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1.
BMC Gastroenterol ; 22(1): 221, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508985

RESUMO

BACKGROUND: Sporadic gastric foveolar-type adenomas are extremely rare and are usually small, flat or slightly raised lesions that occur in the oxyntic mucosa. CASE PRESENTATION: We reported here a case of a 70-year-old female with a sporadic gastric foveolar-type adenoma occurring in the mucosa at the junction of the gastric body/antrum. The adenoma was a protruding lesion of 2 × 1.8 cm sized, causing symptoms of upper gastrointestinal bleeding, and the basal and surrounding mucosa showed pseudopyloric gland metaplasia without atrophy, intestinal metaplasia, H. pylori infection, or active inflammation. It had somatic mutations in both APC and KRAS genes. CONCLUSIONS: This is the first reported case of a large sporadic gastric foveolar-type adenoma that occurred in the mucosa of pseudopyloric gland metaplasia and with Gastritis Cystica Profunda, which modify our understanding of the morphological features and molecular underpinnings of this type of lesion.


Assuntos
Adenoma , Cistos , Gastrite , Neoplasias Gastrointestinais , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adenoma/patologia , Pólipos Adenomatosos , Idoso , Cistos/patologia , Feminino , Mucosa Gástrica/patologia , Gastrite/patologia , Neoplasias Gastrointestinais/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Metaplasia/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
3.
BMC Gastroenterol ; 22(1): 178, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397529

RESUMO

AIM: Gastrointestinal malignant melanoma is a rare mucosal melanoma (MM). Other MM include the respiratory and the genitourinary tract. All mucosal melanomas have a poor prognosis when compared to cutaneous melanomas. Ano-rectal melanomas are by far the most common and most studied gastrointestinal MM. Large-scale clinical data is lacking due to the rarity of the disease. We aim to analyze epidemiology and survival of the Gastrointestinal (G.I.) MM over 45 years using a national database. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients with biopsy-proven G.I. Melanomas. We selected tumor site, intervention, and survival information for oncology codes as per the international classification of diseases. Survival analysis was performed using the SPSS v 27 ® IBM software. RESULTS: Of the 1105 biopsy-proven confirmed cases of primary G.I. melanoma's, 191 (17.3%) received chemotherapy (C.T.), 202 (18.3%) received radiotherapy (R.T.), 63 (5.7%) received both C.T and R.T., while 684 (61.9%) of the population received surgery alone or combined with C.T. and/or R.T. Statistically significant improvement in survival was noted in all treatment strategies that utilized surgery and also when site-specific MM cohorts underwent a surgical approach with or without C.T and/or R.T. CONCLUSION: This is the most extensive study reporting epidemiological and survival data of treatment strategy outcomes of primary G.I. mucosal melanoma elucidating best overall survival with a management strategy involving surgical intervention.


Assuntos
Neoplasias Gastrointestinais , Melanoma , Neoplasias Cutâneas , Bases de Dados Factuais , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Humanos , Melanoma/epidemiologia , Melanoma/terapia , Membrana Mucosa/patologia , Análise de Sobrevida
4.
Zhonghua Yi Xue Za Zhi ; 102(14): 977-981, 2022 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-35399014

RESUMO

Neuroendocrine neoplasms (NENs) originate from neuroendocrine cells diffusely distributed throughout the body. NENs are liable to be misdiagnosed and missed clinically, which brings great difficulties to clinical diagnosis and treatment, and seriously affects their prognosis. This article will introduce the difficulties and hot spots in the diagnosis and treatment of NENs from the aspects of laboratory and pathological examinations, anatomical and functional imaging examinations, including endoscopy, peptide receptor radionuclide therapy, somatostatin analogue and immune checkpoint inhibitor therapy. It aims to provide more ideas for the early diagnosis and early treatment of NENs, standardized diagnosis and treatment of high-grade NENs in the middle and late stages, and to provide more strategies for clinical multidisciplinary experts towards the management of focused dilemmas in NENs.


