Brazilian Society of Surgical Oncology surgical standards for resectable colorectal cancer liver metastases.

The management of colorectal cancer liver metastasis (CRLM) has become complex because of the increasing availability of medical, radiological, and surgical treatment options applied either alone or in combination. However, resection remains the only evidence-based curative therapy. These Brazilian Society of Surgical Oncology surgical standards are intended to guide clinicians in the decision-making process for modern surgical management of CRLM within a multidisciplinary team in an evidence-based framework, focusing on resectable disease.

Surgery or active surveillance for pNETs < 2 cm: Preliminary results from a single center Brazilian cohort.

BACKGROUND AND OBJECTIVES: Incidence of pancreatic neuroendocrine tumors (pNETS) seems to be rising over the years, with many cases incidentally diagnosed. Surgery and active surveillance are current treatment modalities for small pNETS. We review our institutional series and compare outcomes for small asymptomatic and nonfunctioning tumors. METHODS: This retrospective cohort study included patients with 2 cm or less and well differentiated pNETS at a single Brazilian Cancer Center. From 2002 to 2020, patients received active surveillance or surgery as a treatment strategy. Short and long-term results were compared. RESULTS: Sixty-four patients were included, 41 in surgical strategy and 23 in the active surveillance approach. Baseline group characteristics were comparable. More patients on active surveillance underwent abdominal magnetic resonance imaging (MRI) and had tumors located in the pancreatic head (41% vs. 17%, p = 0.038). Minimally invasive procedure was chosen in 80.1% of the surgical patients. No patient died after surgery. Median follow-up period was 38.6 and 46.4 months for active surveillance and surgery cohorts, respectively. No difference in disease progression rate was observed. CONCLUSION: Both approaches seem to be safe for small pNETs. Long-term outcome and quality of life should be considered when discussing such options with patients.

PD-L1 expression in gastric and gastroesophageal junction cancer patients treated with perioperative chemotherapy.

BACKGROUND AND OBJECTIVES: The incidence, predictive, and prognostic impact of programmed cell death (PD-L1) expression in gastric (GC) and gastroesophageal junction tumors (GEJC) treated with perioperative chemotherapy is poorly understood. We aimed to assess PD-L1 expression by immunohistochemistry (IHC) in both pre and posttreatment specimens evaluating its impact on pathological response and survival outcomes. METHODS: Retrospective cohort of patients with GC and GEJ tumors treated in a single western cancer center between 2007 and 2017. PD-L1 expression was assessed by IHC before and after neoadjuvant chemotherapy, in surgical samples, and reported as combined positive score (CPS). CPS > 1% was tested for its association with pathological response and overall survival (OS). RESULTS: We were able to assess PD-L1 expression in at least one tissue sample from 155 subjects. PD-L1 positivity rate was 20%. In 74 paired samples, a 21% discordance between PD-L1 expression in biopsy sample and surgical specimen was observed. With a median follow-up period of 60.3 months, 5-years disease-free survival was 60.5% with a median OS not reached. PD-L1 expression was neither associated with pathological response or survival outcomes. CONCLUSIONS: PD-L1 expression in the setting of locally advanced GC tumors was relatively low and can vary considering the tissue sample analyzed. This expression had no association with survival or pathological response in this population.

Symptomatic Recurrence and Survival Outcomes After Curative Treatment of Gastric Cancer: Does Intensive Follow-up Evaluation Improve Survival?

BACKGROUND: Intensive surveillance after treatment of gastric cancer patients with curative intent may lead to an earlier diagnosis of disease recurrence, but its impact on survival is uncertain. This study aimed to evaluate whether early diagnosis of disease recurrence among asymptomatic patients was associated with long-term survival. METHODS: This retrospective study analyzed patients with stages 1 to 3C gastric adenocarcinoma treated between 1999 and 2018. All recurrence events were classified as symptomatic or asymptomatic (detected by follow-up tests), and their clinicopathologic characteristics, patterns of recurrence, and survival were analyzed. RESULTS: The cohort consisted of 669 patients treated with a total gastrectomy in 48.6% and a D2-lymphadenectomy in 88.8% of the cases. Most of the tumors were pT3-4 (46.5%), with 45.5% involving lymph node metastases and 42.3% manifesting a diffuse histology. During a median follow-up period of 80.1 months (95% confidence interval [CI], 75.3-84.8 months), 166 patients had recurrences (24.8%), 65.7% of which were symptomatic. The peritoneum was the main site of recurrence (37.2%), and peritoneal recurrence was associated with worse overall survival (OS) (hazard ratio, 1.69; 95%CI, 1.2-2.37). The median disease-free, post-recurrence survival, and OS periods in the asymptomatic and symptomatic groups were respectively 13.4 versus 17.2 months (p = 0.04), 11.9 versus 4.7 months (p < 0.001), and 29.9 versus 26.4 months (p = 0.21). When OS was analyzed among the patients with non-peritoneal recurrence, no difference was observed between the two groups (31.3 vs 31.1 months; p = 0.46). CONCLUSION: Early diagnosis of asymptomatic disease recurrence did not affect the OS of the gastric cancer patients treated with curative intent. The use of intensive surveillance strategies in this scenario still requires further evidence.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of oesophageal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of gastric cancer.

