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BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin receptor (SSR) analogs is now an established systemic treatment for neuroendocrine tumors (NET). However, more short- and long-term data about renal and hepatotoxicity is needed. Here we present our experience in this clinical scenario. METHODS: Eighty-six patients with progressive SSR-expressing malignancies underwent PRRT with Lu-177 Dotatate and were followed up for up to 2 years. Laboratory tests were done 1 week before each cycle and every 2 months at follow-up. Hepatic and renal toxicity was determined based on NCI CTCAE V5.0. RESULTS: 55/86 (64%) patients completed all 4 cycles of PRRT; 18/86 (20.9%) are currently being treated; 13/86 (15.1%) had to discontinue PRRT: 4/13 (31%) due to hematologic toxicity, 9/13 (69%) due to non-PRRT-related comorbidities. Out of the patients who finished treatment, only transient grade 2 toxicities were observed during PRRT: hypoalbuminemia in 5.5% (3/55), and renal toxicity (serum creatinine and estimated glomerular filtration rate) in 1.8% (1/55). No grade 3 or 4 liver and renal toxicity occurred. Patients presenting with impaired liver or renal function prior to PRRT, either improved or had stable findings. No deterioration was observed. CONCLUSION: Peptide receptor radionuclide therapy does not have a negative impact on liver and renal function, even in patients with pre-existing impaired parameters. No grade 3 or 4 hepatic or renal toxicity was identified. Only transient grade 2 hypoalbuminemia in 5.5% and nephrotoxicity in 1.8% of patients were seen during PRRT.
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Hipoalbuminemia , Tumores Neuroendocrinos , Insuficiencia Renal , Estudios de Seguimiento , Humanos , Hipoalbuminemia/inducido químicamente , Hígado/patología , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/radioterapia , Octreótido/efectos adversos , Tomografía de Emisión de Positrones , Radioisótopos/efectos adversos , Cintigrafía , Receptores de Somatostatina , Insuficiencia Renal/inducido químicamenteRESUMEN
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.
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Neoplasias de las Glándulas Suprarrenales , Tumores Neuroendocrinos , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/terapia , Humanos , Oncología Médica , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/terapiaRESUMEN
OPINION STATEMENT: Neuroendocrine tumors (NETs) are a heterogenous group of neoplasms characterized by varied biological hallmarks and behavior, ranging from indolent to aggressive. For many decades, somatostatin analogues and few targeted therapies were available for NETs and these therapies had minimal response rates. However, there have been a number of recent treatment advances. Peptide receptor radionuclide therapy (PRRT) is a novel approach to treatment of NETs and has changed the landscape of treatment for NETs. It is a form of targeted therapy in which a radiolabeled somatostatin analogue delivers radiation specifically to tumor cells expressing the somatostatin receptor.
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Braquiterapia/efectos adversos , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Selección de Paciente , Radiofármacos/efectos adversos , Receptores de Péptidos/antagonistas & inhibidores , Investigación Biomédica , Braquiterapia/métodos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Manejo de la Enfermedad , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Tumores Neuroendocrinos/etiología , Guías de Práctica Clínica como Asunto , Dosis de Radiación , Radiofármacos/administración & dosificación , Resultado del TratamientoRESUMEN
Background The COVID-19 pandemic imposed unprecedented challenges on healthcare systems worldwide. The pandemic placed frontline nursing staff working in the ICU and ER at the epicenter of this global crisis. This study aimed to assess the multifaceted impact of sociodemographic characteristics on the quality of life (QOL) of nursing staff during the pandemic. Method A cross-sectional survey was conducted to evaluate the impact of sociodemographic characteristics on the QOL of 322 frontline nurses working in the ICU and ER of five Saudi hospitals from May to July 2022. Participants completed the electronic survey questionnaire including demographic characteristics and four domains of QOL from the World Health Organization Quality of Life Questionnaire (WHOQOL-BREFF). The data was evaluated using descriptive and inferential statistics. Results Among 322 nurse participants, the majority were female (84.8%), married (64.4%), and held a bachelor's degree (92.4%). Age (above 40 years), gender (male), and marital status (married) reported a higher individual domain and overall QOL scores which shows that these characteristics have a direct influence on QOL. Years of work experience, extra working hours, and direct contact with COVID-19 patients were additional significant factors. Pearson correlation coefficients among QOL domains ranged from 0.54 to 0.91, indicating a strong interrelation among these domains. The highest transformed score was in the social domain (70.10) while the lowest score was in the psychological domain (59.20). The overall QOL mean score (SD) was 3.49(0.14) and the mean score (SD) of general health was 3.46(0.15). Conclusion The findings of this study suggest that sociodemographic and work-related factors have a complex and multifaceted impact on the QOL of nurses during the COVID-19 pandemic in Saudi Arabia. It also presents an insight into developing specific interventions to enhance nurses' resilience and well-being amidst pandemic challenges and to improve their QOL.
