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1.
Int J Mol Sci ; 24(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37511344

RESUMO

Colorectal cancer (CRC) has a high incidence and is one of the leading causes of cancer-related death. The accumulation of cancer-associated fibroblasts (CAF) induces an aggressive, stem-like phenotype in tumor cells, and it indicates a poor prognosis. However, cellular heterogeneity among CAFs and the targeting of both stromal and CRC cells are not yet well resolved. Here, we identified CD142high fibroblasts with a higher stimulating effect on CRC cell proliferation via secreting more hepatocyte growth factor (HGF) compared to CD142low CAFs. We also found that combinations of inhibitors that had either a promising effect in other cancer types or are more active in CRC compared to normal colonic epithelium acted synergistically in CRC cells. Importantly, heat shock protein 90 (HSP90) inhibitor selected against CD142high fibroblasts, and both CRC cells and CAFs were sensitive to a BCL-xL inhibitor. However, targeting mitogen-activated protein kinase kinase (MEK) was ineffective in fibroblasts, and an epigenetic inhibitor selected for a tumor cell population with markers of aggressive behavior. Thus, we suggest BCL-xL and HSP90 inhibitors to eliminate cancer cells and decrease the tumor-promoting CD142high CAF population. This may be the basis of a strategy to target both CRC cells and stromal fibroblasts, resulting in the inhibition of tumor relapse.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Colorretais , Humanos , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fibroblastos/metabolismo , Recidiva Local de Neoplasia/patologia , Microambiente Tumoral , Tromboplastina
2.
Cell Mol Life Sci ; 78(21-22): 7009-7024, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34609520

RESUMO

The majority of colorectal cancer (CRC) patients carry mutations in the APC gene, which lead to the unregulated activation of the Wnt pathway. Extracellular vesicles (EV) are considered potential therapeutic tools. Although CRC is a genetically heterogeneous disease, the significance of the intra-tumor heterogeneity in EV uptake of CRC cells is not yet known. By using mouse and patient-derived organoids, the currently available best model of capturing cellular heterogeneity, we found that Apc mutation induced the expression of interferon-induced transmembrane protein 1 (Ifitm1), a membrane protein that plays a major role in cellular antiviral responses. Importantly, organoids derived from IFITM1high CRC cells contained more proliferating cells and they had a markedly reduced uptake of fibroblast EVs as compared to IFITM1low/- cells. In contrast, there was no difference in the intensity of EV release between CRC subpopulations with high and low IFITM1 levels. Importantly, the difference in cell proliferation between these two subpopulations disappeared in the presence of fibroblast-derived EVs, proving the functional relevance of the enhanced EV uptake by IFITM1low CRC cells. Furthermore, inactivating IFITM1 resulted in an enhanced EV uptake, highlighting the importance of this molecule in establishing the cellular difference for EV effects. Collectively, we identified CRC cells with functional difference in their EV uptake ability that must be taken into consideration when using EVs as therapeutic tools for targeting cancer cells.


Assuntos
Antígenos de Diferenciação/genética , Neoplasias Colorretais/genética , Vesículas Extracelulares/genética , Animais , Transporte Biológico/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Organoides/fisiologia , Via de Sinalização Wnt/genética
3.
Int J Mol Sci ; 23(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35216292

RESUMO

Extracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may reflect the molecular composition of the releasing cells and thus, EVs may hold a great promise for tumor diagnostics, the impact of intratumoral heterogeneity on the intensity of EV release is still largely unknown. By using CRC patient-derived organoids that maintain the cellular and molecular heterogeneity of the original epithelial tumor tissue, we proved that CD44high cells produce more organoids with a higher proliferation intensity, as compared to CD44low cells. Interestingly, we detected an increased EV release by CD44high CRC cells. In addition, we found that the miRNA cargos of CD44high and CD44low cell derived EVs largely overlapped and only four miRNAs were specific for one of the above subpopulations. We observed that EVs released by CD44high cells induced the proliferation and activation of colon fibroblasts more strongly than CD44low cells. However, this effect was due to the higher EV number rather than to the miRNA cargo of EVs. Collectively, we identified CRC subpopulations with different EV releasing capabilities and we proved that CRC cell-released EVs have a miRNA-independent effect on fibroblast proliferation and activation.


