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed. CONCLUSIONS: First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Adulto , Idoso , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Carcinoma Neuroendócrino/mortalidade , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Indazóis , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
16.
Oncology ; 76(1): 36-41, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19033714

RESUMO

BACKGROUND: Oxaliplatin has become one of the major cytotoxic agents for the treatment of gastrointestinal tumors. As a result, several cases of the so-called oxaliplatin-associated hypersensitivity reaction have been documented. PATIENTS AND METHODS: We have retrospectively evaluated and characterized these reactions in our patient group by reviewing the files of 1,224 patients exposed to an oxaliplatin-containing regimen in order to provide useful clinical information for diagnosis and management. RESULTS: Three hundred and eight (308) patients who have never been exposed to platinum compounds developed symptoms compatible with a reaction to oxaliplatin that was verified by manifestation of at least similar symptoms on rechallenging. The reactions occurred after the first 5 courses, with a median course number of 9 (range 1-24). These reactions could be distinguished as (1) mild reactions occurring in 195 (63%) patients manifesting with itching and small area erythema either during treatment or within the next hours, and (2) severe reactions occurring in 113 (37%) patients within minutes of drug infusion manifesting with diffuse erythroderma, facial swelling, chest tightness, bronchospasm and changes in blood pressure. Oxaliplatin withdrawal was not required in patients with a mild reaction. Forty-eight (42%) patients having a severe reaction with appropriate premedication and prolongation of the infusion duration could tolerate 2-4 subsequent courses. For the remaining 65 (58%) patients, oxaliplatin withdrawal was inevitable because of the very severe reactions occurring on rechallenging. In addition, 3 patients presented with thrombocytopenia and 3 others with hemolytic anemia, all reversible upon oxaliplatin discontinuation. CONCLUSIONS: Hypersensitivity reactions to oxaliplatin are underestimated. Although the reactions are not frequent during first courses, in extensively pretreated patients, they may become a serious problem. In the majority of patients, drug discontinuation might not be necessary. In patients manifesting a severe reaction, re-exposure to oxaliplatin should be considered only if the patient can tolerate the reaction and there has been clinical benefit from this therapy. Physicians and nursing staff should be aware of the risk and be well prepared.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Hipersensibilidade a Drogas/epidemiologia , Compostos Organoplatínicos/efeitos adversos , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Hipersensibilidade a Drogas/fisiopatologia , Feminino , Neoplasias da Vesícula Biliar/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Oxaliplatina , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Neoplasias Gástricas/tratamento farmacológico
17.
South Med J ; 102(10): 1061-4, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19738519

RESUMO

Diffuse malignant peritoneal mesothelioma (DMPM) represents 90% of all peritoneal forms of mesothelioma. It affects mainly patients 50-69 years old. In 50% of cases there is a history of asbestos exposure. The clinical presentation of the disease is not characteristic: nonspecific abdominal pain, weight loss, and abdominal distension are common. Ascites occurs in 90% of the patients. Bowel obstruction is a late manifestation. We present three patients with DMPM, without a history of asbestos exposure and without ascites, who presented with complete bowel obstruction. All patients underwent emergency operations, and palliative surgical procedures were performed. Each patient died within 3 to 6 months postoperatively.


Assuntos
Obstrução Intestinal/etiologia , Mesotelioma/diagnóstico , Neoplasias Peritoneais/diagnóstico , Adulto , Evolução Fatal , Humanos , Ileostomia , Masculino , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Neoplasias Peritoneais/cirurgia
18.
Rural Remote Health ; 9(4): 1019, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19883145

RESUMO

INTRODUCTION: It has been established that patients prefer receiving health information from primary care physicians. In Greece, recent reforms supporting urban primary healthcare have not been enacted, and long waiting times in Athens' emergency departments are common. AIM: To evaluate cases treated in the emergency department of a Greek general hospital and explore the potential role of primary care in managing these cases. METHODS: A total of 53,926 patients visited the emergency department studied during on-call days from February 2005 to February 2006. The cases were classified into 6 groups according to their main complaint: (1) internal medicine; (2) surgical; (3) orthopedic; (4) otorhinolaryngology (ENT); (5) eye disorders (ophthalmology); and (6) gynecology-obstetric. RESULTS: Of the 53,926 patients studied, 9167 (17%) came from a rural area. The internal medicine department was most commonly attended (15,373; 28.5%), followed by orthopedics (16.9%). In the surgical, ENT, ophthalmology and gynecology groups, almost one in three patients could have been managed by a GP, as could 40% of orthopedic cases. Orthopedic and ENT patients had the highest rate of X-rays performed. CONCLUSION: Many emergency patients visiting hospitals can be managed at the primary care level. The development of a 'practice-based curriculum' for GPs would be an excellent method to obtain higher professional standards.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Medicina de Família e Comunidade/organização & administração , Idoso , Feminino , Grécia , Humanos , Masculino , Serviços de Saúde Rural/organização & administração
19.
Clin Case Rep ; 7(1): 242-243, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30656055

RESUMO

Bronchial rupture following major blunt chest trauma should be suspected in every case of massive and persistent air leak through the intercostal drain tube. Chest radiogram offers indirect signs, while chest CT scan demonstrates specific signs highly suggestive for this extremely rare tracheobronchial injury. Bedside bronchoscopy confirms the diagnosis.

20.
World J Clin Cases ; 7(21): 3524-3534, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31750334

RESUMO

BACKGROUND: The perivascular epithelioid cell tumour (PEComa) family of tumours mainly includes renal and hepatic angiomyolipomas, pulmonary lymphangioleiomyomatosis and clear cell "sugar" tumour of the lung. Several uncommon tumours with similar morphological and immunophenotypical characteristics arising at a variety of sites (abdominal cavity, digestive tract, retroperitoneum, skin, soft tissue and bones) are also included in the PEComa family and are referred to as PEComas not otherwise specified. CASE SUMMARY: We present a 37-year-old female patient who underwent resection of an 8.5 cm × 8 cm × 4 cm retroperitoneal tumour, which eventually was diagnosed as PEComa of uncertain biological behaviour. Three years after the operation, the patient remains without any evidence of recurrence. A search was performed in the Medline and EMBASE databases for articles published between 1996 and 2018, and we identified 31 articles related to retroperitoneal and perinephric PEComas. We focused on sex, age, maximum dimension, histological and immunohistochemical characteristics of the tumour, follow-up and long-term outcome. Thirty-four retroperitoneal (including the present one) and ten perinephric PEComas were identified, carrying a malignant potential rate of 44% and 60%, respectively. Nearly half of the potentially malignant PEComas presented with or developed metastases during the course of the disease. CONCLUSION: Retroperitoneal PEComas are not as indolent as they are supposed to be. Radical surgical resection constitutes the treatment of choice for localized disease, while mammalian target of the rapamycin (mTOR) inhibitors constitute the most promising therapy for disseminated disease. The role of mTOR inhibitors as adjuvant or neoadjuvant therapies needs to be evaluated in the future.

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