Purpose
To determine the risk factors related to adnexal involvement in endometrial cancer (EC) and its implications for ovarian preservation in young women.
Methods
We analyzed a series of 802 ...patients who were treated at AC Camargo Cancer Center from July 1991 to July 2017. Patients who had peritoneal or systemic dissemination (stage IV) were excluded. Chi square and Fisher’s exact tests were used to analyze the correlations between categories and clinicopathological variables. Multivariate analysis was performed by logistic regression.
Results
Forty-nine (6.2%) patients had adnexal involvement—43 (5.4%) ovarian and 24 (2.9%) tubal. After excluding the 14 (28%) cases with suspicious findings, 788 subjects were analyzed and adnexal involvement found in 35 (4.4%) cases. Adnexal involvement was statistically related to non-endometrioid histologies (12.6% vs. 3.1%;
p
< 0.001), lymph node metastasis (17% vs. 2.6%;
p
< 0.001), histological grade 3 tumors (9.4% vs. 2.1%;
p
< 0.001), presence of LVSI (14.2% vs. 2.4%;
p
< 0.001), and deep myometrial invasion (≥ 50%) (10.8% vs. 3.5%;
p
< 0.001). Although age younger than 45 years had higher risk of adnexal involvement, it was not statistically significant (8.9% vs. 4.2%;
p
= 0.13). Seven (14.2%) patients with adnexal involvement were aged < 45 years, 3 of whom (42.8%) had suspicious adnexal masses that were detected before surgery. Notably, all patients aged < 45 years and with adnexal involvement had at least 1 risk factor, such as presence of LVSI, grade 3 disease, node metastasis, or deep myometrial invasion. No patient with clinically normal ovaries and aged under 45 years, with endometrioid grades 1 and 2, superficial myometrial invasion, or node negativity had adnexal involvement.
Conclusions
Ovarian preservation may be considered for patients younger than 45 years old with low-risk EC (grades 1 and 2 tumors, absence of LVSI, and myometrial invasion < 50%).
Background
Gastric adenocarcinoma (GAC) is the third deadliest malignant neoplasm worldwide, mostly because of late disease diagnosis, low chemotherapy response rates, and an overall lack of tumor ...biology understanding. Therefore, tools for prognosis and prediction of treatment response are needed. Quantification of circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) and their expression of biomarkers has potential clinical relevance. Our aim was to evaluate CTCs and CTM and their expression of HER2 and plakoglobin in patients with nonmetastatic GAC, correlating the findings to clinicopathological data.
Materials and Methods
CTC enrichment was performed with isolation by size of epithelial tumor cells, and the analysis was performed with immunocytochemistry and microscopy. Two collections were made: one at diagnosis (55 samples before neoadjuvant treatment) and one after surgery and before adjuvant therapy (33 samples).
Results
A high detection rate of CTCs (90%) was observed at baseline. We evaluated HER2 expression in 45/55 biopsy samples and in 42/55 CTC samples, with an overlap of 36 subjects. Besides the good agreement observed for HER2 expression in primary tumors and paired CTCs for 36 cases (69.4%; κ = 0.272), the analysis of HER2 in CTCs showed higher positivity (43%) compared with primary tumors (11%); 3/5 patients with disease progression had HER2‐negative primary tumors but HER2‐positive CTCs. A significant CTC count drop in follow‐up was seen for CTC‐HER2‐positive cases (4.45 to 1.0 CTCs per mL) compared with CTC‐HER2‐negative cases (2.6 to 1.0 CTCs per mL). The same was observed for CTC‐plakoglobin‐positive cases (2.9 to 1.25 CTCs per mL).
Conclusion
CTC analysis, including their levels, plakoglobin, and HER2 expression, appears to be a promising tool in the understanding the biology and prognosis of GAC.
Implications for Practice
The analysis of circulating tumor cell levels from the blood of patients with gastric adenocarcinoma, before and after neoadjuvant treatment, is useful to better understand the behavior of the disease as well as the patients more likely to respond to treatment.