Assuntos
Neoplasias Colorretais , Vesículas Extracelulares , MicroRNAs , Comunicação Celular , Neoplasias Colorretais/patologia , Vesículas Extracelulares/metabolismo , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Organoides/metabolismo
4.
Stem Cells ; 38(2): 291-300, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31675158

RESUMO

Extracellular vesicles (EV) are membrane-surrounded vesicles that represent a novel way of intercellular communication by carrying biologically important molecules in a concentrated and protected form. The intestinal epithelium is continuously renewed by a small proliferating intestinal stem cell (ISC) population, residing at the bottom of the intestinal crypts in a specific microenvironment, the stem cell niche. By using 3D mouse and human intestinal organoids, we show that intestinal fibroblast-derived EVs are involved in forming the ISC niche by transmitting Wnt and epidermal growth factor (EGF) activity. With a mouse model that expresses EGFP in the Lgr5+ ISCs, we prove that loss in ISC number in the absence of EGF is prevented by fibroblast-derived EVs. Furthermore, we demonstrate that intestinal fibroblast-derived EVs carry EGF family members, such as amphiregulin. Mechanistically, blocking EV-bound amphiregulin inhibited the EV-induced survival of organoids. In contrast, EVs have no role in transporting R-Spondin, a critical niche factor amplifying Wnt signaling. Collectively, we prove the important role of fibroblast-derived EVs as a novel transmission mechanism of factors in the normal ISC niche.


Assuntos
Vesículas Extracelulares/metabolismo , Mucosa Intestinal/fisiopatologia , Intestinos/fisiopatologia , Nicho de Células-Tronco/genética , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
5.
Acta Chir Belg ; 121(5): 327-332, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32496868

RESUMO

INTRODUCTION: Conventional abdominoperineal resection (APR) has a high rate of local recurrence. Extralevator abdominoperineal excision (ELAPE) can potentially diminish the rate of intraoperative tumour perforation (IOTP) and can provide wider circumferential resection margins (CRM) but at the price of higher perineal complication rate. The aim of our study was to compare the short term results of conventional APR to ELAPE. MATERIALS AND METHODS: Thirty-five consecutively operated APRs compared to 38 also consecutively operated ELAPEs. Prospectively collected short-term outcome data were analysed retrospectively. RESULTS: There was no difference in demographics, disease stage or tumour location between groups. IOTP rate and CRM positivity rates were similar between the two groups (p = .608). No difference was found in major (Clavien-Dindo III-V) complications, but we found statistically significant difference in minor (Clavien-Dindo I-II) complications (p = .01) in favour of the ELAPE group. Frequency of perineal SSI was lower in ELAPE group, but the difference was not significant (p = .320). Intraoperative iatrogenic complications occurred at significantly lower rate in ELAPE group (p = .035). Also, postoperative morbidity connected with the dissection in the perineal phase (e.g. urine incontinence, urinary retention) was significantly lower (p = .018) after ELAPE. DISCUSSION AND CONCLUSIONS: In our experience ELAPE operations may diminish the rate of Clavien-Dindo I-II complications compared to conventional APR. This effect is ensuing from the decrease of intraoperative iatrogenic complications and from the decrease of minor postoperative complications.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Protectomia , Neoplasias Retais , Humanos , Recidiva Local de Neoplasia , Períneo/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Cell Mol Life Sci ; 76(12): 2463-2476, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31028424