Assuntos
Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Sistema Digestório/patologia , Neoplasias Gastrointestinais/patologia , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Prognóstico , Somatostatina
5.
Genet Test Mol Biomarkers ; 26(4): 239-248, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35481971

RESUMO

Background: The performance of methylated SEPT9 (mSEPT9) in lower gastrointestinal (GI) cancer (colorectal cancer) has been extensively investigated; however, its performance in upper GI cancer (esophageal cancer and gastric cancer) and the comparison with lower GI cancer have rarely been studied. Methods: A total of 1854 subjects, including 344 upper GI cancer patients, 459 lower GI cancer patients, and 1051 noncancer subjects, were recruited in this prospective cohort study. A modified single polymerase chain reaction test for detecting mSEPT9 was used for plasma detection. Results: The sensitivity of mSEPT9 for upper and lower GI cancers was 45.3% and 74.8%, and the corresponding specificities were 85.6% and 86.5%, with areas under curve (AUC) of 0.71 and 0.80, respectively. mSEPT9 exhibited lower sensitivity in stage I than stage II-IV cancer, while no difference in sensitivity was observed for different locations in upper or lower GI cancer. No difference in sensitivity was found among gross classifications, pathological classifications, and differentiation in upper GI cancer, but a higher sensitivity in infiltrative cancer and moderate and poorly differentiated cancers was observed in the lower GI. No difference in sensitivity was found between male and female in both cancers, while sensitivity increased with age for both cancers. Cancer antigen 724 (CA724) showed the highest sensitivity for upper GI cancers, and carcinoembryonic antigen (CEA) showed the highest sensitivity for lower GI cancers. The combination of CA724 with mSEPT9 increased the sensitivity to 67.5% in upper GI cancers, and the combination of mSEPT9 with CEA increased the sensitivity to 85.4% in lower GI cancers, with an AUC of 0.90 and 0.95, respectively. Conclusions: mSEPT9 exhibited a higher sensitivity in lower GI cancers than upper GI cancers. The combination of mSEPT9 with protein markers significantly enhanced the detection sensitivity in both cancers.


Assuntos
Neoplasias Colorretais , Neoplasias Gastrointestinais , Septinas/metabolismo , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/diagnóstico , Feminino , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Estudos Prospectivos , Septinas/genética
6.
Radiographics ; 42(3): 759-777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35452341

RESUMO

There is a wide spectrum of hereditary and acquired immunodeficiency disorders that are characterized by specific abnormalities involving a plethora of humoral, cellular, and phagocytic immunologic pathways. These include distinctive primary immunodeficiency syndromes due to characteristic genetic defects and secondary immunodeficiency syndromes, such as AIDS from HIV infection and therapy-related immunosuppression in patients with cancers or a solid organ or stem cell transplant. The gut mucosa and gut-associated lymphoid tissue (the largest lymphoid organ in the body), along with diverse commensal microbiota, play complex and critical roles in development and modulation of the immune system. Thus, myriad gastrointestinal (GI) symptoms are common in immunocompromised patients and may be due to inflammatory conditions (graft versus host disease, neutropenic enterocolitis, or HIV-related proctocolitis), opportunistic infections (viral, bacterial, fungal, or protozoal), or malignancies (Kaposi sarcoma, lymphoma, posttransplant lymphoproliferative disorder, or anal cancer). GI tract involvement in immunodeficient patients contributes to significant morbidity and mortality. Along with endoscopy and histopathologic evaluation, imaging plays an integral role in detection, localization, characterization, and distinction of GI tract manifestations of various immunodeficiency syndromes and their complications. Select disorders demonstrate characteristic findings at fluoroscopy, CT, US, and MRI that permit timely and accurate diagnosis. While neutropenic enterocolitis affects the terminal ileum and right colon and occurs in patients receiving chemotherapy for hematologic malignancies, Kaposi sarcoma commonly manifests as bull's-eye lesions in the stomach and duodenum. Imaging is invaluable in treatment follow-up and long-term surveillance as well. Online supplemental material is available for this article. ©RSNA, 2022.


