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OBJECTIVE: In the emergency care of cancer patients, in addition to cancer-related factors, two aspects influence the outcome: (1) where the patient is treated and (2) who will perform the surgery. In Brazil, a significant proportion of patients with surgical oncological emergencies will be operated on in general hospitals by surgeons without training in oncological surgery. OBJECTIVE: The objective was to discuss quality indicators and propose the creation of an urgent oncological surgery advanced life support course. METHODS: Review of articles on the topic. RESULTS: Generally, nonelective resections are associated with higher rates of morbidity and mortality, as well as lower rates of cancer-specific survival. In comparison to elective procedures, the reduced number of harvested lymph nodes and the higher rate of positive margins suggest a compromised degree of radicality in the emergency scenario. CONCLUSION: Among modifiable factors is the training of the emergency surgeon. Enhancing the practice of oncological surgery in emergency settings constitutes a formidable undertaking that entails collaboration across various medical specialties and warrants endorsement and support from medical societies and educational institutions. It is time to establish a national registry encompassing oncological emergencies, develop quality indicators tailored to the national context, and foster the establishment of specialized training programs aimed at enhancing the proficiency of physicians serving in emergency services catering to cancer patients.
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Neoplasias , Humanos , Neoplasias/cirurgia , Indicadores de Qualidade em Assistência à Saúde , Brasil , Oncologia Cirúrgica/normas , Oncologia Cirúrgica/educação , EmergênciasRESUMO
SUMMARY In the emergency care of cancer patients, in addition to cancer-related factors, two aspects influence the outcome: (1) where the patient is treated and (2) who will perform the surgery. In Brazil, a significant proportion of patients with surgical oncological emergencies will be operated on in general hospitals by surgeons without training in oncological surgery. OBJECTIVE: The objective was to discuss quality indicators and propose the creation of an urgent oncological surgery advanced life support course. METHODS: Review of articles on the topic. RESULTS: Generally, nonelective resections are associated with higher rates of morbidity and mortality, as well as lower rates of cancer-specific survival. In comparison to elective procedures, the reduced number of harvested lymph nodes and the higher rate of positive margins suggest a compromised degree of radicality in the emergency scenario. CONCLUSION: Among modifiable factors is the training of the emergency surgeon. Enhancing the practice of oncological surgery in emergency settings constitutes a formidable undertaking that entails collaboration across various medical specialties and warrants endorsement and support from medical societies and educational institutions. It is time to establish a national registry encompassing oncological emergencies, develop quality indicators tailored to the national context, and foster the establishment of specialized training programs aimed at enhancing the proficiency of physicians serving in emergency services catering to cancer patients.
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PURPOSE: Soft tissue sarcomas are rare malignant tumors. Liposarcoma constitutes the most frequent histological subtype of retroperitoneal sarcoma. The prognosis of soft tissue sarcomas depends on clinical and histologic characteristics. OBJECTIVE: Evaluate variables that may be related to the overall and local recurrence-free survival in patients with retroperitoneal liposarcoma and discuss the need for visceral resection en-bloc for tumors. METHODS: A retrospective analysis was conducted of the medical records of 60 patients seen between 1997 and 2017 who underwent surgical resection of retroperitoneal liposarcoma. RESULTS: The overall survival rate at 5 years of follow-up was 75.22% (95% confidence interval [CI] 0.58-0.86). The probability of a local recurrence-free survival at 5 years of follow-up was 26.04% (95% CI 0.11-0.44). The multivariate analysis showed that dedifferentiated or pleomorphic tumors and R2/fragmented resection were associated with a shorter time to recurrence. No other characteristics markedly influenced the overall survival (P > 0.05). CONCLUSION: Patients with dedifferentiated or pleomorphic tumors and incomplete resection were associated with higher local recurrence rates than others. This study reinforces the need for complete and en-bloc resection with organs when there is clear involvement or technical surgical difficulty to maintain the tumor integrity.
