RESUMO
PURPOSE: To determine the impact of the loco-regional treatment modality, on the loco-regional recurrence (LRR) rates and overall survival (OS) in breast cancer patients younger than 40 years. METHODS: Data of 623 breast cancer patients younger than 40 years of age were retrospectively reviewed. Patients were stratified according to the locoregional treatment approach into three groups: the mastectomy group (M), the mastectomy followed by radiation therapy group (MRX) and the breast conservative therapy group (BCT). RESULTS: Median follow-up was 72 months (range, 6-180). Two hundred and nine patients were treated with BCT, 86 with MRM and 328 with MRX. The 10-year rate LRR rates according to treatment modality were: 13.4% for BCT, 15.1% for MRM and 8.5% for MRX (p 0.106). On univariate analysis, T stage (p 0.009), AJCC stage (p 0.047) and Her 2 status (p 0.001) were associated with LRR. Ten-year overall survival (OS) was 72.7% (78.5% in the BCT group, 69.8% in the MRM group and 69.8% in the MRX group, p 0.072). On Univariate analysis, age < 35 (p 0.032), grade III (p 0.001), N3 stage (p 0.001), AJCC stage III (p 0.005), ER negative status (0.04), Her 2-status positive (0.006) and lack of chemotherapy administration (p 0.02) were all predictors of increased mortality. CONCLUSION: For patients younger than 40 years of age, similar LRR and overall survival outcomes were achieved using BCT, M or MRX. Young age at diagnosis should not be used alone in recommending one loco-regional treatment approach over the others.
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Neoplasias da Mama , Mastectomia , Recidiva Local de Neoplasia , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Adulto , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Estadiamento de Neoplasias , Terapia Combinada , Fatores Etários , Adulto Jovem , SeguimentosRESUMO
OBJECTIVES: The aim of the study was to compare, in patients undergoing minor gynecological laparoscopic procedures, the effects of ultrasound (US)-guided transversus abdominis plane (TAP) + rectus sheath (RS) block versus no TAP/RS block in terms of post-surgical pain control using the numeric pain rating scale (NRS) and the degree of patient satisfaction, according to the main goals of Early Recovery After Surgery (ERAS) programs. The primary outcome is to value the postoperative abdominal pain using NRS in both groups. Secondary outcomes are to evaluate blood values, presence of postoperative nausea and vomiting (PONV), postoperative ileus, level of patient expected satisfaction, time of discharge, length of stay (LOS), and the amounts of additional analgesics required. DESIGN: In this prospective randomized controlled trial, patients were randomly assigned to loco-regional anesthesia (LRA) group, who received TAP and RS block under US guidance, or no loco-regional anesthesia (N-LRA) group. Enrolled patients were randomized 1:1 to either receive bilateral TAP/RS block with ropivacaine or sham treatment (patches were applied on the abdominal wall of the patients under general anesthesia). PARTICIPANTS: All patients aged between 18 and 75 years, with ASA (American Society of Anesthesiologists) physical status 1-2, undergoing laparoscopic minor gynecological surgery, were enrolled. SETTING: The study was conducted to the University of Campus Bio-Medico Hospital of Rome. METHODS: Half an hour before surgery, all patients received gabapentin 300 mg per os. Once the patient underwent general anesthesia, US-guided bilateral TAP/RS block was performed by the anesthesiology team, while the uterine manipulator was positioned by a gynecology resident (not involved in the study). In the operative room, all patients received the same standardized anesthetic regimen. Postoperative abdominal pain was assessed at rest, after palpation, during movement, and after a cough by evaluating the patient at 6, 12, 18, 24, 36, 48, and 72 h after surgery, using the NRS from 0 to 10 in both groups. The amount of drug used for analgesia in the first 48 h after surgery was recorded. Moreover, hemoglobin, white blood cells, and c-reactive protein levels were recorded at 24, 48, and 72 h. The presence of PONV and the postoperative ileus was recorded throughout convalescence. The expected level of patient satisfaction at discharge and finally the LOS were assessed. LIMITATIONS: The major weakness of this study is that 60 mL of 0.5% ropivacaine was administered to each patient, without considering weight differences, yet contemporary literature rarely suggests volume/dose titration in fascial blocks. RESULTS: A total of 104 women, undergoing gynecological minor laparoscopic surgery, were enrolled and assigned to LRA group (53 pts) and N-LRA group (51 pts). Postoperative pain was significantly reduced in patients who received TAP/RS block. A reduction in the intake of non-steroidal anti-inflammatory drugs after surgery was registered in LRA group (p < 0.01). Moreover, a significant reduction of LOS (45.97 ± 9.87 vs. 65.08 ± 17.32 h; p < 0.01) and PONV was observed in the LRA group, as well as a better level of patient satisfaction at discharge (9.43 ± 0.94 vs. 8.26 ± 1.19; p < 0.01), compared to the N-LRA group. CONCLUSIONS: US-guided TAP and RS block significantly reduces postoperative pain after minor gynecologic laparoscopic surgery and improves patients' post-operative recovery.