RESUMO

Extracellular vesicles (EVs) are membrane-surrounded structures that transmit biologically important molecules from the releasing to target cells, thus providing a novel intercellular communication mechanism. Since EVs carry their cargo in a protected form and their secretion is generally increased in tumorigenesis, EVs hold a great potential for early cancer diagnosis. By 3D culturing, we provide evidence that colorectal cancer (CRC) patient-derived organoids, representing a state-of-the-art established and essential approach for studying human CRC, is a suitable model for EV analysis. When testing the effects of major factors promoting CRC progression on EV release in the organoid model, we observed that Apc mutation, leading to uncontrolled Wnt activation and thus to tumorigenesis in the vast majority in CRC patients, critically induces EV release by activating the Wnt pathway. Furthermore, the extracellular matrix component collagen, known to accumulate in tumorigenesis, enhances EV secretion as well. Importantly, we show that fibroblast-derived EVs induce colony formation of CRC organoid cells under hypoxia. In contrast, there was no major effect of tumor cell-derived EVs on the activation of fibroblasts. Collectively, our results with CRC and Apc-mutant adenoma organoids identify Apc mutation and collagen deposition as critical factors for increasing EV release from tumors. Furthermore, we provide evidence that stromal fibroblast-derived EVs contribute to tumorigenesis under unfavorable conditions in CRC.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais/patologia , Vesículas Extracelulares/patologia , Intestinos/patologia , Organoides/patologia , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Progressão da Doença , Vesículas Extracelulares/genética , Humanos , Camundongos Endogâmicos C57BL , Mutação , Organoides/metabolismo , Células Tumorais Cultivadas , Via de Sinalização Wnt
7.
Orv Hetil ; 159(21): 823-830, 2018 May.
Artigo em Húngaro | MEDLINE | ID: mdl-29779391

RESUMO

Surgical resection is still the only curative treatment for colorectal liver metastases, but this is one part of a complex therapy. Nowadays a patient with colorectal liver metastasis is not treated only by a surgeon or by an oncologist or even only by an invasive radiologist. Collective decisions, complement treatments give the only chance to treat these patients for longer time. Patients with colorectal liver metastases could be regarded as patients with chronic disease. Specially interesting are the various treatment options of resectable colorectal liver metastases. The efficiency and necessity of preoperative chemotherapy are still a hot spot in the treatment of resectable liver metastases. In this study, we try to summarize the international and local experiences and the current evidence of the use of preoperative chemotherapy in the treatment of colorectal liver metastases. Orv Hetil. 2018; 159(21): 823-830.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Terapia Neoadjuvante/métodos , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/dietoterapia , Neoplasias Hepáticas/cirurgia , Masculino , Estadiamento de Neoplasias , Prognóstico
8.
Mod Pathol ; 29(8): 928-38, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27150162

RESUMO

Exosomes are small membrane vesicles that have important roles in transporting a great variety of bioactive molecules between epithelial compartment and their microenvironment during tumor formation including colorectal adenoma-carcinoma sequence. We tested the mRNA expression of the top 25 exosome-related markers based on ExoCharta database in healthy (n=49), adenoma (n=49) and colorectal carcinoma (n=49) patients using Affymetrix HGU133 Plus2.0 microarrays. Most related genes showed significantly elevated expression including PGK1, PKM, ANXA5, ENO1, HSP90AB1 and MSN during adenoma-carcinoma sequence. Surprisingly, the expression of ALIX (ALG 2-interacting protein X), involved in multivesicular body (MVB) and exosome formation, was significantly reduced in normal vs adenoma (P=5.02 × 10(-13)) and in normal vs colorectal carcinoma comparisons (P=1.51 × 10(-10)). ALIX also showed significant reduction (P<0.05) at the in situ protein level in the epithelial compartment of adenoma (n=35) and colorectal carcinoma (n=37) patients compared with 27 healthy individuals. Furthermore, significantly reduced ALIX protein levels were accompanied by their gradual transition from diffuse cytoplasmic expression to granular signals, which fell into the 0.6-2 µm diameter size range of MVBs. These ALIX-positive particles were seen in the tumor nests, including tumor-stroma border, which suggest their exosome function. MVB-like structures were also detected in tumor microenvironment including α-smooth muscle actin-positive stromal cells, budding off cancer cells in the tumor front as well as in cancer cells entrapped within lymphoid vessels. In conclusion, we determined the top aberrantly expressed exosome-associated markers and revealed the transition of diffuse ALIX protein signals into a MVB-like pattern during adenoma-carcinoma sequence. These tumor-associated particles seen both in the carcinoma and the surrounding microenvironment can potentially mediate epithelial-stromal interactions involved in the regulation of tumor growth, metastatic invasion and therapy response.


