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1.
Sci Rep ; 14(1): 9771, 2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684823

RESUMO

Transpulmonary pressure can be estimated using esophageal balloon (EB) catheters, which come in a variety of manufacturing configurations. We assessed the performance of novel polyurethane EB designs, Aspisafe NG and NG+, against existing alternatives. We created a biomechanical model of the chest cavity using a plastic chamber and an ex-vivo porcine esophagus. The chamber was pressurized (- 20 and + 20 cmH2O) to simulate pleural pressures. We conducted tests with various EB inflation volumes and measured transesophageal pressure (TEP). TEP measurement was defined as accurate when the difference between pressure within the EB and chamber was 0 ± 1 cmH2O. We computed the minimal (Vaccuracy-min) and maximal (Vaccuracy-max) EB inflation volumes of accuracy. Inflation volumes were further validated using a surrogate method derived by the clinically validated positive pressure occlusion test (PPOT). When the esophageal balloons were filled with inflation volumes within the range provided by the manufacturers, the accuracy of TEP measurements was marginal. Our tests found median Vaccuracy-min across EB of 0.00-0.50 mL (p = 0.130), whereas Vaccuracy-max ranged 0.50-2.25 mL (p = 0.002). Post PPOT validation, median TEP was - 0.4 cmH2O (- 1.5 to 0.3) (p < 0.001 among catheters). The Aspisafe NG and NG+ were accurate in 81.7% and 77.8% of the measurements, respectively. We characterized two new EBs, which demonstrated good benchtop accuracy in TEP measurements. However, accuracy was notably influenced by the precise selection of EB inflation volumes.


Assuntos
Catéteres , Esôfago , Pressão , Cavidade Torácica , Animais , Esôfago/fisiologia , Suínos , Fenômenos Biomecânicos , Poliuretanos/química , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação
2.
J Crit Care ; 82: 154773, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38479299

RESUMO

BACKGROUND: Survivors of severe COVID-19 related respiratory failure may experience durable functional impairments. We aimed at investigating health-related quality of life (HR-QoL), physical functioning, fatigue, and cognitive outcomes in COVID-19 patients who received invasive mechanical ventilation (IMV). METHODS: Case-series, prospective, observational cohort study at 18 months from hospital discharge. Patients referring to the Intensive Care Unit (ICU) of Humanitas Research Hospital (Milan, Italy) were recruited if they needed IMV due to COVID-19 related respiratory failure. After 18 months, these patients underwent the 6-min walking test (6MWT), the Italian version of the 5-level EQ-5D questionnaire (EQ-5D-5L), the Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire (FACIT-F), the Trail Making Test-B (TMT-B) and the Montreal Cognitive Assessment-BLIND test (MoCA-BLIND). RESULTS: 105 patients were studied. The population's age was 60 ± 10 years on average, with a median Frailty Scale of 2 (Hodgson et al., 2017; Carenzo et al., 2021a [2,3]). EQ-VAS was 80 [70-90] out of 100, walked distance was 406 [331-465] meters, corresponding to about 74 ± 19,1% of the predicted value. FACIT-F score was 43 [36-49] out of 52, and MoCa-BLIND score was 19 (DeSalvo et al., 2006; von Elm et al., 2008; Herdman et al., 2011; Scalone et al., 2015 [16-20]) out of 22. The median TMT-B time was 90 [62-120] seconds. We found a possible age and gender specific effect on HR-QoL and fatigue. CONCLUSIONS: After 18 months from ICU discharge, survivors of severe COVID-19 respiratory failure experience a moderate reduction in HR-QoL, and a severe reduction in physical functioning. Fatigue prevalence is higher in younger patients and in females. Finally, cognitive impairment was present at a low frequency.


