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Background: Pancreatic cancer is a devastating disease with a 5-year survival rate of 5-10%. Radiation is commonly used in neoadjuvant and adjuvant settings to improve local control. Studies have shown that circulating lymphocyte count depletion after radiation has been associated with poor tumor control and inferior overall survival (OS) outcomes. Method: To better understand the impact of radiation-associated lymphopenia in pancreatic cancer, the authors undertook this systematic review and meta-analysis of clinical studies that have reported radiation-related lymphopenia in pancreatic cancer. Results: A systematic methodology search of PubMed, Embase and the Cochrane Library resulted in 2969 abstracts. Nine studies fulfilled the inclusion criteria. Six studies reported on outcomes in patients undergoing definitive chemoradiation and three studies comparing outcomes in stereotactic body radiotherapy versus definitive chemoradiation. The patients with severe lymphopenia were at increased risk of death with a pooled hazard ratio of 2.33 (95% CI: 1.79, 3.03; I2: 36%; p < 0.001) compared with patients with no severe lymphopenia. The odds of developing severe lymphopenia were 1.12 (95% CI: 0.45, 2.79; I2: 95%; p < 0.81). The pooled mean difference for OS was -6.80 months (95% CI: -10.35, -3.24; I2: 99%; p < 0.002), suggesting that patients who develop grade 3 or 4 lymphopenia have inferior median OS outcomes. Limiting the mean splenic dose to less than 9 Gy as well as various spleen dosimetric parameters such as visit (V)10 <32%, V15 <23% and V20 <15.4% can reduce the incidence of severe lymphopenia. Conclusion: Radiation-related lymphopenia is associated with an increased hazard of death and inferior median OS. Spleen dosimetric parameters correlate with the incidence of severe lymphopenia and with sub-optimal survival outcomes. There is a need to validate these findings in prospective studies.
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Linfopenia , Neoplasias Pancreáticas , Humanos , Contagem de Linfócitos , Linfopenia/etiologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/radioterapia , Estudos Prospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: The impact of radiation-related lymphopenia on clinical outcomes has been reported in various solid malignancies such as high grade gliomas, head and neck cancers, thoracic malignancies and gastro-intestinal malignancies but its impact is not clearly known in the context of common genito-urinary (GU) malignancies. METHODOLOGY: To better understand the effect of radiation-associated lymphopenia in prostate and bladder cancer, we undertook this systematic review of clinical studies that have studied radiation-related lymphopenia in GU malignancies. A systematic methodology search of PubMed, Embase, and Cochrane library resulted in 2125 abstracts. Ten studies fulfilled the inclusion criteria which included any prospective, retrospective study or cohort study of prostate, urinary bladder, kidney, ureter, urethra, penile cancer in humans, and radiation should be part of treatment and intent has to be in definitive or adjuvant settings. Finally the study should have data on radiation-related lymphopenia. RESULTS: Four studies reported on the cancer-specific outcomes related to the lymphopenia. The incidence of low lymphocyte counts were documented in all the studies. Three studies analyzed the factors associated with the Lymphocyte depletion. Pooled incidence of severe lymphopenia was 29.25% and mild to moderate lymphopenia was 60.75%. Bone marrow volume receiving 40 Gy was associated with the incidence of lymphopenia. CONCLUSION: One-third of the patients suffer from severe lymphopenia after radiation in prostate and bladder cancer. There are no clear data to support the correlation between severe lymphopenia and disease outcomes. Bone marrow dosimetry can affect the incidence and severity of lymphopenia. There is need of prospective datasets to identify the impact of radiation-related lymphopenia in GU malignancies focusing on long-term side effects, recurrence rates, and overall survival.