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Lipossarcoma , Neoplasias Retroperitoneais , Sarcoma , Humanos , Estudos Retrospectivos , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Neoplasias Retroperitoneais/cirurgia , Sarcoma/cirurgia , Sarcoma/patologia , Prognóstico , Taxa de Sobrevida , Recidiva Local de NeoplasiaRESUMO
Werner's syndrome is caused by the inactivation of both WRN alleles and is characterized by premature aging and increased risk of neoplasms, especially those of mesenchymal origins, such as sarcomas. Given the characteristic genomic instability, patients with this syndrome are more susceptible to develop toxicities when exposed to cytotoxic agents, such as alkylators and anthracyclines. The impact of the monoallelic WRN mutation on treatment-associated toxicities is poorly understood. Here, we report a patient with locally advanced dedifferentiated liposarcoma of the retroperitoneum harboring a heterozygous germline inactivation mutation in the WRN gene, who was treated with a classic regimen of ifosfamide and doxorubicin and developed exacerbated and prolonged hematological and renal toxicities.
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BACKGROUND: Soft tissue sarcomas (STS) comprise a diverse group of mesenchymal malignancies that require multidisciplinary care. Although surgery remains the primary form of treatment for those with localized disease, radiation therapy (RT) is often incorporated either in the neo- or adjuvant setting. Given the development of modern RT techniques and alternative dosing schedules, stereotactic ablative radiotherapy (SABR) has emerged as a promising technique. However, the current role of SABR in the treatment of STS of the extremities remains uncertain. METHODS AND MATERIALS: This was a single-center, prospective, single-arm phase II trial. Patients with localized STS who were candidates for limb-preservation surgery were included. Experimental treatment consisted of SABR with 40 Gy in 5 fractions, administered on alternate days, followed by surgery after a minimum interval of 4 weeks. The primary outcome was the rate of wound complication. Secondary outcomes included 2-year local control (LC), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) rates (and other toxicities). RESULTS: Twenty-five patients were enrolled between October 2015 and November 2019 and completed the treatment protocol. The median rate of histopathologic regression was 65% (range 0-100) and 20.8% of tumors presented pathologic complete response (pCR). Wound complications were observed in 7/25 patients (28%). Three patients underwent disarticulation by vascular occlusion after plastic reconstruction and one patient was amputated by grade 3 limb dysfunction. After a median follow up of 20.7 months, the 2-year estimated risk of local recurrence, distant metastasis and cause-specific death were 0%, 44.7% and 10.6% respectively. CONCLUSIONS: Neoadjuvant SABR appears to improve the pCR for patients with eSTS, with acceptable rate of wound complications. Nevertheless, this benefit should be weighed against the risk of late of vascular toxicity with SABR regimen since, even in a short median follow-up, a higher rate of amputation than expected was observed. A larger sample size with longer follow-up is necessary to conclude the overall safety of this strategy.
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Radiocirurgia , Sarcoma , Extremidades , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Sarcoma/radioterapia , Sarcoma/cirurgia , Resultado do TratamentoRESUMO
The incidence of colorectal cancer (CRC) is lower in women than in men, and sex steroids can be considered contributing factors because oral contraception usage and estrogen replacement therapy are associated with decreased risk. Conversely, colorectal polyp development in familial adenomatous polyposis (FAP) begins during puberty. The objectives were to evaluate the relationship between the expression of these hormone receptors and adenoma-carcinoma progression, CRC stage and overall survival. We studied 120 A.C. Camargo Cancer Center patients diagnosed with either FAP-associated or spontaneous adenomatous polyps or CRC to determine the immunohistochemical expression levels of estrogen receptor (ER)-α, ER-ß and the progesterone and androgen receptors (480 analyses). The ER-ß expression levels differed between the groups: the group with FAP polyps had lower ER-ß expression than that of the sporadic polyp group. With transformation of the sporadic polyps to cancer, there was a considerable decrease in ER-ß expression (from 90% with strong expression to 80% with absent or weak expression) (p < 0.001). The ER-ß expression was lower in T3/T4 tumors than in T1/T2 tumors (p = 0.015). The 5-year overall survival of CRC patients positively expressing ER-ß exceeded that of patients without detectable expression levels (74.8% vs. 44.3%, respectively; p = 0.035). There was no significant expression of the androgen or progesterone receptor or ER-α among the groups. Differences in ER-ß expression represent a potential mechanism through which estrogen might alter the susceptibility to colon cancer, thereby confirming the possibility of a protective role of estrogen against colorectal carcinogenesis.
