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1.
J Pathol ; 263(4-5): 442-453, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38828498

RESUMO

Biological hallmarks of splenic marginal zone lymphoma (SMZL) remain poorly described. Herein, we performed in-depth SMZL characterization through multimodal single-cell analyses of paired blood/spleen samples. The 3'-single-cell RNA-sequencing, Cellular Indexing of Transcriptomes and Epitopes by sequencing, and 5'-V(D)J single-cell RNA-sequencing datasets were integrated to characterize SMZL transcriptome profiles, including B-cell receptor and T-cell receptor repertoires. Hyperexpanded B-cell clones in the spleen were at a memory-like stage, whereas recirculating tumor B-cells in blood encompassed multiple differentiation stages, indicating an unexpected desynchronization of the B-cell maturation program in SMZL cells. Spatial transcriptomics showed the enrichment of T-effector and T-follicular helper (TFH) signatures in the nodular subtype of SMZL. This latter also exhibited gene-based cell-cell interactions suggestive of dynamic crosstalk between TFH and cancer cells in transcriptomics, further substantiated by using imaging mass cytometry. Our findings provide a comprehensive high-resolution description of SMZL biological hallmarks and characterize, for the first time in situ, inter- and intra-patient heterogeneity at both transcriptomic and protein levels. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Análise de Célula Única , Neoplasias Esplênicas , Transcriptoma , Humanos , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/metabolismo , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/imunologia , Perfilação da Expressão Gênica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Linfócitos B/patologia , Linfócitos B/metabolismo , Idoso , Baço/patologia , Baço/imunologia , Baço/metabolismo
2.
Br J Haematol ; 204(6): 2222-2226, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38420697

RESUMO

To address the lack of contemporary population-based epidemiological studies of hepatosplenic T-cell lymphoma (HSTCL), we undertook a population-based study of ICD-O-3-coded HSTCL in England. We used the National Cancer Registration Dataset and linked datasets on hospital admissions, Systemic Anti-Cancer Therapy, socio-demographics, comorbidities and death, identifying cases from 1 January 2013 to 31 December 2019 with survival data up to 5 January 2021. Crude and directly age-standardised incidence rates per million persons per year were calculated. Crude and adjusted incidence rate ratios compared incidence between groups using Poisson regression. A Cox proportional hazards model estimated mortality risks adjusted for age, sex, ethnicity, deprivation and allogenic stem cell transplant (allo-SCT; time varying). We identified 44 patients, mean age 42 years. Median survival was 11 months, and 1 and 5 year survivals were 48% (95% CI 29%-43%) and 22% (95% CI 12%-42%) respectively. The age-standardised incidence was 0.1 per million/year. Incidence was higher in areas with greater deprivation (0.15 per million/year), and more cases than expected were in non-White patients (39%). Non-Whites had a twofold increased risk of death (adjusted hazard ratio 2.21 [95% CI 1.03-4.78]) even after adjusting for deprivation, younger age and allo-SCT. In conclusion, ethnicity and socio-economic status affect both the incidence and survival of HSTCL.


Assuntos
Linfoma de Células T , Neoplasias Esplênicas , Humanos , Masculino , Feminino , Incidência , Adulto , Pessoa de Meia-Idade , Linfoma de Células T/mortalidade , Linfoma de Células T/epidemiologia , Linfoma de Células T/terapia , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/epidemiologia , Idoso , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Classe Social , Etnicidade/estatística & dados numéricos , Inglaterra/epidemiologia , Adulto Jovem , Adolescente
3.
Blood ; 139(5): 732-747, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34653238

RESUMO

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Neoplasias Esplênicas , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Aberrações Cromossômicas , Imunofenotipagem , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/genética , Família Multigênica , Mutação , Baço/patologia , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/genética , Transcriptoma , Microambiente Tumoral
4.
BMC Cancer ; 24(1): 462, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38614966