Assuntos
Síndrome de Imunodeficiência Adquirida , Enterocolite Neutropênica , Gastroenteropatias , Neoplasias Gastrointestinais , Infecções por HIV , Sarcoma de Kaposi , Síndrome de Imunodeficiência Adquirida/complicações , Duodeno , Enterocolite Neutropênica/complicações , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/etiologia , Neoplasias Gastrointestinais/patologia , Infecções por HIV/complicações , Humanos , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/etiologia , Sarcoma de Kaposi/patologia
7.
Target Oncol ; 17(2): 95-110, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35290591

RESUMO

Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal tract mesenchymal tumours. Tyrosine kinase inhibitors (TKIs) have transformed the management of advanced GIST. Imatinib was the first TKI to gain approval as management for patients with advanced GIST, establishing a new standard of care. Since then, as a result of several trials including the GRID and INVICTUS studies, we now have five lines of approved targeted therapy, including imatinib, sunitinib, regorafenib, ripretinib and avapritinib for the treatment of unresectable, advanced GISTs. In this review, the Australasian Gastrointestinal Trials Group (AGITG) provide an overview of the key trials that have changed clinical practice, discuss the molecular drivers of GISTs, the importance of molecular testing and directing therapy according to molecular targets, as well as future strategies in the management of advanced GISTs.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Sunitinibe/uso terapêutico
8.
Curr Treat Options Oncol ; 23(5): 749-761, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35349049

RESUMO

OPINION STATEMENT: In our practice, we evaluate the mutation status of advanced unresectable disease to guide decisions on use of tyrosine kinase inhibitor (TKI) therapy. This review focuses on management of GIST with KIT and PDGFRA mutations. Imatinib is first-line treatment for unresectable gastrointestinal stromal tumors (GISTs) unless they harbor a PDGFRA D842V mutation; it is recommended to escalate imatinib to twice daily dosing for KIT exon 9 mutant tumors. When patients progress on first-line treatment, treatment is changed to sunitinib followed by regorafenib; while the spectrum of activity against resistance mutations varies with these agents, routine biopsies provide data on one area of disease and ctDNA has not been validated prospectively. For those with a PDGFRA D842V mutation, avapritinib is the first TKI to lead to tumor response and disease control. Ripretinib is approved in the 4th line setting, with limited data on its benefit for PDGFRA D842V GIST. Avapritinib can be considered for treatment beyond ripretinib for KIT mutant disease. The efficacy of other TKIs tested in GIST is reviewed. Ongoing therapy provides palliative benefit and should be continued given rapid decline observed off of treatment.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/etiologia , Tumores do Estroma Gastrointestinal/genética , Humanos , Mesilato de Imatinib/uso terapêutico , Mutação , Inibidores de Proteínas Quinases/farmacologia , Sunitinibe/uso terapêutico
9.
Cancer Lett ; 535: 215639, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35288241

RESUMO

Complete surgical resection, accessible therapeutic targets and effective tyrosine kinase inhibitors (TKIs) have not completely cured gastrointestinal stromal tumours (GISTs), with most patients suffering from residual tumours and recurrence. The existence of nerve infiltration in GIST provides a way for tumour cells to escape local resection and systemic targeted therapy, which may challenge the previous understanding of its behaviour patterns and inspire the development of more radical excision and more precise targeted therapy. Moreover, tumour dormancy has emerged as a major cause of drug resistance and tumour relapse. Among these pathways, the nerve-tumour regulatory axis GDNF-GFRA1 is activated in GISTs, assists tumour cells in achieving dormancy and protects them from apoptosis under environmental stress by enhancing autophagic flux. The concrete mechanism is that the GDNF-regulating interaction between GFRA1 and the lysosomal calcium channel MCOLN1 activates Ca2+-dependent TFEB signalling. Activated TFEB transcriptionally regulates intracellular lysosome levels, which could achieve feedback upregulation of cellular autophagy flux during TKI treatment. This dormancy-transition axis fills parts of the mechanistic vacancy before the onset of secondary mutations, and strategies for TKIs combined with targeting GFRA1-dependent autophagy have distinct promise as prospective clinical therapies.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/uso terapêutico , Autofagia , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Humanos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Estudos Prospectivos
10.
J Healthc Eng ; 2022: 3414302, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345653