Assuntos
COVID-19 , Fadiga , Qualidade de Vida , Respiração Artificial , Humanos , COVID-19/psicologia , COVID-19/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Seguimentos , Itália , SARS-CoV-2 , Cognição , Unidades de Terapia Intensiva , Desempenho Físico Funcional , Insuficiência Respiratória/terapia
3.
Am J Hematol ; 97(11): 1404-1412, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36215667

RESUMO

Coronavirus Disease (COVID-19) can be considered as a human pathological model of inflammation combined with hypoxia. In this setting, both erythropoiesis and iron metabolism appear to be profoundly affected by inflammatory and hypoxic stimuli, which act in the opposite direction on hepcidin regulation. The impact of low blood oxygen levels on erythropoiesis and iron metabolism in the context of human hypoxic disease (e.g., pneumonia) has not been fully elucidated. This multicentric observational study was aimed at investigating the prevalence of anemia, the alterations of iron homeostasis, and the relationship between inflammation, hypoxia, and erythropoietic parameters in a cohort of 481 COVID-19 patients admitted both to medical wards and intensive care units (ICU). Data were collected on admission and after 7 days of hospitalization. On admission, nearly half of the patients were anemic, displaying mild-to-moderate anemia. We found that hepcidin levels were increased during the whole period of observation. The patients with a higher burden of disease (i.e., those who needed intensive care treatment or had a more severe degree of hypoxia) showed lower hepcidin levels, despite having a more marked inflammatory pattern. Erythropoietin (EPO) levels were also lower in the ICU group on admission. After 7 days, EPO levels rose in the ICU group while they remained stable in the non-ICU group, reflecting that the initial hypoxic stimulus was stronger in the first group. These findings strengthen the hypothesis that, at least in the early phases, hypoxia-driven stimuli prevail over inflammation in the regulation of hepcidin and, finally, of erythropoiesis.


Assuntos
Anemia , COVID-19 , Eritropoetina , Eritropoese/fisiologia , Hepcidinas , Humanos , Hipóxia , Inflamação , Ferro
4.
J Anesth Analg Crit Care ; 2(1): 19, 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37386657

RESUMO

BACKGROUND: Spinal anesthesia (SA) is widely used for anesthetic management of patients undergoing hip surgery, and hypotension is the most common cardiovascular side effect of SA. This paper aims to assess the lowest effective dose of SA that reduces the occurrence of intraoperative hypotension in elderly patients scheduled for major lower limb orthopedic surgery. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) performed in elderly patients scheduled for surgical hip repair and a meta-analysis with meta-regression on the occurrence of hypotensive episodes at different effective doses of anesthetics. We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials registered. RESULTS: Our search retrieved 2085 titles, and after screening, 6 were finally included in both the qualitative and quantitative analysis, including 344 patients [15% (10-28) males], with a median (25th to 75th interquartile) age of 82 (80-85). The risk of bias assessment reported "low risk" for 5 (83.3%) and "some concerns" for 1 (16.7%) of the included RCTs. The low dose of SA of [mean 6.5 mg (1.9)] anesthetic was associated with a lower incidence of hypotension [OR = 0.09 (95%CI 0.04-0.21); p = 0.04; I2 = 56.9%], as compared to the high-dose of anesthetic [mean 10.5 mg (2.4)]. CONCLUSIONS: In the included studies of this meta-analysis, a mean dose of 6.5 mg of SA was effective in producing intraoperative comfort and motor block and associated with a lower incidence of hypotension as compared to a mean dose of 10.5 mg. TRIAL REGISTRATION: CRD42020193627.

