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BACKGROUND: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy. PATIENTS AND METHODS: Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection. RESULTS: Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40). CONCLUSION: The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival.
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PURPOSE: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. PATIENTS AND METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]. CONCLUSION: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina/análogos & derivados , Neuroblastoma , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/terapia , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Feminino , Masculino , Pré-Escolar , Lactente , Criança , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Japão/epidemiologia , Estudos Prospectivos , Taxa de Sobrevida , Adolescente , Quimioterapia de Indução , Etoposídeo/administração & dosagem , Seguimentos , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Prognóstico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêuticoRESUMO
Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management.
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Neoplasias da Mama , Humanos , Neoplasias da Mama/terapia , Feminino , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Animais , Fotoquimioterapia/métodos , Compostos Inorgânicos/químicaRESUMO
OBJECTIVES: This study aims to evaluate the efficacy of local treatment (LT), including radiotherapy (RT) and cytoreductive prostatectomy (CRP), in improving outcomes for patients with oligometastatic prostate cancer (OmPCa). METHODS: A systematic review and meta-analysis of articles from PubMed, Embase, and Web of Science published between 2010 and November 2023 were conducted. The study included 11 articles, comprising three randomized controlled trials (RCTs) and eight retrospective analyses. The study assessed overall survival (OS), radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) PFS, cancer-specific survival (CSS), and complication rate (CR). RESULTS: OS was significantly improved in the LT group, with both RCTs and non-RCTs showing statistical significance [hazard ratios (HR) = 0.64; 95% confidence intervals (95% CIs), 0.51-0.80; p < 0.0001; HR = 0.55; 95% CIs, 0.40-0.77; p = 0.0004]. For rPFS, RCTs did not show statistically significant outcomes (HR = 0.60; 95% CIs, 0.34-1.07; p = 0.09), whereas non-RCTs demonstrated significant results (HR = 0.42; 95% CIs, 0.24-0.72; p = 0.002). Both RCTs and non-RCTs showed a significant improvement in PSA-PFS (HR = 0.44; 95%CI, 0.29-0.67; p = 0.0001; HR = 0.51; 95% CIs, 0.32-0.81; p = 0.004). For CSS, RCTs demonstrated statistical differences (HR = 0.65; 95% CIs, 0.47-0.90; p = 0.009), whereas non-RCTs did not (HR = 0.61; 95% CIs, 0.29-1.27; p = 0.19). Regarding CR, the risk difference was -0.22 (95% CIs, -0.32 to -0.12; p < 0.00001). CONCLUSION: LT significantly improved OS and PFS in patients with OmPCa. Further RCTs are necessary to confirm these results.
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Endometrial cancer (EC) is a heterogeneous disease with a rising incidence worldwide. The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). More recently, the International Federation of Gynecology and Obstetrics (FIGO) updated their staging classification to include information about POLE mutation and p53 status, as the prognosis differs according to these characteristics. Other biomarkers are being identified and their prognostic and predictive role in response to therapies are being evaluated. However, the incorporation of molecular aspects into treatment decision-making is challenging. This review explores the available data and future directions on tailoring treatment based on molecular subtypes, alongside the challenges associated with their testing.
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Biomarcadores Tumorais , Neoplasias do Endométrio , Instabilidade de Microssatélites , Humanos , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/metabolismo , Feminino , Biomarcadores Tumorais/genética , Mutação , Patologia Molecular , Prognóstico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Mucormycosis is a rare and serious fungal infection, occurring mainly in immunocompromised, diabetic, polytrauma or burn patients. Current standard treatments include iterative carcinological surgical trimming, systemic treatment with liposomal amphotericin B and second-line Posaconazole or Isavuconazole. We report the case of a 37-year-old female patient with no previous medical history who developed a disseminated mucormycosis, with an estimated 25 % loss of skin substance and major decay of the chest wall. In addition to standard treatment, local instillations of amphotericin B using the VAC Veraflow® system were performed. We believe that local instillations of amphotericin B by VAC could improve the functional prognosis of patients with skin involvement.
