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1.
ANZ J Surg ; 93(12): 2946-2950, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37635313

RESUMO

BACKGROUNDS: Oncological outcomes of the robotic low anterior rectal resection with total mesorectal excision (TME) are still under discussion. Few studies have proven that robotic TME (rTME) is a safe and equivalent method for treatment of rectal carcinoma. But there is almost no comparison between the rTME and conventional TME in terms of the number of lymph nodes obtained and the quality of the TME. METHODS: A single institution retrospective study was designed in a cohort of 261 patients. Cohort was divided into two groups depending on the type of surgery (rTME versus TME) and within these two groups, patients were divided according to whether they underwent neoadjuvant chemoradiation (nCHRT) or did not. The primary objective of the study was to compare obtained number of the lymph nodes in specimen. Secondary objectives were comparison of the quality of the TME and the number of positive circumferential resection margins. RESULTS: Results of the study have shown no significant difference in number of the lymph nodes obtained by the rTME and TME. There was no difference in the quality of the TME, neither in the group with the previous nCHRT nor in the group without a nCHRT. CONCLUSION: With results from the study we consider the rTME to be non-inferior to the conventional TME. Therefore, at least identical oncological results can be expected in patients treated by the rTME.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Laparoscopia/métodos , Resultado do Tratamento , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Linfonodos/cirurgia , Linfonodos/patologia
2.
Acta Chir Belg ; 123(2): 163-169, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34423745

RESUMO

INTRODUCTION: The aim of study was to assess the impact of an enhanced recovery after surgery (ERAS) protocol and minimally invasive approaches on short-term outcomes in rectal surgery. PATIENTS AND METHODS: A consecutive series of patients that underwent open or minimally invasive rectal resections in a single institution between January 2015 and April 2020 were included in the study. An ERAS program was introduced in April 2016. The study cohort was divided into three groups: open surgery without ERAS, open surgery with ERAS, and minimally invasive surgery with ERAS. Outcome measures compared were recovery parameters, surgical stress parameters, 30-day morbidity and mortality, oncological radicality and length of hospital stay. RESULTS: A total of 202 patients were included: 43 in the open non-ERAS group, 92 in the open ERAS group and 67 in the minimally invasive ERAS group. All recovery parameters apart from postoperative nausea and vomiting were significantly improved in both ERAS groups. Surgical stress parameters, prolonged postoperative ileus, and hospital stay were significantly reduced in the minimally invasive ERAS group. The overall 30-day morbidity and mortality and oncological radicality did not significantly differ among the three groups. CONCLUSIONS: Minimally invasive approaches and enhanced recovery care in rectal surgery improve short-term outcomes. Their combination leads to an improvement in recovery parameters and a reduction of prolonged postoperative ileus and hospital stay.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Recuperação Pós-Cirúrgica Melhorada , Íleus , Laparoscopia , Humanos , Assistência Perioperatória/métodos , Intestinos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Íleus/etiologia , Tempo de Internação , Laparoscopia/métodos
3.
Gels ; 8(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35323271

RESUMO

Dead space after rectal resection in colorectal surgery is an area with a high risk of complications. In this study, our goal was to develop a novel 3D implant based on composite hydrogels enriched with fractionalized nanofibers. We employed, as a novel approach in abdominal surgery, the application of agarose gels functionalized with fractionalized nanofibers on pieces dozens of microns large with a well-preserved nano-substructure. This retained excellent cell accommodation and proliferation, while nanofiber structures in separated islets allowed cells a free migration throughout the gel. We found these low-concentrated fractionalized nanofibers to be a good tool for structural and biomechanical optimization of the 3D hydrogel implants. In addition, this nano-structuralized system can serve as a convenient drug delivery system for a controlled release of encapsulated bioactive substances from the nanofiber core. Thus, we present novel 3D nanofiber-based gels for controlled release, with a possibility to modify both their biomechanical properties and drug release intended for 3D lesions healing after a rectal extirpation, hysterectomy, or pelvic exenteration.

4.
Acta Chir Belg ; 121(6): 432-436, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31986986

RESUMO

Hemicorporectomy is the amputation of the lower body - pelvis and lower limbs. It requires transection of the spine and dural sac at the level of aortic bifurcation and inferior lower vein, and permanent urinary and stool derivation. Performance indications are tumour trauma and terminal pelvic osteomyelitis. So far about 60 cases have been published; only 11 operations were performed for terminal osteomyelitis. We have successfully performed hemicorporectomy in a patient with chronic sepsis from terminal pelvic osteomyelitis after exhausting all other treatment options. The experience gained and the important moments of the procedure are given in the case report.


