Open vs robotic gastrectomy with D2 lymphadenectomy: a propensity score-matched analysis on 1469 patients from the IMIGASTRIC prospective database.

BACKGROUND: Comparative data on D2-robotic gastrectomy (RG) vs D2-open gastrectomy (OG) are lacking in the Literature. Aim of this paper is to compare RG to OG with a focus on D2-lymphadenectomy. STUDY DESIGN: Data of patients undergoing D2-OG or RG for gastric cancer were retrieved from the international IMIGASTRIC prospective database and compared. RESULTS: A total of 1469 patients were selected for inclusion in the study. After 1:1 propensity score matching, a total of 580 patients were matched and included in the final analysis, 290 in each group, RG vs OG. RG had longer operation time (210 vs 330 min, p < 0.0001), reduced intraoperative blood loss (155 vs 119.7 ml, p < 0.0001), time to liquid diet (4.4 vs 3 days, p < 0.0001) and to peristalsis (2.4 vs 2 days, p < 0.0001), and length of postoperative stay (11 vs 8 days, p < 0.0001). Morbidity rate was higher in OG (24.1% vs 16.2%, p = 0.017). CONCLUSION: RG significantly expedites recovery and reduces the risk of complications compared to OG. However, long-term survival is similar.

[Experience with endoscopic submucosal dissection for the treatment of early neoplasms of the digestive tract]. / Disección endoscópica submucosa para el tratamiento de neoplasias incipientes del tubo digestivo: experiencia en un centro universitario de alto volumen.

BACKGROUND: Endoscopic submucosal dissection (ESD) allows en-bloc resection of early gastro-intestinal neoplasms (EGIN) with healing potential. AIM: To describe the results of patients treated with ESD for EGIN by our team. PATIENTS AND METHODS: Descriptive study of patients with EGIN who underwent ESD with curative intention between January 2008 and March 2020. RESULTS: One hundred thirty-two ESD were performed in 127 patients. 77% were gastric lesions, 14% colorectal, 8% esophageal and 1% duodenal. En-bloc resection was achieved in 98.4% of ESDs. Eighty eight percent of patients met curative standards. Overall, cancer-specific, and recurrence-free survival were 95%, 100% and 98% respectively. CONCLUSIONS: ESD allows en-bloc resections with curative potential in selected patients, but with a significant reduction in morbidity and mortality and less impact on quality of life. Our results suggest the feasibility to perform ESD in our country with results comparable to those reported in the literature.

The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer.

Reprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Here, we evaluated the role of RPRML and whether its regulation by DNA methylation is a potential non-invasive biomarker of gastric cancer. RPRML expression was evaluated by immunohistochemistry in 90 patients with gastric cancer and associated with clinicopathologic characteristics and outcomes. The role of RPRML in cancer biology was investigated in vitro, through RPRML ectopic overexpression. Functional experiments included colony formation, soft agar, MTS, and Ki67 immunofluorescence assays. DNA methylation-mediated silencing was evaluated by the 5-azacytidine assay and direct bisulfite sequencing. Non-invasive detection of circulating methylated RPRML DNA was assessed in 25 gastric cancer cases and 25 age- and sex-balanced cancer-free controls by the MethyLight assay. Downregulation of RPRML protein expression was associated with poor overall survival in advanced gastric cancer. RPRML overexpression significantly inhibited clonogenic capacity, anchorage-independent growth, and proliferation in vitro. Circulating methylated RPRML DNA distinguished patients with gastric cancer from controls with an area under the curve of 0.726. The in vitro overexpression results and the poor patient survival associated with lower RPRML levels suggest that RPRML plays a tumor-suppressive role in the stomach. Circulating methylated RPRML DNA may serve as a biomarker for the non-invasive detection of gastric cancer.

Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer.

Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for gastric cancer (GC). Here, we prospectively include probands with family history/early onset of diffuse-type of GC. The whole coding sequence of the CDH1 gene was sequenced from genomic DNA in all patients, and a multidisciplinary team managed each family member with a pathogenic sequence variant. Thirty-six cases were included (median age 44 years/male 50%). Twenty-seven (75%) patients had diffuse-type GC at ≤50 years of age and 19 (53%) had first or second-degree family members with a history of HDGC. Two cases (5.5%) carried a non-synonymous germline sequence variant in the CDH1 gene: (a) The c.88C>A missense variant was found in a family with three diffuse-type GC cases; and (b) c.1531C>T a nonsense pathogenic variant was identified in a 22-year-old proband with no previous family history of HDGC. Of note, six family members carry the same nonsense pathogenic variant. Prophylactic gastrectomy in the proband's sister revealed stage I signet-ring cell carcinoma. The finding of 1531C>T pathogenic variant in the CDH1 in proband with no previous family history of HDGC warrants further study to uncover familial clustering of disease in CDH1 negative patients. This finding may be particularly relevant in high incidence countries, such as the case in this report.

Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

National Trend in Laparoscopic Gastrectomy for Gastric Cancer: Analysis of the National Register in Chile.

INTRODUCTION: The laparoscopic approach for the treatment of gastric cancer has many advantages. However, outside Asia there are few large case series. AIM: To evaluate postoperative morbidity, long-term survival, changes in indication, and the results of laparoscopic gastrectomy. METHODS: We included all patients treated with a laparoscopic gastrectomy from 2005 to 2014. We compared results across 2 time periods: 2005-2011 and 2012-2014. Median follow-up was 39 months. RESULTS: Two hundred and eleven patients underwent a laparoscopic gastrectomy (median age 64 years, 55% male patients). In 135 (64%) patients, a total gastrectomy was performed. Postoperative morbidity occurred in 29%. A significant increase in the indication of laparoscopic surgery for stages II-III (32 vs. 45%; p = 0.04) and higher lymph node count (27 vs. 33; p = 0.002) were observed between the 2 periods. The 5-year overall survival was 72%. According to the stage, the 5-year overall survival was 85, 63, and 54% for stage I, II, and III respectively (p < 0.001). CONCLUSIONS: There was an acceptable rate of postoperative complications and the long-term survival was in accordance with the disease stage. There was a higher indication of laparoscopic surgery in stages II-III disease, and higher lymph node count in the latter period of this study.

[Totally laparoscopic gastrectomy for the treatment of gastric tumors]. / Gastrectomía totalmente laparoscópica por neoplasias gástricas: Experiencia en un centro público.

BACKGROUND: The laparoscopic approach for the treatment of gastric tumors has many advantages. AIM: To evaluate the results of a laparoscopic gastrectomy program developed in a public hospital. PATIENTS AND METHODS: Retrospective review of epidemiological, perioperative and follow-up data of patients who were treated with a laparoscopic gastrectomy due to gastric tumors between 2006 and 2013. A totally laparoscopic technique was used for all cases. Complications were evaluated according to the Clavien-Dindo classification. RESULTS: Fifty one patients, aged 65 (36-85) years, underwent a laparoscopic gastrectomy. In 22 patients a total gastrectomy was performed. Conversion rate to open surgery was 8%. Operative time was 330 (90-500) min and bleeding was 200 (20-500) ml. Median hospital stay was 7 (3-37) days. Postoperative morbidity was present in 17 (33%) patients, 3 (6%) patients had complications grade 3 or higher and one patient died (1.9%). Tumor pathology was adenocarcinoma in 39 patients. A complete resection was achieved in 97%. Twenty nine patients (74%) with gastric adenocarcinoma had early gastric cancer and 84% of patients were in stage one. Median lymph node count was 24. Median follow-up was 26 (1-91) months. There was no cancer related mortality among patients subjected to a curative resection. Overall survival for patients with adenocarcinoma was 92% at 3 years. CONCLUSIONS: This study supports the feasibility and safety of a laparoscopic gastrectomy program in a public hospital; with low morbidity, adequate lymph node dissection and long-term survival. This approach must be considered an option for selected patients with gastric cancer.

