LUIZ GUILHERME CERNAGLIA AURELIANO DE LIMA

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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico

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  • article 4 Citação(ões) na Scopus
    High dose image-guided, intensity modulated radiation therapy (IG-IMRT) for chordomas of the sacrum, mobile spine and skull base: preliminary outcomes
    (2022) CHEN, Andre Tsin Chih; HONG, Carlos Bo Chur; NARAZAKI, Douglas Kenji; RUBIN, Virginio; SERANTE, Alexandre Ruggieri; RIBEIRO JUNIOR, Ulysses; LIMA, Luiz Guilherme Cernaglia Aureliano de; COIMBRA, Brian Guilherme Monteiro Marta; CRISTANTE, Alexandre Fogaca; TEIXEIRA, William Gemio Jacobsen
    Purpose To report preliminary outcomes of high dose image-guided intensity modulated radiotherapy (IG-IMRT) in the treatment of chordomas of the sacrum, mobile spine and skull base. Methods Retrospective analysis of chordoma patients treated with surgery and/or radiotherapy (RT) in a single tertiary cancer center. Initial treatment was categorized as (A) Adjuvant or definitive high-dose RT (78 Gy/39fx or 24 Gy/1fx) vs (B) surgery-only or low dose RT. The primary endpoint was the cumulative incidence of local failure. Results A total of 31 patients were treated from 2010 through 2020. Median age was 55 years, tumor location was 64% sacrum, 13% lumbar, 16% cervical and 6% clivus. Median tumor volume was 148 cc (8.3 cm in largest diameter), 42% of patients received curative-intent surgery and 65% received primary RT (adjuvant or definitive). 5-year cumulative incidence of local failure was 48% in group A vs 83% in group B (p = 0.041). Tumor size > 330 cc was associated with local failure (SHR 2.2, 95% CI 1.12 to 7.45; p = 0.028). Eight patients developed distant metastases, with a median metastases-free survival of 56.1 months. 5-year survival for patients that received high dose RT was 72% vs 76% in patients that received no or low dose RT (p = 0.63). Conclusion Our study suggests high-dose photon IG-IMRT improves local control in the initial management of chordomas. Health systems should promote reference centers with clinical expertise and technical capabilities to improve outcomes for this complex disease.
  • article
    Tumor Reduction with Pazopanib in a Patient with Recurrent Lumbar Chordoma
    (2018) RIBEIRO, Mauricio Fernando Silva Almeida; SOUSA, Micelange Carvalho de; HANNA, Samir Abdallah; MALDAUN, Marcos Vinicius Calfat; KURIMORI, Ceci Obara; LIMA, Luiz Guilherme Cernaglia Aureliano de; MATTEDI, Romulo Loss; MUNHOZ, Rodrigo Ramella
    Introduction. Chordomas are rare malignancies of bone origin that occur in the axial skeleton, typically the skull base and lumbar/sacral regions. Although often classified as low-grade neoplasms, its locally infiltrative behavior may result in significant morbidity and mortality. Optimal surgical resection may be curative, but up to 50% of the cases relapse within 5 years, and currently there are no systemic treatments approved in this setting. A large proportion of these tumors express stem-cell factor receptor (c-KIT) and platelet-derived growth factor receptors (PDGFRs), providing a rationale for the use of tyrosine-kinase inhibitors (TKIs). Case report. A 27-year-old male presented with recurrent chordoma of the lumbar spine 4 years after initial diagnosis. Salvage therapies in the interval included repeat resections and radiation therapy. He ultimately developed multifocal recurrence not amenable to complete excision or reirradiation. A comprehensive genomic profiling assay was performed and revealed nondrugable alterations. Decision was made to proceed with systemic treatment with pazopanib 800 mg/day, resulting in tumor reduction (-23.1% reduction in size) and prolonged disease control. Conclusion. For this patient with a multiple recurrent chordoma and limited treatment options, pazopanib resulted in sustained clinical benefit following initial tumor reduction.
