Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management. METHODS: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up. RESULTS: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient's comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards. CONCLUSION: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil.

TNFRSF1B Gene Variants in Clinicopathological Aspects and Prognosis of Patients with Cutaneous Melanoma.

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3'-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3'-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients.

Treatment of patients with multiple brain metastases by isolated radiosurgery: Toxicity and survival.

BACKGROUND: Radiosurgery for multiple brain metastases has been more reported recently without using whole-brain radiotherapy. Nevertheless, the sparsity of the data still claims more information about toxicity and survival and their association with both dosimetric and geometric aspects of this treatment. AIM: To assess the toxicity and survival outcome of radiosurgery in patients with multiple (four or more lesions) brain metastases. METHODS: In a single institution, data were collected retrospectively from patients who underwent radiosurgery to treat brain metastases from diverse primary sites. Patients with 4-21 brain metastases were treated with a single fraction with a dose of 18 Gy or 20 Gy. The clinical variables collected were relevant to toxicity, survival, treatment response, planning, and dosimetric variables. The Spearman's rank correlation coefficients, Mann-Whitney test, Kruskal-Wallis test, and Log-rank test were used according to the type of variable and outcomes. RESULTS: From August 2017 to February 2020, 55 patients were evaluated. Headache was the most common complaint (38.2%). The median overall survival (OS) for patients with karnofsky performance status (KPS) > 70 was 8.9 mo, and this was 3.6 mo for those with KPS ≤ 70 (P = 0.047). Patients with treated lesions had a median progression-free survival of 7.6 mo. There were no differences in OS (19.7 vs 9.5 mo) or progression-free survival (10.6 vs 6.3 mo) based on prior irradiation. There was no correlation found between reported toxicities and planning, dosimetric, and geometric variables, implying that no additional significant toxicity risks appear to be added to the treatment of multiple (four or more) lesions. CONCLUSION: No associations were found between the evaluated toxicities and the planning dosimetric parameters, and no differences in survival rates were detected based on previous treatment status.

PD-L1 Tumor Expression as a Predictive Biomarker of Immune Checkpoint Inhibitors' Response and Survival in Advanced Melanoma Patients in Brazil.

Immune checkpoint blockade (ICB) agents are prominent immunotherapies for the treatment of advanced melanoma. However, they fail to promote any durable clinical benefit in a large cohort of patients. This study assessed clinical and molecular predictors of ICB response and survival in advanced melanoma. A retrospective analysis was performed on 210 patients treated with PD-1 or CTLA-4 inhibitors at Barretos Cancer Hospital, Brazil. PD-L1 expression was assessed by immunohistochemistry using formalin-fixed paraffin-embedded tumor tissues collected prior to ICB therapy. Patients were divided into responders (complete and partial response and stable disease for more than 6 months) and non-responders (stable disease for less than 6 months and progressive disease). Among them, about 82% underwent anti-PD-1 immunotherapy, and 60.5% progressed after the ICB treatment. Patients that received ICB as first-line therapy showed higher response rates than previously treated patients. Higher response rates were further associated with superficial spreading melanomas and positive PD-L1 expression (>1%). Likewise, PD-L1 positive expression and BRAF V600 mutations were associated with a higher overall survival after ICB therapy. Since ICBs are expensive therapies, evaluation of PD-L1 tumor expression in melanoma patients should be routinely assessed to select patients that are most likely to respond.

Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients.

BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient's blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome. Firstly, we performed digital polymerase chain reaction using tumor cell lines for validation and determination of limit of detection (LOD) of each assay and screened plasma samples from healthy individuals to determine the limit of blank (LOB). Then, we selected 19 stage III and IV patients and determined the somatic mutations status in tumor tissue and track them in patients' plasma. We established a specific and sensitive methodology with a LOD ranging from 0.13 to 0.37%, and LOB ranging from of 0 to 5.201 copies/reaction. Somatic mutations occurred in 17/19 (89%) patients, of whom seven (41%) had ctDNA detectable their paired plasma. ctDNA detection was associated with shorter progression free survival (p = 0.01). In conclusion, our data support the use of ctDNA as prognosis biomarker, suggesting that patients with detectable levels have an unfavorable outcome.

Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance.