RESUMO

BACKGROUND: Patients with metastatic gastric cancer (mGC) have poor prognosis. This real-world study aimed to describe treatment regimens and survival of mGC patients. METHODS: A retrospective analysis was conducted using anonymized German claims data (AOK PLUS) covering a period from 2010 to 2021. The study population included newly diagnosed mGC cases identified from 2011 to 2020. The index date was defined as the first diagnosis of metastasis on or after gastric cancer diagnosis. Therapy regimens were identified based on inpatient and outpatient data, and subsequently stratified by line of treatment. Survival analyses were conducted using the Kaplan-Meier method. RESULTS: The cohort consisted of 5,278 mGC incident cases (mean age: 72.7 years; male: 61.9%). Nearly half of the incident cases received mGC-related treatment (49.8%). Treated patients were more often male, younger, and had fewer comorbidities compared to untreated patients. Of the 2,629 mGC patients who started the first line of treatment (1LOT), 32.8% switched to 2LOT, and 10.2% reached 3LOT. Longer survival time was observed among disease-specific treated cases compared with untreated cases (median real-world overall survival (rwOS): 12.7 months [95%CI 12.1 - 13.3 months] vs. 3.7 months [95%CI 3.4 - 4.0 months]). CONCLUSION: Systemic therapy was not received in almost half of the mGC patients. In those patients, a very short median rwOS was observed. Treatment patterns were generally in line with the guideline recommendations, however, therapy switching rates and poor prognosis indicate high unmet needs also in the treated population.


Assuntos
Neoplasias Esplênicas , Neoplasias Gástricas , Humanos , Masculino , Idoso , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/terapia , Estudos Retrospectivos , Pacientes Internados , Pacientes Ambulatoriais , Alemanha/epidemiologia
5.
Anticancer Drugs ; 35(3): 277-283, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37948350

RESUMO

This study aimed to evaluate the efficacy and safety of the combination of sintilimab and apatinib for the treatment of patients with advanced or metastatic gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. This retrospective study analyzed data from 34 patients who had advanced or metastatic GC/GEJ cancer and received the combination therapy of sintilimab and apatinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Among the 34 patients, none achieved a complete response (CR), 3 patients (8.8%) achieved a partial response, 23 patients (67.6%) had stable disease, and 8 patients (23.5%) experienced progressive disease. The ORR and DCR were 8.8% and 76.5%, respectively. The median PFS was 6.0 months (95% CI: 3.6-8.4), and the median OS was 11.6 months (95% CI: 8.1-15.1). Subgroup analysis revealed significant differences in OS between patients with high and low Eastern Cooperative Oncology Group Performance Status scores and between patients with and without a history of gastrectomy. Common adverse events (AEs) during treatment included fatigue (52.9%), anemia (47.1%), leukopenia (26.5%), hypothyroidism (23.5%), nausea and vomiting (20.6%), neutropenia (20.6%), and thrombocytopenia (17.6%), most of which were grade 1 and 2 AEs. No deaths occurred due to AEs. These findings indicate that the combination of sintilimab and apatinib has a favorable therapeutic effect in patients with advanced GC. Moreover, the AEs associated with this therapy are generally manageable.


Assuntos
Neoplasias Esofágicas , Piridinas , Neoplasias Esplênicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados
6.
Mol Cell ; 64(6): 1074-1087, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27889452

RESUMO

Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments. We generated a mutant mouse strain carrying an F832A mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic locations and permits repeat expression. Consistent with maintenance of H3K27me3 at the Hox clusters, these mice are developmentally normal. However, susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive elements may be cancer relevant.