Assuntos
Adenoma/química , Biomarcadores Tumorais/análise , Proteínas de Ligação ao Cálcio/análise , Carcinoma/química , Proteínas de Ciclo Celular/análise , Neoplasias Colorretais/química , Complexos Endossomais de Distribuição Requeridos para Transporte/análise , Exossomos/química , Corpos Multivesiculares/química , Adenoma/genética , Adenoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/genética , Carcinoma/genética , Carcinoma/patologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Exossomos/genética , Exossomos/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Corpos Multivesiculares/genética , Corpos Multivesiculares/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Microambiente Tumoral
9.
Orv Hetil ; 157(20): 796-800, 2016 May 15.
Artigo em Húngaro | MEDLINE | ID: mdl-27156527

RESUMO

The technique and clinical results of liver surgery are constantly evolving in recent years, and this development felt most intensely in the field of laparoscopic liver surgery. Based on the results of comparative studies reported to date, laparoscopic surgery is not inferior to open surgery. Although a very small percentage of liver resections are performed with laparoscopic technique, clearly it has a role in oncological surgery. The minor, major, anatomical, or even multi-stage liver resections can be performed with laparoscopy. The previously general recommendation, that lesions in the front segments of the liver are recommended for the minimally invasive technique is currently outdated. The authors present the history of a 70-year-old female, who underwent complex oncosurgical treatment of a locally advanced rectum carcinoma and a pure laparoscopic resection of a solitary hepatic metastasis of segment VII. With this case report the authors want to underline that malignant lesions in the posterior segments of the liver can be removed safely with laparoscopy.


Assuntos
Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Retais/patologia , Idoso , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
10.
Orv Hetil ; 156(36): 1460-71, 2015 Sep 06.
Artigo em Húngaro | MEDLINE | ID: mdl-26320600

RESUMO

INTRODUCTION: Besides clinicopathological parameters, molecular markers can be very important, and further characterize colorectal carcinomas into chromosomally unstable, microsatellite instable and "CqG-island methylator phenotype" groups. AIM: To study the frequency of microsatellite instability using immunohistochemical evaluation of MLH1, MSH2, MSH6 and PMS2 proteins in colorectal carcinoma. METHOD: 122 colorectal carcinomas as well as in 69 paired liver metastases were evaluated. Additionally, prognostic and predictive potential of mismatch repair status was tested. RESULTS: Microsatellite instable phenotype was identified in 11.5% (14/122) of the tumours. There were no differences regarding staining intensity of tumour regions. Mismatch repair status was discordant in primaries vs. metastases in 20.2%. There was no difference in progression free- and overall survival according to mismatch repair status. The mismatch repair status was not predictive for survival within systemic therapy regimen groups. CONCLUSIONS: The subgroups of colorectal carcinomas could be evaluated in a larger and homogenised patient cohort to predict prognosis and response to therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Reparo de Erro de Pareamento de DNA , Marcadores Genéticos , Neoplasias Hepáticas/cirurgia , Instabilidade de Microssatélites , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Panitumumabe , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida
11.
Magy Seb ; 67(1): 18-23, 2014 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-24566656

RESUMO

Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. AIP belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20-30%. Differentiation of AIP from the more common pancreatic cancer can be very challenging. About 20% of autoimmune pancreatitis is diagnosed postoperatively during final histological examination. While each of diagnostic investigations provide some additional information towards definitive diagnosis, the question still remains whether it is possible to prevent unnecessary pancreatic resection. We demonstrate the differential diagnostic opportunities when we present our case as well as discuss the literature data of this condition. In conclusion, we think that in case of a focal pancreatic lesion AIP should always be considered.