Indoleamine 2,3-dioxygenase (IDO) is associated with the progression of many types of tumors, including melanoma. However, there is limited information about IDO modulation on tumor cell itself and the effect of BRAF inhibitor (BRAFi) treatment and resistance. Herein, IDO expression was analyzed in different stages of melanoma development and progression linked to BRAFi resistance. IDO expression was increased in primary and metastatic melanomas from patients' biopsies, especially in the immune cells infiltrate. Using a bioinformatics approach, we also identified an increase in the IDO mRNA in the vertical growth and metastatic phases of melanoma. Using in silico analyses, we found that IDO mRNA was increased in BRAFi resistance. In an in vitro model, IDO expression and activity induced by interferon-gamma (IFNγ) in sensitive melanoma cells was decreased by BRAFi treatment. However, cells that became resistant to BRAFi presented random IDO expression levels. Also, we identified that treatment with the IDO inhibitor, 1-methyltryptophan (1-MT), was able to reduce clonogenicity for parental and BRAFi-resistant cells. In conclusion, our results support the hypothesis that the decreased IDO expression in tumor cells is one of the many additional outcomes contributing to the therapeutic effects of BRAFi. Still, the IDO production changeability by the BRAFi-resistant cells reiterates the complexity of the response arising from resistance, making it not possible, at this stage, to associate IDO expression in tumor cells with resistance. On the other hand, the maintenance of 1-MT off-target effect endorses its use as an adjuvant treatment of melanoma that has become BRAFi-resistant.

Caution is needed in interpreting the results of comparative studies regarding oncological operations by minimally invasive versus laparotomic access.

We aim to alert the difference between groups while comparing studies of abdominal oncological operations performed either by minimally invasive or laparotomic approaches and potential conflicts of interest in presenting or interpreting the results. Considering the large volume of scientific articles that are published, there is a need to consider the quality of the scientific production that leads to clinical decision making. In this regards, it is important to take into account the choice of the surgical access route. Randomized, controlled clinical trials are the standard for comparing the effectiveness between these interventions. Although some studies indicate advantages in minimally invasive access, caution is needed when interpreting these findings. There is no detailed observation in each of the comparative study about the real limitations and potential indications for minimally invasive procedures, such as the indications for selected and less advanced cases, in less complex cavities, as well as its elective characteristic. Several abdominal oncological operations via laparotomy would not be plausible to be completely performed through a minimally invasive access. These cases should be carefully selected and excluded from the comparative group. The comparison should be carried out, in a balanced way, with a group that could also have undergone a minimally invasive access, avoiding bias in selecting those cases of minor complexity, placed in the minimally invasive group. It is not a question of criticizing the minimally invasive technologies, but of respecting the surgeon's clinical decision regarding the most convenient method, revalidating the well-performed traditional laparotomy route, which has been unfairly criticized or downplayed by many people.

Caution is needed in interpreting the results of comparative studies regarding oncological operations by minimally invasive versus laparotomic access / É necessário cautela na interpretação dos resultados de estudos comparativos de cirurgias oncológicas por acessos minimamente invasivos vs laparotômicos

ABSTRACT We aim to alert the difference between groups while comparing studies of abdominal oncological operations performed either by minimally invasive or laparotomic approaches and potential conflicts of interest in presenting or interpreting the results. Considering the large volume of scientific articles that are published, there is a need to consider the quality of the scientific production that leads to clinical decision making. In this regards, it is important to take into account the choice of the surgical access route. Randomized, controlled clinical trials are the standard for comparing the effectiveness between these interventions. Although some studies indicate advantages in minimally invasive access, caution is needed when interpreting these findings. There is no detailed observation in each of the comparative study about the real limitations and potential indications for minimally invasive procedures, such as the indications for selected and less advanced cases, in less complex cavities, as well as its elective characteristic. Several abdominal oncological operations via laparotomy would not be plausible to be completely performed through a minimally invasive access. These cases should be carefully selected and excluded from the comparative group. The comparison should be carried out, in a balanced way, with a group that could also have undergone a minimally invasive access, avoiding bias in selecting those cases of minor complexity, placed in the minimally invasive group. It is not a question of criticizing the minimally invasive technologies, but of respecting the surgeon's clinical decision regarding the most convenient method, revalidating the well-performed traditional laparotomy route, which has been unfairly criticized or downplayed by many people.

