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We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.
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Uterine carcinosarcoma (UCS) is a highly aggressive gynecologic malignancy. Recurrent or persistent/progressive disease is usually fatal. We aimed to investigate the management and prognosis of these patients. Clinical records of UCS patients from June 1987 to April 2020 were retrospectively reviewed. The stage was re-assigned with the FIGO 2009 staging system. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Of the 168 patients, 98 experienced treatment failure. The median time to treatment failure (TTF) was 8.1 months (range: 0.0-89.1). The median follow-up time of censored patients was 32.0 months (range: 16.8-170.7). The 5-year SAR rates of those with recurrent or persistent/progressive disease were 7.6%. On multivariate analysis, salvage therapy mainly using radiotherapy (HR 0.27, 95% CI: 0.10-0.71) or chemotherapy (HR 0.41, 95% CI: 0.24-0.72) or chemoradiotherapy (CRT) (HR 0.33, 95% CI: 0.15-0.75) were associated with improved SAR, whereas disseminated recurrence was associated with significantly worse SAR (HR 3.94, 95% CI: 1.67-9.31, p = 0.002). Salvage therapy using radiotherapy or chemotherapy or CRT significantly improved SAR. Surgery significantly improved CSS but not SAR, adjusting for confounding factors.
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Carcinossarcoma , Neoplasias Uterinas , Humanos , Feminino , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia , PrognósticoRESUMO
OBJECTIVE: This study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent good prognostic factor and investigate the impact of treatment modalities to cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC). MATERIALS AND METHODS: Patients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were retrospectively (1993-2014) and prospectively (since 2014) enrolled. DNA extraction from paraffin-embedded tissue (FFPE) specimens was used for HPV genotyping. Those with suspected endometrial origin were excluded for analysis. RESULTS: A total of 354 patients with valid HPV results were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types were HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). The HPV16-negativity rates varied widely across hospitals. 322 patients were eligible for prognostic analyses. By multivariate analysis, advanced stage (HR5.8, 95% confidence interval [CI] 2.1-15.8; HR5.8, 95% CI 1.6-20.5), lymph node metastasis (HR4.6, 95% CI 2.7-7.9; HR7.3, 95% CI 3.8-14.0), and HPV16-positivity (HR0.3, 95% CI 0.1-0.6; HR0.3, 95% CI 0.1-0.9) were independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Stage I patients with primary surgery had better 5-year PFS (82.8% vs 50.0% p = 0.020) and OS (89.3% vs 57.1%, p = 0.017) than those with non-primary surgery, while the propensity scores distribution were similar among the treatment groups. CONCLUSION: This study confirmed that HPV16-positivity was a good prognostic factor for PFS and OS in AD/ASC, and patients seemed to have better outcome with primary surgery than non-primary surgery.
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Adenocarcinoma , Carcinoma Adenoescamoso , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Carcinoma Adenoescamoso/terapia , Feminino , Papillomavirus Humano 16/genética , Humanos , Estadiamento de Neoplasias , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research.
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Carcinoma , Carcinossarcoma , Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Carcinoma/patologia , Carcinossarcoma/genética , Carcinossarcoma/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , TaiwanRESUMO
The histological criteria for classifying endometrial hyperplasia (EH) are based on architectural crowding and nuclear atypia; however, diagnostic agreement among pathologists is poor. We investigated molecular biomarkers of endometrial cancer (EC) risk in women with simple hyperplasia or complex hyperplasia without atypia (SH/CH-nonA). Forty-nine patients with EC preceded by SH/CH-nonA were identified, of which 23 were excluded (15 with complex atypical hyperplasia (CAH), six not consenting, one with a diagnosis <6 months prior, and one lost to follow-up). The EH tissues of these patients were compared with those of patients with SH/CH-nonA that did not progress to EC (control) through microRNA (miRNA) array analysis, and the results were verified in an expanded cohort through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). MiRNA arrays analyses revealed 20 miRNAs that differed significantly (p < 0.05, fold change >4) between the control (n = 12) and case (n = 6) patients. Multiplex RT-qPCR for the 20 miRNAs in the expanded cohort (94 control and 25 case patients) led to the validation of miR-30a-3p (p = 0.0009), miR-141 (p < 0.0001), miR-200a (p < 0.0001), and miR-200b (p < 0.0001) as relevant biomarkers, among which miR-141, miR-200a, and miR-200b regulate the expression of phosphatase and tensin homolog (PTEN). For the prediction of EC, the area under the curve for miR-30a-3p, miR-141, miR-200a, and miR-200b was 0.623, 0.754, 0.783, and 0.704, respectively. The percentage of complete PTEN loss was significantly higher in the case group than in the control group (24% vs. 0%, p < 0.001, Fisher's exact test). A combination of complete PTEN loss and miR-200a provided optimal prediction performance (sensitivity = 0.760; specificity = 1.000; positive predictive value = 1.000; negative predictive value = 0.937; accuracy = 0.947). MiR-30a-3p, miR-141, miR-200a, miR-200b, and complete PTEN loss may be useful tissue biomarkers for predicting EC risk among patients with SH/CH-nonA.