Assuntos
Parede Abdominal , Íleus , Laparoscopia , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Ropivacaina/uso terapêutico , Náusea e Vômito Pós-Operatórios/epidemiologia , Estudos Prospectivos , Músculos Abdominais , Dor Pós-Operatória/tratamento farmacológico , Procedimentos Cirúrgicos em Ginecologia , Dor Abdominal , Anestésicos Locais/uso terapêuticoRESUMO
The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.
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Micrometástase de Neoplasia , Neoplasias Cutâneas , Humanos , Metástase Linfática , Micrometástase de Neoplasia/patologia , Neoplasias Cutâneas/patologia , Prognóstico , Pele/patologia , Biópsia de Linfonodo Sentinela , Estadiamento de NeoplasiasRESUMO
OBJECTIVES: We aimed to determine the radioguided occult lesion localization (ROLL) reliability in the reoperation of patients with differentiated thyroid cancer (DTC) and persistent or recurrent non-palpable loco-regional disease who underwent surgery at the Instituto Nacional de Cancerología between 2012 and 2021. DESIGN: Observational retrospective cohort study. PARTICIPANTS: We included data from patients with DTC that underwent resection with ROLL. MAIN OUTCOME MEASURES: Reliability analysed as percentage of patients with complete resection of tumour lesion using ROLL, disease-free survival, second loco-regional relapse, adequate resectability and complications. RESULTS: Two hundred and four cases were obtained. Pathological examination revealed papillary thyroid carcinoma in 202 patients, and follicular thyroid carcinoma in 2. Reliability was 96.57% in patients who underwent ROLL. When wide resection was performed-at surgeon's discretion-the reliability increased to 97.5%. CONCLUSIONS: The high reliability obtained suggests that ROLL was effective to localize non-palpable relapsing lesions. To our knowledge, this is the largest sample size published on this topic to date.
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Recidiva Local de Neoplasia , Neoplasias da Glândula Tireoide , Humanos , Reoperação , Estudos Retrospectivos , Reprodutibilidade dos Testes , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , RecidivaRESUMO
PURPOSE OF REVIEW: Miniaturized PCNL (mi-PCNL) for stone disease is performed under a general anesthesia. However, the role of loco-regional anesthesia in mi-PCNL and its outcomes are not well defined yet. Here, we review the outcomes and complications of loco-regional anesthesia for mi-PCNL. A Cochrane-style review was performed in accordance with the preferred reporting items for systematic reviews to evaluate the outcomes of loco-reginal anesthesia for URS in stone disease, including all English language articles from January 1980 and October 2021. RECENT FINDINGS: Ten studies with a total of 1663 patients underwent mi-PCNL under loco-regional anesthesia. The stone-free rate (SFR) for mi-PCNL under neuro-axial anesthesia ranged between 88.3 and 93.6%, while it ranged between 85.7 and 93.3% for mi-PCNL under local anesthesia (LA). The conversion rate to another anesthesia modality was 0.5%. The complications ranged widely between 3.3 and 85.7%. The majority were Grade I-II complications and none of the patients had grade V complications. Our review shows that mi-PCNL under loco-regional anesthesia is feasible with good SFR and a low risk of major complications. The conversion to general anesthesia is needed in a small minority, with the procedure itself being well tolerated and a big step towards establishing an ambulatory pathway for these patients.