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Linfopenia/etiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Neoplasias da Bexiga Urinária/radioterapia , Humanos , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/diagnóstico , Masculino , Lesões por Radiação/sangue , Lesões por Radiação/diagnóstico , Radioterapia/métodos , Análise de Sobrevida , Resultado do TratamentoRESUMO
A palladium-catalyzed regiospecific decarboxylative ε-allylation of (cyclohexadienylidene)malononitriles is presented for the synthesis of functionalized α-allyl-α-aryl malononitriles. This reaction proceeds via a resonance-stabilized α-aryl malononitrile anion, resulting in a wide range of α-allyl-α-aryl malononitriles in high yields with excellent linear product selectivity. We have also shown that the resulting products can be transformed into valuable synthetic intermediates by decyanation and Mizoroki-Heck arylation. In addition, an enantioselective decarboxylative allylation reaction is also presented.
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A protocol in the preparation of functionalized N-allyl-N-aryl sulfonamides via palladium-catalyzed intramolecular decarboxylative N-allylation reaction is presented. The alkylated 2,5-cyclohexadienyl ketoesters reacted with arylsulfonamides in the presence of titanium tetrachloride and pyridine, which allows the formation of alkylated 2,5-cyclohexadienyl sulfonyl iminoesters which then undergo a palladium-catalyzed intramolecular allylic amidation through decarboxylative aromatization to provide functionalized N-allyl-N-aryl sulfonamides. This allylation protocol proceeds with good regioselectivity. Moreover, we have also shown that N-allyl-N-aryl sulfonamide can be transformed into 4-aryl-1,2,3,4-tetrahydroquinoline and nitrogen-containing ß-hydroxysulfide bioactives.
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OBJECTIVE: To investigate the clinical utility of short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost in patients with primary central nervous system (CNS) germinomas. METHODS: We retrospectively reviewed the clinical records of patients with primary CNS germinomas who received short-course induction chemotherapy (2 cycles of cisplatin 20 mg/m2 plus etoposide 40 or 100 mg/m2 for 5 days) followed by low-dose radiotherapy (dose: 2340 cGy) without a tumor bed boost. Disease-free survival and overall survival served as the main outcome measures. RESULTS: Between February 2002 and June 2018, 24 patients (20 males and 4 females; median age: 14.1 y; age range: 7.9 to 21.2 y) with pathology-proven CNS germinomas were included. The median follow-up time was 106 months (range: 17 to 169 mo). Isolated and multifocal lesions were identified in 13 and 11 patients, respectively. Tumor location was as follows: pineal gland (n=17), suprasellar region (n=13), periventricular region (n=7), and basal ganglia (n=2). Five patients had increased levels (>5 mIU/mL) of beta-human chorionic gonadotropin (ß-hCG), whereas alpha-fetoprotein concentrations were within the reference range in all participants. A total of 16 patients achieved remission after induction chemotherapy. The complete response rates of patients with increased and normal ß-hCG levels were 40.0% and 72.2%, respectively (P=0.208). Low-dose radiotherapy without a tumor bed boost was subsequently delivered to either the whole ventricle (n=16) or the whole brain (n=8), resulting in complete remission in all participants. Compared with patients without increased ß-hCG levels, those with ß-hCG-secreting germinomas had less favorable 5-year disease-free survival rates (100% vs. 60%, respectively, P=0.000115). CONCLUSIONS: Some children with primary CNS germinoma may benefit from short-course induction chemotherapy followed by low-dose radiotherapy to the whole ventricle without a tumor bed boost. The validity of our findings needs to be confirmed in a randomized phase II study for children with ß-hCG levels <5 mIU/mL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Quimiorradioterapia/mortalidade , Gonadotropina Coriônica/sangue , Germinoma/terapia , Quimioterapia de Indução/mortalidade , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/sangue , Neoplasias do Sistema Nervoso Central/patologia , Criança , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Germinoma/sangue , Germinoma/patologia , Humanos , Masculino , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Glycated hemoglobin (HbA1c) levels are an important index for the diagnosis and long-term control of diabetes. This study is the first to use a direct and label-free photoelectric biosensor to determine HbA1c using bacteriorhodopsin-embedded purple membranes (PM) as a transducer. A biotinylated PM (b-PM) coated electrode that is layered with protein A-oriented antibodies against hemoglobin (Hb) readily captures non-glycated Hb (HbA0) and generates less photocurrent. The spectra of bacteriorhodopsin and Hb overlap so the photocurrent is reduced because of the partial absorption of the incident light by the captured Hb molecules. Two HbA0 and HbA1c aptasensors that are prepared by conjugating specific aptamers on b-PM coated electrodes single-step detect HbA0 and HbA1c in 15 min, without cross reactivity, with detection limits of ≤0.1 µg/mL and a dynamic range of 0.1-100 µg/mL. Both aptasensors exhibit high selectivity and long-term stability. For the clinical samples, HbA0 concentrations and HbA1c levels that are measured with aptasensors correlate well with total Hb concentrations and the HbA1c levels that are determined using standard methods (correlation gradient = 0.915 ± 0.004 and 0.981 ± 0.001, respectively). The use of these aptasensors for diabetes care is demonstrated.