RESUMO Objetivamos alertar a desigualdade entre grupos de pacientes, em estudos comparativos de cirurgias oncológicas abdominais por acessos minimamente invasivos ou laparotômicos, e os possíveis conflitos de interesse na demonstração ou interpretação dos resultados. Diante do grande volume de artigos científicos produzidos, há necessidade de se considerar a qualidade da produção científica de estudos para a tomada da decisão clínica quanto à eleição da via de acesso cirúrgico. Ensaios clínicos randomizados e controlados são o padrão para comparar a eficácia entre estas intervenções em situações diversas. Apesar de alguns estudos indicarem vantagens no acesso minimamente invasivo, é preciso cautela na interpretação desses achados. Não se percebe detalhada discussão que alerte, em cada estudo comparativo, sobre os reais limites e indicações possíveis de cirurgias minimamente invasivas, como indicações para casos selecionados, menos avançados, mais eletivos, e em cavidades menos complexas. Diversas cirurgias oncológicas abdominais via laparotômica não seriam plausíveis de serem, completamente, realizadas por acesso minimamente invasivo. Estas deveriam ser, criteriosamente, selecionadas e excluídas do grupo comparativo. A comparação deve ser, equilibradamente, realizada com grupo que, muito provavelmente, também poderia ter sido submetido ao acesso minimamente invasivo a contento, evitando viés de seleção da concentração de casos de complexidade menor no grupo da cirurgia minimamente invasiva. Não se trata, aqui, de desmerecer as tecnologias minimamente invasivas, mas de respeito à decisão clínica do cirurgião pelo método mais conveniente, revalidando a via laparotômica tradicional bem procedida, a qual tem sido, injustamente, criticada ou inferiorizada por muitos em nosso meio.

Characteristics of Brazilian melanomas: real-world results before and after the introduction of new therapies.

OBJECTIVE: This study is a characterization of the treatment patterns and outcomes of a Brazilian melanoma cohort collected of 1848 patients enrolled between 1996 and 2015. RESULTS: The superficial spreading subtype (35.1%) was the most prevalent, and the favoured anatomical location was the trunk (32.8%). The most common clinical stage was I (27.6%). The most frequent initial treatment was surgery (84.7%). Sentinel node biopsy was positive in 23.3% of cases. Chemotherapy was used to treat 298 patients (16.1%), immunotherapy for 67 (3.6%) and targeted therapy for 19 (1.0%). Distant recurrence was commonly observed (22.5%) and the mutation status of the BRAF gene was verified in 132 cases, with 42.4% positivity in this subset of patients. The melanoma specific actuarial 5-year survival for the cohort was 68.8%. There was a higher 5-year survival observed in metastatic melanoma patients who received immunotherapy and/or targeted therapy (34.2%) compared patients treated with just chemotherapy (20.0%). The survival analysis showed that sex, age, Breslow, clinical stage and distant recurrence were significant prognostic factors. This study provides a real-world description of how the introduction of new therapies such as immunotherapy and BRAF inhibitors is changing treatment strategies for melanoma in developing countries.

Comparison of protocols for removal of melanin from genomic DNA to optimize PCR amplification of DNA purified from highly pigmented lesions.

Melanin is produced by melanocytes and protects against DNA damage by ultraviolet light. Unfortunately, the melanin protein present in melanoma tumor cells is often co-purified during DNA extraction, and this contamination may inhibit subsequent PCR methods, which directly impacts research applications and the molecular diagnostic tests needed for targeted therapeutics. There are presently no described purification protocols that efficiently remove melanin from genomic DNA. In this study, we compare six different methods for melanin removal from genomic DNA: Agarose Gel Electrophoresis, 1mg Chelex®-100, Chelex®-100 5%, centrifugation, OneStep™ PCR Inhibitor Removal Kit and centrifugation plus OneStep™ PCR Inhibitor Removal Kit. Each comparison was made using 16 formalin-fixed paraffin-embedded (FFPE) and 11 fresh cell line samples. All samples were initially tested using the multiplex PCR reaction for GAPDH gene that generates different sized amplified products: 100, 200, 300 and 400 base pairs, which could be inhibited by the addition of exogenous melanin. Six purification protocols were then applied, and all samples that amplified at least one GAPDH fragment were sequenced to analyze the presence of the BRAF V600E mutation. The efficiencies of amplification decreased for larger sized fragments in all methods. Our comparisons showed that centrifugation combined with the OneStep™ PCR Inhibitor Removal Kit was superior to all other methods for successful BRAF sequencing with 100% (100bp), 75% (200bp), 50% (300bp), and 31.3% (400bp) amplification efficiencies for the different amplicon sizes. In conclusion, this genomic DNA extraction method is highly efficient for successful PCR when tumor samples are contaminated with melanin.