5.
J Crit Care ; 65: 26-35, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34082252

RESUMO

PURPOSE: Coronavirus disease 2019 (COVID-19) infection may trigger a multi-systemic disease involving different organs. There has been growing interest regarding the harmful effects of COVID-19 on the cardiovascular system. This systematic review aims to systematically analyze papers reporting echocardiographic findings in hospitalized COVID-19 subjects. MATERIALS AND METHODS: We included prospective and retrospective studies reporting echocardiography data in >10 hospitalized adult subjects with COVID-19; from 1st February 2020 to 15th January 2021. RESULTS: The primary electronic search identified 1120 articles. Twenty-nine studies were finally included, enrolling 3944 subjects. Overall the studies included a median of 68.0% (45.5-100.0) of patients admitted to ICU. Ten studies (34.4%) were retrospective, and 20 (68.9%) single-centred. Overall enrolling 1367 subjects, three studies reported normal echocardiographic findings in 49 ± 18% of cases. Seven studies (24.1%) analyzed the association between echocardiographic findings and mortality, mostly related to right ventricular (RV) dysfunction. CONCLUSIONS: Data regarding the use of echocardiography on hospitalized, predominantly ICU, COVID-19 patients were retrieved from studies with heterogeneous designs, variable sample sizes, and severity scores. Normal echocardiographic findings were reported in about 50% of subjects, with LVEF usually not affected. Overall, RV dysfunction seems more likely associated with increased mortality. TRIAL REGISTRATION: CRD42020218439.


Assuntos
COVID-19 , Estado Terminal , Adulto , Ecocardiografia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2
6.
Ann Intensive Care ; 11(1): 91, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34089104

RESUMO

BACKGROUND: Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of invasively mechanically ventilated COVID-19 patients treated in our ICU. METHODS: Prospective, observational cohort study in a follow-up clinic. Patients completed a 6-min walking test (6MWT) to assess their cardio-pulmonary function around 2 months (early follow-up) from hospital discharge, the EQ-5D-5L questionnaire for quality of life assessment around 2 months and at 6 months from hospital discharge and an anonymous web-based Impact of Event Scale-Revised (IES-R) questionnaire for Post-Traumatic Stress symptoms at 2 months. RESULTS: 47 patients attended our follow-up program, mean age 59 ± 10 years, median pre-morbid Clinical Frailty Scale (CFS) 2 [2-3]. The median distance walked in 6 min was 470 [406-516] m, 83 [67-99]% of the predicted value. Overall 1 out 3 patients and 4/18 (22%) among those with a good functional baseline prior to COVID-19 (CFS of 1 or 2) had lower (84%) than predicted 6MWT. EQ-5D-5L quality of life VAS was 80 [70-90] out of 100 at early follow-up with a slight improvement to 85 [77.5-90] at 6 months. Mobility, self-care and usual activities improved between the two timepoints, while pain/discomfort and depression/anxiety did not improve or got worse. The IES-R total score was greater than the threshold for concern of 1.6 in 27/41(66%) respondents. CONCLUSIONS: Patients recovering from severe COVID-19 requiring invasive mechanical ventilation surviving hospital discharge present with early mild to moderate functional impairment, mildly reduced quality of life from hospital discharge with an overall improvement of mobility, self-care and the ability of performing usual activities, while a worsening of pain and depression/anxiety symptoms at 6 months and a large proportion of symptoms of post-traumatic distress soon after hospital discharge.

7.
Crit Care Med ; 49(11): e1157-e1162, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34048368

RESUMO

OBJECTIVES: Joblessness is common in survivors from critical care. Our aim was to describe rates of return to work versus unemployment following coronavirus disease 2019 acute respiratory distress syndrome requiring intensive care admission. DESIGN: Single-center, prospective case series. SETTING: Critical Care Follow-Up Clinic, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. PATIENTS: One hundred and one consecutive laboratory-confirmed coronavirus disease 2019 patients were discharged from our hospital following an ICU stay between March 1, 2020, and June 30, 2020. Twenty-five died in the ICU. Seventy-six were discharged alive from hospital. Two patients refused participation, while three were unreachable. The remaining 71 were alive at 6 months and interviewed. INTERVENTIONS: Baseline and outcome healthcare data were extracted from the electronic patient records. Employment data were collected using a previously published structured interview instrument that included current and previous employment status, hours worked per week, and timing of return to work. Health-related quality of life status was assessed using the Italian EQ-5D-5L questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 71 interviewed patients, 45 (63%) were employed prior to coronavirus disease 2019, of which 40 (89%) of them worked full-time. Thirty-three (73%) of the previously employed survivors had returned to work by 6 months, 10 (22%) were unemployed, and 2 (5%) were newly retired. Among those who returned to work, 20 (85%) of them reported reduced effectiveness at work. Those who did not return to work were either still on sick leave or lost their job as a consequence of coronavirus disease 2019. Reported quality of life of survivors not returning to work was worse than of those returning to work. CONCLUSIONS: The majority of coronavirus disease 2019 survivors following ICU in our cohort had returned to work by 6 months of follow-up. However, most of them reported reduced work effectiveness. Prolonged sick leave and unemployment were common findings in those not returning.


