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2.
Cancers (Basel) ; 14(18)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36139548

RESUMO

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of death worldwide. The management of HCC is complex, with surgical treatment providing long-term survival in eligible patients. This study aims to present the experience of aggressive surgical management of HCC in Greece. Methods: This is a retrospective multicentre clinical study with 242 patients. Results: Most patients were male (79%) and had a median age of 71 yrs. According to the most recent BCLC criteria, 172 patients (71.1%) were classified as BCLC 0-A stage, 33 patients (13.6%) were classified as BCLC B, and 37 (15.3%) were classified as BCLC C. A total of 54% of the patients underwent major hepatectomy. Major postoperative morbidity was 15.6%, and the 90-day postoperative mortality rate was 4.5%. The median follow-up was 33.5 months. Three- and five-year overall survival was 65% and 48%, respectively. The median overall survival was 55 months. Significantly, five-year survival was 55% for BCLC A, and 34% and 21% for BCLC B and C, respectively. In univariate analysis, cirrhosis, type of resection (R status), and BCLC stage were associated with overall survival. Multivariate analysis indicated that R1 and R2 resections compared to R0, and BCLC C compared to BCLC 0-A, were independently associated with increased mortality. Conclusions: Aggressive surgical treatment of HCC offers satisfactory long-term survival prospects. A significant percentage (29%) of HCCs that underwent liver resection were of the intermediate and advanced BCLC stage. The management of patients with HCC should be discussed in multidisciplinary tumour board meetings on a case-by-case basis to be more effective.

3.
Cancer Diagn Progn ; 2(2): 144-149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399180

RESUMO

Distal pancreatectomy with splenectomy is the gold-standard surgery for the treatment of left-sided pancreatic cancer. Margin negative resection accompanied by effective lymphadenectomy are the deciding factors affecting the outcome of tail-body pancreatic adenocarcinoma. Radical antegrade modular pancreatosplenectomy (RAMPS) is considered as a reasonable approach for margin-negative and systemic lymph node clearance. Herein, we aim to present all existing data regarding this novel approach including surgical technique and comparison with standardized procedures. RAMPS has shown oncological superiority comparing to distal pancreatectomy with splenectomy due to radical lymphadenectomy and improved dissection of the posterior pancreatic aspects. Robotic-assisted RAMPS has recently been described as a valuable alternative to open RAMPS. With this novel technique, anterior, posterior or modified approaches can be achieved; favorable clinical and oncological outcomes have been reported in the current literature, with reduced conversion rates compared to other minimally invasive approaches, as well as vastly improved maneuverability, accuracy and vision. Robotic-assisted RAMPS is not only technically feasible but also oncologically safe in cases of well-selected, left-sided pancreatic cancer.

4.
Crit Rev Oncol Hematol ; 173: 103663, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35351582

RESUMO

The long-term remissions induced by immune-checkpoint inhibitors (ICIs) in many types of cancers have opened up the possibility of a broader use of immunotherapy in less immunogenic but genetically heterogeneous tumours. Regarding metastatic colorectal cancer (mCRC), in first-line setting, pembrolizumab has been approved as preferred option and nivolumab, alone or in combination with ipilimumab as alternative option for patients with mismatch-repair-deficient and microsatellite instability-high (dMMR/MSI-H) disease, independently of their eligibility for intensive chemotherapy. In subsequent lines, both these immunotherapeutic regimens (e.g., pembrolizumab and nivolumab+/-ipilimumab) as well as dostarlimab-gxly are currently recommended for patients with dMMR/MSI-H chemo-resistant mCRC who have not previously received an ICI. Beginning from the rationale behind the immune-mediated interplay in the dMMR/MSI-H bowel microenvironment, we provide here an update on the evolution status of all available, approved or not, ICIs in mCRC, describing their efficacy and toxicity profile with an emphasis on the pivotal trials supporting current colorectal indications. For each ICI agent, the results from combinations under investigation, particularly for those being upgraded in clinical phasing, the perspectives but also the limitations of main ongoing trials are thoroughly discussed. In the close future, upcoming data are expected to confirm the clinical benefit of ICIs and to further expand their role in mCRC.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Anticorpos Monoclonais Humanizados , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Ipilimumab/uso terapêutico , Instabilidade de Microssatélites , Nivolumabe/uso terapêutico , Microambiente Tumoral
5.
J Invest Surg ; 35(6): 1329-1339, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35196939