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Anestesia por Condução , Cálculos Renais , Nefrostomia Percutânea , Humanos , Resultado do Tratamento , Anestesia Geral , Grupos MinoritáriosRESUMO
Loco-regional chemotherapy is a strategy used to achieve more precise anticancer drug effect directly on tumor mass, while decreasing whole body exposure, which can lead to undesirable side effects. Thus, the loco-regional chemotherapy is conceptually similar to the targeted drug delivery systems for delivering chemotherapeutics to cancer cells in a certain location of the body. Recently, it has been demonstrated that a novel polymeric film containing the complex between cisplatin (cisPt) and hyaluronan (sodium salt of hyaluronic acid; NaHA) enhanced in vivo efficacy and safety of cisplatin (cisPt) by loco-regional delivery in pleural mesothelioma. Biologically, hyaluronic acid (HA) binds with the CD44 receptor, which is a transmembrane glycoprotein overexpressed by other cancer cells. Thus, administering both cisPt and hyaluronan together as a complex loco-regionally to the tumor site could target cancer cells locally and enhance treatment safety. A slight excess of hyaluronan was required to have more than 85% cisPt complexation. In cell monolayers (2D model) the cisPt/NaHA complex in solution demonstrated dose- and time-dependent cytotoxic effect by decreasing the viability of pancreatic, melanoma, and lung cell lines (they all express CD44). At the same concentration in solution, the complex was as effective as cisPt alone. However, when applied as film to melanoma spheroids (3D model), the complex was superior because it prevented the tumor spheroid growth and, more importantly, the formation of new cell colonies. Hence, cisPt/NaHA complex could work in preventing metastases loco-regionally and potentially avoiding systemic relapses.
Assuntos
Antineoplásicos , Melanoma , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Ácido Hialurônico/metabolismo , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Receptores de Hialuronatos/metabolismoRESUMO
The aim of any oncological treatment is not just to eliminate the tumour, but to maximise patient survival and quality of life. Since the liver has a vital function, any radical treatment that severely compromises liver function will result in a shortening of life expectancy, rather than a prolongation. Furthermore, even non-severe liver damage may prevent the delivery of further effective therapies. This is particularly important in the case of hepatocellular carcinoma (HCC), as it is associated with underlying cirrhosis in most patients - cirrhosis itself is not only a potentially lethal disease and independent prognostic factor in HCC, but it also makes liver function fragile. Accordingly, some information about liver dysfunction is included in most staging systems for HCC and can be used to guide the selection of treatments that the functional liver reserve can tolerate. Unfortunately, the prediction of functional damage to the liver in the case of antitumor treatments is very challenging and still suboptimal in any given patient. Moreover, while the assessment of functional reserve can now be used to avoid postoperative liver failure in the surgical setting, its use has been less well clarified for non-surgical therapies, which is of particular relevance today, as several lines of effective non-surgical treatments, including systemic therapies, have become available. The present article will a) critically review the implications of the assessment of liver functional reserve in patients with HCC, b) illustrate the available tools to assess liver functional reserve and c) discuss the role of functional assessment for each type of non-surgical therapy for HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Cirrose Hepática/terapia , Neoplasias Hepáticas/patologia , Qualidade de VidaRESUMO
PURPOSE: Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). PATIENTS AND METHODS: Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). RESULTS: We enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13-4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68-2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70-2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61-2.05]). CONCLUSION: High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes.