Assuntos
COVID-19/epidemiologia , Cuidados Críticos/estatística & dados numéricos , Síndrome do Desconforto Respiratório/epidemiologia , Retorno ao Trabalho/estatística & dados numéricos , Desemprego/estatística & dados numéricos , Fatores Etários , Idoso , Comorbidade , Feminino , Fragilidade/epidemiologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Qualidade de Vida , Aposentadoria/estatística & dados numéricos , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos
9.
Artigo em Inglês | MEDLINE | ID: mdl-33478004

RESUMO

Hemodynamic optimization during sepsis and septic shock is based on a prompt and large fluid resuscitation strategy associated with early administration of norepinephrine. In our hospital, norepinephrine is administered in the emergency department (ED), within a protocol-guided management context, to reduce norepinephrine infusion timing due to central line insertion. This choice, however, can be associated with side effects. OBJECTIVES: We conducted a retrospective analysis regarding the safety of norepinephrine in the ED. We also appraised the association between in-hospital mortality and predefined ED variables and patients' admission severity scores. DESIGN, SETTINGS, AND PARTICIPANTS: This was a retrospective analysis of electronic sheets of the ED of a tertiary hospital in the North of Italy. Outcomes measure and analysis: Electronic documentation was assessed to identify local and systemic side effects. We considered two subgroups of patients according to the in-hospital clinical paths: (1) those admitted in the intensive care unit (ICU); and (2) those who received a ceiling of care decision. We collected and considered variables related to septic shock treatment in the ED and analyzed their association with in-hospital mortality. MAIN RESULTS: We considered a two-year period, including 108,033 ED accesses, and ultimately analyzed data from 127 patients. Side effects related to the use of this drug were reported in five (3.9%) patients. Thirty patients (23.6%) were transferred to the ICU from the ED, of whom six (20.0%) died. Twenty-eight patients (22.0%) received a ceiling of care indication, of whom 21 (75.0%) died. Of the 69 (54.3%) finally discharged to either medical or surgical wards, 21 (30.4%) died. ICU admission was the only variable significantly associated to in-hospital mortality in the multivariable analysis [OR (95% CI) = 4.48 (1.52-13.22); p-value = 0.007]. CONCLUSIONS: Norepinephrine peripheral infusion in the ED was associated with a low incidence of adverse events requiring discontinuation (3.9%). It could be considered safe within <12 h when a specific line management protocol and pump infusion protocol are adopted. None of the variables related to septic shock management affected in-hospital mortality, except for the patient's ICU admission.


Assuntos
Sepse , Choque Séptico , Serviço Hospitalar de Emergência , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Itália , Norepinefrina/uso terapêutico , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico
10.
Clin Genitourin Cancer ; 12(1): 63-69.e1, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24161525