PD-1/PD-L1 and VEGF-A/VEGF-C expression in lymph node microenvironment and association with melanoma metastasis and survival.

Regional lymph nodes are affected frequently by melanoma metastasis. Its microenvironment may be associated with tumor progression. We investigated sentinel nodes with and without tumor and negative nodes surrounding positive nodes, looking for patterns related to tumor immune interaction and lymphovascular progression. We quantified programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1, vascular endothelial growth factor (VEGF)-A/VEGF-C expressions in lymph nodes of 103 patients who underwent sentinel lymph node biopsy. Two groups were studied: negative sentinel lymph nodes and positive ones. Negative lymph nodes of sequential lymphadenectomy from positive cases were also studied. Markers were assessed by immunohistochemistry. Results were related to clinical/histological outcomes. VEGF-A/VEGF-C analysis showed higher positivity in metastatic nodes and higher positivity in the surrounding negative nodes from positive cases in comparison with nonmetastatic patients. Programmed cell death-ligand 1, studied only in metastasis, presented high positivity, not associated with prognosis. PD-1 expressions were similar in the groups with a 1% cutoff and higher in the metastasis with a 5% cutoff. Higher VEGF-A expression was related to higher pathological stages. PD-1 expression in the lymph node was associated with higher survival. Other clinical and histopatological variables were not associated with marker expression patterns. VEGF-A and VEGF-C expressions in lymph nodes were associated with the presence of lymph node metastasis. PD-1 expression in the lymph node was related to higher survival rates and this should be explored in the context of adjuvant immunotherapy.

Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas.

Acral lentiginous melanoma (ALM) is the less common subtype with singular characterization. TERT (human telomerase reverse transcriptase) promoter mutations have being described as recurrent in melanomas and infrequent in ALM, but their real incidence and clinical relevance is unclear. The objectives of this study were to describe the prevalence of TERT promoter mutations in ALM, and correlate with the molecular profile of other drive genes and clinical features. Sixty-one samples from 48 patients with ALM were analyzed. After DNA isolation, the mutation profiles of the hotspot region of BRAF, NRAS, KIT, PDGFRA, and TERT genes were determined by PCR amplification followed by direct Sanger sequencing. KIT, PDGFRA, and VEGFR2 gene amplification was performed by quantitative PCR. Clinical information such as survival, clinical stage, and Breslow tumor classification were obtained from medical records. TERT promoter mutations were found in 9.3% of the cases, BRAF in 10.3%, NRAS in 7.5%, KIT in 20.7%, and PDGFRA in 14.8% of ALM. None of the cases showed KIT, PDGFRA, or VEGFR2 gene amplification. We found an association between KIT mutations and advanced Clark level (IV and V, P=0.043) and TERT promoter mutations with low mitotic index. No other significant associations were observed between mutation profile and patients' clinical features nor survival rates. Oncogenic TERT promoter mutations are present in a fraction of ALMs. No relevant associations were found between TERT mutation status and clinical/molecular features nor survival. Mutations of KIT and PDGFRA are the most common genetic alterations, and they can be therapeutic targets for these patients.

Melanoma characteristics in Brazil: demographics, treatment, and survival analysis.