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Anfotericina B , Mucormicose , Feminino , Humanos , Adulto , Anfotericina B/uso terapêutico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Mucormicose/cirurgia , Antifúngicos/uso terapêutico , PeleRESUMO
BACKGROUND: Current guidelines recommend indefinite imatinib treatment for advanced gastrointestinal stromal tumor (GIST) patients. Imatinib-refractory progression-free survival (PFS) and overall survival were previously reported not to differ between GIST patients who interrupted imatinib and those who did not. METHODS: Clinical outcomes of 77 consecutive patients with recurrent or metastatic GIST who interrupted imatinib treatment after maintaining years of imatinib treatment in the absence of gross tumor lesions were retrospectively analyzed. Associations between clinical factors and progression-free survival (PFS) following imatinib interruption were analyzed. RESULTS: The median time from the absence of gross tumor lesions to imatinib interruption was 61.5 months. Since imatinib interruption, the median PFS was 19.6 months, and 4 patients (26.3%) remained progression-free for longer than 5 years. Among the patients who had progressive disease following the interruption, imatinib re-introduction led to an 88.6% objective response rate and a 100% disease control rate. Complete removal of the initial gross tumor lesion(s) and complete removal of the residual gross tumor lesion(s) by local treatment (vs. no local treatment or residual lesions after local treatment) were independently associated with favorable PFS. CONCLUSION: Interruption of imatinib following prolonged maintenance in the absence of gross tumor lesions led to disease progression in the majority of cases. However, re-introduction of imatinib resulted in effective tumor control. Unmaintained remission seems to be possible in some patients with metastatic or recurrent GIST after a prolonged remission with imatinib if there is complete removal of any gross tumor lesions.
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Antineoplásicos , Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Mesilato de Imatinib/uso terapêutico , Tumores do Estroma Gastrointestinal/patologia , Estudos Retrospectivos , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Benzamidas , Resultado do Tratamento , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/uso terapêuticoRESUMO
Oligometastasis is defined as the presence of several limited metastatic lesions and is generally limited to three or fewer than five metastatic lesions. Previously, the treatment of metastatic cancer aimed to alleviate symptoms rather than cure them; however, the use of immunotherapy or targeted therapy has greatly improved patient life expectancy. Additionally, the effectiveness and safety of local treatment have recently been proven for oligometastatic cancers and have significantly improved patient survival and decreased recurrence rates. A few metastatic studies on lung cancer have demonstrated the usefulness of combining radiation therapy and immunotherapy. Recently, local and targeted therapy combinations have shown promising results in treating non-small cell lung cancer, predominantly caused by the epidermal growth factor receptor and anaplastic lymphoma kinase gene mutations, suggesting the potential of these new treatment strategies. It is well known that oligometastasis has better clinical results than polymetastasis; however, research on the biological profile of oligometastasis is still lacking. Studies using circulating tumor DNA and circulating tumor cells are at the initial stages of providing a better understanding of oligometastatic cancers, and the biological characteristics of these cancers may be revealed based on more diverse studies. With the development of these treatments, the prognosis for patients with oligometastatic cancers is steadily improving, and if the biological profile is revealed, customized treatment may be provided.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , PrognósticoRESUMO
Ovarian cancer is a malignant disease that affects thousands of patients every year. Currently, we use surgical techniques for early-stage cancer and chemotherapy treatment combinations for advanced stage cancer. Several novel therapies are currently being investigated, with gene therapy and stem cell therapy being the corner stone of this investigation. We conducted a thorough search on PubMed and gathered up-to-date information regarding epithelial ovarian cancer therapies. We present, in the current review, all novel treatments that were investigated in this field over the past five years, with a particular focus on local treatment.
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Antineoplásicos , Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/patologia , Quimioterapia Adjuvante , Quimioterapia CombinadaRESUMO
The authors present complex surgical treatment of a patient with rheumatoid arthritis and persistent wound in the right gluteal region after previous surgical treatment of post-injection abscess. According to these data, active surgical treatment of wounds and purulent-necrotic lesions of any etiology and localization, augmented by modern agents for local and systemic therapy (including phage therapy) provide favorable functional and cosmetic results even in patients with systemic autoimmune diseases receiving glucocorticosteroids. It is important to assess the wound process considering not only clinical data, but also objective information of qualitative and quantitative microbiological and cytological examinations.
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Abscesso , Doenças Autoimunes , Humanos , Abscesso/diagnóstico , Abscesso/etiologia , Abscesso/cirurgia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnósticoRESUMO
BACKGROUND: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy. METHODS: We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM). RESULTS: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages. CONCLUSIONS: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.