Assuntos
Fator de Transcrição E2F1/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Inativação Gênica , Linfoma/genética , Sequências Repetitivas de Ácido Nucleico , Proteína do Retinoblastoma/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Fator de Transcrição E2F1/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Predisposição Genética para Doença , Histonas/genética , Histonas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Linfoma/metabolismo , Linfoma/mortalidade , Linfoma/patologia , Mesentério/metabolismo , Mesentério/patologia , Camundongos , Mutação , Cultura Primária de Células , Ligação Proteica , Proteína do Retinoblastoma/metabolismo , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/metabolismo , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/patologia , Análise de Sobrevida
7.
Vet Pathol ; 61(4): 534-540, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38214328

RESUMO

Canine splenic hemangiosarcoma has a high metastatic rate and short survival time. Currently, the main prognostic parameters are tumor stage and therapy, while data on histologic parameters, such as grade and Ki-67 expression, are scarce. The aims of this study were to compare two methods of assessment of Ki-67, verify their prognostic impact, and define a threshold value based on survival. Thirty-one cases of histologically diagnosed canine splenic hemangiosarcoma, which were treated with splenectomy and had full staging and follow-up information, were collected. Three were stage I, 17 stage II, and 11 stage III. The mean mitotic count (MC) was 23.9 (standard deviation [SD]: 22.1) and the median was 15 (range, 1-93). Immunohistochemistry for Ki-67 was performed, the Ki-67 labeling index (Ki-67LI) was assessed as a percentage of positive neoplastic nuclei per ≥500 cell, and the Ki-67 count (KI-67C) was defined as the average number of positive nuclei using a 1 cm2 optical grid performed in 5, 40× fields. The mean Ki-67LI and Ki-67C were 56.4% (SD: 38.7) and 27.2 (SD: 12.9) and medians were 51% (range, 8.2-55.2) and 26 (range, 5.5-148), respectively. Using a cut-off of 56% and 9, respectively, Kaplan-Meier survival curves showed an association of overall survival with Ki-67LI and MC. In addition to clinical stage, Ki-67LI maintained its prognostic value on multivariate analysis, supporting the role of Ki-67LI as an independent prognostic parameter. Based on these results, we propose a diagnostically applicable cut-off value of 56% for Ki-67LI as a prognostic parameter for canine splenic hemangiosarcoma.


Assuntos
Doenças do Cão , Hemangiossarcoma , Antígeno Ki-67 , Neoplasias Esplênicas , Hemangiossarcoma/veterinária , Hemangiossarcoma/patologia , Hemangiossarcoma/metabolismo , Hemangiossarcoma/diagnóstico , Animais , Antígeno Ki-67/metabolismo , Doenças do Cão/patologia , Doenças do Cão/metabolismo , Doenças do Cão/diagnóstico , Cães , Prognóstico , Neoplasias Esplênicas/veterinária , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/metabolismo , Masculino , Feminino , Imuno-Histoquímica/veterinária , Esplenectomia/veterinária , Índice Mitótico/veterinária , Estadiamento de Neoplasias/veterinária , Biomarcadores Tumorais/metabolismo
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(8): 925-930, 2024 Aug 10.
Artigo em Zh | MEDLINE | ID: mdl-39097273

RESUMO

OBJECTIVE: To explore the genetic basis and pathogenesis for a child with type I Hereditary hemorrhagic telangiectasia (HHTⅠ) and Splenic sinus shore cell hemangioma (LCA). METHODS: A child with HHT complicated with LCA diagnosed at the First Affiliated Hospital of Dali University in April 2022 was selected as the study subject. Clinical data of the child and her relatives were collected, and pathogenic variants were screened by whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 16-year-old female, had recurrent epitaxis since childhood, which sometimes necessitated hemostasis treatment. She also had splenectomy due to splenic rupture and was diagnosed with LCA. Her father and grandmother also had a history of recurrent epitaxis. Her father had deceased due to cerebral vascular rupture. The child was found to harbor a c.360+1G>A variant in the ENG gene. The same variant was not found in her asymptomatic mother and brother. CONCLUSION: The c.360+1G>A variant of the ENG gene probably underlay the pathogenesis in this child.


