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BACKGROUND: Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses. METHODS: Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005-2019). Primary, secondary, and tertiary outcomes were disease-specific survival (DSS), overall survival (OS), and average annual percent change (AAPC) in incidence. RESULTS: Among 4,258 included patients, MACA was most frequently diagnosed at 50 to 69 years (52.0%), with female preponderance (55.9%). MACA incidence AAPC was 3.8 (95% confidence interval [CI] 1.9-5.9). For patients with exclusive, first-diagnosis MACA included in survival analysis (3,222 patients), median DSS and OS were 118 and 88 months, respectively. In DSS-based multivariable analysis, worse prognosis was associated with non-Hispanic Black background (HR 1.36, 95% CI 1.02-1.82; p = 0.036), high grade (grade 3 HR 3.10, 95% CI 2.44-3.92; p < 0.001), lymphatic spread (HR 2.73, 95% CI 2.26-3.30; p < 0.001), and distant metastasis (HR 5.84, 95% CI 3.86-8.83; p < 0.001). In subcohort analysis of patients with rationale for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC, 2,387 patients), CRS-HIPEC was associated with survival benefit compared with surgery alone but only for moderate-grade tumors (median DSS/OS 138/138 vs. 116/87 months; p < 0.001). CONCLUSIONS: Mucinous adenocarcinoma of the appendix incidence is increasing in the United States. Survival rates are affected by both demographics and classical risk factors, and CRS-HIPEC-associated survival benefit predominantly occurs in moderate-grade tumors. Further exploration of biologic and clinicopathologic features may enhance risk stratification for this disease.
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Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Programa de VERF , Humanos , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Femenino , Masculino , Persona de Mediana Edad , Anciano , Tasa de Supervivencia , Pronóstico , Estudios de Seguimiento , Adulto , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Quimioterapia Intraperitoneal Hipertérmica , IncidenciaRESUMEN
BACKGROUND AND OBJECTIVES: Guidelines for Stage II colon cancer recommend adjuvant chemotherapy (AC) only for tumors with high-risk features, but long-term outcomes data are mixed. We aimed to determine if AC was associated with a survival benefit in this population. METHODS: Patients were identified from the National Cancer Database and included if they met the following criteria: diagnosis of Stage II colon cancer, surgery, survival data, and complete data on six high-risk features. The cohort of 57 335 patients was stratified by receipt of AC. Subgroup analysis was performed on patients under the age of 65 years with no comorbidities. Overall survival (OS) was the primary endpoint. RESULTS: An increasing number of high-risk features was associated with significantly decreased median OS. AC was associated with significantly increased OS for patients with 0, 1, 2, and ≥3 high-risk features. On subgroup analysis, receipt of AC was associated with a reduced risk of death (hazard ratio: 0.66; confidence interval: 0.59-0.74). For patients in the subgroup who had a T4 tumor, AC was associated with increased OS (92.7 vs. 83.6 months). CONCLUSIONS: AC should be considered for all younger, healthy patients with Stage II colon cancer and may be associated with a survival benefit for patients with T4 disease.
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Neoplasias del Colon , Anciano , Quimioterapia Adyuvante , Estudios de Cohortes , Neoplasias del Colon/patología , Humanos , Estadificación de Neoplasias , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Desmoid-type fibromatosis (DTF) is a rare benign lesion that usually arises from the abdominal wall or extremities and rarely from the mesentery or intrabdominal organs. Malignant peritoneal mesothelioma is also a rare, yet aggressive disease. To our knowledge, this is the first case report of desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma. CASE PRESENTATION: An early 30-year-old female was referred to our center for large intra-abdominal mass concerning for recurrent malignant peritoneal mesothelioma after previous cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Further investigation revealed a large mesenteric mass, which was resected en bloc with the cecum and terminal ileum. Pathologic findings confirmed a surprising diagnosis of desmoid-type fibromatosis. CONCLUSIONS: No adjuvant therapy was offered to this patient due to negative tumor margins; however, close follow-up will be provided for recurrence of both malignant peritoneal mesothelioma and desmoid-type fibromatosis, which can be differentiated in the future via biopsy in this patient.