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Bacteriorodopsinas , Técnicas Biossensoriais , Animais , Hemoglobinas Glicadas/análise , Humanos , Coelhos , TransdutoresRESUMO
A strategy toward the preparation of substituted allyl aryl ethers from benzoic acids via a dearomatization and decarboxylative allylation (DcA) reaction is presented. The benzoic acids undergo a dearomatization to give alkylated 2,5-cyclohexadienyl ketoesters which are subjected to a palladium-catalyzed DcA reaction, providing a variety of functionalized allyl aryl ethers. In addition, the combination of a resonance stabilized DcA reaction with a Claisen rearrangement for the synthesis of multisubstituted phenols and applying to dihydroplicatin B derivative synthesis is also presented.
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OBJECTIVE: To evaluate the outcomes and prognostic factors in patients with parotid gland cancers treated with adjuvant radiotherapy with or without chemotherapy. METHODS: Eighty-five patients with parotid gland cancers were identified between October 2001 and September 2011. The median radiation dose was 66 Gy (range, 9-76 Gy). The outcomes assessment included overall survival, locoregional control, distant metastasis-free survival and disease-free survival. RESULTS: The stage distribution was 20 patients (23.5%) in stage I, 28 (32.9%) stage II, 14 (16.5%) stage III and 23 (27.1%) stage IV. Fifty-five patients (64.7%) had positive margins and 23 patients (27.1%) had close margins (<0.5 cm). Lymph node extracapsular spreading occurred in nine patients. The adjuvant therapy included radiotherapy alone in 47 patients (55.3%) and concurrent chemoradiotherapy in 38 patients (44.7%). With a median follow-up of 4.5 years (range, 0.4-11 years), the 5-year overall survival, locoregional control, distant metastasis-free survival and disease-free survival were 82.0, 88.4, 82.4 and 77.5%, respectively. Based on multivariate analysis, N1/N2 was a significant negative prognostic factor for distant metastasis-free survival, disease-free survival and overall survival. Perineural invasion was a significant negative prognostic factor for locoregional control, distant metastasis-free survival and disease-free survival. Patients 50 years or older had significantly worse distant metastasis-free survival, disease-free survival and overall survival. CONCLUSIONS: Surgery and radiotherapy treatment could achieve excellent outcomes in a modern cohort. However, N1/N2, perineural invasion and age ≥50 years, but not positive margins, are significant factors associated with a worse prognosis.
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Raios gama/uso terapêutico , Neoplasias Parotídeas/radioterapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
This study was conducted to investigate the effect of the vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse ovarian tissues treated with (experimental group) or without (control group) VEGF and FGF2 was performed. After transplantation to the inguinal region for two or three weeks, graft survival, angiogenesis, follicle development, and oocyte quality were examined after gonadotropin administration. VEGF coupled with FGF2 (VEGF/FGF2) promoted revascularization and significantly increased the survival rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with untreated controls. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of follicles at various stages and of mature oocytes in antral follicles after gonadotropin administration were remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2, may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue.
