Challenges in surgical oncology training in Brazil: From history to a board-certified specialization.

The Brazilian Society of Surgical Oncology was established over 30 years ago. Despite that, surgical oncology was finally recognized as a Board-Certified medical specialty in 2017 and has strengthened its role in the standardization of surgical and multimodal approaches in our country. This article aims to describe the process and the main challenges of the specialists training who are qualified for job opportunities and who meet the expectations of the recently created competence matrix for surgical oncologists in Brazil. Thus, we hope to expose the challenges of teaching surgical oncology, describe its history and experiences in important country services, and outline the minimum requirements for creating a more humanistic surgical oncologist who is updated and fully committed with multidisciplinary treatment for cancer patients. We conclude that the main characteristic that the surgical oncologist must have is the ability to offer holistic treatments to the patient, based on the highest level of evidence, love, and compassion, to direct the treatment and understand all of the afflictions that arise with a cancer diagnosis. Moreover, the surgical oncologist in training and in the field must be continuously updating himself to offer the best options of treatment to patients.

Late assessment of quality of life in patients with rectal carcinoma: comparison between sphincter preservation and definitive colostomy.

PURPOSE: Patients with cancer of the lower and middle rectum who are candidates for curative surgery often have negative opinions on definitive colostomy. The purpose of this study is to compare the quality of life (QoL) of patients who undergo standard treatment for rectal cancer with sphincter preservation or definitive colostomy. METHODS: A total of 125 patients with adenocarcinoma of the lower or middle rectum who underwent radical surgery with curative intent with a follow-up ≥ 1 year were recruited: 83 patients (group 1) were subjected to low anterior resection and low colorectal or coloanal anastomosis-thus preserving their sphincter-and 42 (group 2) were treated with abdominoperineal resection, followed by terminal definitive colostomy. QoL was assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. RESULTS: Health and global quality of life were similar between groups; however, patients who underwent definitive colostomy had higher scores on the emotional (p value = 0.016) and cognitive function scales (p value = 0.017). Patients with sphincter preservation presented with more symptoms that were related to stool frequency (p value < 0.001), intestinal constipation (p value = 0.005), fecal incontinence (p value = 0.001), buttock pain (p value = 0.023), and nausea and vomiting (p value = 0.036), whereas patients with permanent colostomy had higher scores for dysuria (p value = 0.033). CONCLUSION: Although global QoL scores did not differ between groups, patients who underwent definitive colostomy had significantly better functional and symptom scale scores, reflecting greater function with fewer symptoms.

Estrogen Receptor ß as a Prognostic Marker of Tumor Progression in Colorectal Cancer with Familial Adenomatous Polyposis and Sporadic Polyps.

The incidence of colorectal cancer (CRC) is lower in women than in men, and sex steroids can be considered contributing factors because oral contraception usage and estrogen replacement therapy are associated with decreased risk. Conversely, colorectal polyp development in familial adenomatous polyposis (FAP) begins during puberty. The objectives were to evaluate the relationship between the expression of these hormone receptors and adenoma-carcinoma progression, CRC stage and overall survival. We studied 120 A.C. Camargo Cancer Center patients diagnosed with either FAP-associated or spontaneous adenomatous polyps or CRC to determine the immunohistochemical expression levels of estrogen receptor (ER)-α, ER-ß and the progesterone and androgen receptors (480 analyses). The ER-ß expression levels differed between the groups: the group with FAP polyps had lower ER-ß expression than that of the sporadic polyp group. With transformation of the sporadic polyps to cancer, there was a considerable decrease in ER-ß expression (from 90% with strong expression to 80% with absent or weak expression) (p < 0.001). The ER-ß expression was lower in T3/T4 tumors than in T1/T2 tumors (p = 0.015). The 5-year overall survival of CRC patients positively expressing ER-ß exceeded that of patients without detectable expression levels (74.8% vs. 44.3%, respectively; p = 0.035). There was no significant expression of the androgen or progesterone receptor or ER-α among the groups. Differences in ER-ß expression represent a potential mechanism through which estrogen might alter the susceptibility to colon cancer, thereby confirming the possibility of a protective role of estrogen against colorectal carcinogenesis.