Assuntos
Neoplasias da Mama , Apolipoproteína A-I , Neoplasias da Mama/epidemiologia , Dieta , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: There is a paucity of data regarding the prognostic influence of peripheral blood CD4+ T lymphopenia in non-small cell lung cancer (NSCLC). Therefore, we investigated the prognostic value of T lymphopenia in NSCLC. MATERIALS: Treatment-naive patients with a pathological diagnosis of NSCLC, at clinical stage I to IV were included in the prospective TELOCAP1 study. Lymphocytes count was evaluated in peripheral blood by flow cytometry. CD4+ and CD8+ T lymphopenia were defined as an absolute count of < 500/µL and < 224/µL respectively. The prognostic value of T lymphopenia was analyzed in the whole population, in local/loco-regional (stage I-IIIB) and in advanced (stage IV) NSCLC disease, using the Kaplan-Meier method and Cox regression models for survival curves and multivariate analysis, respectively. RESULTS: Between July 2010 and January 2014, 169 evaluable patients with clinical stage I to IV NSCLC were prospectively enrolled. The prevalence of CD4+ and CD8+ T lymphopenia was similar in the study population (around 29%). Patients with CD4+ T lymphopenia showed lower overall survival than those with CD4+ T lymphocytes count > 500/µL (median overall survival (OS) 16.1 versus 21.7 months, hazard ratio (HR): 1.616 [95% CI: 1.1-2.36], p = 0.012). This association with OS was especially marked in local/loco-regional NSCLC stages (median OS, 21.8 versus 72 months, respectively, HR: 1.88 [95% CI: 0.9-3.8], p = 0.035). Multivariate analysis confirmed the worse prognosis associated with CD4+ T lymphopenia in local/loco-regional NSCLC, but not in metastatic patients (HR 2.028 [95% CI = 1.065-3.817] p = 0.02). Restricted cubic spline analysis showed that patients with CD4+ T lymphocytes count ≤500/µL displayed a high risk of death regardless of NSCLC clinical stage. There was no obvious relationship between CD8+ T lymphopenia and clinical outcome. CONCLUSION: We identified CD4+ T lymphopenia as an independent prognostic factor in local/loco-regional stages of NSCLC and CD4+ T lymphopenia is also associated with a high risk of death, regardless of NSCLC clinical stage. TRIAL REGISTRATION: EUDRACT: 2009-A00642-55.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfopenia , Linfócitos T CD4-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Prognóstico , Estudos ProspectivosRESUMO
Background and Objectives: Treatment of cancer patients during the COVID-19 pandemic has been a challenge worldwide. In accordance with the current recommendations for hepatocellular carcinoma (HCC) management during the COVID-19 pandemic, loco-regional therapy such as transarterial chemoembolization (TACE) was proposed with the purpose of achieving local tumor control and improving overall survival. The aim of this prospective cohort study was to evaluate the outcomes of TACE treatment in patients with HCC during the COVID-19 pandemic in comparison with the outcomes of patients treated in the pre-pandemic period. Materials and Methods: Between September 2018 and December 2021, 154 patients were managed by serial TACE procedures for different liver tumors. Ninety-seven patients met the study criteria and were divided into two groups: the study group n = 49 (patients treated from May 2020 to December 2021); the control group n = 48 (patients treated from September 2018 to May 2020). Results: The mean waiting time for TACE was significantly longer in the study group compared to the control group (p < 0.001). No significant difference in survival between the groups is noted (log-rank test p = 0.823). In multivariate analysis, the MELD score (HR 1.329, 95% CI 1.140−1.548, p < 0.001) remained a significant predictor of mortality. Conclusions: COVID-19 pandemic did not affect the final outcome of TACE treatment.
Assuntos
COVID-19 , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Pandemias , Estudos Prospectivos , Países em Desenvolvimento , Resultado do Tratamento , Quimioembolização Terapêutica/efeitos adversos , COVID-19/terapia , Estudos RetrospectivosRESUMO
PURPOSE: The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. METHODS: We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2 years or more after SCRT at the last observation date. RESULTS: One hundred and three patients were enrolled in this study. The median observation period for survivors was 60 months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42 months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24 months and the other patient showed failure at 26.5 months. CONCLUSIONS: The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4 years after SCRT should be performed for those patients.
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Neoplasias Esofágicas , Recidiva Local de Neoplasia , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/radioterapia , Humanos , Japão/epidemiologia , Recidiva Local de Neoplasia/patologia , Terapia de SalvaçãoRESUMO
BACKGROUND AND AIMS: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. METHODS: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. RESULTS: MaVI prevalence was 11.1%, and median survival of these patients was 6.0 months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4 months in those with PS > 1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1 months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). CONCLUSIONS: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.