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Blastocisto/citologia , Sobrevivência Celular/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Oócitos/citologia , Ovário/citologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Blastocisto/efeitos dos fármacos , Criopreservação , Desenvolvimento Embrionário/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Fertilização in vitro , Técnicas Imunoenzimáticas , Camundongos , Oócitos/efeitos dos fármacos , Ovário/efeitos dos fármacos , Tela Subcutânea , Transplante AutólogoRESUMO
OBJECTIVE: To discuss several techniques of hysteroscopic surgery for complete septate uterus. CASE REPORT: A 40-year-old female with unexplained primary infertility was diagnosed with complete septate uterus with septate cervix. Hysteroscopic incision of complete septate uterus was performed by using ballooning technique. The patient conceived naturally shortly after the operation and delivered a healthy, term infant. CONCLUSION: Hysteroscopic incision of complete septate uterus is a safe and prompt way of metroplasty. With the knowledge obtained from a pre-operative MRI, it can be completed without laparoscopy and the need for hospitalization.
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Colo do Útero , Histeroscopia , Útero , Humanos , Feminino , Adulto , Histeroscopia/métodos , Gravidez , Colo do Útero/anormalidades , Colo do Útero/cirurgia , Útero/anormalidades , Útero/cirurgia , Infertilidade Feminina/cirurgia , Infertilidade Feminina/etiologia , Nascimento a Termo , Anormalidades Urogenitais/cirurgia , Anormalidades Urogenitais/diagnóstico por imagem , Útero SeptadoRESUMO
The treatment landscape for localized and regional prostate cancer includes active surveillance, radiation therapy (RT), and radical prostatectomy (RP). Population-based studies comparing RP to radiation reveal conflicting results due to methodological flaws. This systematic review and pooled analysis of studies aim to compare cause-specific survival (CSS), overall survival (OS), disease-free survival (DFS) and toxicity outcomes, comparing RP to RT in the management of prostate cancer. This systematic review search included the PubMed, Embase, and Cochrane libraries according to the PRISMA statement with the inception of each database up to June 24, 2023. Randomized phase 2 or 3 clinical trials that compared RP to RT in prostate cancer were included. The forest plot for the Odds ratio (OR) was plotted using the Mantel-Haenszel method, and the Z test was used to assess significance. A fixed effects model was used for meta-analysis. The search yielded seven completed randomized clinical trials and four ongoing trials. The majority of complete trials had low to intermediate-risk patient populations. OR for OS was 1.00 with 95% CI, 0.71-1.41 (P-value: 0.98), CSS OR was 0.99 with 95% CI, 0.45-2.18 (P-value 0.11), OR for DFS was 1.26 with 95% CI, 0.89-1.78 (P-value 0.19) when comparing RP to RT. The rate of distant metastatic disease was 2.3% in the RP versus 2.9% in the RT at 10 years. The rate of second malignant neoplasms was 4.5% in the RP compared to 4.2% in the RT arm at 10 years. RP caused more urinary symptoms, with a predominance of the need for urinary pads and a higher incidence of sexual dysfunction, and RT caused a higher incidence of bowel symptoms, such as blood in stools and fecal incontinence. This study provides evidence that the treatment-related outcomes are similar in patients with low to intermediate-risk prostate cancer when comparing RP to RT. Multidisciplinary treatment approaches and factoring patients' values and preferences should form the cornerstone of the ideal treatment option for each patient with localized prostate cancer. Patients with prostate cancer have an equal chance of being cancer-free and alive at 10 years with either RP or RT. In terms of side effects, RP causes more urine leakage and loss of erections, whereas RT tends to cause more bowel side effects, such as blood in stools and fecal leakage.