Assuntos
Autoimunidade , Neoplasias Pancreáticas/diagnóstico , Pancreatite/diagnóstico , Pancreatite/imunologia , Anti-Inflamatórios/administração & dosagem , Colangiopancreatografia Retrógrada Endoscópica , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreatite/sangue , Pancreatite/diagnóstico por imagem , Pancreatite/tratamento farmacológico , Tomografia Computadorizada por Raios X
12.
Magy Onkol ; 58(1): 47-51, 2014 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-24712006

RESUMO

Retroperitoneal sarcomas make up 0.15% of all solid tumors. The mainstay of their treatment is surgical resection, though the removal of the often sizable tumors may pose serious challenge to surgeons. There is no clear-cut recommendation for neoadjuvant, nor for adjuvant treatment so far. We collected the data and recommendations concerning the attributes and the treatment options for retroperitoneal sarcomas. Mainly we focused on the possibilities and the recent change in tactics of surgery. There is no prospective randomized study dealing with surgical treatment of retroperitoneal sarcomas. According to data in the literature the en-block R0 resection along with all the possibly involved neighboring organs offers the best chance for cure. The greatest problem is to define the required resection margin which is needed for R0 resection. Radio- and/or chemotherapy can be used for diminishing the possibility of tumor recurrence. The greatest risk factors for recurrence are incomplete resection, high grade tumor, and non-liposarcoma type histology. Survival depends on local recurrence rather than on distant metastases. Retroperitoneal sarcomas are ideally treated in sarcoma centers, where multidisciplinary consultation is available and complex treatment plans can be set. Complete recovery can be achieved with radical surgical excision. The chance for R0 resection is enhanced by chemo- and radiotherapy.


Assuntos
Neoplasias Retroperitoneais/prevenção & controle , Neoplasias Retroperitoneais/cirurgia , Sarcoma/cirurgia , Quimioterapia Adjuvante , Diagnóstico Diferencial , Humanos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Neoplasias Retroperitoneais/mortalidade , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia
13.
Magy Seb ; 66(6): 320-4, 2013 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-24333976

RESUMO

INTRODUCTION: Sentinel biopsy technique was performed in Europe in 1996.It was a great improvement in the surgical treatment of breast cancer, it decreased the number of patients suffering from early and late morbidity following axillary lymph node dissection (ALND). In our paper we demonstrate the evolution of sentinel biopsy technique (SLNB), as well as the changes in our policy on axillary treatment in line with the European trends. METHODS: The authors of this article give an overview and analyse the relevant literature concerning sentinel lymph node biopsy and data of patients on whom sentinel lymph node biopsy was performed from 01/01/2001 to 31/12/2012. RESULTS: Between 2001 and 2013 we performed 3756 breast operations, 2742 of those were done for malignant disease. Altogether we performed 744 sentinel lymph node biopsies in the Uzsoki teaching Hospital. The proportion of SLNB patients is increasing, it was 24.6% between 2001-2006 and 29.2% between 2007-2012, respectively. The indication of SLNB is widening, there might be justification of the technique even by multifocal or multilocular disease, in male patients, after former breats surgery or even in pregnant patients. CONCLUSION: Histological examination of sentinel lymph node and its effect on complex treatment of breats cancer may place the role of surgical axillary staging in a brand new aspect in the near future perhaps.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Excisão de Linfonodo/normas , Linfonodos/patologia , Linfonodos/cirurgia , Biópsia de Linfonodo Sentinela , Axila , Neoplasias da Mama/cirurgia , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/terapia , Feminino , Hospitais Gerais/estatística & dados numéricos , Humanos , Hungria , Masculino , Guias de Prática Clínica como Assunto , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/cirurgia , Biópsia de Linfonodo Sentinela/normas , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Centro Cirúrgico Hospitalar/estatística & dados numéricos
14.
Magy Seb ; 66(6): 316-9, 2013 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-24333975