RESUMO

Background: Short bowel syndrome (SBS) remains an unsolved issue in modern medicine. Numerous experimental surgical techniques have been proposed in the attempt to increase the intestinal absorptive capacity.Materials and Methods: Ten female Landrace pigs, divided in two groups of 5 (A and B), were explored through a midline incision. A spindle-shaped vascularized full-thickness gastric wall flap (GWF) consisting of part of the major curvature with the gastroepiploic arch preserved was de-epithelialized and then placed as a "patch" to cover an antimesenteric border defect of either a nonfunctional blind intestinal loop (group A) or a functional intestinal loop of the gastrointestinal tract (group B). A spindle-shaped curved, rigid, low density polyethylene (LDPE) splint was sutured on the external surface of the patch in order to prevent shrinkage of GWF and collapse of the intestinal wall in group A.Results: There was a decrease of both dimensions of the patch. Microscopically a thin layer of columnar epithelial cells covered the center of the patch, evolving in shorter, blunt, poorly developed villi with increasing maturation laterally. The patch surface was covered by nearly 90%. In the three animals that died prematurely the coverage of GWF was negligent or suboptimal directly dependent on the length of survival.Conclusions: The hereby-described patching technique demonstrated the growth of intestinal neomucosa on the GWF. The capability of the stomach to provide large flaps and the advantages of the use of native tissues render this animal model valuable for the future research in the field.


Assuntos
Síndrome do Intestino Curto , Animais , Modelos Animais de Doenças , Feminino , Mucosa Intestinal/cirurgia , Intestinos , Síndrome do Intestino Curto/cirurgia , Estômago , Suínos
6.
Surg Oncol ; 41: 101724, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35217286

RESUMO

Desmoid-type fibromatosis (DF) is a distinctly rare condition, mostly of younger adults, characterized by the development of locally aggressive tumors of mesenchymal origin. Desmoid tumors (DT) arise either sporadically or in association with FAP (familial adenomatous polyposis), although certain risk factors have also been identified, including pregnancy and antecedent surgical trauma. They can emerge from any connective tissue including muscle, fascia and aponeurosis and are therefore classified, according to location, as intra-abdominal, of the abdominal wall and extra-abdominal. Despite the lack of metastasizing potential, the course can be unpredictable. Various mutations of APC and ß-catenin genes, among others, play a catalytic role in the pathogenesis of this neoplastic entity. Surgery has lost its traditional role as first line treatment of the disease and several other treatment methods are being considered. Cytotoxic chemotherapy, non-cytotoxic systemic therapy and targeted therapy have been revealed as part of different treatment regimens. Recent progress regarding DT biology and molecular pathways has led to the development of promising novel biological agents. In any case, a multidisciplinary approach is required and is gradually employed, espe-cially in intra-abdominal DTs. In this review, we aim to present current knowledge on DF and summarize current treatment regimens as well as their effectiveness, with emphasis on the intraperitoneal type of DT.


Assuntos
Polipose Adenomatosa do Colo , Fibromatose Agressiva , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/terapia , Adulto , Algoritmos , Feminino , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/genética , Fibromatose Agressiva/terapia , Humanos , Mutação , Gravidez , Fatores de Risco
7.
In Vivo ; 36(1): 30-39, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972697

RESUMO

Inadequate weight loss or weight regain after Roux-en-Y gastric bypass (RYGBP) occurs in more than a quarter of patients for various reasons. Available remedying treatment options include endoscopic and surgical techniques for revision of the gastric pouch and the gastro-jejunal anastomosis, conversion of standard to distal gastric bypass (DRYGBP) or the conversion of RYGBP to biliopancreatic diversion (BPD) or duodenal switch (DS). There is quite a variability concerning the technical simplicity, safety, and effectiveness of these techniques and the small number of patients in the numerous single-center reports precludes any meaningful comparisons. This review aimed to describe all available methods and present the advantages and disadvantages of each of them, to facilitate, rather than guide, the decision of the average bariatric surgeon who encounters such a patient.


Assuntos
Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Derivação Gástrica/efeitos adversos , Humanos , Obesidade Mórbida/cirurgia , Reoperação , Estudos Retrospectivos , Aumento de Peso , Redução de Peso
8.
Cancers (Basel) ; 13(21)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34771695

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, characterized by aggressive biological behavior and a lack of response to currently available chemotherapy. Emerging evidence has identified epithelial to mesenchymal transition (EMT) as a key driver of PDAC progression and a central regulator in the development of drug resistance. EMT is a reversible transdifferentiation process controlled by complex interactions between multiple signaling pathways such as TGFb, Wnt, and Notch, which converge to a network of specific transcription factors. Activation of EMT transcriptional reprogramming converts cancer cells of epithelial differentiation into a more mesenchymal phenotypic state. EMT occurrence in pre-invasive pancreatic lesions has been implicated in early PDAC dissemination. Moreover, cancer cell phenotypic plasticity driven by EMT contributes to intratumoral heterogeneity and drug tolerance and is mechanistically associated with the emergence of cells exhibiting cancer stem cells (CSCs) phenotype. In this review we summarize the available data on the signaling cascades regulating EMT and the molecular isnteractions between pancreatic cancer and stromal cells that activate them. In addition, we provide a link between EMT, tumor progression, and chemoresistance in PDAC.