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ABSTRACT: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has shown great treatment efficacy in patients with well-differentiated metastatic neuroendocrine tumors and a metastatic size reduction of ~20% for metastatic lesions <3 cm in size. We present a 66-year-old man with pancreatic neuroendocrine carcinoma, who had a rapidly growing metastatic nodal conglomerate, which measured close to 10 cm in size. After only 2 cycles of PRRT with 177 Lu-DOTATATE, the nodal conglomerate had a striking size reduction greater than 75%. This case highlights the potential efficacy of PRRT with 177 Lu-DOTATATE for treatment of aggressive neuroendocrine neoplasms.
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Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Compuestos Organometálicos , Anciano , Carcinoma Neuroendocrino/diagnóstico por imagen , Carcinoma Neuroendocrino/radioterapia , Humanos , Lutecio , Masculino , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/radioterapia , Octreótido/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Tomografía de Emisión de Positrones , Radioisótopos , Cintigrafía , Radiofármacos/efectos adversos , Receptores de PéptidosRESUMEN
ABSTRACT: Peptide receptor radionuclide therapy (PRRT) is a treatment option for somatostatin receptor-positive, unresectable or metastatic neuroendocrine tumors (NETs). Despite high disease control rates seen with PRRT, a subset of the NET population seems to have a short progression-free interval. We hypothesize that patients with NETs with rapid progression post-PRRT may have mixed low- and high-grade cell populations, and PRRT treats the lower-grade component, allowing the more aggressive high-grade component to progress.We report 7 patients with biopsy-proven NET who received PRRT with 177Lu-DOTATATE at the Stanford Cancer Center who had evidence of progressive disease (PD) on or within 6 months of therapy.All patients had primary pancreatic, metastatic, well-differentiated NET on diagnosis and were heavily pretreated before receiving PRRT. Two patients had PD while on PRRT; 5 had PD within 6 months of completing PRRT. The median time from the last cycle to PD was 3.2 months (range, 1.1-4.6 months). The median progression-free survival was 7.7 months (95% confidence interval, 5.7-9.8 months). Three patients had a repeat biopsy post-PRRT, 2 of which demonstrated higher disease grade compared with their initial pathology. Further evaluation in larger patient cohorts is warranted to elucidate predictive factors of PRRT response/nonresponse to enable better patient selection.
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Tumores Neuroendocrinos/radioterapia , Octreótido/análogos & derivados , Compuestos Organometálicos/uso terapéutico , Receptores de Péptidos/metabolismo , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Octreótido/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Tomografía de Emisión de Positrones/métodos , Radiofármacos/uso terapéuticoRESUMEN
Cutaneous metastases from cancer are relatively uncommon in clinical practice but when present may herald the diagnosis of internal malignancy. The most common sources of primary cancer are the breasts, lungs, large bowel, oral cavity, kidneys, stomach, ovaries, and malignant melanoma. Despite the high incidence of uterine adenocarcinoma, cutaneous metastases are uncommon. The most common presentation of cutaneous metastases is rapidly developing nodules or tumors. The diagnosis of cutaneous metastatic carcinoma hinges on histopathologic evaluation of the involved skin. We discuss and review the diagnosis and management of cutaneous metastasis of uterine adenocarcinoma.
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Adenocarcinoma/patología , Neoplasias Cutáneas/secundario , Neoplasias Uterinas/patología , Anciano , Antineoplásicos/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAP-kinase signaling pathway. While previously considered mutually exclusive, concomitant mutations in both KRAS and BRAF genes have been identified in colorectal cancer (CRC). The clinical outcome of these patients remains undetermined. We present the clinical course of two patients with CRC harboring mutations at codon 12 of KRAS and BRAF non-V600E mutations. More research is needed to determine the clinical-pathological effect of these simultaneous mutations of KRAS and BRAF in CRC on disease course and treatment outcome.