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Fibromatosis Agresiva , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Adulto , Femenino , Fibromatosis Agresiva/patología , Humanos , Mesotelioma/patología , Mesotelioma/cirugía , Recurrencia Local de Neoplasia , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/cirugía , Enfermedades RarasRESUMEN
BACKGROUND: The effects of the coronavirus disease 2019 (COVID-19) pandemic on surgical oncology practice are not yet quantified. The aim of this study was to measure the immediate impact of COVID-19 on surgical oncology practice volume. METHODS: A retrospective study of patients treated at an NCI-Comprehensive Cancer Center was performed. "Pre-COVID" era was defined as January-February 2020 and "COVID" as March-April 2020. Primary outcomes were clinic visits and operative volume by surgical oncology subspecialty. RESULTS: Abouyt 907 new patient visits, 3897 follow-up visits, and 644 operations occurred during the study period. All subspecialties experienced significant decreases in new patient visits during COVID, though soft tissue oncology (Mel/Sarc), gynecologic oncology (Gyn/Onc), and endocrine were disproportionately affected. Telehealth visits increased to 11.4% of all visits by April. Mel/Sarc, Gyn/Onc, and Breast experienced significant operative volume decreases during COVID (25.8%, p = 0.012, 43.6% p < 0.001, and 41.9%, p < 0.001, respectively), while endocrine had no change and gastrointestinal oncology had a slight increase (p = 0.823) in the number of cases performed. CONCLUSIONS: The effects of the COVID-19 pandemic are wide-ranging within surgical oncology subspecialties. The addition of telehealth is a viable avenue for cancer patient care and should be considered in surgical oncology practice.
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COVID-19/complicaciones , Instituciones Oncológicas/normas , Neoplasias/cirugía , Pautas de la Práctica en Medicina/estadística & datos numéricos , SARS-CoV-2/aislamiento & purificación , Oncología Quirúrgica/estadística & datos numéricos , Telemedicina/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/transmisión , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , National Cancer Institute (U.S.) , Neoplasias/patología , Neoplasias/virología , New England/epidemiología , Estudios Retrospectivos , Estados UnidosAsunto(s)
Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Humanos , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/terapia , Tasa de Supervivencia , PronósticoAsunto(s)
Procedimientos Quirúrgicos de Citorreducción , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Anticuerpos Monoclonales de Origen Murino , Estadificación de Neoplasias , Terapia NeoadyuvanteAsunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Mitotano/uso terapéutico , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos Hormonales/uso terapéuticoRESUMEN
OBJECTIVE Stereotactic radiosurgery (SRS) of the spine is a conformal method of delivering a high radiation dose to a target in a single or few (usually ≤ 5) fractions with a sharp fall-off outside the target volume. Although efforts have been focused on evaluating spinal cord tolerance when treating spinal column metastases, no study has formally evaluated toxicity to the surrounding organs at risk (OAR), such as the brachial plexus or the oropharynx, when performing SRS in the cervicothoracic region. The aim of this study was to evaluate the radiation dosimetry and the acute and delayed toxicities of SRS on OAR in such patients. METHODS Fifty-six consecutive patients (60 procedures) with a cervicothoracic spine tumor involving segments within C5-T1 who were treated using single-fraction SRS between February 2006 and July 2014 were included in the study. Each patient underwent CT simulation and high-definition MRI before treatment. The clinical target volume and OAR were contoured on BrainScan and iPlan software after image fusion. Radiation toxicity was evaluated using the common toxicity criteria for adverse events and correlated to the radiation doses delivered to these regions. The incidence of vertebral body compression fracture (VCF) before and after SRS was evaluated also. RESULTS Metastatic lesions constituted the majority (n = 52 [93%]) of tumors treated with SRS. Each patient was treated with a median single prescription dose of 16 Gy to the target. The median percentage of tumor covered by SRS was 93% (maximum target dose 18.21 Gy). The brachial plexus received the highest mean maximum dose of 17 Gy, followed by the esophagus (13.8 Gy) and spinal cord (13 Gy). A total of 14 toxicities were encountered in 56 patients (25%) during the study period. Overall, 14% (n = 8) of the patients had Grade 1 toxicity, 9% (n = 5) had Grade 2 toxicity, 2% (n = 1) had Grade 3 toxicity, and none of the patients had Grade 4 or 5 toxicity. The most common (12%) toxicity was dysphagia/odynophagia, followed by axial spine pain flare or painful radiculopathy (9%). The maximum radiation dose to the brachial plexus showed a trend toward significance (p = 0.066) in patients with worsening post-SRS pain. De novo and progressive VCFs after SRS were noted in 3% (3 of 98) and 4% (4 of 98) of vertebral segments, respectively. CONCLUSIONS From the analysis, the current SRS doses used at the Cleveland Clinic seem safe and well tolerated at the cervicothoracic junction. These preliminary data provide tolerance benchmarks for OAR in this region. Because the effect of dose-escalation SRS strategies aimed at improving local tumor control needs to be balanced carefully with associated treatment-related toxicity on adjacent OAR, larger prospective studies using such approaches are needed.
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Vértebras Cervicales/cirugía , Órganos en Riesgo/patología , Radiocirugia/efectos adversos , Fracturas de la Columna Vertebral/etiología , Neoplasias de la Columna Vertebral/cirugía , Anciano , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Órganos en Riesgo/diagnóstico por imagen , Tolerancia a Radiación , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Factores de Tiempo , Tomógrafos Computarizados por Rayos XRESUMEN
Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged.
