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Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz Juvenal Sanchez Fernando Barreda Daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa hugo fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori HER2 Mismatch repair

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Immunotherapy in triple-negative breast cancer:A literature review and new advances

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World Journal of Clinical Oncology 2022年第3期13卷 219-236页

作者： Guillermo Arturo Valencia Patricia Rioja Zaida Morante Rossana Ruiz hugo fuentes Carlos A Castaneda Tatiana Vidaurre Silvia Neciosup Henry L Gomez Department of Medical Oncology Instituto Nacional de Enfermedades NeoplásicasLima 15036Peru

Triple-negative breast cancer(TNBC)is a highly complex,heterogeneous disease and historically has limited treatment options.It has a high probability of disease recurrence and rapid disease progression despite adequate systemic treatment.Immunotherapy has emerged as an important alternative in the management of this malignancy,showing an impact on progression-free survival and overall survival in selected populations.In this review we focused on immunotherapy and its current relevance in the management of TNBC,including various scenarios(metastatic and early-neoadjuvant,adjuvant-),new advances in this subtype and the research of potential predictive biomarkers of response to treatment.

关键词： Triple-negative breast cancer Early disease Immunotherapy Biomarkers Metastatic disease

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A biomarker study in Peruvian males with breast cancer

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World Journal of Clinical Oncology 2021年第10期12卷 926-934页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Ebert Torres Nancy Suarez Katherine Tello hugo fuentes Jorge Dunstan Miguel De La Cruz Jose Manuel Cotrina Julio Abugattas Henry Guerra Henry L Gomez Faculty of Health Sciences Universidad Cientifica del SurLima 15067Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Breast Cancer Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru

BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female counterpart.Breast cancer clinical and pathological features differ by race in women.Tumor infiltrating lymphocyte(TIL)levels,mismatch repair(MMR)protein loss,androgen receptor(AR)expression,and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC.There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC.AIM To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population.METHODS This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018.Standard pathological features,TIL levels,MMR proteins,AR immunohistochemistry staining,and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material.Percentage of AR and estrogen receptor(ER)positive cells was additionally calculated by software after slide scanning.Statistical analyses included association tests,intraclass correlation test and Kaplan Meier overall survival curves.RESULTS The median age was 63 years and most cases were ER-positive(85.7%),HER2 negative(87.2%),Luminal-A phenotype(60%)and clinical stage II(41.5%)among our male breast tumors.Median TIL was 10%and higher levels tended to be associated with Luminal-B phenotype and higher grade.AR-positive was found in 85.3%and was correlated with ER(intraclass index of 0.835,P0.05).CONCLUSION Male BC is usu

关键词： Male breast neoplasm Androgen receptor Tumor-infiltrating lymphocyte Mismatch repair protein PIK3CA mutation

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Implementation of a Telechemotherapy Module in the Peruvian Jungle with Adequate Quality of Life:Breaking the Access Gaps to Health with Teleoncology

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Journal of Cancer Therapy 2019年第8期10卷 677-691页

作者： Tatiana Vidaurre Jule Vásquez Fernando Valencia Cindy Alcarraz Luis Más Nataly Poma Litol Becerra Gino Rodriguez Socorro Saldana Pepe Diaz Silvia Neciosup Karina Aliaga Roxana Regalado Miriam Salazar Kavita Sarwal Simon Sutcliffe Julio Abugattas Carlos Castaneda Mónica Calderón hugo fuentes Henry Gómez Medical Oncologist Instituto Nacional de Enfermedades Neoplasicas(INEN)LimaPeru Hospital II-E Lamas San MartinPeru Instituto Nacional de Enfermedades Neoplasicas(INEN) LimaPeru International Cancer Control Congress Association(ICCCA) VancouverCanada