[Results of bariatric surgery. Experience over 18 years]. / Experiencia de 18 años de cirugía de obesidad en la Pontificia Universidad Católica de Chile.

BACKGROUND: Bariatric surgery is the gold-standard treatment for morbid obesity because it has low morbidity rates in high-volume centers and generates long term sustained weight loss. AIM: To describe our experience in bariatric surgery since the creation of our bariatric program in 1992. MATERIAL AND METHODS: Retrospective analysis of all patients subjected to bariatric surgery from 1992 to December 2010. Data was obtained from the electronic institutional registry. The Procedures per-formed were open and laparoscopic Roux-en-Y gastric bypass (BPGA and BPGL, respectively), laparoscopic adjustable gastric band (BGAL) and laparoscopic sleeve gastrectomy (GML). RESULTS: A total of 4943 procedures were performed, 768 (16%) BPGA, 2558 (52%) BPGL, 199 (4%) BGAL and 1418 (29%) GML. The number of procedures progressively increased, from 100 cases in 2000 to over 700 cases in 2008. Proportion of femóles and preoperative mean body mass Índex fluctuated between 69 and 79% and 35 and 43 kg/m², respectively, among the different procedures. Early and late complications fluctuated between Oto 1% (higher on BPGA) and 3 to 32.7% (higher on BGAL), respectively. The excess weight lost at five years was 76.1% in BPGA, 92.5% in BPGL and 53.7% in BGAL. The figure for GML at three years was 73.7%. CONCLUSIONS: The complication rates of this series of patients are similar to those reported in large series abroad. BPGL is still the most effective procedure; however GML is an attractive alternative for less obese patients.

Impact of Adjuvant FOLFOX on Quality of Life and Peripheral Neuropathy Incidence in Patients With Gastric Cancer: A Prospective Cohort Study.

OBJECTIVES: Perioperative and adjuvant chemotherapy have demonstrated clinical benefits in localized gastric cancer. Nevertheless, the reports on their effects on patient's health-related quality of life (HRQoL) are scarce. Here, we prospectively assessed quality of life and the incidence of chemotherapy-induced peripheral neuropathy (CIPN) in a cohort of patients treated with adjuvant FOLFOX. METHODS: Localized stomach or gastroesophageal junction adenocarcinoma patients who underwent curative resection were recruited at a single center. All patients received adjuvant FOLFOX6, and HRQoL and CIPN were assessed using the European organization for research and treatment of cancer quality life (EORTC) C30 and the EORTC CIPN20 questionnaires, respectively. Clinically significant deterioration of HRQoL was also assessed as a coprimary outcome in a longitudinal analysis. RESULTS: We recruited a total of 63 patients. Median age was 62.5 years, and 75% had stomach tumors. Twenty-four weeks after the start of treatment, the probability of being free from HRQoL deterioration and CIPN was 29% (95% confidence interval [CI] 18%-42%) and 6% (95% CI 2%-17%), respectively. Five-year disease-free survival was 45% (95% CI 24%-64%) and 5-year overall survival was 63% (95% CI 48%-76%). CONCLUSIONS: Adjuvant FOLFOX is associated with a high rate of long-term survival in localized gastric cancer; nevertheless, it has detrimental effects on patients' quality of life.

Completely laparoscopic versus open gastrectomy for early and advanced gastric cancer: a matched cohort study.