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Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Veias Mesentéricas/patologia , Veia Porta/patologia , Técnicas de Ablação , Idoso , Antineoplásicos/uso terapêutico , Ascite , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , Doença Hepática Terminal , Feminino , Hepatectomia , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Itália , Hepatopatias Alcoólicas/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Hepatopatia Gordurosa não Alcoólica/complicações , Gravidade do Paciente , Prognóstico , Sistema de Registros , Sorafenibe/uso terapêutico , Taxa de Sobrevida , Carga TumoralRESUMO
The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO® technology (MedinCell S.A.) is investigated over 10 days, after a single subcutaneous injection of test item based on a DMSO solution of diblock and triblock polyethylene glycol-polylactic acid copolymers. Injection sites are systematically observed for macroscopic loco-regional skin reactions as well as ultrasound scanning, enabling longitudinal in vivo imaging of the depot. Observations are complemented by histopathological examinations at 72 h and 240 h post-injection. Overall, no treatment-emergent adverse effects are macroscopically or microscopically observed at the subcutaneous injection sites, for the tested injection flow rates of 1 and 8 mL/min and volumes of 0.2 and 1 mL. The histopathology examination confirms an expected foreign body reaction, with an intensity depending on the injected volume. The depot morphology is similar irrespective of the administration flow rates. These results indicate that the ISFD BEPO® technology can be considered safe when administered subcutaneously in Göttingen minipigs, a human-relevant animal model for subcutaneous administrations, in the tested ranges.
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Vias de Administração de Medicamentos/veterinária , Injeções Subcutâneas/efeitos adversos , Injeções Subcutâneas/métodos , Animais , Imuno-Histoquímica , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Pele/patologia , Suínos , Porco Miniatura , UltrassonografiaRESUMO
BACKGROUND: Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~ 1%) but are relatively common (10-50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. Little is known about the incidence and clinical implication of these mutations in early recurrence events, such as local recurrences or newly diagnosed metastatic disease. METHODS: We collected 130 archival tumor samples from 103 breast cancer patients treated with endocrine therapy prior to their local/metastatic recurrence. The cohort consisted of 41 patients having at least 1 sample from local/loco-regional recurrence and 62 patients with metastatic disease (of whom 41 newly diagnosed and 28 with advanced disease). The 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) were analyzed either by targeted sequencing or by droplet digital PCR. Progression-free survival (PFS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were statistically tested by Kaplan-Meier analysis. RESULTS: The prevalence of ESR1 mutations was 5/41 (12%) in newly diagnosed metastatic patients and 5/28 (18%) for advanced metastases, detected at allele frequency > 1%. All mutations in advanced metastases were detected in patients previously treated with both tamoxifen (TAM) and aromatase inhibitors (AI). However, in newly diagnosed metastatic patients, 4/5 mutations occurred in patients treated with TAM alone. PFS on AI treatment in metastatic patients was significantly shorter for ESR1 mutation carriers (p = 0.017). In the local recurrence cohort, ESR1 mutations were identified in 15/41 (36%) patients but only 4/41 (10%) were detected at allele frequency > 1%. Again, most mutations (3/4) were detected under TAM monotherapy. Notably, 1 patient developed ESR1 mutation while on neoadjuvant endocrine therapy. DFS and DRFS were significantly shorter (p = 0.04 and p = 0.017, respectively) in patients that had ESR1 mutations (> 1%) in their loco-regional recurrence tumor. CONCLUSIONS: Clinically relevant ESR1 mutations are prevalent in newly diagnosed metastatic and local recurrence of endocrine-treated breast cancer. Since local recurrences are amenable to curative therapy, these mutations may inform the selection of subsequent endocrine therapies.