9.
Per Med ; 18(6): 613-627, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34676789

RESUMO

Pancreatic duct adenocarcinoma is an aggressive tumor which constitutes the fourth leading cause of cancer-related mortality in the USA. Despite the fact that surgery is an integral part of treatment, 5-year survival rates remain unfavorable, partly because of the complex genetic background, delayed diagnosis and also the absence of effective therapeutic approaches. To optimize surgery's results in recent years, the use of patients' genetic profile has been implemented through classification into subtypes; subtypes based on mutations which could efficiently lead oncologists to the path of targeted novel neoadjuvant regimens. This approach aims to achieve the most effective selection of patients undergoing surgery, to increase the number of potentially resectable tumors and also control micro-metastases, aiming to extend overall survival.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirurgia , Humanos , Ductos Pancreáticos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia
10.
Cancers (Basel) ; 13(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34572936

RESUMO

Laparoscopic total gastrectomy is on the rise. One of the most technically demanding steps of the approach is the construction of esophago-jejunal anastomosis. Several laparoscopic anastomotic techniques have been described, like linear stapler side-to-side or circular stapler end-to-side anastomosis; limited data exist regarding hand-sewn esophago-jejunal anastomosis. The study took place between January 2018 and June 2021. Patients enrolled in this study were adults with proximal gastric or esophago-gastric junction Siewert type III tumors that underwent 3D-assisted laparoscopic total gastrectomy. A hand-sewn esophago-jejunal anastomosis was performed in all cases laparoscopically. Forty consecutive cases were performed during the study period. Median anastomotic suturing time was 55 min, with intra-operative methylene blue leak test being negative in all cases. Median operating time was 240 min, and there were no conversions to open. The anastomotic leak rate and postoperative stricture rate were zero. The 30- and 90-day mortality rates were zero. Laparoscopic manual esophago-jejunal anastomosis utilizing a 3D platform in total gastrectomy for cancer can be performed with excellent outcomes regarding anastomotic leak and stricture rate. This anastomotic approach, although technically challenging, is safe and reproducible, with prominent results that can be disseminated in the surgical community.

11.
Cancers (Basel) ; 13(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207591

RESUMO

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N-G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N-G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6-11.9 months) were enrolled. Of these, 52% were males and; the median age was 68 (40-86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0-11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N-G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p < 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.

12.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208987

RESUMO

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.


Assuntos
Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Tinzaparina/administração & dosagem , Albuminas/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Paclitaxel/farmacologia , Neoplasias Pancreáticas/metabolismo , Tinzaparina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
13.
Am J Clin Oncol ; 44(7): 325-330, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33979098

RESUMO

OBJECTIVES: Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy. MATERIALS AND METHODS: From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy. RESULTS: All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. CONCLUSION: The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eletroporação/métodos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Fluoruracila/uso terapêutico , Humanos , Quimioterapia de Indução/métodos , Irinotecano/uso terapêutico , Laparotomia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
14.
Oncology ; 99(7): 471-482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33853080

RESUMO

BACKGROUND: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. PATIENTS AND METHODS: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. RESULTS: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056-0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049-0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. CONCLUSIONS: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/metabolismo , Proteínas de Membrana/metabolismo , Recidiva Local de Neoplasia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Morbidade , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Fatores de Risco
15.
Acta Oncol ; 60(6): 727-734, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33734917

RESUMO

BACKGROUND: Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. METHODS: A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset. RESULTS: Expression of nestin and CD34 was observed only in the tumor stroma. Patients displaying high expression of nestin and CD34 demonstrated higher rates of T1 and T2 tumors (p = .020), lower vascular invasion (p < .001) and improved 5-year overall survival (65%; 95% CI = 55-73 vs 45%; 95% CI = 37-53) after adjusting for clinicopathological characteristics (HR: 0.67; 95% CI = 0.46-0.96). A moderate to strong correlation (r = 0.37-0.78, p < .03) of nestin and CD34 was demonstrated for the following markers; HIF-1α, CD4, CD8, FOXP3, IRF1, GATA3, CCL2, CCL3, CXCL12 and CCL21. CONCLUSIONS: Combined expression of nestin and CD34 expression is associated with better overall survival possibly by modulating a favorable immune response.