RESUMO

This paper studied the pathological features of 78 cases of primary gastrointestinal lymphoma. All patients with primary gastrointestinal lymphoma diagnosed in PET Center of Zhebei Mingzhou Hospital in Huzhou from August 2013 to April 2021 were analyzed retrospectively. In addition, the pathology and immunohistochemistry of these patients were retrieved from the inpatient system of Huzhou Central Hospital. The results showed that the male-female ratio of these 78 patients was about 1.29/1 (including 44 males and 34 females), with a median age of 63 years old (20-90 years old). The most frequent sites in order of its occurrence were the stomach (51.3%), small intestine (34.6%), ileocecal region (9%) and colon (5.1%). T-cell lymphoma accounted for 10.7% of primary gastrointestinal lymphoma, and all of them were found in small intestines, while B-cell lymphoma accounted for 89.3%.


Assuntos
Neoplasias Gastrointestinais , Linfoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Humanos , Linfoma/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Estômago/patologia , Adulto Jovem
11.
Int J Mol Sci ; 23(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35328567

RESUMO

Cancers affecting the gastrointestinal system are highly prevalent and their incidence is still increasing. Among them, gastric and pancreatic cancers have a dismal prognosis (survival of 5-20%) and are defined as difficult-to-treat cancers. This reflects the urge for novel therapeutic targets and aims for personalised therapies. As a prerequisite for identifying targets and test therapeutic interventions, the development of well-established, translational and reliable preclinical research models is instrumental. This review discusses the development, advantages and limitations of both patient-derived organoids (PDO) and patient-derived xenografts (PDX) for gastric and pancreatic ductal adenocarcinoma (PDAC). First and next generation multicellular PDO/PDX models are believed to faithfully generate a patient-specific avatar in a preclinical setting, opening novel therapeutic directions for these difficult-to-treat cancers. Excitingly, future opportunities such as PDO co-cultures with immune or stromal cells, organoid-on-a-chip models and humanised PDXs are the basis of a completely new area, offering close-to-human models. These tools can be exploited to understand cancer heterogeneity, which is indispensable to pave the way towards more tumour-specific therapies and, with that, better survival for patients.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Gastrointestinais , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/patologia , Modelos Animais de Doenças , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Humanos , Organoides/patologia , Neoplasias Pancreáticas/patologia
12.
Anticancer Res ; 42(3): 1381-1396, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220231

RESUMO

BACKGROUND/AIM: Cancer of unknown primary (CUP), representing 3-5% of all newly diagnosed cancers in the United States, is a presumptive, non-definitive diagnosis rendered when a primary tumor site cannot be identified after exhaustive diagnostic evaluation, including cases of neuroendocrine neoplasms (NENs). CUPs are characterized by findings that are challenging to reconcile, including inconclusive immunohistochemical (IHC) stains, an undifferentiated morphologic phenotype, history of multiple cancers, a clinical presentation that is discordant from histologic findings, an atypical distribution of metastases, or lack of expected response to treatment. For a significant subset of NENs (10%), traditional diagnostic evaluation is unable to determine a primary tumor site using histomorphology and IHC stains. Gene expression profiling (GEP) of either mRNA or microRNA is the technique utilized in the three commercially available platforms that provide a prediction of tumor type in cases of diagnostic uncertainty of CUPs, including those with neuroendocrine differentiation. Case Series Report: Here we present four cases of NENs, where the diagnosis based upon histomorphological and IHC features presented a unique challenge that ultimately benefited from the integration of molecular tumor classification using the validated assay. CancerTYPE ID by Biotheranostics is based on a quantitative RT-PCR assay that uses a computational algorithm to measure the collective expression of 92 genes (87 cancer-related genes and 5 control genes). This case series reports five appropriate clinical scenarios that highlight the utility of a GEP-based assay to effectively provide a molecular tumor classification to identify NEN subtypes and tumor primary site of origin. CONCLUSION: These cases demonstrated that the CancerTYPE ID test was able to resolve challenging diagnoses for primary and metastatic NENs. These cases emphasize the clinical need of utilizing a GEP-based assay for determining the anatomic site of origin and NEN subtyping, both essential for the appropriate clinical management of NENs.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/genética , Perfilação da Expressão Gênica , Neoplasias Primárias Desconhecidas/genética , Tumores Neuroendócrinos/genética , Reação em Cadeia da Polimerase , Transcriptoma , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/análise , Feminino , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/química , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/terapia , Tumores Neuroendócrinos/química , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
13.
J Neuroendocrinol ; 34(4): e13099, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35174558