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Metástase Neoplásica , Neoplasias da Próstata , Radioterapia , Análise de Sobrevida , Fatores Etários , Idoso , Humanos , Estimativa de Kaplan-Meier , Masculino , Metástase Neoplásica/patologia , Metástase Neoplásica/radioterapia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Próstata/patologia , Próstata/efeitos da radiação , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Radioterapia/métodos , Radioterapia/estatística & dados numéricos , Programa de SEER/estatística & dados numéricosRESUMO
BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).
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Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Cicatriz/complicações , Cicatriz/patologia , Neoplasias Colorretais/patologia , Metástase Linfática , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Rectal cancer is mainly cured by radical resection with neoadjuvant chemoradiation or adjuvant chemotherapy. Pathological T1 lesions can be managed by local treatment and radiotherapy thereafter. Lower morbidity is the key benefit of these local treatments. Since nodal metastasis is important for staging, radical resection (RR) is suggested. Rectal cancer has higher surgical morbidity than colon cancer; local treatment has been the preferred choice by patients. METHODS: We retrospectively enrolled data of 244 patients with pT1 rectal adenocarcinoma. A total of 202 patients (82.8%) underwent RR, including low anterior resection (LAR) and abdomino-perineal resection (APR), and 42 patients (17.2%) underwent LT, including transanal excision and colonoscopic polypectomy. RESULTS: In our study, seven patients (16.7%) had loco-regional recurrence and distant metastasis from the LT group while eight patients (4.0%) had distant metastasis without loco-regional recurrence from the RR group. The lymph node metastasis rate in RR group was 8.4%. Forty-seven patients (24.2%) underwent LAR with temporary stoma, and its reversal rate was 100%. In the RR group, postoperative complication rate was 10.4% with a mortality rate of 0.5%. Recurrence-free survival (RFS) was 95.7% for RR and 80.2% for LT (P = 0.001), and overall survival (OS) was 93.7% for RR and 70.0% for LT (P = 0.001). CONCLUSION: This study found that RFS and OS in patients of pT1 rectal adenocarcinoma that had received RR were better than receiving LT. Further adjuvant chemotherapy was possible for some RR patients. A higher recurrence rate after LT must be balanced against the morbidity and mortality associated with RR.
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Adenocarcinoma , Neoplasias Retais , Adenocarcinoma/patologia , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Positive results in the RENAISSANCE Trial will establish oligometastatic gastric cancer as a real independent entity where total surgical treatment will become the standard of care.
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Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Metástase Linfática/terapia , Seleção de Pacientes , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
BACKGROUND: Treatment of early rectal cancer is evolving towards organ-preserving therapy which includes endoscopic resection and transanal approaches. We aimed to explore the role of local treatments such as endoscopic polypectomy (Endoscopic Mucosal Resection (EMR) or Endoscopic submucosal dissection (ESD)) and transanal endoscopic microsurgery/ transanal minimal invasive surgery (TEM/TAMIS) in patients who had early rectal cancer. We considered these outcomes alongside conventional major surgery using total mesorectal excision (TME) for early stage disease. METHODS: All patients identified at MDT with early stage rectal cancer at our institution between 2010 and 2019 were included. Long-term outcomes in terms of local recurrence, survival and procedure-specific morbidity were analysed. RESULTS: In total, 536 patients with rectal cancer were identified, of which 112 were included based on their pre-operative identification at the MDT on the basis that they had node-negative early rectal cancer. Among these, 30 patients (27%) had the lesion excised by flexible endoscopic polypectomy techniques (EMR/ESD), 67 (60%) underwent TEM/TAMIS and 15 (13%) had major surgery. There were no differences in patient demographics between the three groups except for TEM/TAMIS patients being more likely to be referred from another hospital (p < 0.001) and they were less active (WHO performance status p = 0.04). There were no significant differences in overall survival rates and cancer-specific survival between the three treatment groups. The 5-year overall survival rate for endoscopic polypectomy, TEM/TAMIS or major resection was 96% versus 90% and 88%, respectively (p = 0.89). The 5- year cancer-specific survival rate was 96%, versus 96% and 100%, respectively (p = 0.74). CONCLUSION: Endoscopic polypectomy by EMR/ESD is an appropriate local treatment for early stage rectal cancer in selected patients. It is possible to achieve good oncological outcomes with a polypectomy similar to TEM/TAMIS and major surgery; however, a multidisciplinary approach is necessary enabling close surveillance and the use of adjuvant radiotherapy.