Assuntos
Hemangioma , Telangiectasia Hemorrágica Hereditária , Humanos , Feminino , Adolescente , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/complicações , Hemangioma/genética , Linhagem , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/complicações , Masculino , Testes Genéticos , Sequenciamento do Exoma
9.
Rinsho Ketsueki ; 65(1): 41-46, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311388

RESUMO

The patient was a 21-year-old man who had been diagnosed with Crohn's disease and received infliximab and azathioprine six years earlier. He was admitted with fever and fatigue. Peripheral blood examination showed LDH 2,473 U/l and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly. Bone marrow biopsy and liver biopsy showed CD4+CD56+TCRγδ+CD8- atypical cells, leading to a diagnosis of hepatosplenic T-cell lymphoma (HSTCL). The patient was refractory to CHOP and DA-EPOCH, and therefore received cord blood transplantation with myeloablative conditioning. CT showed reduced in hepatosplenomegaly and peripheral blood examination showed LDH 165 U/l and plt 180,000/µl, so the patient was discharged on day117. HSTCL is a tumor of immature γδT cells with a Vδ1 mutation in the spleen, and immunodeficiency has been implicated in its pathogenesis. Patients with inflammatory bowel disease treated with azathioprine are known to have an increased risk of lymphoproliferative disease. In this case, use of immunosuppressive drugs for Crohn's disease may have caused malignant transformation of γδ cells in the intestinal epithelium. Although the patient was refractory to chemotherapy, he was able to achieve remission with early cord blood transplantation and long-term survival is expected.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença de Crohn , Neoplasias Hepáticas , Linfoma de Células T , Neoplasias Esplênicas , Masculino , Humanos , Adulto Jovem , Adulto , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Azatioprina/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Imunossupressores/uso terapêutico , Linfoma de Células T/etiologia , Linfoma de Células T/terapia , Linfoma de Células T/diagnóstico , Neoplasias Esplênicas/etiologia
10.
Br J Haematol ; 202(4): 776-784, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37386877

RESUMO

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma de Zona Marginal Tipo Células B , Neoplasias Esplênicas , Humanos , Rituximab/uso terapêutico , Resultado do Tratamento , Estudos Prospectivos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/patologia , Esplenectomia/efeitos adversos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
11.
Ann Surg Oncol ; 30(12): 7206-7216, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37516724

RESUMO

BACKGROUND: The purpose of current study was to examine the incidence, characteristics, treatment, and survival of splenic marginal zone lymphoma (SMZL). METHODS: Using SEER-18 database, patients diagnosed with SMZL between 2000 and 2018 were included. Effect of splenectomy on survival was evaluated after balancing the confounding factors by propensity score matching. Rates of splenectomy and 1-year relative survival were calculated for each year. A logistic regression model identified factors related to splenectomy, and a Cox regression model assessed factors linked to overall survival (OS). RESULTS: A total of 2790 patients with SMZL were analyzed. The majority were older than 60 years, female, and white. The age-adjusted incidence of SMZL was 0.17/100,000 person-years, with higher incidence in males. Incidence increased by 0.68%/year and peaked at 80-84 years for both genders. The SMZL-specific survival rates at 3 and 5 years were 89.6% and 85.3%, respectively. Meanwhile, the relative survival rates for the same periods were 88.6% and 85.9%, respectively. Splenectomy patients were more likely to be younger, male, and diagnosed with early-stage disease. Despite the decreasing utilization rate of splenectomy from 59.4% in 2000 to 16.2% in 2018, the 1-year relative survival rate remained relatively stable with minor fluctuations over time. Whether or not the patient underwent splenectomy was not found to be a significant prognostic indicator for OS. CONCLUSIONS: Our study demonstrated a decreasing use of splenectomy but a relatively stable survival in patients with SMZL, highlighting the urgency to better understand the role of splenectomy and its associated outcomes.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Neoplasias Esplênicas , Humanos , Masculino , Feminino , Esplenectomia , Neoplasias Esplênicas/cirurgia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais
12.
BMC Cancer ; 23(1): 1239, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102538