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-ß (ERß). The expression of ERß isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. METHODS: This study aimed to investigate the expression levels of the ERß1, ERß2, ERß4 and ERß5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. RESULTS: Decreased expression of ERß isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERß1 and ERß5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERß isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERß was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERß1 and ERß5 expression levels were associated with better disease-free survival (p = 0.002). CONCLUSION: These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08­6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients (AU)

Avaliação da expressão imunoistoquímica de proteínas da via de sinalização mediada por TGFβ como preditores de resposta à quimioterapia pré-operatória em adultos portadores de sarcoma de partes moles de alto grau em extremidades / Protein expression evaluation of protein of genes belonging to the TGFβ pathway as predictors of response to preoperative chemotherapy with doxorubicin and ifosfamide in adult patients with high grade soft tissue sarcomas located in extremities

Introdução: Sarcomas de partes moles (SPM) constituem um grupo de neoplasias raras de comportamentos distintos. O tratamento para os tumores de alto grau, não passiveis de ressecção adequada, é feito por cirurgia, radioterapia (RT) e quimioterapia (QT). Apesar disso, 50% dos pacientes com tumores localizados ao diagnóstico morrem da doença metastática. A QT pré-operatória para o tratamento de tumores localizados, apesar de não ser considerada como padrão, é uma opção promissora. A escassez de preditores biológicos de resposta, e achados de que a superexpressão de genes pertencentes à via mediada por TGFβ estaria relacionada à resistência à QT nos levaram à tentativa de estabelecer a relação entre a expressão de FST, SMAD4, TGFβ e Id com resposta patológica. Objetivos: Avaliar por imunoistoquímica (IQ) a expressão das proteínas produzidas a partir dos genes TGFB, FST, Id1 e SMAD4 da via mediada por TGFβ, correlacionando com a resposta patológica; expandir os resultados clínicos do esquema de QT pré-operatória com doxorrubicina e ifosfamida em vigência no Hospital A.C. Camargo; determinar as taxas de toxicidade e avaliar um método de análise patológica que quantifique a percentagem de células tumorais viáveis em peça operatória. Pacientes e Métodos: 42 pacientes com SPM de alto grau localizados em extremidades, tratados com doxorrubicina e ifosfamida pré-operatória, foram observados de forma prospectiva, desde janeiro de 2005 a agosto de 2012. Amostras das biópsias e das peças operatórias foram obtidas e submetidas à pesquisa da expressão das proteínas já referidas por IQ. Resultados: A expressão das proteínas estudadas não teve correlação estatisticamente significativa com a resposta patológica...

Backgraund: Soft Tissue Sarcomas (STS) are rare neoplasms with many histological subtypes, behaviors and response to different treatments. The treatment of these tumors involves surgery, radiation and chemotherapy. Despite that 50% of patients with localized tumors will develop metastatic disease. Preoperative chemotherapy (CT) although not standard is considered a promising therapeutic option. The lack of biological predictors of response, led us to study the relationship between the expression of FST, SMAD4, TGFβ and Id (TGFβ superfamily genes) in patients submitted to preoperative CT. Objectives: To evaluate the protein expression. Produced by genes belonging to the TGFβ pathway by IH and correlate it with pathologic response; expand the preliminary results of a previous phase II trial testing a schedule of preoperative CT with doxorubicin and ifosfamide in Hospital A.C. Camargo; determine the rate of toxicity and evaluate a method of assessing pathological analysis that quantifies the percentage of viable tumor cells in surgical specimens. Patients and Methods: 42 patients with high grade STS located in extremities treated with preoperative doxorubicin and ifosfamide CT were observed prospectively, on a non controlled fashion since January 2005 to august 2012. Biopsies and surgical specimens were obtained to enable the analysis of TGFβ, FST, SMAD4 and Id protein expressional by immunohistochemistry (IH). Results: The expression of the proteins studied had no significant association with pathological response. The objective response rates of the primary tumor were 17.5% for clinical response and 15% for pathologic complete response. Only 7.5% patients had a limb amputated. The rate of surgical contraindication was 4.7%. Grade 3-4 toxicity occurred in 45.2% of cases. Conclusion: The method of pathological response analysis was considered easily applicable. TGFβ-mediated pathway proteins studied did not correlate with pathological response...