Gastric cancer is among the ten most common types of cancer worldwide. Most cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of gastric carcinomas. The Brazilian Group of Gastrointestinal Tumors (GTG) invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy and follow-up, which was followed by presentation, discussion, and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of gastric carcinomas in several scenarios and clinical settings.

Predictors of long-term survival in patients with hepatic resection of colorectal metastases: Analysis of a Brazilian Cancer Center Cohort.

BACKGROUND: Hepatic metastases are a major cause of death in patients with colorectal cancer. A comprehensive assessment of the prognostic factors associated with long-term survival could improve patient selection for surgical approaches and decrease morbidity and futile locoregional treatments. METHODS: We performed a retrospective analysis of patients who underwent hepatectomy for colorectal liver metastases at a single center from 2000 to 2012. RESULTS: To identify factors associated with 5- and 10-year overall (OS) and disease-free survival (DFS), we analyzed 280 patients and 150 patients in the 5- and 10-year cohorts, respectively. Only seven relapses occurred after 5 years of follow-up, and no relapses occurred after 10 years. Multivariable analysis indicated that bilobar disease and extra-hepatic disease before hepatectomy were independent 5- and 10-year predictors of OS, and major postoperative complications predicted OS in the 5-year survival cohort only. Our analysis indicated that prognostic factors associated with DFS included some confounders and was therefore inconclusive. CONCLUSIONS: Taken together, our results suggest that the predictors of 5- and 10-year OS rates of colorectal cancer patients with hepatic metastases are similar, differing only by postoperative complications that influenced exclusively 5-year survival. Since no relapse occurred 10 years after hepatic resection, oncological remission is likely.

Does hipec improve outcomes in gastric cancer patients treated with perioperative chemotherapy and radical surgery? A propensity-score matched analysis.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with improved survival when compared with surgery alone for non-metastatic gastric cancer patients in randomized trials and meta-analyses. However, little evidence is available regarding the use of HIPEC in nonmetastatic patients who are treated with perioperative chemotherapy and radical surgery. The aim of this study was to investigate the putative survival benefit of HIPEC in the subgroup of gastric cancer patients treated with perioperative chemotherapy and surgery. PATIENTS AND METHODS: This was a retrospective cohort study that included gastroesophageal junction and gastric cancer patients who were treated with perioperative chemotherapy and curative resection in a single cancer center in the period between 2006 and 2017. In this time period, younger patients with diffuse-type tumors and serosa invasion or positive lymph node disease were often offered an adjuvant HIPEC protocol. This study compared the survival outcomes of these patients to the ones of those who received only perioperative chemotherapy and resection. A 2:1 propensity-score matched analysis for the two groups was also performed, and variables used were postchemotherapy T (ypT) and N (ypN) stages, histology and tumor site. RESULTS: The study population comprised 269 subjects, 241 treated with chemotherapy and surgery and 28 who also received HIPEC. The mean age was 59 years old (standard deviation: 12.2) and 60% of all individuals were male. A total gastrectomy was performed in 137 patients and a distal resection in 132, with a D2-lymphadenectomy in 97.4% of the sample. Overall 60-day morbidity and mortality rates were 35.3% and 3.3%, respectively. In the HIPEC group, patients were younger, and more frequently had American Society of Anesthesiologists (ASA) 1 to 2 classification, tumors located in the gastric body, had diffuse histology, and ypN+ disease. Overall survival (OS; 5 years) results in the HIPEC and no HIPEC group were 59.5% vs 68.7% (P = .453), and disease-free survival (DFS) ones were 49.5% and 65.8% (P = .060), respectively. In the multivariable Cox regression model, ypT and ypN were independent overall and DFS predictors; also, ASA 3 to 4 classification and diffuse histology were associated with worse OS. In the matched analysis, HIPEC did not improve either overall (53.5% vs 59.5%; P = .517) or DFS (50.0% vs 49.5%; P = .993). CONCLUSION: Treatment with HIPEC in patients who received perioperative chemotherapy and a D2-resection did not improve survival outcomes. Both ypT and ypN stages remained as the most important survival predictors in this cohort.