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Macroglobulinemia de Waldenström/terapia , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Clorhidrato de Bendamustina , Ácidos Borónicos/uso terapéutico , Bortezomib , Ensayos Clínicos como Asunto , Conferencias de Consenso como Asunto , Progresión de la Enfermedad , Everolimus , Trasplante de Células Madre Hematopoyéticas , Humanos , Factores Inmunológicos/uso terapéutico , Compuestos de Mostaza Nitrogenada/uso terapéutico , Pirazinas/uso terapéutico , Rituximab , Terapia Recuperativa , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , Resultado del Tratamiento , Vidarabina/análogos & derivados , Vidarabina/uso terapéuticoRESUMEN
We investigated a recent (January 1999 to December 2009) cohort of 95 elderly Hodgkin lymphoma subjects. At diagnosis, median age was 67 years (range, 60-89 years), whereas 61% had significant comorbidity, 26% were unfit, 17% had a geriatric syndrome, and 13% had loss of activities of daily living. Overall response rate to therapy was 85%, whereas incidence of bleomycin lung toxicity was 32% (with associated mortality rate, 25%). With 66-month median follow-up, 2-year and 5-year overall survival were 73% and 58%, respectively (advanced-stage, 63% and 46%, respectively). Most International Prognostic Score factors were not prognostic on univariate analyses, whereas Cox multivariate regression identified 2 risk factors associated with inferior overall survival: (1) age more than 70 years (2.24; 95% CI, 1.16-4.33, P = .02) and (2) loss of activities of daily living (2.71; 95% CI, 1.07-6.84, P = .04). Furthermore, a novel survival model based on number of these risk factors (0, 1, or 2) showed differential 2-year OS of 83%, 70%, and 13%, respectively (P < .0001) and 5-year OS of 73%, 51%, and 0%, respectively (P < .0001).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVES: Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak. METHODS: This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models. RESULTS: One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant. DISCUSSION: Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.
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Glucocorticoides , Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/fisiopatología , Masculino , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Preescolar , Niño , Estudios Prospectivos , Resultado del Tratamiento , Evaluación de Resultado en la Atención de Salud , Factores de EdadRESUMEN
Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8 + T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.
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BACKGROUND: Ocular adnexal mucosal-associated lymphoid tissue lymphomas (MALTomas) are rare, and there are no phase III trials to guide treatment. Primary radiation therapy has been the typical management. This retrospective series reports the experience of a single institution and adds to the current literature. METHODS: Our electronic medical record system and available paper charts were used to identify patients with MALTomas of the lacrimal gland or sac, conjunctiva, and orbital structures, including extraocular muscles. In order to determine pathology, staging, treatment information, local and distant control, salvage treatments, and late toxicity, records were reviewed. RESULTS: Sixteen patients with ocular adnexal MALTomas had local radiation between 1992 and 2011 for primary or recurrent disease. Fifty percent of patients had lymphoma in the conjunctiva, 25% had lymphoma in the lacrimal sac/gland, and 25% of patients had lymphoma in the posterior orbit. Stage IAE disease occurred in 75% of patients, 6% had stage IIAE disease, and 19% of patients had a positive bone marrow biopsy. One patient received chemotherapy as part of initial therapy. The median radiation dose was 30 Gy (25.5-36 Gy) delivered with electrons (31%) or photons (69%). After a mean follow-up of 62.8 months, 2 patients had residual/progressive disease, 2 had contralateral recurrence, and 1 patient had a distant failure, for local control of 87.5% and overall disease control of 68.75%. Recurrence/progression occurred at a median of 35.45 months. Two patients with residual/progressive disease and 1 patient with a contralateral recurrence were followed, successfully salvaged, and have no evidence of disease. Fourteen patients are still alive, and there were no disease-related/toxicity deaths. Seven patients developed cataracts in the treated eye, 2 patients had radiation retinopathy, 2 had permanent dry eye syndrome, and 1 patient had severe keratopathy requiring enucleation. Six patients (3.75%) had worsening visual acuity of unclear etiology. CONCLUSIONS: Primary radiation therapy for ocular adnexal MALTomas with a median dose of 30 Gy led to excellent local control. Patients who did recur were successfully salvaged. Radiation was generally well tolerated, with expected cataractogenesis, given the dose required to achieve local control (with only 1 patient developing severe keratopathy after receiving the highest dose in this series).