Assuntos
Osteomielite , Sepse , Amputação Cirúrgica , Humanos , Osteomielite/cirurgia , Pelve , Sepse/diagnóstico , Sepse/etiologia , Coluna Vertebral
5.
Front Oncol ; 10: 1028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793464

RESUMO

Introduction: Patients with locally advanced rectal cancer (LARC) are undergoing neoadjuvant chemoradiotherapy (NCRT) prior to surgery. Although in some patients the NCRT is known to prevent local recurrence, it is also accompanied by side effects. Accordingly, there is an unmet need to identify predictive markers allowing to identify non-responders to avoid its adverse effects. We monitored circulating tumor DNA (ctDNA) as a potential liquid biopsy-based biomarker. We have investigated ctDNA changes plasma during the early days of NCRT and its relationship to the overall therapy outcome. Methods and Patients: The studied cohort included 36 LARC patients (stage II or III) undergoing NCRT with subsequent surgical treatment. We have detected somatic mutations in tissue biopsies taken during endoscopic examination prior to the therapy. CtDNA was extracted from patient plasma samples prior to therapy and at the end of the first week. In order to optimize the analytical costs of liquid-biopsy testing, we have utilized a two-level approach in which first a low-cost detection method of denaturing capillary electrophoresis was used followed by examination of initially negative samples by a high-sensitivity BEAMING assay. The ctDNA was related to clinical parameters including tumor regression grade (TRG) and TNM tumor staging. Results: We have detected a somatic mutation in 33 out of 36 patients (91.7%). Seven patients (7/33, 21.2%) had ctDNA present prior to therapy. The ctDNA positivity before treatment reduced post-operative disease-free survival and overall survival by an average of 1.47 and 1.41 years, respectively (p = 0.015, and p = 0.010). In all patients, ctDNA was strongly reduced or completely eliminated from plasma by the end of the first week of NCRT, with no correlation to any of the parameters analyzed. Conclusions: The baseline ctDNA presence represented a statistically significant negative prognostic biomarker for the overall patient survival. As ctDNA was reduced indiscriminately from circulation of all patients, dynamics during the first week of NCRT is not suited for predicting the outcome of LARC. However, the general effect of rapid ctDNA disappearance apparently occurring during the initial days of NCRT is noteworthy and should further be studied.

6.
Cancer Epidemiol ; 63: 101621, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31634775

RESUMO

INTRODUCTION: The incidence of colorectal cancer in young patients is increasing. The goal of this study was to investigate whether clinicopathological features and survival differed between young, middle-aged and elderly patients. METHODS: The Czech National Cancer Registry was searched to identify all cases of colorectal cancer between 1982 and 2014. Three subgroups of patients were created: young patients, defined as being between 18 and 40 years of age, middle-aged patients, defined as being between 41 and 74 years of age, and elderly patients, defined as being over the age of 75 years. RESULTS: A total of 192,241 patients diagnosed with colorectal cancer between the years 1982 and 2014 were included in the study. Out of these, 3,287 patients (1.7%) were between 18 and 40 years of age, 134,139 patients (69.8%) were between 41 and 74 years of age and 54,815 patients (28.5%) were 75 years of age or older. The young patients had a higher incidence of mucinous adenocarcinoma and signet ring cell carcinoma, more advanced disease and more rectal tumours than elderly patients. Nonetheless, young patients received treatment more frequently and had better cancer-specific survival than the older patients. CONCLUSION: The better prognosis in young patients is presumably due to their better physiological reserve and lower incidence of comorbidities. Efforts should be made in younger patients to diagnose early and treat aggressively.


Assuntos
Neoplasias Colorretais/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , República Tcheca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
J Chromatogr A ; 1600: 127-136, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31047664

RESUMO

Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.


