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1.
J Surg Res ; 279: 256-264, 2022 11.
Article in English | MEDLINE | ID: mdl-35797753

ABSTRACT

INTRODUCTION: Selecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. METHODS: This was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. RESULTS: Among 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease-HR 0.67 [0.49-0.92]; N+ disease-HR 0.55 [0.45-0.66]) or not (ypN + disease-HR 0.78 [95% CI 0.65-0.93]). CONCLUSIONS: Clinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients' survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Bayes Theorem , Cohort Studies , Esophageal Neoplasms/pathology , Humans , Neoadjuvant Therapy , Neoplasm Staging , Retrospective Studies , Survival Rate
2.
J Surg Oncol ; 126(6): 986-994, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35819061

ABSTRACT

BACKGROUND: Neoadjuvant therapy (NAT) improves survival among patients with locally advanced gastric cancer (GC), but it remains unclear whether its benefit is contingent on treatment response. METHODS: This is a national cohort study of stage Ib-III GC patients in the National Cancer Data Base (2006-2015) treated with upfront resection or NAT followed by surgery. Bayesian analysis was used for NAT patients to ascertain staging concordance and to account for down-staging. We used multivariable Cox regression to evaluate the association between staging concordance, treatment, response to NAT, and survival. RESULTS: The cohort included 13 340 patients treated at 1124 hospitals. Staging concordance ranged from 86.1% for cT3-4N+ to 34.7% for cT2N0 patients. Relative to accurately staged patients treated with upfront surgery, NAT was associated with a decreased risk of death if there was disease down-staging among those with cT1-2N+ (hazard ratio [HR]: 0.43 [0.30-0.61]), cT3-4N0 (HR: 0.69 [0.54-0.88]), and cT3-4N+ (HR: 0.51 [0.48-0.58]) tumors, and in the absence of down-staging among cT3-4N+ patients (HR: 0.83 [0.74-0.92]). Conversely, NAT without down-staging increased the risk of death among those with intermediate-stage disease. CONCLUSIONS: NAT is associated with improved survival for GC, but it seems to be contingent on treatment response among patients with intermediate-stage disease.


Subject(s)
Stomach Neoplasms , Bayes Theorem , Cohort Studies , Humans , Neoadjuvant Therapy , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/therapy
3.
Ann Surg ; 275(3): 415-421, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35120060

ABSTRACT

OBJECTIVE: To evaluate the association between staging concordance, treatment sequencing, and response to neoadjuvant therapy (NAT) on the survival of patients with pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: NAT is increasingly utilized in the management of patients with PDAC, but it is unclear whether its benefit is contingent on tumor down-staging. METHODS: This was a cohort study of stage I-III PDAC patients in the National Cancer Database (2006-2015) treated with upfront resection or NAT followed by surgery. We determined staging concordance using patients' clinical and pathological staging data. For NAT patients, we used Bayesian analysis to ascertain staging concordance accounting for down-staging. RESULTS: Among 16,597 patients treated at 979 hospitals, 13,982 had an upfront resection and 2,615 NAT followed by surgery. Overall survival (OS) at 5-years ranged from 26.0% (95% CI 24.9%-27.1%) among cT1-2N0 patients to 18.6% (17.9%-19.2%) among cT1-3N+ ones. Patients with cT3-4 or cN+ tumors had improved OS after NAT compared to upfront surgery (all p< 0.001), while there was no difference among patients with cT1-2N0 (P = 0.16) disease. Relative to accurately staged cT1-2-3N+ or cT4 patients treated with upfront surgery, NAT was associated with a lower risk of death [HR 0.46 (0.37-0.57) for N+; HR 0.56 (0.40-0.77) for T4 disease], even among those without tumor down-staging [HR 0.81 (0.73-0.90) for N+; HR 0.48 (0.39-0.60) for T4]. CONCLUSIONS: NAT is associated with improved survival for PDAC, particularly for patients with more advanced disease and regardless of down-staging. Consideration should be given to recommending NAT for all PDAC patients.


Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/pathology , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Adenocarcinoma/therapy , Bayes Theorem , Carcinoma, Pancreatic Ductal/therapy , Cohort Studies , Humans , Neoadjuvant Therapy , Neoplasm Staging , Pancreatic Neoplasms/therapy , Survival Rate
4.
Ann Thorac Surg ; 113(1): 279-285, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33484675

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Cohort Studies , Combined Modality Therapy , Humans , Neoplasm Staging , Practice Guidelines as Topic
5.
Sci Rep ; 11(1): 6346, 2021 03 18.
Article in English | MEDLINE | ID: mdl-33737639

ABSTRACT

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.


Subject(s)
Delivery of Health Care , Health Services Accessibility , Healthcare Disparities , Pancreatic Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Data Management , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Proportional Hazards Models , Young Adult
7.
Ann Surg Oncol ; 28(6): 3186-3195, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33174146

ABSTRACT

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.


Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Adenocarcinoma/surgery , Cohort Studies , Humans , Neoadjuvant Therapy , Pancreatectomy , Pancreatic Neoplasms/surgery
8.
J Surg Oncol ; 122(8): 1630-1638, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32976667

ABSTRACT

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.


Subject(s)
Adenocarcinoma/classification , Adenocarcinoma/pathology , Gastrointestinal Neoplasms/classification , Gastrointestinal Neoplasms/pathology , Hospitals/statistics & numerical data , Neoplasm Staging/standards , Cohort Studies , Humans
10.
Ann Surg Oncol ; 27(8): 2822-2826, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32080810

ABSTRACT

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%).


Subject(s)
Endometrial Neoplasms , Ovary , Adult , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Prognosis , Retrospective Studies
11.
J Surg Oncol ; 121(5): 707-717, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31970764

ABSTRACT

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.


Subject(s)
Curriculum , Education, Medical, Graduate/organization & administration , Surgical Oncology/education , Brazil , Certification , Clinical Competence/standards , Humans , Internship and Residency/organization & administration , Societies, Medical , Specialization , Specialty Boards
12.
Oncologist ; 24(9): e854-e863, 2019 09.
Article in English | MEDLINE | ID: mdl-30846515

ABSTRACT

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.


Subject(s)
Embolism/pathology , Neoplastic Cells, Circulating/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Biomarkers, Tumor/blood , Embolism/blood , Female , Humans , Male , Middle Aged , Neoplastic Cells, Circulating/metabolism , Prognosis , Receptor, ErbB-2/metabolism , Stomach Neoplasms/blood , Stomach Neoplasms/surgery , Survival Rate
13.
Int J Cancer ; 145(4): 1090-1098, 2019 08 15.
Article in English | MEDLINE | ID: mdl-30779121

ABSTRACT

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.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/pathology , Mutation/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , DNA Mutational Analysis/methods , Female , Follow-Up Studies , Humans , Liquid Biopsy/methods , Male , Middle Aged , Stomach/pathology , Tumor Suppressor Protein p53/genetics
14.
J Gastrointest Oncol ; 10(6): 1110-1119, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31949928

ABSTRACT

BACKGROUND: Patients with stage I gastric cancer are considered to have an exquisite prognosis. Nonetheless, the fact that some patients experience disease relapse highlights that a subgroup might benefit from multimodality treatment. We aimed to evaluate the survival of patients with stage I gastric cancer and look for harbingers of gastric cancer recurrence. METHODS: We looked for patients with stage I gastric cancer treated exclusively with surgery from 1996 to 2015. The competing risks survival method was used to allow for concurrent causes of mortality. Also, we calculated subdistribution hazards (SH) to reveal factors associated with cancer recurrence and death from unrelated causes. RESULTS: A total of 185 patients constitute the study population. Thirty-seven patients had pT2N0 tumors. Most patients (80.5%) were treated with D2 lymphadenectomy. The probability of relapse at 5 years was 3.0% and 8.6% in the study population and the pT2N0 subgroup, respectively. Among all 26 deaths, only six were related to gastric cancer. In multivariate analysis, perineural invasion (PNI) was associated with increased risk of gastric cancer recurrence. CONCLUSIONS: The prognosis of stage I gastric cancer treated with D2 lymphadenectomy is excellent. PNI may indicate higher likelihood of recurrence. Further work in this field should account for the higher risk of death from unrelated causes.