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The systemic treatment options for advanced gastric cancer (GC) have evolved rapidly in recent years. We have reviewed the recent data of clinical trial incorporating targeted agents, including inhibitors of angiogenesis, human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition, epidermal growth factor receptor, mammalian target of rapamycin, claudin-18.2, programmed death-1 and DNA. Addition of trastuzumab to platinum-based chemotherapy has become standard of care as front-line therapy in advanced GC overexpressing HER2. In the second-line setting, ramucirumab with paclitaxel significantly improves overall survival compared to paclitaxel alone. For patients with refractory disease, apatinib, nivolumab, ramucirumab and TAS-102 have demonstrated single-agent activity with improved overall survival compared to placebo alone. Pembrolizumab has demonstrated more than 50% response rate in microsatellite instability-high tumors, 15% response rate in tumors expressing programmed death ligand 1, and non-inferior outcome in first-line treatment compared to chemotherapy. This review summarizes the current state and progress of research on targeted therapy for advanced GC.
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BACKGROUND: Nivolumab is an immune checkpoint inhibitor targeting programmed death-1 protein and has been approved for the treatment of multiple advanced malignancies. Adverse effects of immune checkpoint inhibitors are distinct from conventional cytotoxic chemotherapy and can be life-threatening if left unrecognized. Here, we present a case of nivolumab-induced pericardial effusion successfully managed with high-dose corticosteroids. CASE PRESENTATION: A 70-year-old Caucasian female with a history of 50-pack-year cigarette smoking was diagnosed of recurrent adenocarcinoma of lung after initial surgery. She progressed through multiple lines of chemotherapy and was eventually started on nivolumab. She developed a large pericardial effusion, grade 3 by Common Terminology Criteria for Adverse Events v4.0, about 4 days after receiving first nivolumab treatment. She was treated with oral prednisone at 1 mg/kg daily with gradual resolution of pericardial effusion over 5 weeks while she still received nivolumab every 2 weeks. Prednisone treatment was eventually tapered off about 10 weeks from initial nivolumab treatment. However 1 week after stopping prednisone, she again presented with shortness of breath and bilateral ankle edema, imaging confirmed recurrent pericardial effusion measuring 2.8 cm. Nivolumab was stopped and patient was again started back on prednisone 1 mg/kg daily which resulted in complete resolution of pericardial effusion in 3 weeks. Nivolumab was resumed 1 week afterwards while patient was on tapering dose of prednisone. There was no recurrent pericardial effusion when she continued low-dose prednisone during the remaining course of nivolumab treatment. CONCLUSIONS: With increasing use of immune checkpoint inhibitors, clinicians need to be aware of the unusual immune-related adverse events in order to provide timely management and effective patient care. To our knowledge, this is the first reported case of immune-related pericardial effusion from nivolumab successfully managed with high-dose corticosteroids. Furthermore, recurrent pericardial effusion was prevented by using low-dose corticosteroids as maintenance in order for patient to continue nivolumab treatment.
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Mucosa-associated lymphoid tissue (MALT)-type lymphomas most commonly occur in the stomach and have been associated with Helicobacter pylori infection. However, MALT-type lymphoma of the colon is a rare entity. It commonly manifests with symptoms of weight loss, low-grade fever, constipation, melena, and hematochezia. Unlike gastric lymphoma, it is difficult to detect MALT-type lymphoma of the colon by imaging. Colonoscopy may reveal lesions whose biopsy most commonly shows abundant B lymphocytes. There is no universal immunohistochemistry profile for MALT-type lymphoma but CD 20 staining is commonly seen. Trisomies and translocations have been described and their presence has been correlated with treatment response. Due to the rarity of colonic MALT-type lymphoma, no standard guidelines are available for its management. It often occurs individually and rarely occurs simultaneously with concurrent colon adenocarcinoma. This case report describes the presentation and clinical course of a secondary MALT-type lymphoma in a patient who underwent colectomy for a prior colon adenocarcinoma.
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Neoplasias del Colon/diagnóstico , Linfoma de Células B de la Zona Marginal/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Anciano , Neoplasias del Colon/secundario , Neoplasias del Colon/terapia , Humanos , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/terapia , Masculino , Recurrencia Local de Neoplasia/terapiaRESUMEN
Gastrointestinal stromal tumors (GISTs) are rare abdominal tumors which arise from the interstitial cells of Cajal in the gastrointestinal tract. Gastric GISTs are the most commonly seen GIST tumors and may grow to a very large size. They are often associated with abdominal pain, anorexia and weight loss. Most of them can be detected by CT. These tumors have been found to harbor mutations in CD117 which causes constitutional activation of the tyrosine kinase signaling pathway and is considered to be pathognomic. Tyrosine kinase inhibitors such as imatinib have revolutionized the treatment of these tumors, which are otherwise resistant to conventional chemotherapy and radiotherapy. Although surgical resection is the mainstay of treatment, tyrosine kinase inhibitors have been useful in prolonging the recurrence-free survival of these patients. Resistance to imatinib has been reported in GISTs with specific mutations. We present a case of gastric GIST which grew to a very large size and was associated with abdominal pain and weight loss. It was successfully resected and the patient was commenced on imatinib therapy.