  • article 1 Citação(ões) na Scopus
    Complete response to alectinib following crizotinib in an ALK-positive tumor with CNS involvement
    (2021) XAVIER, Camila B.; CANEDO, Felipe S. N. A.; LIMA, Fabiola A. S.; MELO, Raissa R.; LIMA, Luiz Guilherme C. A.; MARIN, Jose Flavio G.; SOUZA, Ciro E.; FEHER, Olavo
    Inflammatory myofibroblastic tumor (IMT) is a rare entity that affects mostly children and young adults. The lungs are the most frequent primary site. When feasible, surgical resection is the standard of care and it is associated with long-term survival benefit. Metastatic disease is rare, and central nervous system involvement is very infrequent. There is paucity of data regarding systemic treatment of recurrent or metastatic disease but most IMTs present with ALK rearrangements, becoming potential targets to ALK inhibition. Diagnosis of ALK rearrangements by FISH or RT-PCR is standard and discordant results from immunohistochemistry are rare. Crizotinib is considered the standard therapy in ALK-positive cases. Data supporting the use of other ALK inhibitors are scant and derived only from case reports. We report a case of a patient harboring an ALK-positive by IHC, FISH-negative IMT, that initially responded well to crizotinib but progressed in the CNS, presenting a complete CNS response with second-generation ALK inhibitor alectinib.
  • article 0 Citação(ões) na Scopus
    Rectal leiomyosarcoma as the initial phenotypic manifestation of Li–Fraumeni-like syndrome: a case report and review of the literature
    (2022) SEVERINO, N. P.; WAISBERG, J.; FRAGOSO, M. C. B. V.; LIMA, L. G. C. A. de; BALSAMO, F.; HENRIQUES, A. C.; BIANCO, B.; GEHRKE, F. de Sousa
    Background: Leiomyosarcoma is a rare malignant tumor of smooth muscle origin and represents 10–20% of all soft tissue sarcomas. Primary colon and rectal sarcomas constitute < 0.1% of all large bowel malignancies. In Li–Fraumeni syndrome, sarcomas are the second most frequent cancer (25%). Li–Fraumeni syndrome is a genetic disease with a familial predisposition to multiple malignant neoplasms. This syndrome has an autosomal dominant pattern of inheritance and high penetrance characterized by germline TP53 mutations. Patients with a history of cancer who do not meet all the “classic” criteria for Li–Fraumeni syndrome are considered to have Li–Fraumeni-like syndrome. To the best of our knowledge, this article is the first report of a patient with rectal leiomyosarcoma as the initial phenotypic manifestation of Li–Fraumeni-like syndrome. The authors also present a literature review. Case presentation: A 67-year-old Brazilian woman underwent anterior rectosigmoidectomy and panhysterectomy secondary to rectal leiomyosarcoma. She subsequently developed carcinomatosis and died 2 years after the operation. Her family medical history consisted of a daughter who died at 32 years of age from breast cancer, a granddaughter diagnosed with adrenocortical carcinoma at 6 years of age and two siblings who died from prostate cancer. A genetic study was carried out to identify a pathogenic variant of Li–Fraumeni syndrome. In the DNA extracted from the peripheral blood leukocyte, restriction fragment length polymorphism was analyzed to search for mutations in the TP53 gene. The DNA sequencing identified the germline pathogenic variant p. R337H heterozygous in exon 10 of TP53. The patient was classified as having Li–Fraumeni-like syndrome. Conclusion: In patients with rectal leiomyosarcoma, it is advisable to investigate the family history of cancer and perform genetic studies to screen for Li–Fraumeni syndrome. © 2022, The Author(s).
  • article 2 Citação(ões) na Scopus
    Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival
    (2023) CAVALHEIRO, Vitor J.; CAMPOS, Ana Carolina P.; LIMA, Luiz G. C. A.; ROEA, Cairo Thome; DOCEMA, Marcos Fernando L.; LANCELLOTTI, Carmen Lucia P.; MARTINEZ, Raquel C. R.; PAGANO, Rosana L.; CHAMMAS, Roger; TEIXEIRA, Manoel J.; MALDAUN, Marcos V. C.; NEVILLE, Iuri S.
    Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohisto-chemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median pe-ripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.
  • article 2 Citação(ões) na Scopus
    Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?
    (2023) BALZI, Ana Paula de Carvalho Canela; OTSUKI, Denise Aya; ANDRADE, Lucia; PAIVA, Wellingson; SOUZA, Felipe Lima; AURELIANO, Luiz Guilherme Cernaglia; MALBOUISSON, Luiz Marcelo Sa
    BackgroundRestoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS.MethodsThirty-two pigs weighing 20-30 kg were randomly allocated into four groups: control (no treatment), saline (60 ml/kg of 0.9% NaCl), terlipressin (2 mg of terlipressin), and saline plus terlipressin (20 ml/kg of 0.9% NaCl + 2 mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40 mmHg. After 30 min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05.ResultsThe terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment.ConclusionsThe treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.