15.
World J Surg Oncol ; 16(1): 62, 2018 Mar 22.
Article in English | MEDLINE | ID: mdl-29566715

ABSTRACT

BACKGROUND: The association of preoperative systemic and intraperitoneal chemotherapy has been described in Eastern patients with very good outcomes in treatment responders. The aim of this paper is to describe the initial results of this multidisciplinary regimen in gastric cancer patients with very advanced peritoneal metastases. CASE PRESENTATION: We present here the first four cases who received the treatment protocol. They had a baseline PCI between 19 and 33. Two patients had received systemic chemotherapy prior to this regimen. Three of them had significant response and were taken to cytoreductive surgery, while one patient who had 12 cycles of chemotherapy previously showed signs of disease progression and subsequently died. There was no significant postoperative morbidity, and three patients remain alive, two of them with no signs of recurrence. CONCLUSION: Systemic and intraperitoneal chemotherapy led to a marked response in peritoneal disease extent in our initial experience and allowed three of four patients with very advanced disease to be treated with cytoreductive surgery.


Subject(s)
Chemotherapy, Cancer, Regional Perfusion/methods , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Neoadjuvant Therapy , Neoplasm Recurrence, Local/therapy , Peritoneal Neoplasms/therapy , Stomach Neoplasms/therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Peritoneal Neoplasms/secondary , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology , Survival Rate
16.
Arch Med Sci ; 13(6): 1262-1268, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29181056

ABSTRACT

INTRODUCTION: Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays a critical role in carcinogenesis and resistance to anticancer drugs. In this study, gastric carcinomas (GC) were investigated and statistical analyses were performed concerning the correlation between the clinicopathological features and activation of the PI3K/AKT pathway. MATERIAL AND METHODS: Immunohistochemistry for p-AKT, p-mTOR and PTEN was performed in 239 GC and 200 non-neoplastic gastric tissues. The clinicopathological parameters were recorded from the medical charts. Statistical significance was defined by a p-value < 0.05. RESULTS: High p-AKT expression was observed in 10% of the normal gastric tissue and in 90% of GC, and it was significantly associated with tumor size (p < 0.001), T3/T4 tumors (p < 0.001), and presence of metastases (p = 0.02). Similarly, p-mTOR positivity was found in GC cells, but not in the normal gastric mucosa, and was correlated with perineural invasion (p = 0.02) and T3/T4 tumors (p = 0.03). On the other hand, PTEN expression was weak and focal in the tumor cells, while in the normal gastric tissue this staining was strong and diffuse. Importantly, the expression of p-mTOR and PTEN was associated with overall survival. CONCLUSIONS: The results of the present study, characterized by the loss of PTEN expression and higher expression of p-AKT and p-mTOR in the majority of tumor cells, apparently are implicated in the carcinogenesis and progression of GC. The identification of p-mTOR and PTEN expression as prognostic factors corroborates the identification and use of potential target drugs that could be more efficient for the treatment of these patients.

17.
Article in English | MEDLINE | ID: mdl-28616601

ABSTRACT

The minimally invasive surgery for gastric cancer in Brazil has begun about two years after the first laparoscopic gastrectomy (LG) performed by Kitano in Japan, in 1991. Although the report of first surgeries shows the year of 1993, there was no dissemination of the technique until the years 2010. At that time with the improvement of optical devices, laparoscopic instruments and with the publications coming from Asia, several Brazilian surgeons felt encouraged to go to Korea and Japan to learn the standardization of the LG. After that there was a significant increase in that type of surgery, especially after the IRCAD opened a branch in Brazil. The growing interest for the subject led some services to begin their own experience with the LG and, since the beginning, the results were similar with those found in the open surgery. Nevertheless, there were some differences with the papers published initially in Japan and Korea. In those countries, the surgeries were laparoscopic assisted, meaning that, in the majority of cases, the anastomoses were done through a mini-incision in the end of the procedure. In Brazil since the beginning it was performed completely through laparoscopic approach due to the skills acquired by Brazilian surgeons in bariatric surgeries. Another difference was the stage. While in the east the majority of cases were done in T1 patients, in Brazil, probably due to the lack of early cases, the surgeries were done also in advanced cases. The initial experience of Zilberstein et al. revealed low rates of morbidity without mortality. Comparing laparoscopic and open surgery, the group from Barretos/IRCAD showed shorter surgical time (216×255 minutes), earlier oral or enteral feeding and earlier hospital discharge, with a smaller number of harvested lymph nodes (28 in laparoscopic against 33 in open surgery). There was no significant difference regarding morbidity, mortality and reoperation rate. In the first efforts to publish a multicentric study the Brazilian Gastric Cancer Association (BGCA) collected data from three institutions analyzing 148 patients operated from 2006 to 2016. There were 98 subtotal, 48 total and 2 proximal gastrectomies. The anastomoses were totally laparoscopic in 105, laparoscopic assisted in 21, cervical in 2, and 20 open (after conversion). The reconstruction methods were: 142 Roux-en-Y, two Billroth I, and three other types. The conversion rate was 13.5% (20/148). The D2 dissection was performed in 139 patients. The mean number of harvested lymph nodes was 34.4. If we take only the D2 cases the mean number was 39.5. The morbidity rate was 22.3%. The mortality was 2.7%. The stages were: IA-59, IB-14, IIA-11, IIB-15, IIIA-9, IIIB-19, IIIC-11 and stage IV-three cases. Four patients died from the disease and 10 are alive with disease. The participating services have already begun the robotic gastrectomy with satisfactory results. The intention of this group is to begin now a prospective multicentric study to confirm the data already obtained with the retrospective studies.