RESUMO

INTRODUCTION: Laparoscopic appendectomy is one of the first developed minimally invasive surgical procedures, nevertheless its judgement is contradictory up to the present day as far as its advantages and indications are concerned. METHODS: The authors of this article give an overview and analyse the relevant literature concerning laparoscopic appendectomy and the data of patients on whom appendectomy was performed from 01/01/2005 to 30/09/2013 with laparoscopic and open technique. RESULTS: At the Surgical Department of the Uzsoki Hospital 1214 patients had appendectomy because of acute appendicitis from 01/01/2005 to 30/09/2013. The applied surgical procedure was laparoscopy with 1065 patients (87.73%) and the open technique with 149 patients (12.27%). Since January 2006 our main principle has been that in case of appendicitis the primary technique to be applied is laparoscopic appendectomy. We were forced to conversion with 16.5% of patients and as the operational experience of the department grows, the proportion of conversions tends to decrease. CONCLUSION: The advantages of laparoscopic appendectomy as opposed to open surgery have become obvious in the past decade, and the procedure may be recommended for all age groups. In case acute appendicitis is suspected the primary procedure to be applied in our department is the laparoscopic operation, the results of which are at least as good as that of open appendectomy. The routine application of laparoscopic appendectomy provides an excellent basis for the acquisition of advanced laparoscopic surgery thus appendectomy will not lose its training character due to the laparoscopic approach.


Assuntos
Apendicectomia/métodos , Apendicectomia/normas , Conversão para Cirurgia Aberta/estatística & dados numéricos , Laparoscopia , Doença Aguda , Apendicectomia/estatística & dados numéricos , Apendicite/cirurgia , Hospitais Gerais/estatística & dados numéricos , Humanos , Hungria/epidemiologia , Laparoscopia/métodos , Centro Cirúrgico Hospitalar/estatística & dados numéricos
15.
Magy Seb ; 66(6): 325-30, 2013 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-24333977

RESUMO

INTRODUCTION: The only curative treatment of colorectal liver metastases (CRLM) is surgical resection. Preoperative/neoadjuvant chemotherapy can be used for resectable, for borderline resectable or even for irresectable CRLM patients. PATIENTS: Data of CRLM patients treated with surgical resection at the Uzsoki Hospital were analysed. Patients were classified into two groups, (A) who received preoperative chemotherapy before hepatic resection, and (B) who received no chemotherapy before resection. RESULTS: Between 01.01.2007. and 31.12.2010. 128 CRLM patients were treated with hepatic resection. 68 patients (53%) received chemotherapy before hepatic resection, 60 patients (47%) were resected without neoadjuvant chemotherapy. There was no significant difference in the complications between the groups (p = 0.39). Median overall survival was 41 months. The progression free survival (PFS) at 3 and 5 years were 25%, the 3 and 5 year overall survival (OS) were 55% and 31%. Both PFS and OS were significantly worse in the chemotherapy group (p = 0.014, p = 0.015). The subgroup of patients receiving bevacizumab containing preoperative chemotherapy has significanly better PFS than patients receiving only cytotoxic chemotherapy (p = 0.004). CONCLUSION: Surgical resection of CRLM patients results good survival data even in non-selected patients, although the very long survival results reported in the literature couldn't have been reproduced in this patient population. When preoperative chemotherapy was combined with bevacizumab, survival was similar to the upfront resected patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Ácido Fólico/administração & dosagem , Hepatectomia/métodos , Hospitais Gerais/estatística & dados numéricos , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Tempo de Internação , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Centro Cirúrgico Hospitalar/estatística & dados numéricos , Resultado do Tratamento
16.
NPJ Breast Cancer ; 9(1): 100, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102162

RESUMO

Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP'). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0.001). 'Pure r-HGP' predicts worse PFS (HR: 2.65; CI: (1.45-4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29-7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'. These findings suggest that HGP could be considered to refine treatment approaches.