Assuntos
Cromatografia Líquida , Fezes/química , Metaboloma , Espectrometria de Massas por Ionização por Electrospray , Ácidos e Sais Biliares/análise , Eicosanoides/análise , Feminino , Voluntários Saudáveis , Humanos , Masculino , Metabolômica , Fosfolipídeos/análise , Projetos Piloto
8.
World J Gastroenterol ; 25(48): 6939-6948, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31908397

RESUMO

BACKGROUND: One of the most notable applications for circulating tumor DNA (ctDNA) detection in peripheral blood of patients with metastatic colorectal cancer (mCRC) is a long-term postoperative follow-up. Sometimes referred to as a "liquid (re)biopsy" it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals (months or even weeks). The presence of the disease and the actual extent of the tumor burden (tumor mass) within the patient's body can be monitored. This is of particular importance, especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence. AIM: To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer. METHODS: A total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers. Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling. In addition to the baseline ctDNA testing prior to surgery, a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals. The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient. RESULTS: Among the monitored patients, the R0 (curative) resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures (26/28, 93%). In the remaining cases of R0 surgeries that displayed ctDNA, both patients were diagnosed with a recurrence of the disease after 6 months. In 7 patients who underwent an R1 resection, 4 ctDNA positivities (4/7, 57%) were detected after surgery and associated with the confirmation of early disease recurrence (after 3 to 7 months). All 15 patients (15/15, 100%) undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period. In 22 cases of recurrence, ctDNA positivity was detected 22 times (22/22, 100%) compared to 16 positives (16/22, 73%) by imaging methods and 15 cases (15/22, 68%) of elevated tumor markers. CONCLUSION: ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Neoplasias Colorretais/cirurgia , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/isolamento & purificação , DNA Tumoral Circulante/isolamento & purificação , Colectomia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , República Tcheca , Progressão da Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Biópsia Líquida/métodos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/secundário , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Período Pós-Operatório , Estudos Prospectivos , Carga Tumoral
9.
Int J Nanomedicine ; 13: 3129-3143, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29881270

RESUMO

PURPOSE: Incisional hernia repair is an unsuccessful field of surgery, with long-term recurrence rates reaching up to 50% regardless of technique or mesh material used. Various implants and their positioning within the abdominal wall pose numerous long-term complications that are difficult to treat due to their permanent nature and the chronic foreign body reaction they trigger. Materials mimicking the 3D structure of the extracellular matrix promote cell adhesion, proliferation, migration, and differentiation. Some electrospun nanofibrous scaffolds provide a topography of a natural extracellular matrix and are cost effective to manufacture. MATERIALS AND METHODS: A composite scaffold that was assembled out of a standard polypropylene hernia mesh and poly-ε-caprolactone (PCL) nanofibers was tested in a large animal model (minipig), and the final scar tissue was subjected to histological and biomechanical testing to verify our in vitro results published previously. RESULTS: We have demonstrated that a layer of PCL nanofibers leads to tissue overgrowth and the formation of a thick fibrous plate around the implant. Collagen maturation is accelerated, and the final scar is more flexible and elastic than under a standard polypropylene mesh with less pronounced shrinkage observed. However, the samples with the composite scaffold were less resistant to distracting forces than when a standard mesh was used. We believe that the adverse effects could be caused due to the material assembly, as they do not comply with our previous results. CONCLUSION: We believe that PCL nanofibers on their own can cause enough fibroplasia to be used as a separate material without the polypropylene base, thus avoiding potential adverse effects caused by any added substances.


Assuntos
Hérnia , Herniorrafia/métodos , Nanofibras/química , Telas Cirúrgicas , Parede Abdominal/cirurgia , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Herniorrafia/instrumentação , Teste de Materiais , Camundongos , Poliésteres , Polipropilenos/química , Suínos , Porco Miniatura , Alicerces Teciduais/química
10.
Cas Lek Cesk ; 157(2): 90-95, 2018.
Artigo em Tcheco | MEDLINE | ID: mdl-29790359

RESUMO

Cancer is the second most common cause of death in our population just after cardiovascular diseases, since each third individual will become affected by it during their lifetime. Breast cancer is the most common malignancy in women. The lifetime cumulative risk of breast cancer in women under the age of 75 is around 8 % according to Czech statistics. In 70-75 % of all individuals sporadic breast carcinomas are found, with 5-10 % of all women suffer from the hereditary breast and ovarian cancer (HBOC) syndrome. Radical, bilateral, removal of the mammary gland is the most effective prevention of breast cancer in BRCA positive women. We present a summary of 37 BRCA positive Czech patients who underwent prophylactic bilateral mastectomy and whose mean age was 46.5 years. Surgical solution is currently the only effective therapeutic way to prevent breast cancer in BRCA positive women with high genetic risk. The cosmetic consequences of this radical surgery can be solved through many reconstruction tasks.