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An effective early diagnosis is important for rheumatoid arthritis (RA) management. This study reveals a novel RA detection method using bacteriorhodopsin as a photoelectric transducer, a light-driven proton pump in purple membranes (PMs). It was devised by covalently conjugating a PM monolayer-coated electrode with a citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)542-556 peptide that recognizes the serum RA-associated autoantibodies. The direct serum coating decreased the photocurrents in the biosensor, with the reduction in the photocurrent caused by coating with an RA-patient serum that is significantly larger than that with a healthy-control serum (38.1% vs. 20.2%). The difference in the reduction in the photocurrent between those two serum groups widened after the serum-coated biosensor was further labeled with gold nanoparticle (AuNP)-conjugated anti-IgA (anti-IgA-AuNP) (53.6% vs. 30.6%). Both atomic force microscopic (AFM) and Raman analyses confirmed the sequential peptide, serum, and anti-IgA-AuNP coatings on the PM-coated substrates. The reductions in the photocurrent measured in both the serum and anti-IgA-AuNPs coating steps correlated well with the results using commercial enzyme-linked immunosorbent assay kits (Spearman rho = 0.805 and 0.787, respectively), with both a sensitivity and specificity close to 100% in both steps. It was shown that an RA diagnosis can be performed in either a single- or two-step mode using the developed biosensor.
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Artrite Reumatoide , Bacteriorodopsinas , Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Ouro , Artrite Reumatoide/diagnóstico , Peptídeos , Ensaio de Imunoadsorção EnzimáticaRESUMO
BACKGROUND: The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We, therefore, developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and their underlying mechanisms. METHODS: The differential responsiveness of QPP lines was assessed in the brain and flank in untreated, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on the responsiveness of each tumor was measured through whole exome sequencing. The immune microenvironments of sensitive (QPP7) versus resistant (QPP8) lines were compared in the brain using flow cytometry. Drivers of flank sensitivity versus brain resistance were also measured for QPP8. RESULTS: QPP lines are syngeneic to C57BL/6J mice and demonstrate varied sensitivities to T cell immune checkpoint blockade ranging from curative responses to complete resistance. Infiltrating tumor immune analysis of QPP8 reveals improved T cell fitness and augmented effector-to-suppressor ratios when implanted subcutaneously (sensitive), which are absent on implantation in the brain (resistant). Upregulation of PD-L1 across the myeloid stroma acts to establish this state of immune privilege in the brain. In contrast, QPP7 responds to checkpoint immunotherapy even in the brain likely resulting from its elevated neoantigen burden. CONCLUSIONS: These syngeneic QPP models of glioblastoma demonstrate clinically relevant profiles of immunotherapeutic sensitivity and potential utility for both mechanistic discovery and evaluation of immune therapies.
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Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/patologia , Camundongos Endogâmicos C57BL , Imunoterapia/métodos , Linfócitos T/metabolismo , Microambiente TumoralRESUMO
Oncogenic KRAS (KRAS*) contributes to many cancer hallmarks. In colorectal cancer, KRAS* suppresses antitumor immunity to promote tumor invasion and metastasis. Here, we uncovered that KRAS* transforms the phenotype of carcinoma-associated fibroblasts (CAF) into lipid-laden CAFs, promoting angiogenesis and tumor progression. Mechanistically, KRAS* activates the transcription factor CP2 (TFCP2) that upregulates the expression of the proadipogenic factors BMP4 and WNT5B, triggering the transformation of CAFs into lipid-rich CAFs. These lipid-rich CAFs, in turn, produce VEGFA to spur angiogenesis. In KRAS*-driven colorectal cancer mouse models, genetic or pharmacologic neutralization of TFCP2 reduced lipid-rich CAFs, lessened tumor angiogenesis, and improved overall survival. Correspondingly, in human colorectal cancer, lipid-rich CAF and TFCP2 signatures correlate with worse prognosis. This work unveils a new role for KRAS* in transforming CAFs, driving tumor angiogenesis and disease progression, providing an actionable therapeutic intervention for KRAS*-driven colorectal cancer. SIGNIFICANCE: This study identified a molecular mechanism contributing to KRAS*-driven colorectal cancer progression via fibroblast transformation in the tumor microenvironment to produce VEGFA driving tumor angiogenesis. In preclinical models, targeting the KRAS*-TFCP2-VEGFA axis impaired tumor progression, revealing a potential novel therapeutic option for patients with KRAS*-driven colorectal cancer. This article is featured in Selected Articles from This Issue, p. 2489.
