RESUMO
Irinotecan is an effective drug in the treatment of colorectal cancer. However, there are reports of an association between certain UGT1A1 genetic polymorphisms and the development of adverse reactions(such as neutropenia)related to irinotecan metabolism. We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic polymorphisms in these patients yielded the following classifications: a wild-type group( *1/*1)comprising 13 patients(52%), a heterozygous group(*1/ *28, *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2 patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group, 30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4 neutropenia only occurred in the homozygous group. These results suggest that a dose reduction of irinotecan should be considered for patients who fall into the homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such patients might be susceptible to grade 4 neutropenia.
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Glucuronosiltransferase/genética , Leucopenia/induzido quimicamente , Neutropenia/induzido quimicamente , Polimorfismo Genético , Adulto , Idoso , Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Liquid biopsies can be a rapid, cost-effective and non-invasive alternative to tumour biopsies for detecting genetic mutations in somatic tumours. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their distribution in a small study cohort. We studied the genomic profiles of 99 blood samples from 85 patients with 21 different types of cancer using two commercially available liquid biopsy tests. The mean circulating free DNA (cfDNA) concentration was 162.7 ± 352.3 nanograms per 20 millilitres. Amongst cfDNA, the circulating tumour DNA (ctDNA) percentage ranged from 0.006% to 90.6%. With the exception of samples with gene amplification and high microsatellite instability, the number of mutations in each sample varied from zero to 21, with an average of 5.6 mutations in each patient. Amongst these mutations, nonsynonymous mutations were the most frequently observed type of mutation (90% of the sample, with an average frequency of 3.6 mutations per patient). Mutations were observed in 76 different genes. TP53 mutations constituted more than 16% of the detectable mutations, especially in non-small cell lung cancer. All the tumour types, except the ovary, kidney and apocrine gland tumours, harboured at least one type of TP53 mutation. KRAS (mainly in pancreatic cancer) and PIK3CA (mostly in breast cancer) mutations, were responsible for an additional 10% of the mutations in the studied samples. The tumour mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication amongst the patients. These findings indicate that liquid biopsy can detect specific molecular changes of tumour, which is useful for precision oncology and personalized cancer treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias Pulmonares , Feminino , Humanos , DNA Tumoral Circulante/genética , Biomarcadores Tumorais/genética , Medicina de Precisão , Biópsia Líquida , Estudos de CoortesRESUMO
We herein report the first case of a single-incision laparoscopic access (SILA) adrenalectomy in Japan. A 74-year-old woman who was a hepatitis B virus carrier was referred to our hospital because of an abnormal screening result during a routine health checkup. Abdominal computed tomography and an endocrinologic workup revealed a 2-cm left adrenal tumor with primary aldosteronism. We prioritized the safety of the SILA adrenalectomy by choosing a left lower abdominal approach. A SILS port was inserted through a 2.5-cm incision. An ultrasonic coagulator was the main tool used during the surgical procedure. The duration of the surgery was 105 min and the blood loss was 1 ml. This result was comparable to that of a conventional laparoscopic adrenalectomy. Based on our experience, an SILA adrenalectomy is thus considered to be feasible and safe, with better cosmetic results and a greater overall patient satisfaction than that of a conventional laparoscopic adrenalectomy. However, further studies will be necessary before the universal adoption of this new technique can be considered.
Assuntos
Adrenalectomia/métodos , Hiperaldosteronismo/cirurgia , Laparoscopia , Idoso , Feminino , Humanos , Hiperaldosteronismo/diagnósticoRESUMO
The proliferation and activation of CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T lymphocytes (CTLs) that produce interferonγ (IFNγ) is an essential action of effective cancer vaccines. Recently, a novel Wilms' tumor 1 (WT1) helper peptide (WT1 HP3451; amino acid sequence, WAPVLDFAPPGASAYGSL) applicable for various human leukocyte antigen (HLA) subtypes (HLADR, HLADP and HLADQ) was reported to increase peptide immunogenicity; however, the function of WT1 HP3451 remains unclear. In the present study, mature dendritic cells (mDCs) pulsed with WT1 HP3451 (mDC/WT1 HP3451) activated not only WT1specific CD4+ T cells but also CD8+ T cells that produced IFNγ following stimulation with immature dendritic cells (imDCs) pulsed with WT1 killer peptide (imDC/WT1 KP3745) in an HLAA*02:01 or HLAA*02:06restricted manner. Furthermore, the activated WT1reactive CD4+ Th1 cells were predominantly effector memory (EM) T cells. In 5 of 12 (41.7%) patients with cancer carrying the HLAA*02:01 or HLAA*02:06 allele, WT1reactive CD8+ T cells stimulated with mDC/WT1 HP3451 enhanced their levels of WT1 KP3745specific IFNγ production, with an increase >10%. Simultaneous activation of CD4+ and CD8+ T cells occurred more often when stimulation with mDC/WT1 HP3451 was combined with imDC/WT1 KP3745 restimulation. These results indicated that the novel mDC/WT1 HP3451 combination induced responses by WT1specific EM CD4+ Th1 cells and HLAA*02:01 or HLAA*02:06restricted CD8+ CTLs, suggesting its potential as a WT1targeting cancer vaccine.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Antígeno HLA-A2/imunologia , Neoplasias Renais/terapia , Fragmentos de Peptídeos/farmacologia , Proteínas WT1/imunologia , Tumor de Wilms/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/transplante , Feminino , Humanos , Imunoterapia Adotiva/métodos , Neoplasias Renais/sangue , Neoplasias Renais/imunologia , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Tumor de Wilms/sangue , Tumor de Wilms/imunologiaRESUMO
We describe a rare complication and the treating experience of it after pedicled omental grafting for mediastinitis. The patient was diagnosed as an acute mediastinitis soon after the total arch replacement was performed. A two-staged strategy to treat postoperative mediastinitis was scheduled, i.e., the setting up of a vacuum-assisted closure system until the improvement of inflammation followed by wound closure with pedicled omental grafting. The treatment for acute mediastinitis was successful and the patient followed a favorable postoperative course. During the follow-up, chest X-ray film suggested the gradual enlargement of mediastinum and CT showed the herniation of transverse colon into mediastinum. Surgical correction for the hernia was scheduled and performed successfully by the laparoscopic procedure to prevent a possible cardiac and pulmonary dysfunction.