RESUMO

BACKGROUND: Novel ADC drugs provide a new therapeutic strategy for gastric cancer.The present study aimed to analyze the clinical efficacy and drug toxicities of disitamab vedotin (RC48) plus immune checkpoint inhibitors(ICIs) and RC48 as third-line therapies and beyond for advanced and metastatic gastric cancer patients. METHODS: This was an observational multicenter real-world study.From August 2021 to January 2022,patients with HER2-positive or HER2-low advanced and metastatic gastric cancer and failed from two or more lines of prior therapy were enrolled and treated with RC48 plus ICIs or RC48. In this study, progression free survival(PFS) was the primary end point. Other evaluation indicators were objective response rate(ORR),disease control rate(DCR),overall survival(OS) and drug toxicities. RESULTS: 45 patients were enrolled,of which 25 patients received RC48 plus ICIs,20 patients received RC48.Patients who received RC48 plus ICIs obtained better ORR (36.0% vs. 10.0%, P = 0.044) and DCR (80.0% vs. 50.0%, P = 0.034) compared with RC48,and simultaneously,the median PFS in RC48 plus ICIs group were superior to RC48 group(6.2 m vs. 3.9 m).The median OS was not reached.No statistically differences were found between HER2-positive and HER2-low group with respect to ORR (27.3% vs. 16.7%, P = 0.464),DCR (66.7% vs. 66.7%, P = 1.000),median PFS(5.7 m vs. 4.3 m, P = 0.299).The most common adverse events (AEs) were decreased white blood count,decreased neutrophil count,fatigue,hypoaesthesia and alopecia.Grade 3-4 AEs occurred in 7(35.0%) patients of RC48 group and 10(40.0%) patients of RC48 plus ICIs group,respectively. CONCLUSION: Compared with RC48 monotherapy, ICIs plus RC48 demonstrated superior third-line and beyond therapeutic efficacy for HER2-positive or HER2-low advanced and metastatic gastric cancer patients with manageable safety.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Esplênicas , Neoplasias Gástricas , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Gástricas/tratamento farmacológico , Alopecia
13.
Surg Endosc ; 37(4): 2538-2547, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36922428

RESUMO

BACKGROUND: The SAGES University Colorectal Masters Program is a structured educational curriculum that is designed to aid practicing surgeons develop and maintain knowledge and technical skills for laparoscopic colorectal surgery. The Colorectal Pathway is based on three anchoring procedures (laparoscopic right colectomy, laparoscopic left and sigmoid colectomy for uncomplicated and complex disease, and intracorporeal anastomosis for minimally invasive right colectomy) corresponding to three levels of performance (competency, proficiency and mastery). This manuscript presents focused summaries of the top 10 seminal articles selected for laparoscopic left and sigmoid colectomy for complex benign and malignant disease. METHODS: A systematic literature search of Web of Science for the most cited articles on the topic of laparoscopic complex left/sigmoid colectomy yielded 30 citations. These articles were reviewed and ranked by the SAGES Colorectal Task Force and invited subject experts according to their citation index. The top 10 ranked articles were then reviewed and summarized, with emphasis on relevance and impact in the field, study findings, strength and limitations and conclusions. RESULTS: The top 10 seminal articles selected for the laparoscopic left/sigmoid colectomy for complex disease anchoring procedure include advanced procedures such as minimally invasive splenic flexure mobilization techniques, laparoscopic surgery for complicated and/or diverticulitis, splenic flexure tumors, complete mesocolic excision, and other techniques (e.g., Deloyers or colonic transposition in cases with limited colonic reach after extended left-sided resection). CONCLUSIONS: The SAGES Colorectal Masters Program top 10 seminal articles selected for laparoscopic left and sigmoid colectomy for complex benign and malignant disease anchoring procedure are presented. These procedures were the most essential in the armamentarium of practicing surgeons that perform minimally invasive surgery for complex left and sigmoid colon pathology.