RESUMO

The 2019 Word Health Organization (WHO) subclassified grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) into neuroendocrine carcinoma (NEC) or tumours (G3 NET) based on morphology and proliferation. Yet, few data exist on molecular profiles for G3 NEN. We compared clinicopathological and molecular characteristics of these two groups. We retrospectively reviewed consecutive G3 GEP NEN patients and had their tumour tissues reviewed, reclassified as per the WHO 2019, and analyzed by a next-generation sequencing (NGS) panel. Between 2000 and 2019, 43 patients had pathology revision: 29 (67%) were NEC and 14 (33%) were G3 NET, with a 23% change in diagnosis. Median overal survival for G3 NET and NEC patients was 55.6 and 11.9 months, respectively (hazard ratio = 2.78 [95% confidence interval = 1.09-7.11], p = .042), which was confirmed by an adjusted analysis (hazard ratio = 2.90 NEC vs. G3 NET; p = .03). NGS was performed in 32 cases: 21 NEC and 11 G3 NET. Mutations in RB1 and PTEN were exclusively encountered in NEC. Median tumour mutational burden was 5 (0-67) mutations per megabase in NEC and 4.5 (0-9) among G3 NET. Microsatellite instability was found in 3 (14.3%) NEC cases. In conclusion, pathology revision is essential to estimate prognosis and therapeutic plan. G3 GEP NEN generally harbour low tumor mutation burden and fewer actionable mutations, but 14% of NEC cases were microsatellite unstable and could benefit from immune checkpoint inhibitors.


Assuntos
Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos
14.
Clin Cancer Res ; 28(8): 1507-1517, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35110417

RESUMO

PURPOSE: This phase Ib trial was designed to evaluate the safety and early efficacy signal of the combination of imatinib and binimetinib in patients with imatinib-resistant advanced gastrointestinal stromal tumors (GISTs). PATIENTS AND METHODS: This trial used a standard 3 + 3 design to determine the recommended phase II dose (RP2D). Additional patients were enrolled on an expansion cohort at the RP2D enriching for succinate dehydrogenase (SDH)-deficient GISTs to explore potential efficacy. RESULTS: The trial enrolled nine patients in the dose-escalation cohort and 14 in the dose-expansion cohort including six with SDH-deficient GISTs. Imatinib 400 mg daily with binimetinib 45 mg twice daily was established as the RP2D. Dose-limiting toxicity (DLT) was asymptomatic grade 4 creatinine phosphokinase (CPK) elevation. The most common non-DLT grade 3/4 toxicity was asymptomatic CPK elevation (69.6%). Other common ≥grade 2 toxicities included peripheral edema (17.4%), acneiform rash (21.7%), anemia (30.4%), hypophosphatemia (39.1%), and aspartate aminotransferase (AST) increase (17.4%). Two serious adverse events occurred (grade 2 dropped head syndrome and grade 3 central retinal vein occlusion). No unexpected toxicities were observed. Limited clinical activity was observed in KIT-mutant GIST. For SDH-deficient GISTs, one of five had confirmed RECIST1.1 partial response (PR). The median progression-free survival (mPFS) in patients with SDH-deficient GIST was 45.1 months [95% confidence interval (CI), 15.8-not estimable (NE)]; the median overall survival (mOS) was not reached (95% CI, 31.6 months-NE). One patient with a refractory metastatic SDH-deficient GIST had an exceptional pathologic response and durable clinical benefit. CONCLUSIONS: The combination of imatinib and binimetinib is safe with manageable toxicity and has encouraging activity in SDH-deficient but not imatinib-refractory KIT/PDGFRA-mutant GISTs. The observed clinical benefits provide a motivation for a larger trial of the combination strategy in SDH-deficient GISTs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/uso terapêutico
16.
Int J Clin Oncol ; 27(5): 840-849, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35178624