Assuntos
Neoplasias da Mama , Predisposição Genética para Doença , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Mutação , Fatores de Risco
11.
Acta Chir Belg ; 117(6): 356-362, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28468569

RESUMO

INTRODUCTION: Colorectal cancer (CRC) in young patients is not an uncommon disease. Reports on its behaviour in young patients are conflicting. The aim of this study was to investigate patient and tumour characteristics, treatment and prognosis of this disease. METHODS: Our study group comprised all patients under the age of 40 years treated with CRC at the Department of Surgery at Motol University Hospital in Prague between the years 2005 and 2015. RESULTS: Thirty-eight patients under 40 years of age diagnosed with CRC were included in the study. Five patients had Lynch syndrome and six had first-degree relatives with CRC. There were 22 rectal tumours. All but four patients underwent resection of the primary tumour, all patients received chemotherapy and 13 patients received biological therapy. Disease recurrence occurred in 25.8%. Five-year survival was 47.9%. Advanced disease and adverse histological subtypes were identified as poor prognostic factors. CONCLUSIONS: Colorectal cancer in young patients has a high incidence of predisposing conditions, aggressive histological features and advanced disease. Young patients are of a good state of health and thus should receive aggressive therapy. Clinicians should pay more attention to symptoms of CRC in young patients to be able to initiate early treatment.


Assuntos
Adenocarcinoma/terapia , Neoplasias Colorretais/terapia , Centros Médicos Acadêmicos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Índice de Massa Corporal , Carcinoma de Células em Anel de Sinete/terapia , Criança , Colectomia/métodos , Neoplasias do Colo/terapia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/terapia , República Tcheca , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Obesidade/complicações , Sobrepeso/complicações , Prognóstico , Neoplasias Retais/terapia , Estudos Retrospectivos , Fatores de Risco , Centro Cirúrgico Hospitalar , Resultado do Tratamento
12.
Cancer Biomark ; 17(1): 97-106, 2016 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-27314298

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed. METHODS: Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTC patients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed. RESULTS: XRCC1 T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics. CONCLUSION: It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics.


Assuntos
Carcinoma/genética , Ciclo Celular/genética , Reparo do DNA/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Glândula Tireoide/genética , Adulto , Alelos , Carcinoma/patologia , Carcinoma Papilar , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estadiamento de Neoplasias , Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia
13.
Int J Nanomedicine ; 10: 2635-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25878497

RESUMO

Incisional hernia is the most common postoperative complication, affecting up to 20% of patients after abdominal surgery. Insertion of a synthetic surgical mesh has become the standard of care in ventral hernia repair. However, the implementation of a mesh does not reduce the risk of recurrence and the onset of hernia recurrence is only delayed by 2-3 years. Nowadays, more than 100 surgical meshes are available on the market, with polypropylene the most widely used for ventral hernia repair. Nonetheless, the ideal mesh does not exist yet; it still needs to be developed. Polycaprolactone nanofibers appear to be a suitable material for different kinds of cells, including fibroblasts, chondrocytes, and mesenchymal stem cells. The aim of the study reported here was to develop a functionalized scaffold for ventral hernia regeneration. We prepared a novel composite scaffold based on a polypropylene surgical mesh functionalized with poly-ε-caprolactone (PCL) nanofibers and adhered thrombocytes as a natural source of growth factors. In extensive in vitro tests, we proved the biocompatibility of PCL nanofibers with adhered thrombocytes deposited on a polypropylene mesh. Compared with polypropylene mesh alone, this composite scaffold provided better adhesion, growth, metabolic activity, proliferation, and viability of mouse fibroblasts in all tests and was even better than a polypropylene mesh functionalized with PCL nanofibers. The gradual release of growth factors from biocompatible nanofiber-modified scaffolds seems to be a promising approach in tissue engineering and regenerative medicine.


Assuntos
Materiais Biocompatíveis , Plaquetas/citologia , Hérnia Incisional/cirurgia , Nanofibras , Poliésteres , Polipropilenos , Telas Cirúrgicas , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Nanofibras/química , Nanofibras/toxicidade , Poliésteres/química , Poliésteres/toxicidade , Polipropilenos/química , Polipropilenos/toxicidade
14.
Int J Nanomedicine ; 9: 3263-77, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25031534

RESUMO

Incisional hernia affects up to 20% of patients after abdominal surgery. Unlike other types of hernia, its prognosis is poor, and patients suffer from recurrence within 10 years of the operation. Currently used hernia-repair meshes do not guarantee success, but only extend the recurrence-free period by about 5 years. Most of them are nonresorbable, and these implants can lead to many complications that are in some cases life-threatening. Electrospun nanofibers of various polymers have been used as tissue scaffolds and have been explored extensively in the last decade, due to their low cost and good biocompatibility. Their architecture mimics the natural extracellular matrix. We tested a biodegradable polyester poly-ε-caprolactone in the form of nanofibers as a scaffold for fascia healing in an abdominal closure-reinforcement model for prevention of incisional hernia formation. Both in vitro tests and an experiment on a rabbit model showed promising results.