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Endometrial cancer (EC) usually presented as a localized disease at diagnosis (67%), 20% of patients diagnosed with regional spread, and distant metastasis accounted for 9%. The standard treatments include hysterectomy, bilateral salpingo-oophorectomy, and pelvic with/without paraaortic lymph node dissection/biopsy. Adjuvant therapy is arranged according to risk factors and stages. Risk group classification varied among different guidelines and studies and evolved with time. Adjuvant modalities include chemotherapy, radiotherapy, chemoradiotherapy, antiangiogenesis agents, immune checkpoint inhibitors, and multi-target agents. We review the recent literature to incorporate important advances in trial results, real-world big data, and knowledge in biomarkers of EC to update appropriate adjuvant therapy and post-surgical treatment of EC patients.
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Neoplasias do Endométrio , Excisão de Linfonodo , Quimioterapia Adjuvante , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Metástase Linfática , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
OBJECTIVE: Recurrent cervical cancer is hard to treat when occurring in a previous radiated area and unresectable or distant metastasis. We present three such cases who achieved complete remission (CR) after chemoradiotherapy and pembrolizumab. CASE REPORT: Case 1 was diagnosed with cervical adenocarcinoma, stage IVB. She obtained CR after concurrent chemoradiotherapy (CCRT) and post-CCRT adjuvant chemotherapy and bevacizumab. Recurrence at previous irradiated sacral bone was controlled with pembrolizumab and CCRT using proton therapy (PT). Case 2 was diagnosed with stage IVB squamous cell carcinoma. First recurrence occurred at inguinal lymph node (LN). Secondary recurrence occurred at paraaortic LN ten years later. PT with chemotherapy and pembrolizumab achieved CR. Case 3 had a small cell carcinoma (stage IVB) with bone metastasis. She had CR to CCRT with etoposide-cisplatin. Liver metastasis was salvaged with CCRT and pembrolizumab. CONCLUSION: CCRT with pembrolizumab is potentially curative for recurrent cervical cancer conventionally amenable for palliation.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Recidiva Local de Neoplasia/terapia , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: To investigate the prognostic factors and impact of adjuvant treatment on uterine carcinosarcoma (UCS). METHODS: A retrospective review of UCS patients treated between 2005 and 2019 was conducted. International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system was used. Multivariate stepwise Cox proportional hazard regression models were used to identify the independent predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 138 patients were eligible for descriptive analysis. Excluding 12 patients without surgery, 126 patients with adequate clinicopathologic data were included for prognostic analysis. The median follow-up for survivors was 51.8 months. 5-year OS and PFS rates for FIGO stage I, II, III, IV were 64.5% and 51.8%, 60.8% and 57.7%, 47.7% and 45.9%, 5.1% and 4.1%, respectively. By multivariate analysis, six models each for PFS and OS were formulated including highly correlated variables alternatively. Adjuvant chemoradiation was consistently selected as an independent prognostic factor for OS (hazard ratio [HR] 0.10-0.22, all p < 0.001) and PFS (HR 0.12-0.23, all p < 0.001), while adjuvant chemotherapy (HR 0.33-0.41), age≥58 years (HR 1.80-1.91), stage III/IV (HR 3.36-13.34), and adnexal metastasis (HR 2.06-5.02) in three to four of the six models for OS. Stratified analyses revealed that adjuvant chemoradiation significantly improved outcome compared with adjuvant chemotherapy for stage IA patients with lymphovascular space invasion and stage IB-IV, lymph node metastasis, and adnexal metastasis. CONCLUSION: Adjuvant chemoradiation was confirmed as an independent good prognostic factor, while older age, stage III/IV, and adnexal metastasis were associated with poor outcome in UCS.
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Carcinossarcoma , Neoplasias Uterinas , Idoso , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapiaRESUMO
Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.
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Alphapapillomavirus/genética , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Alphapapillomavirus/patogenicidade , Conização , Progressão da Doença , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Teste de Papanicolaou , Estudos Prospectivos , Taiwan , Resultado do Tratamento , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND/PURPOSE: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. METHODS: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). RESULTS: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8-25.2] vs recurrence group: 43.6 months [range, 7.1-217.8]; p < 0.001). Patients with solitary recurrence had significantly better SAR than those with disseminated relapse (median: not reached vs 10.4 months, p < 0.001). On multivariate analysis, six models each for SAR and CSS were formulated alternatively including highly correlated variables for the recurrence group. Of these models, solitary relapse pattern (HR: 0.07, p < 0.001), progression-free interval (PFI) > 12 months (HR: 0.22-0.40, p = 0.001 and p = 0.023), CA125 < 35 U/mL at initial recurrence (HR: 0.32, p = 0.007), and overall salvage treatment including radiotherapy (HR: 0.19, p = 0.001) were significant predictors of favorable SAR. The same significant predictors were selected for CSS. CONCLUSION: Recurrent OCCC can be treated with curative intent if the relapse is solitary and can be completely resected or encompassed with radiotherapy, whereas novel therapies are needed for disseminated relapse or progression during primary treatment.