INTRODUCTION: The application of laparoscopic gastric surgery has rapidly increased for the treatment of early gastric cancer. However, laparoscopic gastrectomy for advanced tumor remains controversial, particularly in terms of oncologic outcomes. This study was designed to compare 3-year survival of laparoscopic versus open curative gastrectomy in early and advanced gastric cancer. METHODS: This was a retrospective matched cohort study. We included patients between 2003 and 2010 with an R0 resection. A totally laparoscopic technique was used and D2 lymph node dissection was practiced routinely. We performed an intracorporeal hand-sewn esophagojejunostomy in all laparoscopic total gastrectomy cases. We matched all laparoscopic cases 1:1 with open cases according to TNM AJCC seventh edition. We used Mann-Whitney or t test and Chi-square test to compare both groups. Kaplan-Meier analysis with log-rank test was performed to compare survival. RESULTS: We included 31 open and 31 laparoscopic cases (mean age 63 ± 14 years; 66% males). Both groups were identical in type of gastrectomy (71% total and 29% subtotal). There were no statistical difference between laparoscopic and open groups in age, sex, N category, tumor location and size, histological differentiation, and T category (48% T1, 13% T2, 16% T3, and 23% T4 in both groups), with 48% early and 52% advanced tumors. The median number of resected lymph nodes was similar: 35 (23-53) for laparoscopic and 39 (23-45) for open cases (P = 0.81). The median follow-up was 50 months. The overall 3-year survival was 82% for laparoscopic surgery and 87% for the open surgery group (P = 0.56). There were no difference in 3-year survival for the laparoscopic versus the open surgery groups for advanced tumors (74 vs. 75%, P = 0.88), N+ tumors (73 vs. 73%, P = 0.99) and for the different AJCC stages (stage 1: 94 vs. 100%, stage 2: 89 vs. 82%, and stage 3: 50 vs. 50%, P = 0.32, 0.83, and 0.98 respectively). CONCLUSIONS: In this preliminary report, with 52% of advanced tumor, the 3-year overall and stage-by-stage survival was comparable for laparoscopic and open curative gastrectomy.

Two-stage esophagojejunal anastomosis: An alternative reconstruction in emergency gastrectomy for high-risk gastric cancer patients.

Emergency total gastrectomy for patients with gastric cancer who are in shock carries a high risk of esophagojejunal anastomosis leakage. No alternatives have been reported to reduce this risk. This study reports two patients with gastric cancer who were in shock and underwent emergency gastrectomy and two-stage esophagojejunal anastomosis with good results. In the first stage, immediately after gastrectomy, the esophagus was attached to a Roux-en-Y jejunal loop that prevented retraction of the esophagus into the mediastinum. In the second stage, in a second surgery, the esophagojejunal anastomosis was completed under better clinical conditions.

[Results of pancreaticoduodenectomy in the treatment of periampullary tumors]. / Resultados actuales de la pancreatoduodenectomía para el tratamiento de los tumores periampulares y análisis de factores pronósticos de sobrevida.

BACKGROUND: The diagnosis and treatment of periampullary tumors represents a challenge for current medicine. AIM: To review the results of pancreaticoduodenectomy (PDD) in the treatment of periampullary tumors and to identify risk factors that impact the long-term survival. PATIENTS AND METHODS: We performed a retrospective study of patients who underwent a PDD for periampullary tumors between 1993 and 2009. We reviewed perioperative results and long term survival. We performed a multivariate analysis for long-term survival. RESULTS: A PDD was performed in 181 patients aged 58 ± 12 years (98 females). Pyloric preservation was done in 53% and a pancreatogastric anastomosis was used in 94% of cases. Morbidity was 62% and postoperative mortality was 5.5%. Pancreatic cancer was the most frequent pathological finding in 41%, followed by ampullary cancer in 28% and distal bile duct cancer in 16%. Median survival was 17 months, with a five years survival of 24%. Survival for ampullary tumors was 28 months with a five years survival of 32%. The median and five years survival were 14 months and 16% for bile duct cancer and 11 months and 14% for pancreatic cancer. Multivariate analysis identified tumor type (pancreas /bile duct) and lymph node dissemination as independent predictors of mortality. CONCLUSIONS: One quarter of patients experienced long term survival. Mortality predictors were tumor type and lymph node dissemination.

Acute abdomen due to pancreatic pseudocyst with splenic extension and rupture.