Assuntos
Técnicas de Fechamento de Ferimentos Abdominais/instrumentação , Hérnia/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Nanofibras/uso terapêutico , Poliésteres/uso terapêutico , Polipropilenos/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Células 3T3 , Abdome/cirurgia , Animais , Fenômenos Biomecânicos , Regeneração Tecidual Guiada , Histocitoquímica , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Camundongos , Nanofibras/química , Poliésteres/química , Polipropilenos/química , Coelhos , Telas Cirúrgicas , Cicatrização/efeitos dos fármacos
15.
PLoS One ; 6(8): e24114, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21901162

RESUMO

The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in Europe. To evaluate whether sporadic CRCs in Czech patients have specific mutational profiles we analysed somatic genetic changes in known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH) at the APC locus, microsatellite instability (MSI), and methylation of the MLH1 promoter) in 103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9% of tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%) and CTNNB1 (1.9%). Heterozygous germline MUTYH mutations in 2 patients were unlikely to contribute to the development of their CRCs. LOH at the APC locus was found in 34.3% of tumours, MSI in 24.3% and MLH1 methylation in 12.7%. Seven tumours (6.9%) were without any changes in the genes tested. The analysis yielded several findings possibly specific for the Czech cohort. Somatic APC mutations did not cluster in the mutation cluster region (MCR). Tumours with MSI but no MLH1 methylation showed earlier onset and more severe mutational profiles compared to MSI tumours with MLH1 methylation. TP53 mutations were predominantly located outside the hot spots, and transitions were underrepresented. Our analysis supports the observation that germline MUTYH mutations are rare in Czech individuals with sporadic CRCs. Our findings suggest the influence of specific ethnic genetic factors and/or lifestyle and dietary habits typical for the Czech population on the development of these cancers.


Assuntos
Neoplasias Colorretais/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , República Tcheca , DNA Glicosilases/genética , Metilação de DNA/genética , Feminino , Mutação em Linhagem Germinativa/genética , Humanos , Perda de Heterozigosidade/genética , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteína Supressora de Tumor p53/genética , População Branca/genética , Adulto Jovem , beta Catenina/genética , Proteínas ras/genética
16.
Hum Immunol ; 72(11): 1022-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21884745

RESUMO

The prognosis of newly diagnosed colorectal cancer patients relies mostly on tumor-node metastasis classification. However, analyses of tumor-infiltrating lymphocytes and several molecular markers have also shown promising prognostic value. Mutations in the proto-oncogene KRAS, which occur early in colorectal carcinogenesis, have been demonstrated to be common in human colorectal cancer (CRC); however, their prognostic significance remains controversial. We examined the correlations between KRAS mutational status and tumor-infiltrating immune cells with respect to CRC recurrence. Mutations in KRAS were identified in 45.5% of the primary carcinomas in our cohort of patients: 65% in codon 12 and 35% in codon 13. Although codon 13 KRAS mutations were associated with disease relapse, they were present in both disease-free and relapsed patients. However, disease-free and relapsed patients differed markedly in their patterns of tumor-infiltrating immune cells. There was a trend toward decreased density of tumor-infiltrating lymphocytes (TILs) within the group of relapsed cases. In addition, relapsed patients with codon 13 mutations had markedly lower levels of tumor-infiltrating mature DC-LAMP(+) dendritic cells (DCs) and higher frequency of CD1a(+) cells compared with disease-free patients. Our data suggest that CRC patients with low levels of TILs, a high CD1a(+)/DC-LAMP(+) tumor-infiltrating DC ratio, and a KRAS mutation in codon 13 are at a high risk of disease recurrence.