Short-term outcomes after vascular resection for pancreatic tumors: Lessons learned from 72 cases from a single Brazilian Cancer Center.

INTRODUCTION: Pancreatic malignant tumors are resectable at diagnosis in only 15% to 20% of cases and invasion of vascular structures is commonly present. Therefore, extended resections are needed for adequate local control and negative margins. However, morbidity and mortality associated with these enlarged resections are limiting factors. The aim of this study was to correlate demographic and technical aspects that influenced early and late outcomes. MATERIALS AND METHODS: Between October 2007 and May 2019, 523 pancreatic surgeries were performed, of which 72 required vascular resections. Clinical and histopathological data, surgical techniques, and perioperative parameters were analyzed in a prospectively collected database. RESULTS: Of the 72 cases of vascular resection, 31 were male and 41 females with a mean age of 60.9 years (34-81). The most commonly affected vascular structure was the portal vein (in 40.3%). Free margins were obtained in 77.8% of cases. Postoperative mortality rate at 60 days was 13.9%. American Society of Anesthesiologists (ASA) and age were the most important predictors of major complications. CONCLUSION: Extended resections with vascular involvement in pancreatic surgeries are feasible and safe; furthermore, patient selection plays are key. ASA and age were the most important factors in the decision-making process for extended resections.

Predicting overall and major postoperative morbidity in gastric cancer patients.

BACKGROUND: Postoperative complications after gastric cancer resection vary in different series and they might have a significant impact in long-term outcomes. Our aim was to build a prediction rule on gastric cancer patients' overall and major morbidity risks. METHODS: This retrospective study included 1223 patients from a single center who were resected between 1992 and 2016. Overall and major morbidity predictors were identified through multiple logistic regression. Models' performances were assessed through discrimination, calibration, and cross-validation, and nomograms were constructed. RESULTS: The mean age was 61.3-year old and the male gender was more frequent (60%). The most common comorbidities were hypertension (HTN), diabetes, and chronic obstructive pulmonary disease (COPD). A D2-distal gastrectomy was the most frequent procedure and 87% of all lesions were located in the middle or distal third. Age, COPD, coronary heart disease, chronic liver disease, pancreatic resection, and operative time were independent predictors of overall and major morbidity. The extent of resection and splenectomy was associated with overall events and HTN with major ones. Both models were very effective in predicting events among patients at higher risk. CONCLUSIONS: The overall and major morbidity models and nomograms included clinical- and surgical-related data that were very effective in predicting events, especially for high-risk patients.

Impact of ypT, ypN, and Adjuvant Therapy on Survival in Gastric Cancer Patients Treated with Perioperative Chemotherapy and Radical Surgery.

BACKGROUND: Perioperative chemotherapy and surgery is the standard of care in advanced gastroesophageal cancer patients, but its impact among those treated with radical surgery still needs further assessment. We present the results of this multimodality treatment approach in a gastric cancer patients cohort treated with D2 lymphadenectomy. We aimed to identify prognostic factors associated with improved survival. PATIENTS AND METHODS: This retrospective cohort study enrolled patients treated with perioperative chemotherapy and resection in a single cancer center in Brazil between 2006 and 2016. Subjects presenting tumors of the gastric stump, esophageal tumors, or treated with intraperitoneal chemotherapy were excluded. Intention-to-treat survival analysis was performed for all subjects who started neoadjuvant chemotherapy, and prognostic factors were determined among those who had R0 resection. RESULTS: This study included 239 patients, of whom 198 had R0 resection. The mean age was 59.9 years, and most had clinical stage IIB or III disease (88%). Among the 239 patients who started neoadjuvant chemotherapy, 207 (86.6%) completed all neoadjuvant treatment cycles, and surgical resection was performed in 225 subjects (94.1%). Overall 60-day morbidity and mortality rates were 35.6% and 4.4%, respectively. For the entire cohort, median survival was 78 months and the 5-year survival rate was 55.3%. Factors associated with worse survival were ypT3-4 stage, ypN + stage, extended resection, and no adjuvant chemotherapy. CONCLUSIONS: Perioperative chemotherapy resulted in very good outcomes for patients treated with radical surgery, and downstaging after chemotherapy was shown to be a major determinant of prognosis.

Noncurative Resection for Gastric Cancer Patients: Who Could Benefit? : Determining Prognostic Factors for Patient Selection.

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.

Pancreatic mucinous cystadenoma with serum CA 19-9 over 1,000,000 U/mL: a case report and review of the literature.