17.
Magy Seb ; 65(6): 407-15, 2012 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-23229032

RESUMO

By definition the liver hanging manoeuvre (LHM) means that a slip is passed between the liver parenchyma and the inferior vena cava. It was first published by Belghiti in 200l, and several changes in the indication as well as in the method have been published since then. In parallel, the anatomical and histological basis has been clarified for LHM, too. According to general consensus LHM increases safety and radicality of liver surgery. Initially LHM was applied for removal of huge tumours infiltrating the diaphragm. Authors worked out two modifications for LHM. Tumours / primary or secondary / in segment IVA are sometimes located in close proximity to the median hepatic vein and inferior vena cava , and the resectability of these tumors can determined by the hanging manoeuvre. Tumors in segment VII can be removed by partial resection of vena cava facilitated by LHM. Four patients with LHM are discussed, and based on this limited experience as well as the latest observations from relevant literature the authors claim that LHM increases the safety of resections from segment IVA and VII. Vascular infiltration of the vena cava is always a technical challenge, which can be suspected on preoperative imaging modalities, but in borderline cases only the intraoperative ultrasound and surgical judgment together with LHM would lead to the exact diagnosis and makes the resection possible.


Assuntos
Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/cirurgia , Idoso , Veias Hepáticas/cirurgia , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Ultrassonografia , Neoplasias Vasculares/secundário , Veia Cava Inferior/patologia
18.
Orv Hetil ; 152(15): 606-9, 2011 Apr 10.
Artigo em Húngaro | MEDLINE | ID: mdl-21436025

RESUMO

The research group takes samples for molecular genetical examinations from tumors removed during operations within ischemic time interval. Samples are stored in liquid nitrogen. Clinical data of these patients are recorded in an informatics system developed by the group. Patients are followed in an out-patient clinic set up for this purpose not financed by the National Health Insurance Fund. Tissue samples and follow up data are used to cooperate with molecular genetical laboratories.


Assuntos
Manejo de Espécimes , Bancos de Tecidos , Humanos , Hungria , Cooperação Internacional , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/cirurgia , Manejo de Espécimes/normas , Manejo de Espécimes/tendências , Bancos de Tecidos/organização & administração , Bancos de Tecidos/normas , Bancos de Tecidos/tendências
19.
Orv Hetil ; 162(50): 2010-2016, 2021 12 12.
Artigo em Húngaro | MEDLINE | ID: mdl-34896985