Assuntos
Neoplasias Colorretais , Laparoscopia , Neoplasias Esplênicas , Humanos , Colo Sigmoide/cirurgia , Laparoscopia/métodos , Anastomose Cirúrgica/métodos , Colectomia/métodos , Neoplasias Esplênicas/cirurgia , Neoplasias Colorretais/cirurgia , Resultado do Tratamento
14.
Langenbecks Arch Surg ; 409(1): 18, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147144

RESUMO

PURPOSE: Robotic surgery is becoming increasingly widely used in the field of pediatric surgery. The present study aimed to evaluate the safety and feasibility of robot-assisted resection of benign pediatric splenic tumors and to discuss the technical points. METHODS: A total of 32 patients who were diagnosed with benign splenic tumors and underwent minimally invasive surgery from January 2017 to September 2023 were included in the study. The clinical data including demographic criteria, operative details, and postoperative outcomes were analyzed retrospectively. RESULTS: Thirteen patients underwent robot-assisted surgery, and 19 patients underwent laparoscopic surgery. The median operation time was 150 min, with an interquartile range (IQR) of 120 to 200 min for the robot-assisted group and 140 min with an IQR of 105 to 180 min in the laparoscopic group (P = 0.318). Despite four cases in the laparoscopic group (21%) being converted to laparotomy because of intraoperative bleeding, compared with none in the robot-assisted group, there was no significant difference between two groups (P = 0.128). The intraoperative volume of blood loss was significantly less (P = 0.041), and the hospitalization expense was significantly higher (P = 0.000) in the robot-assisted group than for the laparoscopic group. There was no significant difference in patients' age, tumor size, postoperative feeding time, and the postoperative hospitalization time between two groups (P > 0.05). CONCLUSION: Robot-assisted benign splenic tumor resection was safe and feasible, and it reduced surgical trauma for the pediatric patient.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Esplênicas , Humanos , Criança , Neoplasias Esplênicas/cirurgia , Estudos Retrospectivos
15.
J Postgrad Med ; 69(2): 108-110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36891941

RESUMO

Littoral cell angioma (LCA) is a rare benign tumor originating exclusively from the venous sinus lining cells of the splenic red pulp. These cells are unique in having a distinctive hybrid endothelial/histiocytic phenotype. Also, there are reports of the association of LCA with internal malignancies. We present a case report highlighting an unusual association of LCA with conventional renal cell carcinoma (RCC), masquerading as a metastatic lesion. Knowledge of such an association is necessary to avoid misdiagnosis and prevent potential overtreatment.


Assuntos
Carcinoma de Células Renais , Hemangioma , Neoplasias Renais , Neoplasias Esplênicas , Humanos , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/cirurgia , Neoplasias Esplênicas/complicações , Neoplasias Esplênicas/cirurgia , Neoplasias Esplênicas/diagnóstico , Hemangioma/complicações , Hemangioma/diagnóstico , Hemangioma/patologia
16.
Z Gastroenterol ; 61(5): 515-521, 2023 May.
Artigo em Alemão | MEDLINE | ID: mdl-36126930