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Adenocarcinoma de Células Claras/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida , Taiwan , Falha de TratamentoRESUMO
BACKGROUND: Several reports have indicated the benefits of the acute care surgery (ACS) model in surgical outcomes. We tried to delineate the impact of the ACS model on surgical efficiency and quality. METHODS: Before the ACS model was implemented, abdominal surgical emergencies were evaluated by an on-call nontrauma general surgeon (pre-ACS model). An in-house trauma surgeon treated all patients with trauma or nontrauma abdominal surgical emergencies after the ACS model. Patients with acute appendicitis who underwent appendectomies were included. We conducted a pre- and poststudy to compare the time patients were in the emergency department and surgical qualities. RESULTS: There were 146 and 159 patients enrolled in the pre-ACS model and ACS model, respectively. The overall ED length of stay in the ACS model was significantly shorter than that in the pre-ACS model (300.3 ± 61.7 vs 719.1 ± 339.0 minutes, P < .001). Hospital LOS was also significantly shorter in the ACS model than in the pre-ACS model (2.44 ± 1.39 vs 3.83 ± 2.21 days, P = .022). CONCLUSION: The ACS model may improve abdominal surgical efficiency and quality. Our study results echoed the benefits of the implementation of the ACS model shown in North America.
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Apendicectomia , Apendicite/cirurgia , Cuidados Críticos/métodos , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos/organização & administração , Serviço Hospitalar de Emergência , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Indicadores de Qualidade em Assistência à Saúde , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Transarterial embolization has become an effective method in the management of pelvic fracture-related retroperitoneal hemorrhage. However, the selection of bilateral embolization or selective unilateral embolization remains controversial. The anterior-posterior compression (APC) pelvic fracture creates a complete diastasis of the anterior pelvis, which might be associated with bilateral sacroiliac joint injuries and further bilateral arterial injuries. In the current study, we evaluated the correlation between APC pelvic fracture and the need for bilateral internal iliac artery (IIA) embolization. METHODS: During the 78-month investigational period, patients who received either unilateral or bilateral IIA embolization over the injured site, as determined by angiographic findings, were enrolled. The patients with bilateral contrast extravasation (CE) revealed by angiography were compared with the patients with unilateral CE revealed by angiography. Among the patients with only unilateral positive findings (CE or hematoma formation) on computed tomographic scanning, the characteristics and risk factors of patients who required bilateral IIA embolization were analyzed. The patients with postembolization hemorrhage who had received repeat transarterial embolization were also identified and discussed. RESULTS: Seventy patients were enrolled in the current study. The rate of APC pelvic fracture among patients who received bilateral IIA embolization was 66.7% (18/27), which was significantly higher than the rate among patients who received unilateral IIA embolization (30.2%; 3/43) (P = .006). Of the patients with only unilateral positive findings on computed tomographic scanning, 21.6% (11/51) underwent bilateral IIA embolization because of bilateral CE revealed by angiography. There were also more patients with APC pelvic fracture in this group. CONCLUSION: In the management of APC pelvic fracture, more attention should be paid to the higher probability of bilateral hemorrhage. Bilateral IIA embolization should be considered in patients with APC pelvic fracture.
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Embolização Terapêutica/métodos , Fraturas Ósseas/complicações , Hemorragia/etiologia , Hemorragia/terapia , Ossos Pélvicos/lesões , Adulto , Angiografia , Distribuição de Qui-Quadrado , Feminino , Fraturas Ósseas/diagnóstico por imagem , Hemorragia/diagnóstico por imagem , Humanos , Artéria Ilíaca , Modelos Logísticos , Masculino , Sistema de Registros , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: The FAST (focused assessment of sonography for trauma) examination can rapidly identify free fluid in the abdominal or thoracic cavity, which is indicative of hemorrhage requiring emergency surgery in multiple-trauma patients. In patients with negative FAST examination results, it is difficult to identify the site of the hemorrhage and to plan treatment accordingly. We attempted to delineate the role of selective computed tomography (CT) and transarterial angioembolization (TAE) in the management of such unstable patients. METHODS: From January 2005 to April 2011 patients with concomitant unstable hemodynamics and negative FAST examination results were identified. Their demographic and time to start of embolization were recorded. The initial systolic blood pressure (SBP) in emergency department patients was compared with the SBP after TAE. RESULTS: A total of 33 patients were enrolled, and 85% required TAE. SBP improved significantly after TAE. There were 18 patients who received TAE without CT scan because the site of hemorrhage was obvious. Fifteen patients received a CT scan during the time required for angiography preparation. Ten of them received subsequent TAE based on the CT scan findings, and the treatment plan was changed in the other five patients. There was no significant difference between patients with or without a CT scan with respect to the time interval between arrival and starting embolization. CONCLUSIONS: Transarterial angioembolization is suggested in the management of patients with concomitant unstable hemodynamics and negative FAST examination results. During the time interval required for angiography preparation, a CT scan can be performed. This approach provides valuable information for further decision making without delaying definitive treatment.