BACKGROUND: The incidence of melanoma, one of the most aggressive of the skin cancers, has been increasing worldwide in the last few decades. Data from Latin America and Brazil remain scarce. We aimed to describe the demographic, clinical, and histopathological data; therapy characteristics; and survival rates of the Brazilian melanoma patient population. RESULTS: We collected and analysed retrospective data from 15 years at a tertiary cancer centre. We describe patient characteristics and treatment. We calculated survival, and identified the main prognostic factors through univariate and multivariate analysis. We analysed a total of 1073 patients, with a mean age of 56.7 years. Men and women experienced similar prevalence, and 91.2% of patients had white skin. The most prevalent subtype was superficial spreading, and the most prevalent anatomic location was the trunk (32.2%), followed by the lower extremities (28%). Of all cases, 567 (52.9%) were assigned to clinical stages I and II, while 382 (32.6%) were stages III and IV. Surgery was the main treatment. Sentinel node biopsy was performed in 373 patients, with 23.8% positivity. Overall actuarial 5-year survival was 67.6%. Multivariate analysis showed that gender, serum lactate dehydrogenase (LDH) levels at diagnosis; anatomic location, TNM stage, and local recurrence were significant prognostic factors. CONCLUSIONS: Overall survival was lower than worldwide rates. The main factors influencing survival were similar to those in other populations. Local recurrence was independently associated with lower survival rates. The high prevalence of advanced cases reinforces the importance of strategies to diagnose melanomas in the early stages. There is a need for future multi-institutional prospective studies to attain a better understanding of possible socioeconomic and other influences on survival among melanoma populations in Brazil and Latin America.

The Hospital de Câncer de Barretos Registry: an analysis of cancer survival at a single institution in Brazil over a 10-year period.

BACKGROUND: Epidemiological studies that describe cancer survival statistics at specific hospitals are scarce. Cancer registries, which are collections of cancer patient characteristics, treatment and outcome data, help determine quality of care and treatment indicators. METHODS: This study analysed data from patients treated between 2000 and 2009 at the Hospital de Câncer de Barretos, a referral cancer hospital in Brazil. The analysis included all cases among the nine most common types of cancer diagnosed between 2000 and 2009. The main characteristics of the patients, tumours, treatment procedures and survival were described and discussed. The five-year survival rate of patients with cancer diagnosed between 2000 and 2005 were estimated using Kaplan-Meier methods. Multivariable analysis was performed using Cox proportional hazards regression. RESULTS: It was analyzed 42,825 cancer cases relating to the nine primary locations in more frequent at the institution. Most of the patients were men (52.8%) and over the age of 60 years (65.1%). Approximately 1% of the treated cancers were not staged, and 0.4% lacked follow-up data. Excluding nonmelanoma skin cancer, the most common tumours were prostate and breast cancer, which were mainly diagnosed at early stages. Five-year survival for these cancers were 78.2% and 74.8%, respectively. CONCLUSIONS: During this ten-year period, the Hospital de Câncer de Barretos Registry collected, processed and analysed data related to all cases treated at the institution, providing relevant information about patient characteristics and survival.

[Boerhaave's syndrome: case report]. / Síndrome de Boerhaave: relato de caso.

Spontaneous esophageal rupture carries high morbidity and mortality. The main prognostic factor is early diagnosis, before 12 hours, and appropriate treatment. This is a case report of a 41-years-old man with late esophageal rupture diagnosis treated successfully with transmediatinal esophagectomy and esophageal-gastric tube cervical anastomosis.

Síndrome de Boerhaave: relato de caso / Boerhaave´s syndrome: case report

Spontaneous esophageal rupture carries high morbidity and mortality. The main prognostic factor is early diagnosis, before 12 hours, and appropriate treatment. This is a case report of a 41-years-old man with late esophageal rupture diagnosis treated successfully with transmediatinal esophagectomy and esophageal-gastric tube cervical anastomosis.

Fatores prognósticos em portadores de carcinoma epidermóide cutâneo de tronco e extremidades localmente avançado / Prognostic factors in patients with locally advanced cutaneous squamous cell carcinoma of trunk and extremities