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Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/mortalidade , Resistencia a Medicamentos Antineoplásicos , Receptor alfa de Estrogênio/genética , Mutação , Recidiva Local de Neoplasia/mortalidade , Neoplasias Hormônio-Dependentes/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The primary aim was to test the hypothesis that deriving pre-treatment 3D magnetic resonance tumour volume (mrTV) quantification improves performance characteristics for the prediction of loco-regional failure compared with standard maximal tumour diameter (1D) assessment in patients with squamous cell carcinoma of the anus undergoing chemoradiotherapy. METHODS: We performed an early evaluation case-control study at two UK centres (2007-2014) in 39 patients with loco-regional failure (cases), and 41 patients disease-free at 3 years (controls). mrTV was determined using the summation of areas method (Volsum). Reproducibility was assessed using intraclass concordance correlation (ICC) and Bland-Altman limits of agreements. We derived receiver operating curves using logistic regression models and expressed accuracy as area under the curve (ROCAUC). RESULTS: The median time per patient for Volsum quantification was 7.00 (inter-quartile range, IQR: 0.57-12.48) minutes. Intra and inter-observer reproducibilities were generally good (ICCs from 0.79 to 0.89) but with wide limits of agreement (intra-observer: - 28 to 31%; inter-observer: - 28 to 46%). Median mrTVs were greater for cases (32.6 IQR: 21.5-53.1 cm3) than controls (9.9 IQR: 5.7-18.1 cm3, p < 0.0001). The ROCAUC for mrT-size predicting loco-regional failure was 0.74 (95% CI: 0.63-0.85) improving to 0.82 (95% CI: 0.72-0.92) when replaced with mrTV (test for ROC differences, p = 0.024). CONCLUSION: Preliminary results suggest that the replacement of mrTV for mrT-size improves prediction of loco-regional failure after chemoradiotherapy for squamous cell carcinoma of the anus. However, mrTV calculation is time consuming and variation in its reproducibility are drawbacks with the current technology.
Assuntos
Neoplasias do Ânus/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Estudos de Casos e Controles , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. METHODS: A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. RESULTS: Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). CONCLUSION: Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.
Assuntos
Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Metástase Linfática , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , PrognósticoRESUMO
OBJECTIVE: To evaluate the efficacy of different surgical procedures on post burn contracture of hand. METHODS: A quasi-experimental study design was conducted at the Department of Plastics and Reconstructive Surgery, Dow University of Health Science, DR. Ruth KM Pfau, Civil Hospital, Karachi, Pakistan from 1st June 2019 to 30th November 2019. Ninety-three participants of burned hand contracture of either gender, aged between 6- 60 years were included in the study. Resurfacing surgery with skin graft and loco-regional flaps were done according to type of contracture with individualization for each patient. All patients were kept under follow up for ninety days to assess efficacy of contracture release for each surgical procedure was noted. SPSS version 23 was used to analyse data. RESULTS: Full thickness skin graft (FTSG) was performed in 60.2% cases, 17.2% with split thickness skin graft (STSG) and 12.9% with cross finger flaps. About 25% of recurrence was observed in cross finger flaps, whereas no recurrence was seen in Z-plasties and posterior interosseous flap. The significant association was between recurrence and surgical procedures (p<0.05). CONCLUSION: Z-plasty followed by FTSG was effective in the management of post burn contractures of hand.
RESUMO
BACKGROUND: Population-based estimates of the long-term risk of loco-regional recurrence and distant metastases of breast cancer (BRC) patients are scant, as most published studies used hospital-based cohorts or participants of clinical trials. This work aims to extend available knowledge by providing population-based long-term estimates of the cumulative risk of BRC recurrence up to 10 years after diagnosis. METHODS: Data from the population-based Saarland Cancer Registry were used and included 9359 female patients with primary invasive BRC diagnosed between 1999 and 2009. Estimates of the cumulative incidence (CI) of BRC recurrence were derived for patients who had received local surgery with free resection margins by type of recurrence and stratified by age, tumor characteristics and major treatment options, taking into account mortality from any cause as a competing risk. RESULTS: The 10-year CI of BRC recurrence was 16%. For loco-regional recurrence and distant metastases alone it was 8 and 11%, respectively. The estimates showed substantial variation and were particularly increased if tumors were advanced (T1/2N+ 23%, T3/4N0 24%, T3/4N+ 34%), of high grade (23%), or of 'HER2/neu positive' (28%) or 'triple negative' subtype (23%), respectively. CONCLUSIONS: The derived estimates reflect the risk of 'real world' patients and may therefore extend available knowledge. These data are thus of great relevance for clinicians, their patients and researchers. The study likewise demonstrated the usefulness of cancer registries for a population-based monitoring of the effectiveness of cancer care in terms of disease recurrence as a major treatment related outcome measure.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Sistema de Registros/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Metástase Neoplásica , Recidiva Local de Neoplasia , Fatores de RiscoRESUMO
