RESUMO
BACKGROUND: Recent studies have observed an association between immune-related adverse events (irAE) and favorable clinical outcomes in the setting of cancer treatment with immune checkpoint inhibitors (ICI). However, results have been variable and inconclusive. Therefore, we have conducted a pan-cancer meta-analysis evaluating the relationship between irAEs and clinical outcomes. MATERIALS AND METHODS: The search included studies published in PubMed, Embase, and Web of Science from conception to 12.28.2019 as well as abstracts published in the ASCO and ESMO meetings from 2015 to 2019. Studies were included if ICI was used in advanced or metastatic cancer settings and excluded if data contained only combination therapy regimens or contained anti-CTLA-4. Raw data for overall response rate (ORR), hazard ratios (HR), number of patients (n), and p values for overall survival (OS) and progression-free survival (PFS) were extracted. Pooled sensitivity (SN), specificity (SP), positive (PPV) and negative predictive values (NPV), and odds ratios (ORs) were calculated using the 2 × 2 table and logit transformed proportions; and summary receiver operating curve (sROC) was generated using the bivariate approach for ORR. Pooled HRs were calculated using the means weighted by inverse of the variance for OS and PFS. Heterogeneity was assumed and random effects model was used throughout the analyses. RESULTS: Final analysis included 32 studies, among which ORR data were available in 15 studies, OS in 17, and PFS in 16. 17 studies evaluated non-small cell lung cancer (NSCLC), two studies melanoma, one study gastric cancer, three studies renal cell carcinoma (RCC), seven studies various cancer types, two studies urothelial carcinoma, and one study head and neck cancer (HNSCC). With respect to ORR, pooled SN, SP, PPV and NPV, and OR were 0.522 [0.423-0.619], 0.810 [0.771-0.844], 0.516 [0.413-0.618], 0.819 [0.764-0.864], and 4.59 [3.24-6.50], respectively. The area under the curve (AUC) derived from the sROC was 0.773. HR for OS and PFS were 0.47 [95% CI 0.37-0.60] and 0.46 [95% CI 0.37-0.56], respectively. Between-study publication bias was present for ORR, OS, and PFS; however, results remained significant after trim-fill analysis. CONCLUSION: irAEs predict OR, OS, and PFS across different types of cancer and may represent useful biomarkers in the clinical setting.
Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/terapia , Área Sob a Curva , Antígeno B7-H1/antagonistas & inibidores , Viés , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/terapia , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/terapia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Complexo Antígeno L1 Leucocitário/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/terapia , Neoplasias/imunologia , Neoplasias/mortalidade , Intervalo Livre de Progressão , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Resultado do TratamentoRESUMO
INTRODUCTION: Many patients with Prune Belly Syndrome (PBS) require abdominoplasty alone or in combination with correction of any urogenital abnormalities. This video presents a simplified technique with which to treat the abdominal flaccidity in PBS. METHODS: A longitudinal xypho-pubic fusiform figure is drawn on the abdomen, based on the area of skin and subcutaneous tissue to be removed. This is performed with preservation of the musculo-fascial layer and the umbilicus. A lateral elliptical single xypho-pubic line is drawn in the most lax side of the fascia, which is incised along this line. After urinary tract reconstruction and orchidopexy, closure is initiated by suturing the medial edge of the wider fascial flap laterally to the peritoneal side of the contralateral flap. Next, the now outer fascial flap is laid over the inner flap, and a buttonhole is made to expose the umbilicus. The subcutaneous tissue of the inner flap is laterally undermined to gain extra distance for the suture of the outer flap over the inner flap. The subcutaneous tissue and skin are sutured in the midline, incorporating the umbilicus. RESULTS: In a 30-year period, 43 PBS patients underwent this procedure with good cosmetic and long-term functional results. CONCLUSION: This abdominoplasty technique is simple and presents good functional and cosmetic results in PBS patients.
Assuntos
Abdominoplastia/métodos , Síndrome do Abdome em Ameixa Seca/cirurgia , Retalhos Cirúrgicos , Seguimentos , Humanos , Orquidopexia/métodos , Estudos Retrospectivos , Técnicas de SuturaRESUMO
A doubled haploid (DH) barley (Hordeum vulgare L.) population of 334 lines (ND24260 × Flagship) genotyped with DArT markers was used to map genes for adult plant resistance (APR) to leaf rust (Puccinia hordei Otth) under field conditions in Australia and Uruguay. The Australian barley cultivar Flagship carries an APR gene (qRphFlag) derived from the cultivar Vada. Association analysis and composite interval mapping identified two genes conferring APR in this DH population. qRphFlag was mapped to the short arm of chromosome 5H (5HS), accounting for 64-85% of the phenotypic variation across four field environments and 56% under controlled environmental conditions (CEC). A second quantitative trait locus (QTL) from ND24260 (qRphND) with smaller effect was mapped to chromosome 6HL. In the absence of qRphFlag, qRphND conferred only a low level of resistance. DH lines displaying the highest level of APR carried both genes. Sequence information for the critical DArT marker bPb-0837 (positioned at 21.2 cM on chromosome 5HS) was used to develop bPb-0837-PCR, a simple PCR-based marker for qRphFlag. The 245 bp fragment for bPb-0837-PCR was detected in a range of barley cultivars known to possess APR, which was consistent with previous tests of allelism, demonstrating that the qRphFlag resistant allele is common in leaf rust resistant cultivars derived from Vada and Emir. qRphFlag has been designated Rph20, the first gene conferring APR to P. hordei to be characterised in barley. The PCR marker will likely be effective in marker-assisted selection for Rph20.
Assuntos
Basidiomycota/patogenicidade , Mapeamento Cromossômico , Genes de Plantas , Hordeum/genética , Doenças das Plantas/genética , Austrália , Cromossomos de Plantas , Regulação da Expressão Gênica de Plantas , Genótipo , Hordeum/imunologia , Hordeum/microbiologia , Imunidade Inata , Fenótipo , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Imunidade Vegetal , Folhas de Planta/genética , Folhas de Planta/microbiologia , Locos de Características Quantitativas , UruguaiRESUMO
About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma (International Federation of Gynecology and Obstetrics Stages Ia to IIc). All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43). In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy. The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent.
Assuntos
Neoplasias Ovarianas/terapia , Adulto , Terapia Combinada , Feminino , Humanos , Melfalan/administração & dosagem , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Radioisótopos de Fósforo/uso terapêutico , Prognóstico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
De todas as fistulas enterocutaneas, aquelas que envolvem o jejuno-ileo e cujo desenvolvimento e brutal ou progressivo na superficie de uma evisceracao, constituem uma complicacao particularmente dificil de ser manuseada. Os auotres analisam 112 fistulas de delgado, enfantizando sua fisiopatologia e etiologia e formulando novas regras indispensaveis para sua profilaxia. Recomendam condutas terapeuticas baseando este grupo de medidas em alguns metodos originais de reanimacao que resultam numa diminuicao da taxa mortalidade desta grave patologia