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Adenoma/patologia , Polipose Adenomatosa do Colo/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Receptor beta de Estrogênio/metabolismo , Pólipos/patologia , Adenoma/metabolismo , Adenoma/cirurgia , Polipose Adenomatosa do Colo/metabolismo , Polipose Adenomatosa do Colo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos/metabolismo , Pólipos/cirurgia , Prognóstico , Taxa de SobrevidaRESUMO
Leiomyosarcoma (LMS) of inferior vena cava (IVC) is a rare neoplasm affecting approximately 1/100,000 people. The prognosis is poor and potential curative intent occurs through challenging operations, such as vena cava resection, occasionally multivisceral when required, and vascular reconstruction. There are few retrospective series regarding this retroperitoneal neoplasm, and the aim of the present study was to discuss the experience at the São Paulo Cancer Institute and Clinics Hospital of University of São Paulo Medical School, São Paulo, Brazil. The current study is a retrospective review of 7 patients treated in the two tertiary hospitals between 2005 and 2013. Oncological and operative aspects were discussed, primarily regarding surgical aspects highlighting en bloc resection, vascular reconstruction, and the overall survival and recurrence rates. All the patients were treated with radical intent, 4 of whom underwent multivisceral resection, with the kidney being the most resected organ. The location of the IVC tumor was described using Kulaylat's description and the median tumor size was 10 cm. Vascular reconstruction was necessary in 4 patients. The overall survival rate at 3 and 5 years was 100, and 25%, respectively. The disease-free survival rate at 3 and 5 years was 57 and 20%, respectively. In conclusion, IVC LMS is a rare and severe retroperitoneal neoplasm, with multivisceral resections remaining a surgical challenge. The treatment requires numerous experienced surgeons and the impact of microscopic free margins remains unclear. Vascular reconstruction depends on several aspects regarding primarily the topography of the tumor.
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Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.086.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients (AU)
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Humanos , Masculino , Feminino , Prognóstico , Imuno-Histoquímica , Neoplasias Colorretais , Análise de Sobrevida , Estudos de Coortes , Metabolismo dos Lipídeos , HipóxiaRESUMO
Lynch syndrome (LS) accounts for 3-5% of all colorectal cancers (CRC) and is inherited in an autosomal dominant fashion. This syndrome is characterized by early CRC onset, high incidence of tumors in the ascending colon, excess of synchronous/metachronous tumors and extra-colonic tumors. Nowadays, LS is regarded of patients who carry deleterious germline mutations in one of the five mismatch repair genes (MMR), mostly in MLH1 and MSH2, but also in MSH6, PMS1 and PMS2. To comprehensively characterize 116 Brazilian patients suspected for LS, we assessed the frequency of germline mutations in the three minor genes MSH6, PMS1 and PMS2 in 82 patients negative for point mutations in MLH1 and MSH2. We also assessed large genomic rearrangements by MLPA for detecting copy number variations (CNVs) in MLH1, MSH2 and MSH6 generating a broad characterization of MMR genes. The complete analysis of the five MMR genes revealed 45 carriers of pathogenic mutations, including 25 in MSH2, 15 in MLH1, four in MSH6 and one in PMS2. Eleven novel pathogenic mutations (6 in MSH2, 4 in MSH6 and one in PMS2), and 11 variants of unknown significance (VUS) were found. Mutations in the MLH1 and MSH2 genes represented 89% of all mutations (40/45), whereas the three MMR genes (MSH6, PMS1 and PMS2) accounted for 11% (5/45). We also investigated the MLH1 p.Leu676Pro VUS located in the PMS2 interaction domain and our results revealed that this variant displayed no defective function in terms of cellular location and heterodimer interaction. Additionally, we assessed the tumor phenotype of a subset of patients and also the frequency of CRC and extra-colonic tumors in 2,365 individuals of the 116 families, generating the first comprehensive portrait of the genetic and clinical aspects of patients suspected of LS in a Brazilian cohort.