RESUMO

BACKGROUND: Rescue of patients who fail to be cured after 2 or 3 chemotherapy combinations (including high-dose chemotherapy [HDCT]) or whose disease is refractory to cisplatin is still an unmet need. We assessed the efficacy of a triple-combination chemotherapy in the salvage setting, beyond second-line regimens. PATIENTS AND METHODS: We retrospectively reviewed institutional data on consecutive patients who received paclitaxel 80 mg/m(2) intravenously (IV), cisplatin 50 mg/m(2) IV, and gemcitabine 800 mg/m(2) IV on days 1 and 8 every 3 weeks for a maximum of 8 administrations, followed by surgery. Response, survival (progression-free survival [PFS] and overall survival [OS]), and safety/toxicity outcomes were the end points. The Kaplan-Meier method was used for survival estimates, and multiple Cox regression models were used to analyze the prognostic factors. RESULTS: Seventy-five patients were treated from April 1999 to July 2011. Eight complete responses (CR, 10.7%), 29 partial responses with normal markers (PRm(-), 38.7%), and 13 cases of incomplete response/stable disease were recorded, for a major response rate (CR + PRm(-)) of 49%. Thirty-three patients (44%) underwent surgery, which was radical in 14 cases (42.4%). Two-year PFS was 14.8% (95% confidence interval [CI], 8.5%-25.8%), whereas 2-year OS was 29.5% (95% CI, 20.3%-42.7%). Five-year OS in disease-free patients (no evidence of disease) was 60.3% (95% CI, 42.2%-86.2%), and median OS between patients with and without evidence of disease was significantly different (71 [interquartile range {IQR}, 14-116] vs. 12.5 [IQR, 8-19] months with a 6-month landmark analysis; P = .0019). CONCLUSION: TPG is an effective combination, and best results were achieved if a radical clearance of residual disease could be accomplished. A randomized comparison with dose-intensified regimens is advisable.


Assuntos
Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Terapia de Salvação , Sobrevida , Resultado do Tratamento , Gencitabina
11.
Urologia ; 79(2): 81-8, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-22344569

RESUMO

The treatment of tumors of the testis represents an ideal model of care for cancer. Many different, intersecting strategies are available for managing germ-cell cancers, particularly in the early-stage disease. Which is 'right' remains a matter of debate, and requires balancing efficacy against late effects, bearing in mind the complexity of treatment strategies and the available expertise. The cornerstone of this model of success is linked to the quality and appropriateness of care. The current therapeutic strategy is very complex (Fig. 1). High-tech surgery, medical oncology and radiotherapy are involved at various levels of diagnostic techniques of the latest generation. The choice of therapy, alone or integrated, is often influenced by prognostic factors. In this article we will examine the important points and sometimes the subject of controversy in both diagnosis and treatment of these early-stage tumors (Clinical Stage I: disease confined to the testis; Clinical Stage IIA: retroperitoneal lymph nodes < 2 cm).


Assuntos
Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Humanos , Excisão de Linfonodo , Irradiação Linfática , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/classificação , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/secundário , Orquiectomia , Prognóstico , Radioterapia , Indução de Remissão , Espaço Retroperitoneal , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia
12.
Urologia ; 79 Suppl 19: 15-9, 2012 Dec 30.
Artigo em Italiano | MEDLINE | ID: mdl-23371266

RESUMO

Surgery in germ cell tumors of the testis (TGT) may result in andrological disorders, both after orchiectomy and after retroperitoneal lymphadenectomy (RPLND). Bilateral orchiectomy suppresses both testicular functions: exocrine and endocrine. In selected cases with bilateral TGT (metachronous/synchronous), or in the case of TGT in monorchid patients, partial orchiectomy (enucleation of the tumor) can preserve both functions with a low risk of relapse in residual testicular parenchyma, in the absence of intraepithelial neoplasia (TIN). In cases of TIN and normal testosterone levels (80%), the fertility is maintained in 50% of patients. In these cases the use of radiotherapy on the residual testicular parenchyma can prevent the future development of invasive cancer, though compromising the hormonal function. The RPLND (open or laparoscopic) can produce major side effects, such as retrograde ejaculation. Knowledge of the adrenergic fiber retroperitoneal neuroanatomy enables to implement a "nerve sparing" surgery with an almost total reduction of this serious side effect, but that option is only available in few centers of excellence. Semen cryopreservation has become a common practice performed before any treatment that might impact on the andrological function of patients.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Testiculares , Humanos , Excisão de Linfonodo , Masculino , Recidiva Local de Neoplasia/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia
13.
J Urol ; 186(4): 1298-302, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21849196