RESUMO

BACKGROUND: Granulomatous diseases as sarcoidosis can impair the staging of metastatic diseases since metastasis are hard to distinguish from granulomas in standard imaging. This case report describes the diagnostic workup and therapy in a patient with simultaneous sarcoidosis and rectal cancer with hepatic metastasis and how a curative stadium was achieved. CASE DESCRIPTION: A 71-year old male patient was diagnosed with an adenocarcinoma of the rectum after presenting with involuntary weight loss and anemia. Further diagnostics raised strong suspicion of hepatic, pulmonary and splenic metastasis. Histology after bronchoscopy surprisingly discovered non-caseating granulomas, leading to the diagnosis of sarcoidosis. Due to an obstructive tumor, a rectum resection was performed. Due to a high suspicion of splenic metastasis during surgery, the spleen was removed. Histology revealed no metastasis in the spleen but multiple granulomas due to sarcoidosis. After surgery, biopsy of a suspicious lesion in the liver revealed both metastasis and sarcoidosis in the same sample. The patient was treated with a pseudo(neo)adjuvant chemotherapy with 5-Fluorouracil, Leukovorin, Oxaliplatin (FOLFOX) and Panitumumab (Anti-EGF-antibody). After treatment, CT scan revealed two hepatic lesions decreasing in size, while all other lesions were metrically stable. A right hemihepatectomy followed and histology revealed both sarcoidosis and metastasis. The curated patient was sent to aftercare and there is no suspicion for a relapse (13 month after last surgery). DISCUSSION: The simultaneous appearance of metastatic tumors and sarcoidosis creates a diagnostic dilemma since both manifestations can barely be distinguished in regular imaging technologies. This case report demonstrates that the histological work-up of affected organs with consecutive resections can cure a patient of a metastatic tumor disease, even in the context of simultaneous sarcoidosis.


Assuntos
Carcinoma , Neoplasias Retais , Sarcoidose , Neoplasias Esplênicas , Masculino , Humanos , Idoso , Recidiva Local de Neoplasia , Sarcoidose/diagnóstico , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , Granuloma
17.
Tech Coloproctol ; 27(11): 1073-1081, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37071308

RESUMO

PURPOSE: There is an ongoing debate regarding the extent of resection for splenic flexure tumors (SFT). The purpose of this study was to compare segmental and extended resections in terms of overall survival (OS) and pathologic outcomes. METHODS: Retrospective analysis of all patients surgically treated for SFT in the National Cancer Database (NCDB) for the period 2010-2019. Outcomes of segmental and extended resections were compared and a 1:1 propensity score matching was used to match for confounders. Primary outcome was OS. RESULTS: In total 3498/668,852 (0.5%) patients with clinical stage I-III splenic flexure adenocarcinoma in the NCDB were included. Of these, 1533 (43.8%) underwent segmental resection while 1965 (56.1%) underwent extended resection. After matching, mean OS was similar between the groups (92 vs 91 months; p = 0.94). When survival was stratified by clinical N stage, an 8-month survival benefit was shown in the extended resection group for clinical N-positive status (86 vs 78); however, this difference did not achieve statistical significance (p = 0.078). Median number of harvested lymph nodes was significantly lower in the segmental resection group (16 vs 17; p < 0.001) and the percentage of patients with fewer than 12 harvested nodes was significantly higher (18.4% vs 11.6%; p < 0.001). Length of stay was significantly shorter in the segmental resection group (5 vs 6 days; p = 0.027). There were no significant differences between the groups in terms of 30-day readmission or 30- or 90-day mortality. CONCLUSIONS: While segmental and extended resections were associated with similar OS for clinically node-negative SFT, there might be a survival benefit for extended resection in patients with clinical evidence of lymph node involvement.


Assuntos
Adenocarcinoma , Colo Transverso , Neoplasias Esplênicas , Humanos , Colo Transverso/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Adenocarcinoma/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Resultado do Tratamento , Análise de Sobrevida
18.
Vet Radiol Ultrasound ; 64(2): 224-232, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36285434