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Adenosina Trifosfatases/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Mutação em Linhagem Germinativa , Proteínas de Neoplasias/genética , Adolescente , Adulto , Brasil , Neoplasias Colorretais Hereditárias sem Polipose/genética , Variações do Número de Cópias de DNA , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteínas MutL , Adulto JovemRESUMO
BACKGROUND: Topoisomerase 2 alpha (TOP2A), HER-2/neu, and survivin are genes that lie on chromosome 17 and correlate with the prognosis and prediction of target-driven therapy against tumors. In a previous study, we showed that TOP2A transcripts levels were significantly higher in soft tissue sarcomas (STS) than in benign tumors and desmoid-type fibromatoses (FM). Because these genes have been insufficiently examined in STS, we aimed to identify alterations in TOP2A and HER-2 expression by fluorescent in situ hybridization and immunohistochemistry, as well as that of survivin, and correlate them with clinicopathologic findings to assess their prognostic value. METHODS: Eighteen FM and 244 STS were included. Fluorescent in situ hybridization and immunohistochemistry were performed on a tissue microarray. RESULTS: TOP2A and survivin were more highly expressed in sarcomas than in FM. TOP2A was an independent predictor of an unfavorable prognosis; it was combined with formerly established prognostic factors (primarily histologic grade and tumor size at diagnosis) to create a prognostic index that evaluated overall survival. Gene amplification/polysomy (13%) did not correlate with protein overexpression. Survivin and HER-2 expression were not associated with patient outcomes. CONCLUSIONS: These findings might become valuable in the management of patients with STS and possibly in the prospective evaluation of responses to new target-driven therapies.
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Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Cromossomos Humanos Par 17/genética , Amplificação de Genes , Sarcoma/mortalidade , Sarcoma/patologia , Adolescente , Adulto , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Fibroma/mortalidade , Fibroma/patologia , Fibroma/terapia , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/patologia , Fibromatose Agressiva/terapia , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Sarcoma/terapia , Sarcoma Sinovial/mortalidade , Sarcoma Sinovial/patologia , Sarcoma Sinovial/terapia , Taxa de Sobrevida , Survivina , Adulto JovemRESUMO
Historically, scleroderma and other collagenous diseases have been considered a relative contraindication to radiation. The literature has few studies describing poor outcomes and cosmesis in this situation and there are almost no data concerning about reirradiation and colagenosis. The authors describe a case of a patient with a soft tissue sarcoma in the arm submitted to conservative surgery. They describe the outcome, cosmesis and function of this rare twice-irradiated scleroderma patient.