18.
Ann Surg Oncol ; 23(4): 1212-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26542593

ABSTRACT

BACKGROUND: Resections have long been recommended for patients with incurable gastric cancer. However, high morbidity rates and more efficient chemotherapy regimens have demanded more accurate patient selection. The aim of this study was to analyze the results of gastric cancer patients treated with noncurative resection in a single cancer center. METHODS: Medical charts of patients treated with a noncurative resection between January 1988 and December 2012 were analyzed. Individuals who had M1 disease were included, along with those with no metastasis but who had an R2 resection. Morbidity, mortality, and survival prognostic factors were analyzed. RESULTS: In the period, 192 patients were resected, 159 with previously diagnosed metastatic disease and the other 33 having resection with macroscopic residual disease (R2). A distal gastrectomy was performed in 117 patients and a total resection in 75, with a more limited lymph node dissection in 70 % of cases. A multivisceral resection was deemed necessary in 42 individuals (21.9 %). Overall morbidity was 26.6 % and 60-day mortality was 6.8 %. Splenectomy was the only independent prognostic factor for higher morbidity. Median survival was 10 months, and younger age, distal resection, and chemotherapy were independent prognostic factors for survival. A prognostic score obtained from these factors identified a 20-month median survival in patients with these favorable characteristics. CONCLUSION: Noncurative surgery may be considered in selected gastric cancer patients as long as it has low morbidity and allows the realization of chemotherapy.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy/methods , Lymph Node Excision/methods , Neoplasm, Residual/diagnosis , Patient Selection , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Morbidity , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology , Survival Rate , Time Factors , Young Adult
19.
Ann Surg Oncol ; 22(3): 750-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25366586

ABSTRACT

BACKGROUND: Advanced gastric cancer in the upper or middle third of the stomach is routinely treated with a total gastrectomy, albeit in some cases with higher morbidity and mortality. The aim of this study was to describe the morbimortality and survival results in total gastrectomy in a single center. METHODS: This retrospective study included patients with gastric adenocarcinoma treated with a total gastrectomy at a single Brazilian cancer center between January 1988 and December 2011. Clinical, surgical, and pathology information were analyzed through time, with three 8-year intervals being established. Prognostic factors for survival were evaluated only among the patients treated with curative intent. RESULTS: The study comprised 413 individuals. Most were male and their median age was 59 years. The majority of patients had weight loss and were classified as American Society of Anesthesiologists 2. A curative resection was performed in 336 subjects and a palliative resection was performed in 77 subjects. Overall morbidity was 37.3% and 60-day mortality was 6.5%. Temporal analysis identified more advanced tumors in the first 8-year period along with differences in the surgical procedure, with more limited lymph node dissections. In addition, a significant decrease in mortality was observed, from 13 to 4%. With a median follow-up of 74 months among living patients, median survival was 56 months, and 5-year overall survival was 49.2%. Weight loss, lymphadenectomy, tumor size, and T and N stages were prognostic factors in multivariate analysis. CONCLUSIONS: Total gastrectomy is a safe and feasible treatment in experienced hands. Advances in surgical technique and perioperative care have improved outcomes through time.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy/mortality , Postoperative Complications , Stomach Neoplasms/surgery , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate , Young Adult
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