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Linfoma de Células B de la Zona Marginal/radioterapia , Neoplasias Orbitales/radioterapia , Adulto , Anciano , Humanos , Linfoma de Células B de la Zona Marginal/mortalidad , Linfoma de Células B de la Zona Marginal/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orbitales/mortalidad , Neoplasias Orbitales/patología , Radioterapia/efectos adversos , Dosificación Radioterapéutica , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome that increases lifetime risk of diffuse-type gastric cancer which carries a dismal overall survival. Due to the high prevalence of cancer in patients with CDH1 variants, early screening and prophylactic total gastrectomy (PTG) are recommended. This review aims to summarize the current understanding of CDH1 and HDGC, highlighting its molecular and cellular implications as well as its clinical management and research efforts. METHODS: A review of PubMed and ClinicalTrials.gov was conducted. Articles published in English and with full text were considered. PubMed was searched using the terms 'CDH1' AND 'Hereditary Diffuse Gastric Cancer'. KEY CONTENT AND FINDINGS: Loss-of-function mutations in the CDH1 gene, which encodes the cell adhesion protein E-cadherin, have been identified as the primary cause of HDGC. The loss of E-cadherin expression disrupts cell-cell adhesion and activates oncogenic signaling pathways, ultimately promoting cancer cell growth and dissemination. Prophylactic total gastrectomy (PTG) is recommended for pathogenic CDH1 variant carriers with a family history of diffuse gastric cancer (DGC). However, recent studies of endoscopic surveillance utilizing specific biopsy protocols have demonstrated the potential for surveillance as an alternative to total gastrectomy in selected patients. Researchers are actively investigating the consequences of E-cadherin loss in gastric epithelium and have identified potential molecular drivers of HDGC development using animal models and organoids. These discoveries provide promise for chemoprevention strategies, biomarker discovery, and targeted therapies for diffuse-type gastric cancer. CONCLUSIONS: The understanding of HDGC has significantly advanced in recent years, with the loss of E-cadherin expression identified as a crucial factor in disease pathogenesis. The use of advanced in vitro models offers substantial promise for investigating the molecular mechanisms underlying HDGC and identifying novel therapeutic targets. By leveraging advanced models, continuing clinical trials, and improving clinical management of affected individuals, researchers can work towards the development of more effective treatment strategies for HDGC. The goal is to prevent cancers from developing in patients with CDH1 gene variants and minimize the burden of cancer.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Mutación de Línea Germinal , Mutación , Gastrectomía/métodos , Cadherinas/genética , Predisposición Genética a la EnfermedadRESUMEN
Traumatic duodenal injuries are rare and often challenging to diagnose and treat. Management of these injuries remains controversial and continues to evolve. Here, we performed a review of the literature and guidelines for the diagnosis and management of traumatic duodenal injuries.A common recommendation in more recent literature is primary, tension-free repair of duodenal injuries when possible if surgical repair is necessary. Conversely, if duodenal injuries are unamenable to primary repair, more complex procedures such as Roux-en-Y duodenojejunostomy or pancreaticoduodenectomy may be necessary. Regardless of injury grade or type of surgical repair, the literature continues to support wide extraluminal drainage. Over time, the management of complex duodenal injuries has evolved to favor simple primary repair whenever possible. According to recent studies, more complex procedures are associated with higher rates of post-operative complications and should be reserved for severe injuries when primary repair is not possible.
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Traumatismos Abdominales , Heridas Penetrantes , Humanos , Estudios Retrospectivos , Duodeno/cirugía , Duodeno/lesiones , Pancreaticoduodenectomía , Heridas Penetrantes/cirugía , Anastomosis Quirúrgica/métodos , Traumatismos Abdominales/diagnóstico , Traumatismos Abdominales/cirugíaRESUMEN
Data on outcome, prognostic factors, and treatment for very elderly non-Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients ≥80 years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily living (ADLs), and co-morbidities using the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). We identified 303 patients: 170 aggressive NHL (84% B cell/16% T cell) and 133 indolent NHL (82% B cell/18% T cell). Median age was 84 years (80-95). A geriatric syndrome was present in 26% of patients, 18% had ≥1 grade 4 CIRS-G, and 14% had loss of ADLs. At 49-month median follow-up, 4-year progression-free (PFS) and overall survival (OS) for aggressive NHLs were 31% and 44% respectively (stage I/II: PFS 53% and OS 66%; stage III/IV: PFS 20% and OS 32%; P < 0·0001 and 0·0002, respectively). Four-year PFS and OS for indolent NHL were 44% and 66% respectively, regardless of stage. Multivariate regression analysis identified two key factors that predicted inferior PFS and OS for both NHL groups: lack of CR and loss of ADLs. Prospective studies for very elderly NHL that incorporate geriatric tools, especially ADLs, are warranted.
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Linfoma no Hodgkin/patología , Linfoma no Hodgkin/terapia , Factores de Edad , Anciano de 80 o más Años , Comorbilidad , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Certain malignant B cells rely on B-cell receptor (BCR)-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.