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Ressecção Endoscópica de Mucosa , Neoplasias Retais , Microcirurgia Endoscópica Transanal , Ressecção Endoscópica de Mucosa/métodos , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Radioterapia Adjuvante , Neoplasias Retais/patologia , Reto/patologia , Microcirurgia Endoscópica Transanal/métodos , Resultado do TratamentoRESUMO
Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.
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Adenoviridae/genética , Neoplasias do Colo/terapia , Vesículas Extracelulares/transplante , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Vesículas Extracelulares/virologia , Células HCT116 , Humanos , Camundongos , Vírus Oncolíticos/genética , Tropismo Viral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Oligometastatic prostate cancer (PCa) can be defined as cancer with a limited number of metastases, typically fewer than 5 lesions, and involves lesions contained within the axial versus the appendicular skeleton. Patients can present with de novo oligometastatic, oligorecurrent, or oligoprogressive PCa. Oligometastatic PCa patients demonstrate considerable improvements in survival outcomes, with a better prognosis than patients with extensive metastatic disease. However, the management of patients that present with nonsymptomatic oligometastatic PCa remains difficult. In the oligometastatic setting, the benefit of local therapies such as prostatectomy and radiotherapy on survival outcomes is an intriguing topic; however, their impact on oncological outcomes is still unknown.
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Neoplasias da Próstata , Humanos , Masculino , Oncologia , Metástase Neoplásica , Prognóstico , Prostatectomia , Neoplasias da Próstata/patologiaRESUMO
Osteoarthritis (OA) can be defined as the result of pathological processes of various etiologies leading to damage to the articular structures. Although the mechanism of degenerative changes has become better understood due to the plethora of biochemical and genetic studies, the drug that could stop the degenerative cascade is still unknown. All available forms of OA therapy are based on symptomatic treatment. According to actual guidelines, comprehensive treatment of OA should always include a combination of various therapeutic options aimed at common goals, which are pain relief in the first place, and then the improvement of function. Local treatment has become more common practice, which takes place between rehabilitation and pharmacological treatment in the hierarchy of procedures. Only in the case of no improvement and the presence of advanced lesions visible in imaging tests, should surgery be considered. Currently, an increasing number of studies are being published suggesting that intra-articular injections may be as effective or even more effective than non-steroidal anti-inflammatory drugs (NSAIDs) and result in fewer systemic adverse events. The most commonly used preparations are hyaluronic acid (HA), glucocorticosteroids (GS), and also platelet-rich plasma (PRP) in recent years. This review aims to present the mechanism of action and clinical effectiveness of different pharmacological options in relieving pain and improving functions in OA as well as the emerging approach in intra-articular treatment with PRP.
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Osteoartrite/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Injeções Intra-Articulares , Osteoartrite/complicações , Dor/etiologia , Plasma Rico em Plaquetas/químicaRESUMO
The review is devoted to the world trends in epidemiology of colorectal cancer and treatment of colorectal cancer liver metastases. The authors analyze the effectiveness of traditional (resection) and modern minimally invasive methods of local destruction (radiofrequency thermoablation, microwave ablation, cryoablation), stereotactic radiotherapy, radiosurgery, targeted therapy and endovascular techniques (chemoinfusion, chemoembolization, radioembolization). It was emphasized that searching for new chemotherapeutic and targeted drugs is one of the reserve ways to improve treatment outcomes in patients with potentially resectable colorectal cancer liver metastases. The possibilities and prospects of liver transplantation as a priority treatment strategy for patients with unresectable bilobar colorectal cancer liver metastases are highlighted.
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Ablação por Cateter , Neoplasias Colorretais , Neoplasias Hepáticas , Transplante de Fígado , Ablação por Cateter/métodos , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/secundárioRESUMO
Venous trophic ulcer is a common complication of chronic venous diseases that have a negative impact on the quality of life and result negative socio-economic consequences. There are three main theories of development of venous trophic ulcers. The criterion is visible trophic changes of skin (CEAP class C4). If correction of etiological factor of ulcer is impossible, local management is preferred. There are various wound coverings which can be used for the treatment of trophic ulcers. However, data on their effectiveness are sometimes unavailable. Therefore, it is necessary to systematize knowledge about modern measures and methods of exposure to trophic ulcers. The authors also discuss current understanding of pathophysiology, symptoms and diagnosis of venous trophic ulcers.