OBJECTIVE: To design and assess the perioperative analgesic efficacy of an ultrasound (US)-guided radial (R), ulnar (U), median (M) and musculocutaneous (Mc) nerve blocks, performed together in the axillary space by a single, in-plane approach. STUDY DESIGN: Anatomical research and prospective clinical study. ANIMALS: A group of three dog cadavers and 15 client-owned dogs undergoing orthopaedic thoracic limb surgery. METHODS: Phase 1: Anatomical dissection and US study of the axillary space were performed to design the US-guided proximal RUMM block. The technique was considered successful if a total volume of 0.15 mL kg-1 new methylene blue solution completely stained the four nerves in two cadavers for ≥2 cm. Phase 2: In 15 client-owned dogs undergoing orthopaedic thoracic limb surgery, the RUMM block designed in phase 1 was performed to provide analgesia using a total volume of 0.15 mL kg-1 of ropivacaine 0.5%. The block was considered effective if the intraoperative fentanyl requirement was <1.2 mcg kg-1 hour-1 and until the postoperative pain score was [short-form Glasgow Composite Measure Pain Scale (SF-GCMPS)] ≤5/20. RESULTS: Phase1: Detection of the four nerves was always feasible in a single US-window. The axillary artery and Mc nerve were used as landmarks. In-plane needling approach was feasible in both cadavers. All the nerves were completely stained for >2 cm. No intrathoracic dye spread was found. Phase 2: In 14/15 anaesthetized dogs, mean intraoperative fentanyl requirement was 0.25 ± 0.05 mcg kg-1 hour-1. Postoperatively, all dogs had SF-GCMPS ≤5/20 up to 8 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The US-guided proximal RUMM block performed at the axillary level with a single, in-plane needling approach using 0.15 mL kg-1 of ropivacaine 0.5% minimized fentanyl requirement during thoracic limb surgery, contributing to postoperative analgesia up to 8 hours after execution of the peripheral nerve block.
Assuntos
Cães/cirurgia , Bloqueio Nervoso/veterinária , Procedimentos Ortopédicos/veterinária , Ultrassonografia de Intervenção/veterinária , Analgésicos Opioides/uso terapêutico , Animais , Cadáver , Fentanila/uso terapêutico , Membro Anterior/cirurgia , Azul de Metileno/análogos & derivados , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/veterinária , Estudos Prospectivos , Ultrassonografia de Intervenção/métodosRESUMO
AIM: To evaluate the outcomes in patients with local recurrences (LR) of colon cancer. MATERIAL AND METHODS: Prospective study included 52 patients with local recurrences of colon cancer MR and no distant metastases or disseminated carcinomatosis. Patients have been treated at Ryzhikh State Research Center for Coloproctology for the period 2009-2017. Median of local recurrence was 17.6 months. By the moment of diagnosis, CEA was increased in 24 (46.2%), CA 19-9 - in 4 (7.7%) patients. Forty-eight (92%) patients underwent surgery for local recurrences of colon cancer. In 26 (54%) cases, low ligation of supplying vessel was made during primary tumor excision that was confirmed by significant fragment of intact mesentery of the colon. RESULTS: Radical surgery for LR was possible in 34 (70.8%) patients, resection of more than one organ was required in 60% of cases. R1-resection was obtained in 12 (25.0%) cases, palliative resections - in 2 (4.2%) patients. Various complications occurred in 34 (70.8%) patients. Additional intraperitoneal chemotherapy was need in 12 (23.1%) cases. Lethal outcomes were absent. Forty-six out of 48 (95.8%) patients were followed-up. Mean follow-up was 19.5 (8.6-34.7) months. Twelve (26.1%) patients were free from recurrent cancer. Only distant metastases developed in 16 (34.8%) patients. Redo LR occurred in 18 (39.1%) patients including 12 of them with distant metastases. Overall 5-year survival was 38%, disease-free survival - 17.5%, median overall survival - 42.8 months, median disease-free survival - 15.2 months. Intraperitoneal chemotherapy did not significantly affect overall survival. Multivariate analysis confirmed high level of CEA and CA 19-9, positive resection margin as negative predictors. Moreover, impaired survival (p=0.03) was noted in case of LR after non-radical surgery for primary tumor with high ligation of the vessel. CONCLUSION: R0-resection is essential to improve survival and reduce incidence of recurrences. Intraoperative intra-abdominal chemotherapy does not affect the outcomes in patients with LR of colon cancer. Adherence to surgical principles for cancer can reduce the incidence of LR.