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INTRODUCTION: Ovarian cancer is one of the leading causes of death in women with cancer. First-line chemotherapy with platinum compounds and taxane compounds has been effective, but most patients develop a relapse of the disease due to drug resistance. There is growing evidence that this resistance may be due to the presence of ovarian cancer stem cells. DISCUSSION: Cells with properties of cancer stem cells have been isolated from the ascitic fluid of ovarian cancer patients. This subset of cells is highly tumourigenic compared to the rest of the cells in the ascitic fluid. They are known to exude harmful chemicals from their cytoplasm and have been found to be resistant to chemotherapeutic agents. This property has been utilized to purify them by fluorescence assisted cytometry to yield a subset of cells which are called 'side population'. These cells exhibit the properties of cancer stem cells and their role in disease progression is being currently investigated. The course of the disease can be potentially characterized at the cellular level by closely studying this cell population. They can also be cultured in different combinations of chemotherapeutic agents at varying concentrations to obtain 'chemograms' which are sensitivity charts. Chemotherapeutic agents which produce the most effective kill curves can then be rationally used as a second-line chemotherapy if the disease relapses. These sensitivity charts can provide insight into emerging patterns of chemoresistance and also help discover surface markers that accurately identify ovarian cancer stem cells. CONCLUSION: The high rate of disease relapse in patients with ovarian cancer requires a new and different approach utilizing the sensitivity of cancer stem cells. Isolating and characterizing the resistance patterns of ovarian cancer stem cells may provide a rational approach towards an effective and individualized chemotherapeutic regimen.
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Progresión de la Enfermedad , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Ensayo de Tumor de Célula Madre , Monitoreo de Drogas/métodos , Resistencia a Antineoplásicos , Femenino , Humanos , Ensayo de Tumor de Célula Madre/métodosRESUMEN
Primary effusion lymphoma (PEL) is a subset of large B cell lymphomas and has been mostly associated with human immunodeficiency virus infection. Rare cases have been reported in organ transplant recipients and chronic hepatitis C patients. It typically presents as an effusion in the pleural and pericardial spaces but rarely disseminates. However, involvement of the gastrointestinal tract, lymph nodes and bone marrow has been reported. Diagnosis is based on characteristic clinical, histopathological and immunohistochemical features. We present a case with a right atrial mass which tested positive for human herpes virus 8 (HHV-8), CD20, CD30 and lambda light chains and negative for CD138, kappa light chain, PAX5, Epstein-Barr virus, latent membrane protein 1, CD2, CD3, CD8 and CD56. Bilateral pleural effusions and pericardial effusions were noted which tested positive for HHV-8, CD30 and CD45. The patient responded well to the R-EPOCH regimen with complete resolution of the effusions and a significant decrease in the size of the right atrial mass. This case report illustrates the atypical manifestation of PEL as a right atrial mass.
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Uterine leiomyosarcoma is a rare malignancy and carries a poorer prognosis when compared to endometrial carcinoma. It has been observed to metastasize to all the major organs. It presents with symptoms of abdominal distension, vaginal bleeding and may pass unnoticed until an advanced stage in patients with leiomyomas. Surgery is a viable option in patients with disease limited to the uterus, but metastasis to the heart may require surgery to prevent acute and catastrophic complications. The case described here involves metastasis to the tricuspid valve, which caused severe tricuspid regurgitation in the setting of acute pulmonary embolism. Surgical resection restored cardiac function and stabilized the patient. This case illustrates a rare site of metastasis of leiomyosarcoma which required immediate intervention and resulted in a favorable outcome.
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Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon, fast-growing, pigmented neoplasm of neural crest origin. It primarily affects the maxilla of the infants during the first year of life. Approximately, a few hundred of these tumors have been reported in medical literature. We present a case of a newborn with MNTI involving the anterior maxillary region. The treatment included surgical excision of the lesion with safe margins, using an intraoral approach and removal of associated developing tooth buds. We made no attempt at immediate bone grafting. The patient had no recurrence at 1 year postoperatively. The diagnostic features and management alternatives of MNTI are discussed.