摘要
背景。胃腺癌 (GAC) 是全球第三大致命恶性肿瘤，主要原因是疾病诊断较晚、化疗疗效较低以及对肿瘤生物学的整体认识不足。因此，我们需要用于预后及治疗反应预测工具。循环肿瘤细胞 (CTC) 和循环肿瘤微栓 (CTM) 的量化及其生物标志物的表达具有潜在的临床意义。我们的目的是评估 CTC 和 CTM 及其 HER2 和 plakoglobin在非转移性 GAC 患者中的表达，并将该发现与临床病理数据相关联。
材料和方法。使用上皮肿瘤细胞大小分离法进行 CTC 富集，并用免疫细胞化学和电子显微镜进行分析。制作了两个集合:一个在诊断时(新辅助化疗前 55 个样本)，一个在手术后和辅助性化疗前(33 个样本)。
结果。在基线观察到 CTC 检出率高 (90%)。我们评估了 45/55 个活检样本和 42/55 个 CTC 样本中的 HER2 的表达情况，其中有 36 名受试者表达重叠。除了在原发性肿瘤和成对 CTC 中观察到 HER2 表达的良好一致性 36 例(69.4%; κ = 0.272)，CTC 中 HER2 的分析显示与原发性肿瘤(11%)相比具有更高的阳性(43%)；3/5 名疾病进展的患者具有 HER2 阴性原发性肿瘤但为 HER2 阳性 CTC。与 CTC‐HER2 阴性病例(每毫升 2.6 至 1.0 个 CTC)相比，CTC‐HER2 阳性病例(每毫升 4.45 至 1.0 个 CTC)的跟进中 CTC 计数显着下降。在 CTC ‐ plakoglobin阳性病例(每毫升 2.9 至 1.25 个 CTC)中观察到相同情况。
结论。CTC 分析，包括其水平、plakoglobin和 HER2 表达，似乎是理解 GAC 生物学及预后的一种极具前途的工具。
实践意义:在新辅助治疗之前和之后对来自胃腺癌患者的血液中的循环肿瘤细胞水平进行分析有助于更好地理解疾病行为以及更可能对治疗产生反应的患者。
Gastric adenocarcinoma is the third deadliest malignant neoplasm worldwide. This article describes the results of an evaluation of HER2 expression in circulating tumor cells and plakoglobin in circulating tumor microemboli from nonmetastatic gastric adenocarcinoma patients.
Little is known about the features and outcomes of Brazilian patients with pancreatic cancer. We sought to describe the socio-economic characteristics, patterns of health care access, and survival of ...patients diagnosed with malignant pancreatic tumors from 2000 to 2014 in São Paulo, Brazil. We included patients with malignant exocrine and non-classified pancreatic tumors according to the International Classifications of Disease (ICD)-O-2 and -O-3, diagnosed from 2000 to 2014, who were registered in the FOSP database. Prognostic factors for overall survival (OS) in the subgroup of patients with ductal or non-specified (adeno)carcinoma were evaluated using Cox proportional hazard model. The study population consists of 6855 patients. Median time from the first visit to diagnosis and treatment were 13 (Interquartile range IQR 4-30) and 24 (IQR 8-55) days, respectively. Both intervals were longer for patients treated in the public setting. Median OS was 4.9 months (95% confidence interval 95% CI 4.7-5.2). Increasing age, male gender, lower educational level, treatment in the public setting, absence of treatment, advanced stage, and treatment from 2000 to 2004 were associated with inferior OS. From 2000-2004 to 2010-2014, no improvement in OS was seen for patients treated in the public setting. Survival of patients with malignant pancreatic tumors remains dismal. Socioeconomical variables, especially health care funding, are major determinants of survival. Further work is necessary to decrease inequalities in access to medical care for patients with pancreatic cancer in Brazil.
Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next‐generation deep sequencing of TP53—a highly mutated and ...informative gene in GAC—to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash—GW). We evaluated their potential to reveal tumor‐derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon‐capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post‐treatment (196 samples), with high vertical coverage >8,000×. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW‐ (15.2%) and 6/46 PL‐samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW‐exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene‐panel designed for this malignancy.
What's new?
The detection of mutations in gastric adenocarcinoma (GAC) potentially can facilitate diagnosis and treatment. A promising means of GAC mutation detection is liquid biopsy from plasma and gastric fluids, though these approaches have yet to be fully explored in GAC. Here, deep sequencing of gastric wash‐derived DNA from GAC patients revealed 11 different TP53 mutations, four of which were absent from original primary tumor biopsies, suggesting possible tumor heterogeneity. Analysis of plasma and gastric washes collected after treatment in these patients revealed increased rates of TP53 mutation, indicating a possible role for liquid biopsy in GAC monitoring during treatment.