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Humanos , Braquiterapia , Escleroderma Sistêmico , RadioterapiaRESUMO
Lynch syndrome (LS) is an autosomal dominant syndrome that predisposes individuals to development of cancers early in life. These cancers are mainly the following: colorectal, endometrial, ovarian, small intestine, stomach and urinary tract cancers. LS is caused by germline mutations in DNA mismatch repair genes (MMR), mostly MLH1 and MSH2, which are responsible for more than 85% of known germline mutations. To search for germline mutations in MLH1 and MSH2 genes in 123 unrelated South American suspected LS patients (Bethesda or Amsterdam Criteria) DNA was obtained from peripheral blood, and PCR was performed followed by direct sequencing in both directions of all exons and intron-exon junctions regions of the MLH1 and MSH2 genes. MLH1 or MSH2 pathogenic mutations were found in 28.45% (34/123) of the individuals, where 25/57 (43.85%) fulfilled Amsterdam I, II and 9/66 (13.63%) the Bethesda criteria. The mutations found in both genes were as follows: nonsense (35.3%), frameshift (26.47%), splicing (23.52%), and missense (9%). Thirteen alterations (35.14%) were described for the first time. The data reported in this study add new information about MLH1 and MSH2 gene mutations and contribute to better characterize LS in Brazil, Uruguay and Argentina. The high rate of novel mutations demonstrates the importance of defining MLH1 and MSH2 mutations in distinct LS populations.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Mutação em Linhagem Germinativa , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Argentina , Brasil , Códon sem Sentido , Neoplasias Colorretais Hereditárias sem Polipose/etnologia , Análise Mutacional de DNA , Mutação da Fase de Leitura , Humanos , Proteína 1 Homóloga a MutL , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase , UruguaiRESUMO
O câncer colorretal se destaca entre as neoplasias malignas mais incidentes no Brasil e no mundo. Estratégias de rastreamento incluem a pesquisa de sangue oculto nas fezes ou a colonoscopia, aplicadas às populações sob maior risco. A sintomatologia é pouco específica e a colonoscopia é o método ideal para diagnóstico, sendo indicada sempre que houver sinais e sintomas intestinais. O estadiamento define as modalidades de tratamento e é direcionado para as vias mais comuns da disseminação da doença: linfática, hematogênica, contiguidade e implantes. Quando o diagnóstico se faz em estádios iniciais, o tratamento do câncer colorretal proporciona elevadas taxas de cura. Este artigo resume de forma esquemática as modalidades atuais de tratamento, estratificadas em função do estadiamento.
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Humanos , Metástase Neoplásica/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapiaRESUMO
INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m(2)) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5%, 46.7% and 58.3%, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3% and 41.2%, respectively. Severe wound complications were observed in 41.8% of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7% (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.
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Terapia Neoadjuvante/efeitos adversos , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante/efeitos adversos , Doxorrubicina/efeitos adversos , Métodos Epidemiológicos , Extremidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Radioterapia Adjuvante/efeitos adversos , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m²) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5 percent, 46.7 percent and 58.3 percent, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3 percent and 41.2 percent, respectively. Severe wound complications were observed in 41.8 percent of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7 percent (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Terapia Neoadjuvante/efeitos adversos , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Quimioterapia Adjuvante/efeitos adversos , Doxorrubicina/efeitos adversos , Métodos Epidemiológicos , Extremidades , Recidiva Local de Neoplasia , Radioterapia Adjuvante/efeitos adversos , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Resultado do Tratamento , Adulto JovemRESUMO
Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50%) and MSH2 (40%), while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.
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Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Mutação em Linhagem Germinativa/genética , HumanosRESUMO
Lynch syndrome represents 1-7 percent of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50 percent) and MSH2 (40 percent), while others account for 10 percent. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.
A síndrome de Lynch representa de 1-7 por cento de todos os casos de câncer colorretal. É uma síndrome de herança autossômica dominante que predispõe ao câncer e é causada por mutações nos genes de reparo de ácido desoxirribonucléico (DNA). Desde a descoberta dos principais genes com função de reparo de DNA, mutações nos genes MSH2, MLH1, MSH6, PMS2 e PMS1 estão relacionadas com a susceptibilidade à síndrome de Lynch. Outro gene, MLH3, tem sido proposto como tendo papel na predisposição à síndrome de Lynch, porém mutações de significância clínica nesse gene não são claras. De acordo com o banco de dados InSiGHT (International Society for Gastrointestinal Hereditary Tumors), aproximadamente 500 diferentes mutações associadas à síndrome de Lynch são conhecidas, envolvendo primeiramente MLH1 (50 por cento), MSH2 (40 por cento) e outros (10 por cento). Grandes progressos têm ocorrido para nosso entendimento das bases moleculares da síndrome de Lynch. A caracterização molecular será a forma mais precisa para definirmos a síndrome de Lynch e irá fornecer informações preditivas mais precisas sobre o risco de câncer colorretal e extra-colônico, além de permitir regimes otimizados de manejo.