Assuntos
Carcinoma/diagnóstico , Carcinoma/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Células Dendríticas/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Antígenos CD1/biossíntese , Biomarcadores Tumorais/genética , Carcinoma/patologia , Carcinoma/fisiopatologia , Moléculas de Adesão Celular Neuronais/biossíntese , Diferenciação Celular/genética , Movimento Celular/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/fisiopatologia , Análise Mutacional de DNA , Células Dendríticas/imunologia , Células Dendríticas/patologia , Detecção Precoce de Câncer , Feminino , Seguimentos , Proteínas Ligadas por GPI/biossíntese , Estudos de Associação Genética , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Mutação/genética , Recidiva Local de Neoplasia , Prognóstico , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/genética
17.
Cas Lek Cesk ; 150(2): 97-9, 2011.
Artigo em Tcheco | MEDLINE | ID: mdl-21560448

RESUMO

BACKGROUND: Nijmegen breakage syndrome (NBS) is one of the chromosomal instability syndromes due to DNA repair disorder. The syndrome is autosomal recessive determined, in homozygotes is characterized by many disorders including high predisposition to lymphoreticular malignancy in childhood and adolescence. METHODS: Laboratory findings represent low level of immunoglobulins, B and T lymphocytes, increased sensitivity to the mutagens, especially hyperradiosensitivity and increased chromosomal instability. Heterozygotes show also elevated radiosensitivity and have an increased cancer risk in adult age. There is no predilection of the malignancy. Colorectal cancer was found often among the relatives of patients with NBS. Majority of the NBS patients are of the Central and Eastern European origin and carry the common founder mutation 657del5 in the NBN gene. The formation of second malignancy both in homozygotes and heterozygotes can be prevented by excluding any radiation. The aim of study is estimation of frequency of 657del5 heterozygotes among patients with colorectal cancer. RESULTS AND CONCLUSIONS: Within a group of 161 patients with colorectal cancer 5 heterozygotes with 657del5 mutation were registered, e.g. 5-times higher incidence than expected. The elemental prevention in patients with proved positivity of Slavic mutation in NBN gene is to exclude any radiation.


Assuntos
Proteínas de Ciclo Celular/genética , Neoplasias Colorretais/genética , Heterozigoto , Mutação , Proteínas Nucleares/genética , Adulto , Idoso , Neoplasias Colorretais/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Quebra de Nijmegen/complicações , Síndrome de Quebra de Nijmegen/genética , Eslováquia
18.
Dis Colon Rectum ; 54(1): 29-34, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21160310

RESUMO

BACKGROUND: No randomized controlled trial has compared no rectopexy with rectopexy for external full-thickness rectal prolapse. OBJECTIVE: This study was performed to test the hypothesis that recurrence rates following no rectopexy are not inferior to those following rectopexy for full-thickness rectal prolapse. DESIGN: This was a multicenter randomized controlled trial. Eligible patients were randomly assigned to no rectopexy or rectopexy. The end point was recurrence rates defined as the presence of external full-thickness rectal prolapse after surgery. A prerandomized controlled trial meta-analysis suggested a sample size of 251 patients based on a 15% expected difference in the 5-year cumulative recurrence rate. Recurrence-free curves were generated and compared using the Kaplan-Meier method and log-rank test, respectively. Data were presented as median (range). SETTING: This study was conducted in 41 tertiary centers in 21 countries. PATIENTS: Patients with prior surgery for rectal prolapse or pelvic floor descent were not included. INTERVENTIONS: The no-rectopexy arm was defined as abdominal surgery with rectal mobilization only. The rectopexy arm was defined as abdominal surgery with mobilization and rectopexy. Sigmoid resection was not randomized and was added in the presence of constipation. MAIN OUTCOME MEASURES: Two hundred fifty-two patients with external full-thickness rectal prolapse were randomly assigned to undergo no rectopexy or rectopexy in 41 centers. All patients but one underwent the allocated intervention. One hundred sixteen no-rectopexy patients were comparable to 136 rectopexy patients for age (P = .21), body mass index (P = .61), ASA grade (P = .29), and previous abdominal surgery (P = .935), but not for sex (P = .013) and external full-thickness rectal prolapse length (8 (1-25) cm vs 5 (1-20) cm, P = .026). Sigmoid resection was performed more frequently in the no-rectopexy arm (P < .001). There was no significant difference in complication rates (11% vs 17.9%; P = .139). The mortality rate was 0.8%. The loss of patients to 5-year follow-up was 10.3%. Actuarial analysis demonstrated a significant difference in 5-year recurrence rates between study arms (8.6% vs 1.5%) (log-rank, P = .003). LIMITATIONS: Limitations were the high proportion of male patients, randomization timing, the lack of standardization for rectopexy technique, and the 10% loss to follow-up. CONCLUSIONS: Recurrence rates following no rectopexy are inferior to those following rectopexy for external full-thickness rectal prolapse.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Prolapso Retal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Resultado do Tratamento
19.
Rozhl Chir ; 87(8): 391-2, 2008 Aug.
Artigo em Tcheco | MEDLINE | ID: mdl-18988477
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