Background
Decisions about multimodality treatment for upper gastrointestinal malignancies are largely predicted on clinical staging information. However, hospital‐level accuracy of clinical staging ...is currently unknown.
Methods
A national cohort study of patients with adenocarcinoma of the esophagus, stomach, or pancreas in the NCDB (2006–2015) who were treated with upfront resection. Hospital‐level staging accuracy (ascertained by comparing clinical stage to pathologic stage) was calculated. Within hospital correlation of staging accuracy across disease sites was evaluated using risk and reliability adjustment.
Results
Overall, 1246 hospitals were evaluated. Median hospital T‐staging accuracy was 77.5%, 73.7%, and 60.8% for esophageal, gastric, and pancreatic cancer, respectively. Median hospital N‐staging accuracy was 80.2%, 72.9%, and 61.8%, respectively. For T‐stage, over‐staging was most frequently observed in esophageal patients (11.2%) while under‐staging was most frequent in pancreatic patients (36.1%). For N‐stage, over‐staging was infrequent for all three, while under‐staging was most common in pancreatic patients (37.4%). Correlation across disease sites was weak for both T‐ (best observed, r = .34) and N‐stages (r = .30). When high volume hospitals were evaluated, correlation improved but accuracy rates were similar.
Conclusions
Despite the importance of clinical staging in multimodality treatment planning, hospitals inaccurately stage 20–40% of patients, with low correlation across disease sites.
Background
Pancreatic cancer plays an important role in cancer‐related mortality. Few studies have been performed in Brazil to characterize patients affected by this disease. We aimed to describe the ...clinico‐pathological characteristics and the survival of patients with pancreatic cancer seen at AC Camargo Cancer Center (ACCCC).
Methods
We included patients ≥ 18‐year old, with a histologically confirmed diagnosis of exocrine pancreatic cancer, that attended at least one visit at ACCCC from 2008 to 2016.
Results
The study included 739 patients. Median age at diagnosis was 64 years. Most patients were male. About 5% presented a family history of pancreatic cancer. A total of 40% had diabetes and 51.4% presented with ECOG performance status 1. Tumors most often arose in the pancreatic head and roughly half of the patients had metastatic disease at presentation. Median overall survival of patients with potentially resectable disease submitted to surgery at ACCCC was 35.4 months. Median overall survival times of patients with the unresectable and metastatic disease were 14.1 and 9.3 months, respectively.
Conclusions
The features of our population match those of studies done in developed countries. We believe multicentric data from patients with pancreatic cancer in Brazil could enable more effective preventive and therapeutic approaches to the disease.
Treatment selection for patients with esophageal adenocarcinoma is predicated on clinical staging information, which is inaccurate in 20% to 30% of cases and could impact the delivery of ...guideline-concordant treatment. We aimed to evaluate the association between staging concordance at the patient and hospital levels with the delivery of guideline-concordant treatment among esophageal adenocarcinoma patients.
This was a national cohort study of resected esophageal adenocarcinoma patients in the National Cancer Data Base (2006 to 2015) treated either with upfront resection or neoadjuvant therapy followed by surgery. Patient- and hospital-level clinical and pathologic staging concordance and deviations from treatment guidelines were ascertained. For neoadjuvant therapy patients, staging concordance was predicted through Bayesian analysis. Reliability adjustment was used when evaluating hospital-level concordance.
Among 9393 esophageal adenocarcinoma patients treated at 927 hospitals, 41% had upfront surgery. Among upfront surgery patients, staging concordance was 85.1% for T1N0 and 86.9% for T3-T4N+ disease, but less than 50% for all others. Among patients treated with neoadjuvant therapy, treatment downstaging was observed in 33.9%. Deviations from treatment guidelines were identified in 38.5% of upfront surgery patients and 3.3% of neoadjuvant therapy patients. The proportion of concordantly staged patients ranged from 60.1% to 87.9%, and deviations from treatment guidelines were observed among 14.9% to 22.7% of the patients. Patient staging concordance increased, and deviations from guidelines decreased, as hospital-level concordance increased (trend test, P values less than .001 for all).
Deviations from treatment guidelines in esophageal adenocarcinoma patients appear to be a function of inaccurate clinical staging information, which should be a new focus for quality improvement efforts.
Background
Neoadjuvant therapy (NAT) is increasingly being used in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC); however, there is a lack of evidence regarding ...the benefit among these patients.