BACKGROUND: The diagnosis of pancreatic cystic neoplasms has become more accurate recently. In some cases, however, doubt remains regarding the lesion's malignant potential. CA 19-9 has long been identified as a reliable biomarker in differentiating pancreatic benign and malignant lesions, especially in non-jaundiced patients. CASE REPORT AND DISCUSSION: We report a case of a young female who presented with a mucinous lesion in the tail of the pancreas and a serum CA 19-9 over 1,000,000 U/mL. She was taken to surgery and had a distal pancreatectomy and splenectomy. Pathology reports showed only a mucinous cystadenoma. After 1 year of follow-up, her serum CA 19-9 was normal. Following that, the work-up in these lesions, the role of the biomarker in pancreatic adenocarcinoma and in the differentiation between benign and malignant lesions is discussed.

Total gastrectomy for gastric cancer: an analysis of postoperative and long-term outcomes through time: results of 413 consecutive cases in a single cancer center.

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.

Adjuvant chemoradiotherapy after d2-lymphadenectomy for gastric cancer: the role of n-ratio in patient selection. results of a single cancer center.

BACKGROUND: Adjuvant chemoradiotherapy is part of a multimodality treatment approach in order to improve survival outcomes after surgery for gastric cancer. The aims of this study are to describe the results of gastrectomy and adjuvant chemoradiotherapy in patients treated in a single institution, and to identify prognostic factors that could determine which individuals would benefit from this treatment. METHODS: This retrospective study included patients with pathologically confirmed gastric adenocarcinoma who underwent surgical treatment with curative intent in a single cancer center in Brazil, between 1998 and 2008. Among 327 patients treated in this period, 142 were selected. Exclusion criteria were distant metastatic disease (M1), T1N0 tumors, different multimodality treatments and tumors of the gastric stump. Another 10 individuals were lost to follow-up and there were 3 postoperative deaths. The role of several clinical and pathological variables as prognostic factors was determined. RESULTS: D2-lymphadenectomy was performed in 90.8% of the patients, who had 5-year overall and disease-free survival of 58.9% and 55.7%. The interaction of N-category and N-ratio, extended resection and perineural invasion were independent prognostic factors for overall and disease-free survival. Adjuvant chemoradiotherapy was not associated with a significant improvement in survival. Patients with node-positive disease had improved survival with adjuvant chemoradiotherapy, especially when we grouped patients with N1 and N2 tumors and a higher N-ratio. These individuals had worse disease-free (30.3% vs. 48.9%) and overall survival (30.9% vs. 71.4%). CONCLUSION: N-category and N-ratio interaction, perineural invasion and extended resections were prognostic factors for survival in gastric cancer patients treated with D2-lymphadenectomy, but adjuvant chemoradiotherapy was not. There may be some benefit with this treatment in patients with node-positive disease and higher N-ratio.

Safety and preliminary results of perioperative chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) for high-risk gastric cancer patients.

BACKGROUND: Gastric cancer relapse occurs in about 30% of the patients treated with gastrectomy and D2-lymphadenectomy, mainly as distant or peritoneal metastases. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with an improvement in survival and lower peritoneal recurrence, albeit with increased morbidity. The aim of this study is to report the preliminary results of the association of perioperative chemotherapy, radical surgery and HIPEC in high-risk gastric patients in a single institution. METHODS: Treatment protocol was started in 2007 and included patients younger than 65 years old, with good performance status and gastric adenocarcinoma with serosa involvement and lymph node metastases, located in the body or antrum. Patients should receive three preoperative cycles of DCF (Docetaxel 75 mg/m2, Cisplatin 75 mg/m2 and continuous intravenous infusion of 5-Fluorouracil 750 mg/m2 for 5 days), followed by gastric resection with D2-lymphadenectomy, hyperthermic intraperitoneal chemotherapy with Mytomicin C 34 mg/m2 and three more postoperative cycles of DCF. RESULTS: Ten patients were included between 2007 and 2011. Their median age was 47 years old and six were male. Nine were staged with cT4 cN + tumors and one as cT3 cN+. Nine patients completed all three preoperative chemotherapy cycles. Eight individuals were treated with a total gastrectomy and the other two had a distal gastrectomy, all having HIPEC. Postoperative morbidity was 50%, with no deaths. Regarding postoperative chemotherapy, only 5 patients completed three cycles. With a median follow-up of 25 months, three relapses were identified and 7 patients remain disease-free, two with more than 4 years of follow-up. CONCLUSION: The association of perioperative systemic and intraperitoneal chemotherapy plus radical surgery is a feasible multimodality treatment, with acceptable morbidity. With a longer follow-up and a larger group of patients, we hope to be able to determine if it also influences survival outcomes and patterns of recurrence. MINI-ABSTRACT: The association of perioperative chemotherapy, gastric resection and D2-lymphadenectomy and hyperthermic intraperitoneal chemotherapy proved to be associated with acceptable morbidity. For survival analysis, a longer follow-up is needed.