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Fibroblastos Associados a Câncer , Neoplasias do Colo , Proteínas Proto-Oncogênicas p21(ras) , Animais , Humanos , Camundongos , Angiogênese , Fibroblastos Associados a Câncer/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fibroblastos/metabolismo , Lipídeos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral/genéticaRESUMO
Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.
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Supriya MallickIntroduction Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes. Methods A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for the analysis. Results Nineteen studies were included in the final systematic review and 12 studies were included in the meta-analysis. The odds of developing severe lymphopenia were 0.39 (95% CI:0.19, 0.81, I 2 = 94%, p = 0.01). Patients with severe lymphopenia were at increased risk of death with a pooled HR = 2.19 (95% CI: 1.70, 2.83, I 2 = 0%, p <0.00001) compared to patients with no severe lymphopenia. The mean difference in survival between patients with severe lymphopenia and no severe lymphopenia was -6.72 months (95% CI: -8.95, -4.49, I 2 = 99%, p <0.00001), with a better mean survival in the no severe lymphopenia group. Conclusion Radiation-induced severe lymphopenia was associated with poor overall survival and increased risk of death. Photon therapy, larger planning target volume, higher brain dose, higher hypothalamus dose, and female gender were associated with increased risk of severe lymphopenia.
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OBJECTIVE: We present prenatal diagnosis of trisomy 11 in a single colony of cultured amniocytes at amniocentesis and the perinatal outcome. CASE REPORT: A 36-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+11[1]/46,XX[16]. In 17 colonies of cultured amniocytes, all five cells in one colony had a karyotype of 47,XX,+11, while the rest 16 colonies had a normal karyotype. The parental karyotypes were normal. Repeat amniocentesis was performed at 21 weeks of gestation. Interphase fluorescence in situ hybridization (FISH) was applied on the uncultured amniocytes, and the result revealed 0.9% mosaicism (1/101 cells) for trisomy 11 with only one cell with three signals, while the other 100 cells had two signals, compared with no trisomy 11 signals (0/100 cells) in the normal control. Uniparental disomy (UPD) 11 was excluded by polymorphic DNA marker analysis on the DNAs extracted from uncultured amniocytes and parental bloods. The cultured amniocytes at repeat amniocentesis revealed a karyotype of 46, XX in 28/28 colonies. Prenatal ultrasound findings were unremarkable. The pregnancy was continued to 38 weeks of gestation, and a 2724-g healthy female baby was delivered. The cord blood had a karyotype of 46,XX. The interphase FISH analysis on buccal mucosal cells revealed no trisomy 11 signals (0/100 cells). When follow-up at three months of age, the neonate manifested normal psychomotor and physical development. CONCLUSION: Prenatal diagnosis of mosaic trisomy 11 in a single colony at amniocentesis without abnormal fetal ultrasound and UPD 11 can be associated with a favorable outcome.
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Amniocentese , Cromossomos Humanos Par 11/genética , Nascido Vivo/genética , Trissomia/diagnóstico , Adulto , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Cariótipo , Cariotipagem , Mosaicismo , Gravidez , Trissomia/genéticaRESUMO
The coronavirus disease-2019 (COVID-19) pandemic caused by SARS-CoV-2 has exacted an enormous toll on healthcare systems worldwide. The cytokine storm that follows pulmonary infection is causally linked to respiratory compromise and mortality in the majority of patients. The sparsity of viable treatment options for this viral infection and the sequelae of pulmonary complications have fueled the quest for new therapeutic considerations. One such option, the long-forgotten idea of using low-dose radiation therapy, has recently found renewed interest in many academic centers. We outline the scientific and logistical rationale for consideration of this option and the mechanistic underpinnings of any potential therapeutic value, particularly as viewed from an immunological perspective. We also discuss the preliminary and/or published results of prospective trials examining low-dose radiation therapy for COVID-19.