RESUMO

BACKGROUND: Neuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological data have not been analyzed in Japan. To elucidate the present status of NEN diagnosis and treatment in Japan, we started a registry cohort study in January 2015. METHODS: Patients pathologically diagnosed with NENs of the pancreas, gastrointestinal tract, lungs, bronchi, or thymus after January 2012 were enrolled in this registry after the date of ethics review committee approval in each hospital or institute. Follow-up was continued for enrolled patients. RESULTS: During 5 years of enrollment between January 2015 and December 2019, a total of 1526 participants from 63 departments were enrolled in this registry (mean, 305.2 participants/year), covering approximately 5.8% of the annual incidence of NENs in Japan. For pancreatic NEN, 41.9% of patients had metastasis and the dominant metastatic site was the liver, at twice the rate of lymph node metastasis in the current registry. In contrast, the frequency of lymph node metastasis from gastrointestinal (GI)-NEN was similar to that of the liver. The distribution of WHO 2019-based grades varied according to the primary site. Low-to-intermediate grade (G1-G2) was dominant for duodenal, jejunal/ileal, rectal, and pancreatic NENs, whereas high grade (G3 or NEC) was dominant for esophageal, stomach, and colon NENs. For PanNENs, G3 and NEC accounted only for 1.6% and 2.9%, respectively. CONCLUSIONS: These cohort data provide crucial information for clinical research to clarify the characteristics of NENs in Japan.


Assuntos
Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Brônquios/patologia , Estudos de Coortes , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/patologia , Humanos , Japão/epidemiologia , Metástase Linfática , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Sistema de Registros , Estudos Retrospectivos
17.
Endoscopy ; 54(4): 412-429, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35180797

RESUMO

1: ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape), but EUS alone is not able to distinguish among all types of SEL.Strong recommendation, moderate quality evidence. 2: ESGE suggests providing tissue diagnosis for all SELs with features suggestive of gastrointestinal stromal tumor (GIST) if they are of size > 20 mm, or have high risk stigmata, or require surgical resection or oncological treatment.Weak recommendation, very low quality evidence. 3: ESGE recommends EUS-guided fine-needle biopsy (EUS-FNB) or mucosal incision-assisted biopsy (MIAB) equally for tissue diagnosis of SELs ≥ 20 mm in size.Strong recommendation, moderate quality evidence. 4: ESGE recommends against surveillance of asymptomatic gastrointestinal (GI) tract leiomyomas, lipomas, heterotopic pancreas, granular cell tumors, schwannomas, and glomus tumors, if the diagnosis is clear.Strong recommendation, moderate quality evidence. 5: ESGE suggests surveillance of asymptomatic esophageal and gastric SELs without definite diagnosis, with esophagogastroduodenoscopy (EGD) at 3-6 months, and then at 2-3-year intervals for lesions < 10 mm in size, and at 1-2-year intervals for lesions 10-20 mm in size. For asymptomatic SELs > 20 mm in size that are not resected, ESGE suggests surveillance with EGD plus EUS at 6 months and then at 6-12-month intervals.Weak recommendation, very low quality evidence. 6: ESGE recommends endoscopic resection for type 1 gastric neuroendocrine neoplasms (g-NENs) if they grow larger than 10 mm. The choice of resection technique should depend on size, depth of invasion, and location in the stomach.Strong recommendation, low quality evidence. 7: ESGE suggests considering removal of histologically proven gastric GISTs smaller than 20 mm as an alternative to surveillance. The decision to resect should be discussed in a multidisciplinary meeting. The choice of technique should depend on size, location, and local expertise.Weak recommendation, very low quality evidence. 8: ESGE suggests that, to avoid unnecessary follow-up, endoscopic resection is an option for gastric SELs smaller than 20 mm and of unknown histology after failure of attempts to obtain diagnosis.Weak recommendation, very low quality evidence. 9: ESGE recommends basing the surveillance strategy on the type and completeness of resection. After curative resection of benign SELs no follow-up is advised, except for type 1 gastric NEN for which surveillance at 1-2 years is advised.Strong recommendation, low quality evidence. 10: For lower or upper GI NEN with a positive or indeterminate margin at resection, ESGE recommends repeating endoscopy at 3-6 months and another attempt at endoscopic resection in the case of residual disease.Strong recommendation, low quality evidence.