Pancreatic pseudocyst is a common complication of acute and chronic pancreatitis. However, spleen involvement in pancreatitis is rare. We present a patient with a pancreatic tail pseudocyst with splenic extension and rupture. Due to initial stability, conservative management was decided. However, he developed tachycardia with severe abdominal pain associated with signs of peritoneal irritation, requiring an emergency laparotomy. A large pancreatic tail pseudocyst was identified in addition to a ruptured spleen. Splenectomy and double layer hand-sewn gastrocystic anastomosis were performed. The patient had a satisfactory recovery and was discharged on the 11th postoperative day. Conservative management is an option in stable patients but with a high rate of failure. Surgery remains the standard choice in these cases.

Laparoscopic Compared with Open D2 Gastrectomy on Perioperative and Long-Term, Stage-Stratified Oncological Outcomes for Gastric Cancer: A Propensity Score-Matched Analysis of the IMIGASTRIC Database.

BACKGROUND: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. RESULTS: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p < 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p < 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p < 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). CONCLUSION: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

Long-term Results of Endoscopic Submucosal Dissection (ESD) for the Treatment of Early Gastric Cancer (EGC) in a High-volume Latin American Center.

BACKGROUND: Gastric cancer is the second leading cause of death by cancer worldwide. Endoscopic submucosal dissection (ESD) is a technique that allows en bloc resection of early lesions of the digestive tract. It has curative potential in selected patients and benefits over gastrectomy for the treatment of early gastric cancer (EGC). The aim of this study is to present the results of ESD for EGC in a high-volume center in Chile. MATERIALS AND METHODS: Retrospective descriptive study of patients who underwent ESD for EGC at the Doctor Sótero del Río Hospital. RESULTS: A total of 100 ESDs were performed in 96 patients between 2008 and 2020. Fifty-five percent were female patients, the average age was 68 years (range, 45 to 89 y). En bloc resection was achieved in 98% of cases and the rate of complications Clavien grade III or higher was 8.3%. There were no cases of perioperative mortality. Ninety-three percent of the dissections were classified as R0 and 83% met curative standards according to expanded criteria. The mean follow-up was 42 months (range, 1 to 144 mo). Overall survival was 97%. Cancer-specific survival was 100% and recurrence-free survival was 97%. CONCLUSIONS: The present study describes the largest series of ESD for the treatment of EGC reported in Latin America. Our results support the feasibility of implementing ESD in Chile and indicate good oncological outcomes comparable to those reported in the large Asian series published to date.

SURVIVAL AND PERIOPERATIVE MORBIDITY OF TOTALLY LAPAROSCOPIC VERSUS OPEN GASTRECTOMY FOR EARLY GASTRIC CANCER: ANALYSIS FROM A SINGLE LATIN AMERICAN CENTRE.

BACKGROUND: Laparoscopic gastrectomy has numerous perioperative advantages, but the long-term survival of patients after this procedure has been less studied. AIM: To compare survival, oncologic and perioperative outcomes between completely laparoscopic vs. open gastrectomy for early gastric cancer. METHODS: This study was retrospective, and our main outcomes were the overall and disease-specific 5-year survival, lymph node count and R0 resection rate. Our secondary outcome was postoperative morbidity. RESULTS: Were included 116 patients (59% men, age 68 years, comorbidities 73%, BMI 25) who underwent 50 laparoscopic gastrectomies and 66 open gastrectomies. The demographic characteristics, tumour location, type of surgery, extent of lymph node dissection and stage did not significantly differ between groups. The overall complication rate was similar in both groups (40% vs. 28%, p=ns), and complications graded at least Clavien 2 (36% vs. 18%, p=0.03), respiratory (9% vs. 0%, p=0.03) and wound-abdominal wall complications (12% vs. 0%, p=0.009) were significantly lower after laparoscopic gastrectomy. The lymph node count (21 vs. 23 nodes; p=ns) and R0 resection rate (100% vs. 96%; p=ns) did not significantly differ between groups. The 5-year overall survival (84% vs. 87%, p=0.31) and disease-specific survival (93% vs. 98%, p=0.20) did not significantly differ between the laparoscopic and open gastrectomy groups. CONCLUSION: The results of this study support similar oncologic outcome and long-term survival for patients with early gastric cancer after laparoscopic gastrectomy and open gastrectomy. In addition, the laparoscopic approach is associated with less severe morbidity and a lower occurrence of respiratory and wound-abdominal wall complications.