  • article 0 Citação(ões) na Scopus
    Glioneuronal and Neuronal Tumors: Who? When? Where? An Update Based on the 2021 World Health Organization Classification
    (2023) AYRES, A. S.; BANDEIRA, G. A.; FERRACIOLLI, S. F.; TAKAHASHI, J. T.; MORENO, R. A.; GODOY, L. F. de Souza; CASAL, Y. R.; LIMA, L. G. C. A. de; FRASSETO, F. P.; LUCATO, L. T.
    Neuronal and glioneuronal tumors usually have a benign course and may have typical imaging characteristics, allowing their diagnosis based on MR imaging findings. The most common lesions are dysembryoplastic neuroepithelial tumors and gangliogliomas, which have typical imaging characteristics. The fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System, recently published in 2021, places greater emphasis on molecular markers to classify tumors of the CNS, leading to extensive changes in the classification of tumors, including neuronal and glioneuronal tumors. The 2021 revision included 3 new tumors types: multinodular and vacuolating neuronal tumor, diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (a provisional type), and myxoid glioneuronal tumor. Following these recent changes in the World Health Organization classification, we aimed to review the main imaging features of these lesions in relation to their histopathologic and molecular features. Learning Objectives: To list the neuronal and glioneuronal tumors; recognize the main imaging findings and histologic characteristics of neuronal and glioneuronal tumors; know the typical location of each neuronal and glioneuronal tumor; and become familiar with the main molecular alterations of neuronal and glioneuronal tumors to better understand their behavior
  • article 4 Citação(ões) na Scopus
    CLIPPERS With Exclusive Extra Pontine Involvement
    (2021) PICARELLI, Helder; YAMAKI, Vitor Nagai; CASAL, Yuri Reis; BRITO, Marcelo Houat de; LIMA, Luiz Guilherme Cernaglia Aureliano de; AYRES, Aline Sgnolf; OLIVEIRA, Marcos Castello Barbosa de
  • article 11 Citação(ões) na Scopus
    Neoadjuvant stereotactic ablative radiotherapy (SABR) for soft tissue sarcomas of the extremities
    (2021) LEITE, Elton Trigo Teixeira; MUNHOZ, Rodrigo Ramella; CAMARGO, Veridiana Pires de; LIMA, Luiz Guilherme Cernaglia Aureliano de; REBOLLEDO, Daniel Cesar Seguel; MAISTRO, Carlos Eduardo Bravin; BUSNARDO, Fabio de Freitas; FERREIRA, Fabio de Oliveira; SALVAJOLI, Joao Victor; CARVALHO, Heloisa de Andrade
    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.
  • article 1 Citação(ões) na Scopus
    Measurement of extracapsular extension in sentinel lymph node as a possible predictor of residual axillary disease in breast cancer
    (2023) FREITAS, Gabriela Boufelli de; MOTA, Bruna Salani; MAESAKA, Jonathan Yugo; PINHEIRO, Cintia Cardoso; LIMA, Luiz Guilherme Cernaglia Aureliano de; JR, Jose Maria Soares; BARACAT, Edmund Chada; FILASSI, Jose Roberto
    Background: The presence of Extracapsular Extension (ECE) in the Sentinel Lymph Node Biopsy (SLNB) is still a doubt in the literature. Some studies suggest that the presence of ECE may be related to a greater number of posi-tive axillary lymph nodes which could impact Disease Free Survival (DFS) and Overall Survival (OS). This study searches for the clinical significance of the ECE. Methods: Retrospective cohort comparing the presence or absence of ECE in T1-2 invasive breast cancer with posi-tive SLNB. All cases treated surgically at the Cancer Institute of the State of Sa not similar to o Paulo (ICESP) between 2009 and 2013 were analyzed. All patients with axillary disease in SLNB underwent AD.Outcomes: Identify the association between the presence and length of ECE and additional axillary positive lymph nodes, OS and DFS between both groups. Results: 128 patients with positive SLNB were included, and 65 had ECE. The mean metastasis size of 0.62 (SD = 0.59) mm at SLNB was related to the presence of ECE (p < 0.008). The presence of ECE was related to a higher mean of positive sentinel lymph nodes, 3.9 (+/- 4.8) vs. 2.0 (+/- 2.1), p = 0.001. The median length of fol-low-up was 115 months. The OS and DFS rates had no differences between the groups. Conclusion:The presence of ECE was associated with additional positive axillary lymph nodes in this study. There-fore, the OS and DFS were similar in both groups after 10 years of follow-up. It is necessary for additional studies to define the importance of AD when SLNB with ECE.