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COVID-19/radioterapia , Doses de Radiação , SARS-CoV-2/efeitos da radiação , Internalização do Vírus/efeitos da radiação , Replicação Viral/efeitos da radiação , COVID-19/epidemiologia , COVID-19/virologia , Citocinas/metabolismo , Relação Dose-Resposta à Radiação , Interações Hospedeiro-Patógeno/efeitos da radiação , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/efeitos da radiação , Leucócitos Mononucleares/virologia , Pandemias , Dosagem Radioterapêutica , SARS-CoV-2/fisiologiaRESUMO
BACKGROUND: Cancer patients with coronavirus disease 2019 (COVID-19) have been reported to have double the case fatality rate of the general population. METHODS: A systematic search of PubMed, Embase, and Cochrane Central was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio (OR) and forest plots (random-effects model) were constructed for both primary and secondary outcomes. RESULTS: This systematic review of 38 studies and meta-analysis of 181 323 patients from 26 studies included 23 736 cancer patients. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (n = 165 980, OR = 2.54, 95% confidence interval [CI] = 1.47 to 4.42), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated. Among cancer subtypes, the mortality was highest in hematological malignancies (n = 878, OR = 2.39, 95% CI = 1.17 to 4.87) followed by lung cancer (n = 646, OR = 1.83, 95% CI = 1.00 to 3.37). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of comorbidities. There was insufficient data to assess the association of COVID-19-directed therapy and survival outcomes in cancer patients. CONCLUSION: Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19-directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.
Assuntos
COVID-19/complicações , Bases de Dados Factuais/estatística & dados numéricos , Neoplasias/complicações , Neoplasias/terapia , Idoso , COVID-19/epidemiologia , COVID-19/virologia , Transtornos Cerebrovasculares/complicações , Feminino , Mortalidade Hospitalar/tendências , Humanos , Hepatopatias/complicações , Pneumopatias/complicações , Masculino , Doenças Metabólicas/complicações , Pessoa de Meia-Idade , Neoplasias/mortalidade , Pandemias , Insuficiência Renal Crônica/complicações , SARS-CoV-2/fisiologiaRESUMO
OBJECTIVE: To investigate the clinical outcomes and failure patterns of patients with unresectable cholangiocarcinoma (CC) who had been treated with proton beam therapy (PBT). METHODS: The authors retrospectively examined 30 patients with unresectable CC who had undergone PBT between November 2015 and December 2017. Survival curves were plotted with the Kaplan-Meier method. Independent predictors of survival were identified by multivariate Cox proportional hazard regression analyses. Complications were assessed using the Common Terminology Criteria for Adverse Events v4.0. RESULTS: The median tumor size was 7 cm. Seventeen patients (56.7%) had regional lymph node metastases. The median radiation dose was 72.6 cobalt gray equivalents, and 23 patients (76.7%) received concurrent chemotherapy. The 1-year local control, regional control, and distant metastases-free rates were 88%, 86%, and 68%, respectively. The median overall survival and progression-free survival were 19.3 and 10.4 months, respectively. The median jaundice-free survival was 13 months, with a 1-year biliary tract infection (BTI)-free rate of 58%. Patients who received concurrent chemotherapy had a better median progression-free survival (12.1 vs. 4.7 mo). The most common form of acute toxicity from PBT was acute skin reactions which were rarely severe (grade III: 7% of patients). Three and 2 patients had grade III-IV toxicities and radiation-induced liver disease. There were no deaths caused by PBT or concurrent chemotherapy. CONCLUSIONS: PBT is clinically useful in patients with unresectable CC, even in the presence of large tumors or regional nodal metastases. Its use may induce durable symptom relief, without increasing acute or late toxicity.