Objective
The aim of this study was to evaluate overall survival (OS) in PDAC patients with resectable disease treated with NAT or upfront resection through instrumental variable (IV) analysis.
Design
A national cohort study of resectable PDAC patients in the National Cancer Data Base (2007–2015) treated with either upfront surgery or resection after NAT. Using multivariable modeling and IV methods, OS was compared between those treated with NAT and upfront resection. The IV was hospital-level NAT utilization in the most recent year prior to treatment.
Results
The cohort included 16,666 patients (14,012 upfront resection; 2654 NAT) treated at 779 hospitals. Among those treated with upfront resection, 59.9% received any adjuvant therapy. NAT patients had higher median (27.9 months, 95% confidence interval CI 26.2–29.1) and 5-year OS (24.1%, 95% CI 21.9–26.3%) compared with those treated with upfront surgery (median 21.2 months, 95% CI 20.7–21.6; 5-year survival 20.9%, 95% CI 20.1–21.7%). After multivariable modeling, NAT was associated with an approximately 20% decrease in the risk of death (hazard ratio HR 0.78, 95% CI 0.73–0.84), and this effect was magnified in the IV analysis (HR 0.61, 95% CI 0.47–0.79).
Conclusions
In patients with resectable PDAC, NAT is associated with improved survival relative to upfront resection. Given the benefits of multimodality therapy and the challenges in receiving adjuvant therapy, consideration should be given to treating all PDAC patients with NAT.
ABSTRACT Objective: to suggest a script for surgical oncology assistance in COVID-19 pandemic in Brazil. Method: a narrative review and a “brainstorming” consensus were carried out after discussion ...with more than 350 Brazilian specialists and renowned surgeons from Portugal, France, Italy and United States of America. Results: consensus on testing for COVID-19: 1- All patients to be operated should be tested between 24 and 48 before the procedure; 2- The team that has contact with sick or symptomatic patients should be tested; 3 - Chest tomography was suggested to investigate pulmonary changes. Consensus on protection of care teams: 1 - Use of surgical masks inside the hospitals. Use of N95 masks for all professionals in the operating room; 2 - Selection of cases for minimally invasive surgery and maximum pneumoperitoneal aspiration before removal of the surgical specimen; 2 - Optimization of the number of people in teams, with a minimum number of professionals, reducing their occupational exposure, the consumption of protective equipment and the circulation of people in the hospital environment; 3 - Isolation of contaminated patients. Priority consensus: 1- Construction of service priorities; 2 - Interdisciplinary discussion on minimally invasive or conventional pathways. Conclusion: the Brazilian Society of Surgical Oncology (BSSO) suggests a script for coping with oncological treatment, remembering that the impoundment in the assistance of these cases, can configure a new wave of overload in health systems.
RESUMO Objetivo: sugerir roteiro de assistência oncológica cirúrgica em meio à pandemia COVID-19 no Brasil. Método: foi realizada revisão narrativa da literatura e consenso tipo “brainstorming” após discussão com mais de 350 especialistas brasileiros e cirurgiões renomados de Portugal, França, Itália e Estados Unidos da América. Resultados: consenso sobre testagem para COVID-19: 1-Todos os pacientes a serem operados devem ser testados entre 24 e 48 antes do procedimento; 2-Equipe que tenha contato com doentes ou sintomáticos deve ser testada; 3-Tomografia de tórax foi sugerida para pesquisa de alterações pulmonares. Consenso sobre proteção das equipes de assistência: 1-Uso de máscaras cirúrgicas dentro de hospitais. Uso de máscaras N95 para todos os profissionais na sala cirúrgica; 2-Seleção dos casos para cirurgia minimamente invasiva e aspiração máxima do pneumoperitônio antes da retirada da peça cirúrgica; 2-Otimização das equipes, com número mínimo de profissionais, reduzindo a exposição ocupacional, o consumo de equipamento de proteção e a circulação de pessoas no ambiente hospitalar; 3 -Isolamento de pacientes contaminados. Consenso sobre priorizações: 1-Construção de prioridades de atendimento; 2- Discussão interdisciplinar sobre via minimamente invasiva ou convencional. Conclusão: a Sociedade Brasileira de Cirurgia Oncológica (SBCO) sugere roteiro de enfrentamento para o tratamento oncológico, lembrando que o represamento na assistência desses casos, pode configurar uma nova onda de sobrecarga em sistemas de saúde.
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