O carcinoma epidermóide cutâneo de tronco e extremidades (CECTE) é doença localizada e tratável na maioria dos casos, com alta prevalência tanto em nosso meio como mundialmente. Apesar disto, pode cursar com progressão local, metastatização regional e distante, com morbidade e mortalidade. Fatores prognósticos relacionados a doença localmente avançada são pouco conhecidos e pesquisados. Este estudo objetiva conhecer a expressão de marcadores moleculares da família HER (EGFR, HER-2, HER-3, HER-4), E-caderina e podoplanina além de fatores clínicos, anatomopatológicos e dos próprios marcadores moleculares relacionados a metástases linfonodais e prognóstico em portadores de CECTE localmente avançado. A análise realizada foi retrospectiva com 63 pacientes de duas instituições Hospital de Câncer de Barretos e Amaral Carvalho de Jaú, portadores de CECTE localmente avançado (T3 e T4), através de pesquisa em prontuário dos pacientes, revisão dos blocos de parafina e lâminas para análise de dados anatomopatológicos e confecção de Tissue Micro Array para análise por técnica de imunohistoquímica da expressão dos marcadores da família HER, E-caderina e podoplanina nos tumores primários e nas metástases linfonodais quando presentes. Como resultados, tivemos no tumor primário EGFR com expressão aumentada (positiva) em 25,5% dos casos, HER-2 negativa em todos, HER-3 positiva em 87,3% e HER-4 em 47,3%, E-caderina positiva na membrana em 47,3% e citoplasma em 29,1%, podoplanina positiva em 29,1%. Nas metástases linfonodais EGFR teve expressão positiva em 40,0%, HER-2 negativa em todos, HER-3 positiva em 84%, HER-4 positiva em 44,0%, E-caderina positiva na xvii membrana em 28,0% e 3,6% no citoplasma, e a podoplanina em 40,0%. O infiltrado linfocitário intratumoral foi o único fator associado a presença de metástases linfonodais (53,3% contra 16,4%; p=0,046). Pacientes com tumores T3 tiveram maior taxa de sobrevida específica por câncer em cinco anos que os T4 (62,5% contra...

Cutaneous squamous cell carcinoma of trunk and extremities is a local and easily treatable disease in most of cases, with high prevalence in our community and worldwide. Despite of this, it can present local progression, regional (lymph node) and distant metastasis with morbidity and mortality. Prognostic factors related to locally advanced disease are not well established being reported in few studies. The aim of this study is to determine the expression of molecular markers as HER family (EGFR, HER- 2,HER-3, HER-4), E-cadherin, podoplanin, and clinical and histopathological factors related to lymph node metastasis and prognosis in patients with locally advanced cutaneous squamous cell carcinoma of trunk and extremities (CSCCTE). There were 63 patients studied from two institutions: Hospital Amaral Carvalho de Jaú and Hospital de Câncer de Barretos with locally advanced CSCCTE (T3 and T4), retrospectively analyzed through review of medical records and tumor paraffin blocks and slides, and construction of a Tissue Micro Array for immunohistochemical analysis of molecular markers expression in the primary tumors and lymph node metastasis. The results showed in the primary tumor, EGFR positive (hyperexpression) in 25,5%, HER-2 negative in all, HER-3 positive in 87,3% and HER-4 in 47,3%. E-cadherin was positive in the membrane in 47,3% and in the cytoplasm in 29,1% and podoplanin was positive in 29,1%. Lymph node metastasis expression: EGFR was positive in 40,0%, HER-2 negative in all, HER-3 positive in 84%, HER-4 positive in 44,0%. E-cadherin was positive in the membrane in 28,0% and 3,6% in the cytoplasm. Podoplanin was positive in 40,0%. Intratumoral lymphocytic infiltrate was the only factor related to lymph node metastasis (53,3% contra 16,4%; p=0,046). Patients xix with T3 tumors presented higher cancer specific 5-years survival rate than T4 ones (62,5% contra 26,8%; p=0,012) and patients without lymph node metastasis presented higher cancer survival rate...

Initiation of a program in peritoneal surface malignancy.

The initiation of a Program in Peritoneal Malignancy is a long and complex process. The novelty, technically demanding nature and steep learning curve that characterize this treatment strategy calls for a carefully planned, systematic, controlled, and informed introduction is an institution, for which an Institutional Review Board approved protocol is suggested. Commitment of a surgical team and institution, education of other physician, nurses, and ancillary personnel involved in the procedure, safety precaution for patients and health care workers, and proper patient selection are important requirements for initiating the program. This manuscript provides a guide for implementation of this treatment strategy with a minimum of untoward events, reduced apprehension of medical and nursing colleagues, and a maximum benefit for patients.