RESUMO

Splenic hemangiosarcoma has morphological similarities to benign nodular hyperplasia. Computed tomography (CT) texture analysis can analyze the texture of images that the naive human eye cannot detect. Recently, there have been attempts to incorporate CT texture analysis with artificial intelligence in human medicine. This retrospective, analytical design study aimed to assess the feasibility of CT texture analysis in splenic masses and investigate predictive biomarkers of splenic hemangiosarcoma in dogs. Parameters for dogs with hemangiosarcoma and nodular hyperplasia were compared, and an independent parameter that could differentiate between them was selected. Discriminant analysis was performed to assess the ability to discriminate the two splenic masses and compare the relative importance of the parameters. A total of 23 dogs were sampled, including 16 splenic nodular hyperplasia and seven hemangiosarcoma. In each dog, total 38 radiomic parameters were extracted from first-, second-, and higher-order matrices. Thirteen parameters had significant differences between hemangiosarcoma and nodular hyperplasia. Skewness in the first-order matrix and GLRLM_LGRE and GLZLM_ZLNU in the second, higher-order matrix were determined as independent parameters. A discriminant equation consisting of skewness, GLZLM_LGZE, and GLZLM_ZLNU was derived, and the cross-validation verification result showed an accuracy of 95.7%. Skewness was the most influential parameter for the discrimination of the two masses. The study results supported using CT texture analysis to help differentiate hemangiosarcoma from nodular hyperplasia in dogs. This new diagnostic approach can be used for developing future machine learning-based texture analysis tools.


Assuntos
Doenças do Cão , Hemangiossarcoma , Neoplasias Esplênicas , Cães , Animais , Humanos , Neoplasias Esplênicas/diagnóstico por imagem , Neoplasias Esplênicas/veterinária , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/veterinária , Hemangiossarcoma/patologia , Hiperplasia/veterinária , Inteligência Artificial , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/veterinária , Biomarcadores , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia
19.
Gan To Kagaku Ryoho ; 50(13): 1703-1705, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38303179

RESUMO

A 59-year-old woman underwent simple abdominal total hysterectomy with bilateral salpingo-oophorectomy, partial omentectomy, and extirpation of intrapelvic disseminated nodules for right fallopian tube cancer with rectal metastasis and peritoneal dissemination as primary debulking surgery(PDS). The histopathological diagnosis was high grade serous carcinoma( HGSC)of the right fallopian tube. After adjuvant chemotherapy with 4 courses of paclitaxel-carboplatin(TC), low anterior resection of the rectum for rectal metastasis and pelvic and para-aortic lymph node dissection were performed as interval debulking surgery(IDS). Histopathologically, lymph node metastasis was detected only in the right obturator lymph node. After adjuvant chemotherapy with 4 courses of TC, bevacizumab maintenance monotherapy was administered. Three years after PDS, laparoscopic splenectomy for splenic metastasis and extirpation of the solitary peritoneal metastases were performed as secondary debulking surgery(SDS). After adjuvant chemotherapy with 4 courses of TC, olaparib maintenance monotherapy was administered. The patient has remained alive without recurrence for 4 years after SDS and for 7 years after PDS. No case of metachronous splenic metastasis from fallopian tube cancer with synchronous rectal metastasis has been reported; however, long-term prognosis may be expected with PDS, IDS and SDS for platinum-sensitive HGSC.


Assuntos
Neoplasias das Tubas Uterinas , Laparoscopia , Neoplasias Retais , Neoplasias Esplênicas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias das Tubas Uterinas/patologia , Esplenectomia , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/cirurgia , Linfonodos/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia
20.
Khirurgiia (Mosk) ; (3): 77-82, 2023.
Artigo em Russo | MEDLINE | ID: mdl-36800873

RESUMO

Splenic lymphangioma is a rare malformation of splenic lymphatic channels characterized by cysts resulting from increased number of enlarged thin-walled lymphatic vessels. In our case, there were no clinical manifestations. Lymphangioma was congenital and diagnosed by ultrasound as an accidental finding. Surgery is the only method of radical treatment of splenic lymphangioma. We describe an extremely rare case of pediatric isolated splenic lymphangioma and laparoscopic resection of spleen as the most advantageous variant of surgical treatment.


Assuntos
Linfangioma , Neoplasias Esplênicas , Humanos , Criança , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/cirurgia , Tomografia Computadorizada por Raios X , Linfangioma/diagnóstico , Linfangioma/cirurgia , Esplenectomia
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