RISK FACTORS FOR SEVERE POSTOPERATIVE COMPLICATIONS AFTER GASTRECTOMY FOR GASTRIC AND ESOPHAGOGASTRIC JUNCTION CANCERS.

BACKGROUND: Gastrectomy is the main treatment for gastric and Siewert type II-III esophagogastric junction (EGJ) cancer. This surgery is associated with significant morbidity. Total morbidity rates vary across different studies and few have evaluated postoperative morbidity according to complication severity. AIM: To identify the predictors of severe postoperative morbidity. METHODS: This was a retrospective cohort study from a prospective database. We included patients treated with gastrectomy for gastric or EGJ cancers between January 2012 and December 2016 at a single center. Severe morbidity was defined as Clavien-Dindo score ≥3. A multivariate analysis was performed to identify predictors of severe morbidity. RESULTS: Two hundred and eighty-nine gastrectomies were performed (67% males, median age: 65 years). Tumor location was EGJ in 14%, upper third of the stomach in 30%, middle third in 26%, and lower third in 28%. In 196 (67%), a total gastrectomy was performed with a D2 lymph node dissection in 85%. Two hundred and eleven patients (79%) underwent an open gastrectomy. T status was T1 in 23% and T3/T4 in 68%. Postoperative mortality was 2.4% and morbidity rate was 41%. Severe morbidity was 11% and was mainly represented by esophagojejunostomy leak (2.4%), duodenal stump leak (2.1%), and respiratory complications (2%). On multivariate analysis, EGJ location and T3/T4 tumors were associated with a higher rate of severe postoperative morbidity. CONCLUSION: Severe postoperative morbidity after gastrectomy was 11%. Esophagogastric junction tumor location and T3/T4 status are risk factors for severe postoperative morbidity.

High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study.

Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.

Two-Layer Hand-Sewn Esophagojejunostomy in Totally Laparoscopic Total Gastrectomy for Gastric Cancer.

PURPOSE: Different esophagojejunostomy (EJ) reconstruction methods are used after totally laparoscopic total gastrectomy (TLTG), and none is considered a standard technique. This report describes a 2-layer hand-sewn EJ technique during TLTG; we also evaluated postoperative morbidity associated with this technique. MATERIALS AND METHODS: This retrospective cohort study included all consecutive patients who underwent TLTG for gastric cancer (GC) from 2012 to 2016 at 2 affiliated teaching hospitals. All participating surgeons performed standardized intracorporeal 2-layer hand-sewn EJ. RESULTS: We included 51 patients who underwent TLTG for GC and standardized EJ anastomosis. Twenty-seven (53%) were male, and the median age was 60 (36-87) years. The average operative time was 337±71 minutes and intraoperative bleeding was 160±107 mL. There were no open conversions related to EJ. Postoperative morbidity was observed in 9 (17.0%) patients. There was no postoperative mortality. EJ leakage was observed in 2 patients (3.8%) and 1 patient (1.9%) developed EJ stenosis. Patients with leakage were managed non-operatively and the patient with stenosis required endoscopic dilation. The median length of hospital stay was 8 (6-29) days. CONCLUSIONS: Two-layer hand-sewn EJ during TLTG for GC is a feasible and safe technique. This method avoids a laparotomy for reconstruction and the disadvantages associated with laparoscopic introduction of mechanical staplers for EJ, and provides an alternative for alimentary tract reconstruction after TLTG.

MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer.

BACKGROUND: Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. RESULTS: Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3'UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson's correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer. CONCLUSIONS: Comprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer.