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Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 883-893页

作者： Brendha Cação Coimbra Marina Alessandra Pereira Leonardo Cardili Venancio Avancini Ferreira Alves Evandro Sobroza de Mello Ulysses Ribeiro Jr marcus fernando kodama pertille ramos Department of Gastroenterology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil Department of Pathology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão Paulo 01246000Brazil

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological *** We retrospectively reviewed 284 GC patients who underwent ***-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive *** PD-L1+PT staged as pN+were also tested for PD-L1 expression in their ***-L1(-)GC with pN+served as the comparison *** Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the *** PD-L1(-)PT,9.1%(4/44)had PD-L1+in the *** agreement between PT and LNM had a kappa value of *** tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both *** was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched *** disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

关键词： Gastric cancer Lymph node Programmed death ligand 1 Stomach neoplasms Immunohistochemistry Metastasis

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Expression profiles of gastric cancer molecular subtypes in remnant tumors

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World Journal of Gastrointestinal Oncology 2021年第4期13卷 265-278页

作者： marcus fernando kodama pertille ramos Marina Alessandra Pereira Leonardo Cardili Evandro Sobroza de Mello Ulysses Ribeiro Jr Bruno Zilberstein Ivan Cecconello Department of Gastroenterology Instituto do CancerHospital das ClinicasHCFMUSPFaculdade de MedicinaUniversidade de São PauloSão Paulo 01249000São PauloBrazil Department of Pathology Instituto do CancerHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de São PauloSão Paulo 01249000São PauloBrazil

BACKGROUND Remnant gastric cancer(RGC)is a carcinoma arising in the stomach remnant after previous gastric *** is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer(PGC).However,as it is less frequent,its profile regarding the current molecular classifications of gastric cancer has not been *** To evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and *** Consecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels:Epstein-Barr virus in situ hybridization,immunohistochemistry for mismatch repair proteins(MutL homolog 1,MutS homolog 2,MutS homolog 6,and PMS1 homolog 2),p53 protein,and E-cadherin *** characteristics and survival of these patients were compared to 284 PGC *** A total of 40 RGC patients were enrolled in this *** to PGC,older age(P<0.001),male(P<0.001),lower body mass index(P=0.010),and lower hemoglobin level(P<0.001)were associated with RGC *** difference was observed regarding Lauren’s type and pathologic Tumor Node Metastasis stage between the *** the profiles evaluated,EBV-positive tumors were higher in RGC compared to PGC(P=0.039).The frequency of microsatellite instability,aberrant p53 immunostaining,and loss of E-cadherin expression were similar between RGC and *** rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC(P<0.001).According to the molecular classification,the subtypes were defined as EBV in nine(22.5%)cases,microsatellite instability in nine(22.5%)cases,genomically stable in one(2.5%)case,and chromosomal instability in 21(52.5%)*** was no significant difference in survival between molecular subtypes in RGC *** RGC w

关键词： Stomach neoplasms Gastric remnant Gastric remnant cancer Adenocarcinoma Immunohistochemistry

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Preoperative albumin-bilirubin score is a prognostic factor for gastric cancer patients after curative gastrectomy

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World Journal of Gastrointestinal Surgery 2023年第6期15卷 1125-1137页

作者： Daniel Jose Szor Marina Alessandra Pereira marcus fernando kodama pertille ramos Francisco Tustumi Andre Roncon Dias Bruno Zilberstein Ulysses Ribeiro Jr Department of Gastroenterology Instituto do CancerHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao Paulo 01246000Brazil

BACKGROUND Albumin-bilirubin(ALBI)score is an indicator of liver dysfunction and is useful for predicting prognosis of hepatocellular ***,this liver function index has been used to predict prognosis in other ***,the significance of ALBI score in gastric cancer(GC)after radical resection has not been *** To evaluate the prognostic value of the preoperative ALBI status in patients with GC who received curative *** Patients with GC who underwent curative intended gastrectomy were retrospectively evaluated from our prospective *** score was calculated as follows:(log10 bilirubin×0.660)+(albumin×-0.085).The receiver operating characteristic curve with area under the curve(AUC)was plotted to evaluate the ability of ALBI score in predicting recurrence or *** optimal cutoff value was determined by maximizing Youden’s index,and patients were divided into low and high-ALBI *** Kaplan-Meier curve was used to analyze the survival,and the log-rank test was used for comparison between *** A total of 361 patients(235 males)were *** median ALBI value for the entire cohort was-2.89(IQR-3.13;-2.59).The AUC for ALBI score was 0.617(95%CI:0.556-0.673,P<0.001),and the cutoff value ***,211(58.4%)patients were classified as low-ALBI group and 150(41.6%)as high-ALBI *** age(P=0.005),lower hemoglobin level(P<0.001),American Society of Anesthesiologists classification III/IV(P=0.001),and D1 lymphadenectomy P=0.003)were more frequent in the high-ALBI *** was no difference between both groups in terms of Lauren histological type,depth of tumor invasion(pT),presence of lymph node metastasis(pN),and pathologic(pTNM)*** postoperative complication,and mortality at 30 and 90 days were higher in the high-ALBI *** the survival analysis,the high-ALBI group had worse disease-free survival(DFS)and overall survival(OS)compared to those with low-ALBI(P<0.001).

关键词： Stomach neoplasms Adenocarcinoma Albumin-bilirubin Biomarker Prognosis Survival

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Gastric partitioning for the treatment of malignant gastric outlet obstruction

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World Journal of Gastrointestinal Oncology 2019年第12期11卷 1161-1171页

作者： marcus fernando kodama pertille ramos Leandro Cardoso Barchi Rodrigo Jose de Oliveira Marina Alessandra Pereira Donato Roberto Mucerino Ulysses Ribeiro Jr Bruno Zilberstein Ivan Cecconello Department of Gastroenterology Hospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao Paulo

BACKGROUND Gastric outlet obstruction(GOO)is one of the main complications in stage IV gastric cancer *** condition is usually managed by gastrojejunostomy(GJ).However,gastric partitioning(GP)has been described as an alternative to overcoming possible drawbacks of GJ,such as delayed gastric emptying and tumor *** To compare the outcomes of patients who underwent GP and GJ for malignant *** We retrospectively analyzed 60 patients who underwent palliative gastric bypass for unresectable distal gastric cancer with GOO from 2009 to *** clinicopathological characteristics including age,nutritional status,body mass index,and performance status were *** symptoms were graded according to GOO score(GOOS).Surgical outcomes evaluated included duration of the procedure,surgical complications,mortality,and length of hospital *** of oral diet after the procedure,weight gain,and overall survival were the long-term outcomes *** GP was performed in 30 patients and conventional GJ in the other 30 *** mean follow-up was 9.2 ***-nine(81.6%)patients died during that *** variables were similar between groups,with the exception of worse performance status in GP *** mean operative time was higher in the GP group(161.2 vs 85.2 min,P<0.001).There were no differences in postoperative complications and surgical mortality between *** median overall survival was 7 and 8.4 mo for the GP and GJ groups,respectively(P=0.610).The oral acceptance of soft solids(GOOS 2)and low residue or full diet(GOOS 3)were reached by 28(93.3%)GP patients and 22(75.9%)GJ patients(P=0.080).Multivariate analysis demonstrated that GOOS 2 and GOOS 3 were the main prognostic factors for survival(hazard ratio:8.90,95%confidence interval:3.38-23.43,P<0.001).CONCLUSION GP is a safe and effective procedure to treat *** to GJ,it provides similar surgical outcomes with a trend to better solid diet accep

关键词： Stomach neoplasms Gastric outlet obstruction Palliative surgery Gastrojejunostomy Gastric cancer

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Remnant gastric cancer:An ordinary primary adenocarcinoma or a tumor with its own pattern?

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World Journal of Gastrointestinal Surgery 2021年第4期13卷 366-378页

作者： marcus fernando kodama pertille ramos Marina Alessandra Pereira Andre Roncon Dias Anna Carolina Batista Dantas Daniel Jose Szor Ulysses Ribeiro Jr Bruno Zilberstein Ivan Cecconello Department of Gastroenterology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão PauloSão Paulo 01249000Brazil

BACKGROUND Remnant gastric cancer(RGC)is defined as a tumor that develops in the stomach after a previous gastrectomy and is generally associated with a worse ***,there little information available regarding RGCs and their prognostic factors and *** To evaluate the clinicopathological characteristics and prognosis of RGC after previous gastrectomy for benign *** Patients who underwent curative resection for primary gastric cancer(GC)at our institute between 2009 and 2019 were retrospectively *** RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in this *** proximal GC(PGC)who underwent total gastrectomy was selected as the comparison *** and pathological data were collected from a prospective medical *** A total of 41 patients with RGC and 120 PGC were *** age(P=0.001),lower body mass index(P=0.006),hemoglobin level(P<0.001),and number of resected lymph nodes resected(LN)(P<0.001)were associated with the RGC *** type,pathological tumor-node-metastasis,and perioperative morbimortality were similar between RGC and *** was no difference in disease-free survival(P=0.592)and overall survival(P=0.930)between *** status was the only independent factor related to *** RGC had similar clinicopathological characteristics to *** the lower number of resected LN,RGC had a similar prognosis.

关键词： Stomach neoplasms Gastric remnant Gastric cancer Remnant gastric cancer Peptic ulcer Gastric stump

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Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy

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Chinese Journal of Cancer Research 2018年第5期30卷 526-536页

作者： Marina Alessandra Pereira marcus fernando kodama pertille ramos ANDre Roncon Dias Sheila Friedrich Faraj Cinthya dos Santos Cirqueira EvANDro Sobroza de Mello Bruno Zilberstein Venancio Avancini Ferreira Alves Ulysses Ribeiro Jr Department of Gastroenterology Cancer InstituteUniversity of Sao Paulo Medical School Department of Pathology Cancer InstituteUniversity of Sao Paulo Medical School Department of Pathology Instituto Adolfo Lutz

Objective： Adjuvant chemotherapy with 5-fluorouracil （5-FU） has been widely used in gastric cancer （GC） patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase （TS）, and high levels of TS correlate with resistance to treatment with fluoropyfimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. Methods： We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry （IHC） in tumor cells by tissue microarray （TMA）. TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score： negative, low and high. Results： TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age （P=0.007）, high neutrophil/lymphocyte ratio （P=0.048）, well/moderately differentiated histology （P=0.001）, intestinal Lauren type （P〈0.001） and absence of perineural invasion （P=0.003）. Among 285 patients, 133 stage IUIII patients （46.7%） received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival （DFS） in stage III GC patients who received 5-FU-based chemotherapy （P=0.007）. Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. Conclusions： High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy.

关键词： Gastric cancer adjuvant therapy thymidylate synthase 5-fluorouracil-based chemotherapy

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Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer

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Chinese Journal of Cancer Research 2022年第6期34卷 612-622页

作者： Marina Alessandra Pereira marcus fernando kodama pertille ramos André Roncon Dias Leonardo Cardili Rafael Dyer Rodrigues de Moraes Renan Ribeiro E Ribeiro Venancio Avancini Ferreira Alves Bruno Zilberstein Evandro Sobroza de Mello Ulysses Ribeiro Jr Department of Gastroenterology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil Department of Pathology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil

Objective:Remnant gastric cancer(RGC)is usually associated with a worse *** they are less common and very heterogeneous tumors,new prognostic and reliable determinants are required to predict patients’clinical course for *** study aimed to investigate the tumor-infiltrating lymphocytes(TILs)and programmed cell death ligand 1(PD-L1)status as prognostic biomarkers in a cohort of patients with RGC to develop an immunerelated ***:Patients with gastric cancer(GC)who underwent curative intent gastrectomy were retrospectively *** resections with histological diagnosis of gastric adenocarcinoma were enrolled in the *** risk score based on immune parameters was developed using binary logistic regression *** were divided into high-risk(HR),intermediate-risk(IR),and low-risk(LR)groups based on their immune *** markers(CD3+,CD4+/CD8+T cells and PD-L1)were selected for their potential prognostic,therapeutic value,and evaluated by immunohistochemistry(IHC).Results:A total of 42 patients with RGC were enrolled in the *** score based on immune parameters exhibited an accuracy of 79%[the area under the receiver operating characteristic curve(AUC)=0.79,95%confidence interval(95%CI),0.63-0.94,P=0.002],and the population was divided into 3 prognostic groups:10(23.8%)patients were classified as LR,15(35.7%)as IR,and 17(40.5%)as HR *** were no differences in clinicopathological and surgical characteristics between the three *** survival analysis,HR and IR groups had worse disease-free survival and overall survival rates compared to the LR *** the multivariate analysis,lymph node metastasis and the immune score risk groups were independent factors related to worse ***:A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with ***,tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic bi

关键词： Stomach neoplasms gastric remnant tumor-infiltrating lymphocytes immune microenvironment

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Risk factors for blood transfusion and its prognostic implications in curative gastrectomy for gastric cancer

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World Journal of Gastrointestinal Surgery 2023年第4期15卷 643-654页

作者： Lucas Eiki Kawakami Pedro Barzan Bonomi Marina Alessandra Pereira Fabrício Oliveira Carvalho Ulysses Ribeiro Jr Bruno Zilberstein Luciana Ribeiro Sampaio Luiz Augusto Carneiro-D'Albuquerque marcus fernando kodama pertille ramos Department of Gastroenterology Instituto do CancerHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao Paulo 01249000Brazil Blood Transfusion Unit Instituto do CancerHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao Paulo 01249000Brazil