Assuntos
Endoscopia Gastrointestinal/métodos , Endossonografia/normas , Neoplasias Gastrointestinais/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Endoscopia Gastrointestinal/normas , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Trato Gastrointestinal Superior/diagnóstico por imagem
19.
Curr Oncol Rep ; 24(2): 151-159, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35061196

RESUMO

PURPOSE OF REVIEW: This article critically revisits novel data on tyrosine kinase inhibitors that have shown clinical activity in the treatment of gastrointestinal stromal tumor (GIST). RECENT FINDINGS: GIST therapeutic development exploits the oncogene addiction to KIT or PDGFRA receptor tyrosine kinases. Based on this principle, two new drugs were approved in 2020: ripretinib in GIST patients after progression to all standard treatments and avapritinib, the first agent ever active in the multiresistant PDGFRA D842V-mutant GIST. Additionally, cabozantinib has also shown encouraging activity in imatinib-resistant GIST patients. Finally, novel agents targeting NTRK-driven GIST have emerged as a breakthrough for the treatment of a subset of KIT/PDGFRA wild-type GIST patients. GIST is a paradigmatic tumor model for the rational and successful development of molecularly targeted agents directed against driver mutations in cancer.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Humanos , Mesilato de Imatinib/uso terapêutico , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética
20.
PLoS One ; 17(1): e0261649, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35015763

RESUMO

BACKGROUND: Research evidence has established the beneficial effects of diet in cancer prevention; various epidemiological studies have suggested that olive oil component could play a role in decreasing cancer risk. This systematic review and meta-analysis aims to investigate the association between olive oil consumption, cancer risk and prognosis. METHODS: A systematic search was conducted in PubMed, EMBASE and Google Scholar databases (end-of-search: May 10, 2020). Pooled relative risk (RR) and 95% confidence intervals (95% CIs) were estimated with random-effects (DerSimonian-Laird) models. Subgroup analyses, sensitivity analyses and meta-regression analysis were also performed. RESULTS: 45 studies were included in the meta-analysis; 37 were case-control (17,369 cases and 28,294 controls) and 8 were cohort studies (12,461 incident cases in a total cohort of 929,771 subjects). Highest olive oil consumption was associated with 31% lower likelihood of any cancer (pooled RR = 0.69, 95%CI: 0.62-0.77), breast (RR = 0.67, 95%CI: 0.52-0.86), gastrointestinal (RR = 0.77, 95%CI: 0.66-0.89), upper aerodigestive (RR = 0.74, 95%CI: 0.60-0.91) and urinary tract cancer (RR = 0.46, 95%CI: 0.29-0.72). Significant overall effects spanned both Mediterranean and non-Mediterranean participants, studies presenting a multivariate and a univariate analysis and all subgroups by study quality. CONCLUSIONS: Olive oil consumption seems to exert beneficial actions in terms of cancer prevention. Additional prospective cohort studies on various cancer types and survivors, as well as large randomized trials, seem desirable.


Assuntos
Neoplasias/prevenção & controle , Azeite de Oliva/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/prevenção & controle , Humanos , Neoplasias/patologia , Fatores de Risco , Neoplasias Urológicas/patologia , Neoplasias Urológicas/prevenção & controle
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