Background: Cancer is a leading cause of death worldwide as well as in Peru. The national cancer plan includes decentralization, but one of the greatest barriers is our complicated geography. San Martin is a department located in the Peruvian jungle where there are no public services for cancer care. Our aim was to implement a “distance telemedicine-enabled” outpatient chemotherapy module, monitored by oncologists. Methods: The implementation was conducted in 3 stages: 1) Planning and Organization: working teams were formed, a chemotherapy room was developed and people were trained. 2) Execution: patients from San Martín region, aged >18 years with pathological confirmation of cancer, requiring systemic chemotherapy, ECOG <3, and first course of chemotherapy received at INEN without adverse reaction were selected. 3) Evaluation: adverse events, cost-user evaluation and quality of life (QoL) were assessed. Results: By November 2015, a module with a chemotherapy room with 18 chairs, a pharmacy, a hospitalization room, 1 medical office, a training room, a nutrition area, and a nursing station was implemented. 3 physicians, 3 nurses and 1 pharmacist were trained. Through March 2018, 501 sessions of teleoncology were completed to deliver 232 cycles of chemotherapy for 56 patients aged 19 - 78 years with different solid tumors, with no serious adverse event, without negatively affecting their QoL, and with an average out-of-pocket expense saving of 500 PEN. Conclusions: Using information and communication technology, a telechemotherapy module was successfully implemented in the Peruvian jungle, without adversely affecting the QoL of patients. Neither patients nor family members needed to travel to Lima to receive chemotherapy. This first program can be replicated in other rural and remote regions through non-specialized personnel and facilities, providing chemotherapy services equivalent to a tertiary center through trained health care professionals, supported through telemedicine.

关键词： Telechemotherapy Module Cancer Treatment Urban Tertiary Center Teleoncology

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Nerve Fibres Detection in Paired Eutopic and Ectopic Endometria from Women with Endometriosis: Correlation with Nerve Growth Factor Expression

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Open Journal of Obstetrics and Gynecology 2015年第7期5卷 417-426页

作者： Sebastián Venegas Edward Parada M. Angélica Boric hugo Sovino Ariel fuentes Fernando Gabler Reinaldo González-Ramos M. Cecilia Johnson Institute of Maternal and Child Research Faculty of Medicine University of Chile Santiago Chile Medical Technology School Faculty of Medicine University of Chile Santiago Chile San Borja Arriarán Clinical Hospital Santiago Chile Department of Pathology Faculty of Medicine University of Chile Santiago Chile

Endometriosis, disorder characterized by the presence of endometrium outside the uterus cavity, is associated with chronic pelvic pain. Nerve growth factor (NGF) participates in development, repair and survival of neurons. We evaluated NGF and nerve fibres in eutopic and ectopic endometria from women with endometriosis and in normal endometrium from control patients without endometriosis. In endometrium collected during surgery for endometriosis (paired eutopic and ectopic endometria, proliferative n = 6 and secretory n = 7 phases) or during tubal ligation or hysterectomy for no endometrial disease (control, proliferative n = 6 and secretory n = 6 phases), NGF and neurofilament (NF) of nerve fibres were studied by immunohistochemistry measuring integrated optical density (IOD). Cytoplasmic NGF was detected in glands and stroma in all control, eutopic and ectopic endometrial samples;no statistical differences were found throughout the menstrual cycle. However, total (gland plus stroma) NGF IOD was higher in eutopic than in ectopic endometria during the secretory phase. NF was detected only in ectopic endometrium being eutopic and control endometria negative to this antibody, and no differences were observed between proliferative and secretory phases. Negative and significant correlation was found between NGF and NF expression in ectopic endometria only during the secretory phase. In conclusion, our results show a significant negative correlation between NGF and myelinated nerve fibres in secretory ectopic endometria. NGF expression was not significantly modified throughout the menstrual cycle in control and in endometriosis, even higher in eutopic than in ectopic tissues;the NGF secretion from lesions to pelvic cavity cannot be ruled out, and could explain the negative correlation observed. Although NF and NGF are not useful as diagnostic markers for endometriosis, their expression may be related to endometrial physiology and pathophysiology of the disease.

关键词： NGF Nerves Fibres Eutopic Endometrium Ectopic Endometrium Endometriosis

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