BACKGROUND Gastric cancer(GC)is still a prevalent neoplasm around the world and its main treatment modality is surgical *** need for perioperative blood transfusions is frequent,and there is a long-lasting debate regarding its impact on *** To evaluate the factors related to the risk of receiving red blood cell(RBC)transfusion and its influence on surgical and survival outcomes of patients with *** Patients who underwent curative resection for primary gastric adenocarcinoma at our Institute between 2009 and 2021 were retrospectively *** and surgical characteristics data were *** patients were divided into transfusion and non-transfusion groups for *** A total of 718 patients were included,and 189(26.3%)patients received perioperative RBC transfusion(23 intraoperatively,133 postoperatively,and 33 in both periods).Patients in the RBC transfusions group were older(P<0.001),and had morecomorbidities(P=0.014),American Society of Anesthesiologists classification III/IV(P<0.001),and lower preoperative hemoglobin(P<0.001)and albumin levels(P<0.001).Larger tumors(P<0.001)and advanced tumor node metastasis stage(P<0.001)were also associated with the RBCtransfusion *** rates of postoperative complications(POC)and 30-d and 90-d mortalitywere significantly higher in the RBC transfusion group than in the non-transfusion *** and albumin levels,total gastrectomy,open surgery,and the occurrence of POC werefactors associated with the RBC *** analysis demonstrated that the RBCtransfusions group had worse disease-free survival(DFS)and overall survival(OS)compared withpatients who did not receive transfusion(P<0.001 for both).In multivariate analysis,RBCtransfusion,major POC,pT3/T4 category,pN+,D1 lymphadenectomy,and total gastrectomywere independent risk factors related to worse DFS and *** RBC transfusion is associated with worse clinical condition

关键词： Stomach neoplasms Blood transfusion Red blood cells Postoperative complications Survival Prognosis

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Jejunostomy in the palliative treatment of gastric cancer:A clinical prognostic score

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World Journal of Clinical Oncology 2021年第10期12卷 935-946页

作者： marcus fernando kodama pertille ramos Marina Alessandra Pereira Andre Roncon Dias Erica Sakamoto Ulysses Ribeiro Jr Bruno Zilberstein Sergio Carlos Nahas Department of Gastroenterology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão Paulo 01246000Brazil

BACKGROUND Clinical stage IV gastric cancer(GC)may need palliative procedures in the presence of symptoms such as *** palliative resection is not possible,jejunostomy is one of the ***,the limited survival of these patients raises doubts about who benefits from this *** To create a prognostic score based on clinical variables for 90-d mortality for GC patients after palliative *** We performed a retrospective analysis of Stage IV GC who underwent *** preoperative clinical variables were selected to define the score categories,with 90-d mortality as the main *** randomization,patients were divided equally into two groups:Development(J1)and validation(J2).The following variables were used:Age,sex,body mass index(BMI),American Society of Anesthesiologists classification(ASA),Charlson Comorbidity index(CCI),hemoglobin levels,albumin levels,neutrophil-lymphocyte ratio(NLR),tumor size,presence of ascites by computed tomography(CT),and the number of disease *** score performance metric was determined by the area under the receiver operating characteristic(ROC)curve(AUC)to define low and high-risk *** Of the 363 patients with clinical stage IVCG,80(22%)patients underwent *** were predominantly male(62.5%)with a mean age of 62.4 years *** randomization,the binary logistic regression analysis was performed and points were assigned to the clinical variables to build the *** high NLR had the highest *** ROC curve derived from these pooled parameters had an AUC of 0.712(95%CI:0.537–0.887,P=0.022)to define risk *** the validation cohort,the diagnostic accuracy for 90-d mortality based on the score had an AUC of 0.756,(95%CI:0.598–0.915,P=0.006).According to the cutoff,in the validation cohort BMI less than 18.5 kg/m2(P<0.001),CCI≥1(P=0.001),ASA III/IV(P=0.002),high NLR(P=0.012),and the presence of ascites on CT exam(P=0.004)were significantly assoc

关键词： Stomach neoplasms Gastric cancer Palliative surgery Jejunostomy Gastric cancer with outlet obstruction Stage IV gastric cancer

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Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization:Analysis in western patients after curative-intent surgery

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World Journal of Clinical Oncology 2021年第8期12卷 688-701页

作者： marcus fernando kodama pertille ramos Marina Alessandra Pereira Evandro Sobroza de Mello Cinthya dos Santos Cirqueira Bruno Zilberstein Venancio Avancini Ferreira Alves Ulysses Ribeiro-Junior Ivan Cecconello Department of Gastroenterology Instituto do CancerHospital das ClinicasHCFMUSPFaculdade de MedicinaUniversidade de São PauloSão Paulo 01249000Brazil Department of Pathology Instituto do CancerHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSão Paulo 01249000Brazil Department of Pathology Instituto Adolfo LutzSão Paulo 01246000Brazil

BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic ***,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further *** To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative *** instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by *** microarrays were constructed for *** characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification *** A total of 287 GC patients were *** on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were *** location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV *** subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)*** tumors and mic

关键词： Stomach neoplasms Gastric cancer Translational medical research Molecular classification Immunohistochemistry Biomarkers

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