Assuntos
Neoplasias Colorretais , Neovascularização Patológica , Antígenos CD34 , Neoplasias Colorretais/genética , Humanos , Imuno-Histoquímica , Nestina/genética
16.
Ann Gastroenterol ; 34(2): 130-141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654350

RESUMO

Neuroendocrine neoplasms (NEN) are frequently characterized by a high propensity for metastasis to the liver, which appears to be a dominant site of distant-stage disease, affecting quality of life and overall survival. Liver surgery with the intention to cure is the treatment of choice for resectable neuroendocrine liver metastases (NELM), aiming to potentially prolong survival and ameliorate hormonal symptoms refractory to medical control. Surgical resection is indicated for patients with NELM from well-differentiated NEN, while its feasibility and complexity are largely dictated by the degree of liver involvement. As a result of advances in surgical techniques over the past decades, complex 1- and 2-stage, or repeat liver resections are performed safely and effectively by experienced surgeons. Furthermore, liver transplantation for the treatment of NELM should be anchored in a multimodal and multidisciplinary therapeutic strategy and restricted only to highly selected individual cases. A broad spectrum of interventional radiology treatments for NELM have recently been available, with expanding indications that are more applicable, as they are less limited by patient- and tumor-related parameters, being therefore important adjuncts or alternatives to surgery. Overall, liver-targeted treatment modalities may precede the administration of systemic molecular targeted agents and chemotherapy for patients with liver-dominant metastatic disease; these appear to be a crucial component of multimodal management of patients with NEN. In the present review, we discuss surgical and non-surgical liver-targeted treatment approaches for NELM, each complementing the other, with a view to assisting physicians in optimizing multimodal NEN patient care.

18.
BMC Cancer ; 21(1): 153, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579217

RESUMO

BACKGROUND: Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assessed its prognostic significance in colorectal cancer. METHODS: One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. RESULTS: Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate to high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250-12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401-8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. CONCLUSIONS: High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/patologia , Proteínas dos Microfilamentos/metabolismo , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Progressão da Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
19.
Hepatobiliary Pancreat Dis Int ; 20(2): 117-127, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33536138

RESUMO

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare benign chronic inflammatory disease of the gallbladder that often presents as cholecystitis and most of the times requires surgical management. In addition, distinguishing XGC from gallbladder cancer preoperatively is still a challenge. The aim of the present systematic review was to outline the clinical presentation and surgical approach of XGC. DATA SOURCES: The present systematic review was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases from inception until June 2020. RESULTS: The laparoscopic cholecystectomy rate (34%) was almost equal to the open cholecystectomy rate (47%) for XGC. An important conversion rate (35%) was observed as well. The XGC cases treated by surgery were associated with low mortality (0.3%), limited intraoperative blood loss (58-270 mL), low complication rates (2%-6%), along with extended operative time (82.6-120 minutes for laparoscopic and 59.6-240 minutes for open cholecystectomy) and hospital stay (3-9 days after laparoscopic and 8.3-18 days after open cholecystectomy). Intraoperative findings during cholecystectomies for XGC included empyema or Mirizzi syndrome. In addition, complex surgical procedures, like wedge hepatic resections and bile duct excision were required during operations for XGC. CONCLUSIONS: XGC seemed to be a rare, benign inflammatory disease that presents similar features as gallbladder cancer. The mortality and complication rates of XGC were low, despite the complex surgical procedures that might be required in some cases.


Assuntos
Colecistite , Xantomatose , Colecistite/cirurgia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estudos Retrospectivos , Xantomatose/diagnóstico , Xantomatose/cirurgia
20.
Int J Colorectal Dis ; 36(5): 903-910, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33409567

RESUMO

BACKGROUND: Diverticular disease (DD) refers to the presence of diverticula throughout the gastrointestinal (GI) tract, mainly along colon. DD might evolve into diverticulitis that is accompanied by severe clinical presentation, which includes abscess formation, perforation, stricture, obstruction and/or fistula. AIM: The aim of the present review is to summarize the role of molecular and genetic factors in DD development, as well as their possible contribution towards new prognostic indicators, diagnostic algorithms and new therapeutic approaches. METHODS AND RESULTS: Except from common predisposing parameters, several genetic mutations, immune factors, neurotransmitters, hormones and protein dysfunctions have been associated to the early onset of DD symptoms, pathogenesis and prognosis of the disease. Specific structural changes in the colonic wall, altered matrix composition and compromised motility have been verified as possible pathogenic factors for the development of DD. Dysregulation in peristaltic activity and reduced ability of the longitudinal muscle to relax following contraction has been also associated with DD evolution. In addition, it has been suspected that genetic defects combined with alterations in intestinal microbiota might play an important role in diverticulitis presentation.


Assuntos
Doenças Diverticulares , Doença Diverticular do Colo , Diverticulite , Divertículo , Microbioma Gastrointestinal , Colo , Doenças Diverticulares/genética , Doença Diverticular do Colo/genética , Humanos
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