RESUMO

Összefoglaló. Bevezetés: A colorectalis eredetu májáttétek (CRCLM-ek) kuratív célú kezelésében elsodleges a sebészi reszekció. A mutét elott különbözo képalkotó vizsgálatok végezhetok, az egyik ilyen speciális vizsgálat a májsejtspecifikus kontrasztanyaggal végzett MR-vizsgálat. Célkituzés: Tanulmányunkban a májsejtspecifikus kontrasztanyaggal végzett MR-vizsgálat helyét és szerepét vizsgáltuk a májsebészeti gyakorlatban colorectalis áttétes betegek esetében. Módszer: Az Uzsoki Utcai Kórház Sebészeti-Onkosebészeti Osztályán 2017. 01. 01. és 2019. 12. 31. között CRCLM miatt májreszekcióra kerülo betegek adatait elemeztük. Retrospektív módon vizsgáltuk a betegek általános sebészeti és onkosebészeti paramétereit, a képalkotó diagnosztikai eredményeket, a mutéti adatokat és a patológiai leleteket. Eredmények: 132, CRCLM miatt operált betegbol 73 szoliter áttét (55%), míg 59 beteg (45%) többszörös áttét miatt került mutétre. 94 betegnél (71%) történt májsejtspecifikus MR-vizsgálat. Szoliter áttét esetén 60%-ban, multiplex áttétek esetén 85%-ban történt májsejtspecifikus MR-vizsgálat (p = 0,02). A szoliter áttétes betegek 8%-ában, míg a multiplex áttétes betegek 39%-ában mutatott további áttétet a májspecifikus kontrasztanyaggal végzett MR-vizsgálat (p = 0,001). A betegek 5%-ában igazolódott fals pozitivitás és 6%-ában fals negativitás a májsejtspecifikus MR-vizsgálat során. 264 góc vizsgálata alapján a májspecifikus kontrasztanyaggal végzett MR-vizsgálat szenzitivitása CRCLM esetén 95%-os, míg pozitív prediktív értéke 93%-os volt vizsgálatunkban. Következtetés: A májsejtspecifikus kontrasztanyaggal végzett MR-vizsgálat hasznos diagnosztikai módszer a CRCLM-ek sebészi reszekciója elott. Leginkább többszörös áttétek esetén, preoperatív szisztémás onkológiai kezelést követoen, illetve más képalkotó vizsgálaton igazolt eltunt áttét esetén javasolható az alkalmazása. Orv Hetil. 2021; 162(50): 2010-2016. INTRODUCTION: Liver resection is the only curtive treatment option of colorectal cancer liver metastases (CRCLMs). While different diagnostic modalities are available before surgery, a specific diagnostic tool is the liver-specific contrast-enhanced MRI. OBJECTIVE: The purpose of this study was to evaluate the role of liver-specific contrast-enhanced MRI before resection of colorectal liver metastases. METHOD: Patients with CRCLM, resected at the Department of Surgical Oncology, Uzsoki Teaching Hospital, between 01. 01. 2017 and 31. 12. 2019 were enrolled in our study. Clinical data, diagnostic, intraoperative and pathological findings were analyzed in a retrospective setting. RESULTS: 132 CRCLM patients were resected in this period, 73 patients had solitary (55%), and 59 patients (45%) had multiple metastases. Liver-specific contrast-enhanced MRI was performed in 94 patients (71%). 60% of the patients with solitary and 85% of the patients with multiple CRCLM had liver-specific contrast-enhanced MRI (p = 0.02). Compared to other modalities, liver-specific contrast-enhanced MRI showed additional metastases in 8% of the patients with solitary, and in 39% of the patients with multiple metastases (p = 0.001). Liver-specific contrast-enhanced MRI had a 5% false-positivity and a 6% false-negativity rate. 264 leasions were analyzed, and the sensitivity of the liver-specific contrast-enhanced MRI was 95% with a predictive positive value of 93%. CONCLUSION: Liver-specific contrast-enhanced MRI is a useful diagnostic tool in CRCLM patients before liver resection. It is highly recommended in the case of multiple metastases, after preoperative chemotherapy and in the case of disappearing metastases. Orv Hetil. 2021; 162(50): 2010-2016.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Estudos Retrospectivos
20.
Orv Hetil ; 151(11): 449-52, 2010 Mar 14.
Artigo em Húngaro | MEDLINE | ID: mdl-20211806

RESUMO

Mesenteric cysts are rare intraabdominal tumors, which cause plain symptoms. Despite the modern imaging techniques, the correct preoperative diagnosis is difficult. The optimal treatment is surgical excision of the cysts with open surgery, laparoscopy, or even retroperitoneoscopy. Surgical excision needs to be considered in case of complaints, growing cyst, or suspicion of malignancy. Indications for urgent surgery treatment are: bleeding, volvulus, torquation or ileus. Most frequently, mesenterial cysts are diagnosed during the operation of an unknown palpable abdominal cystic resistance. We present a case of a 32-year-old female patient with a jejunal mesenteric cyst, treated by laparoscopic resection. Postoperative period was uneventful, and after an early discharge the patient's recovery was free of symptoms. Histopathological examination revealed a benign cyst. We conclude that laparoscopic resection of abdominal cysts with unknown origin is a safe operation and can be recommended.


Assuntos
Laparoscopia , Cisto Mesentérico/diagnóstico , Cisto Mesentérico/cirurgia , Adulto , Feminino , Humanos , Jejuno , Laparoscopia/métodos , Cisto Mesentérico/diagnóstico por imagem , Cisto Mesentérico/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia
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