RESUMO

PURPOSE: We reviewed the slides of patients with clinical stage I nonseminomatous germ cell testicular tumors who underwent retroperitoneal lymph node dissection to evaluate the concordance between original and reviewed vascular invasion status, and other histological correlates. MATERIALS AND METHODS: Between 2002 and 2007 at our institution 202 consecutive patients underwent retroperitoneal lymph node dissection. We requested the slides of 183 patients who underwent orchiectomy elsewhere. The risk of nodal metastasis was considered high in those with vascular invasion and/or greater than 90% embryonal carcinoma, and low in those with no vascular invasion and embryonal carcinoma less than 90%. Using Cohen's κ we assessed the concordance index between original and reviewed parameters (vascular invasion and risk category). Using the chi-square test we also evaluated the association between nodal status at retroperitoneal lymph node dissection and original vs reviewed parameters. RESULTS: The original report did not contain vascular invasion information on 98 of 183 cases (53.4%). A total of 164 patients were evaluable since we had no slides for 19. Vascular invasion absence and presence were confirmed in 27 (73.0%) and 30 (78.9%) of 37 patients, respectively (Cohen's κ = 0.16). Low and high risk status was confirmed in 20 of 28 patients (71.4%) and in 47 of 64 (50.6%), respectively (Cohen's κ = 0.22). Reviewed vascular invasion and risk category were significantly associated with nodal status at retroperitoneal lymph node dissection (chi-square test p = 0.03 and 0.01, respectively), although the original parameters were not. CONCLUSIONS: In half of the patients no information was available on vascular invasion in the original reports. Concordance between original and reviewed reports was generally poor. Reviewed parameters better predicted nodal status at retroperitoneal lymph node dissection. These findings may have important implications in clinical practice.


Assuntos
Excisão de Linfonodo , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/patologia , Neoplasias Vasculares/patologia , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Prognóstico , Espaço Retroperitoneal , Neoplasias Testiculares/cirurgia
14.
BJU Int ; 107(7): 1088-94, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20868391

RESUMO

OBJECTIVE: • To investigate the optimal management and prognostic factors of patients with malignant transformation (MT) in germ-cell tumour (GCT) by re-evaluating Institutional series. PATIENTS AND METHODS: • Patients with an MT within GCT have been identified from the institutional database and all slides have been reviewed by the referral pathologist. RESULTS: • From June 1982 to October 2009, 48 patients and 13 somatic histologies have been identified. Twelve patients presented with stage I, 12 with stage II and 24 with stage III disease. All stage I patients are alive and disease-free after a median follow up of 88 months (interquartile range 38-103). • Of the 36 metastatic cases, 11 underwent GCT-oriented chemotherapy plus surgery and seven of them are currently disease-free. Three patients underwent MT-chemotherapy, one relapsed and is still under treatment. Overall, 17 patients relapsed (35%) and three of them have been rescued by GCT-chemotherapy. Five-year overall survival was 100% for stage I, 80% (95% CI 40-94) for stage II and 44% (95% CI 19-67) for stage III patients. Stage III disease at MT, incomplete surgical removal and primitive neuroectodermal tumours plus adenocarcinoma histologies were significant adverse prognostic factors for survival. CONCLUSIONS: • New insights emerged into the impact of histology and chemotherapy on MT. The development of an adenocarcinoma component as well as the possible efficacy of a GCT-tailored chemotherapy in a multimodal strategy are addressed for the first time, while disease extent at transformation and extent of radical surgery are confirmed as significant prognosticators. • An international web database for registration of all cases of MT worldwide is presented.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transformação Celular Neoplásica , Tumores Neuroectodérmicos/terapia , Orquiectomia , Teratoma/terapia , Adulto , Transformação Celular Neoplásica/patologia , Terapia Combinada , Humanos , Masculino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/terapia , Estadiamento de Neoplasias , Tumores Neuroectodérmicos/patologia , Prognóstico , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/terapia , Teratoma/patologia , Teratoma/secundário , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Resultado do Tratamento
15.
Eur Urol ; 58(6): 912-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20817343

RESUMO

BACKGROUND: The best management for patients with clinical stage I (CS1) nonseminomatous germ cell tumours (NSGCT) is still under debate. OBJECTIVE: We evaluated the long-term oncologic outcome of retroperitoneal lymph node dissection (RPLND) in patients with CS1 NSGCTs and reevaluated the traditional predictors of recurrence in a set of patients not undergoing adjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: Between 1985 and 1995, 322 consecutive CS1 NSGCT patients underwent primary RPLND not followed by adjuvant chemotherapy in a single referral centre. Patients were followed until relapse for a median time of 17 yr. MEASUREMENTS: We estimated the crude cumulative incidence of any recurrence. Categories pN and pT, vascular invasion (VI), percentage of embryonal carcinoma, and presence of teratoma were evaluated as 2-yr recurrence predictors of event in a binary logistic model. RESULTS AND LIMITATIONS: Fifty patients had a recurrence (46 in ≤ 2 yr and only 4 [1.2%] in > 2 yr). The 10-yr recurrence incidence was 15.2%. Significant predictors of recurrence at multivariable analysis were pN+, pT > 1, and the presence of VI. However, the discriminative ability of the model was modest (Harrell C = 0.74); only 9% and 3% of patients had a predicted recurrence probability > 30% and > 50%, respectively. CONCLUSIONS: RPLND alone could prevent recurrence in 85% of patients and minimise late relapses to 1.2%. Most patients could avoid the immediate and late toxicity of chemotherapy. Prognostic parameters combined into the multivariable model appeared of limited use in identifying a subset of patients at high risk of recurrence.


Assuntos
Excisão de Linfonodo , Recidiva Local de Neoplasia , Orquiectomia , Neoplasias Testiculares/cirurgia , Adulto , Quimioterapia Adjuvante , Humanos , Itália , Modelos Logísticos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Embrionárias de Células Germinativas/cirurgia , Seleção de Pacientes , Espaço Retroperitoneal/cirurgia , Medição de Risco , Fatores de Risco , Neoplasias Testiculares/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
BJU Int ; 104(3): 340-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19239440

RESUMO

OBJECTIVE: To retrospectively review the long-term activity, efficacy and toxicity of the combination of paclitaxel, cisplatin and gemcitabine (TPG) as third- or further-line chemotherapy in patients with germ-cell tumours (GCTs) who are not cured after at least two courses of standard-dose chemotherapy, high-dose chemotherapy or both. PATIENTS AND METHODS: We evaluated 22 consecutive men treated between April 1999 and December 2000. Half of them were classified as absolutely refractory to cisplatin and a further two as refractory. The median (range) number of previous courses of chemotherapy was 8 (5-11). Treatment consisted of paclitaxel 80 mg/m(2), cisplatin 50 mg/m(2) and gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for four courses, followed by surgery of actual residual resectable masses. RESULTS: The follow-up was updated at August 2007. There were no deaths from toxicity and only one patient needed suspension of therapy for toxicity. There was both grade 3-4 thrombocytopenia and neutropenia in 15 patients (68%), and anaemia in nine (41%). There were partial remissions in eight (36%) patients. Six (27%) patients were rendered disease-free with surgical removal of a residual mass after chemotherapy (two still containing viable cancer). Four (18%) patients are long-term survivors at more than 80, 81, 94 and 99 months. The median (range) overall survival of the whole series was 13.5 (1->99) months. CONCLUSION: This combination had a toxicity profile that was acceptable and comparable with other third-line regimens. There were eight (36%) major responses. After a 6-year minimum follow-up, four (18%) patients were long-term disease-free survivors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Terapia de Salvação/métodos , Neoplasias Testiculares/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Métodos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Indução de Remissão , Terapia de Salvação/efeitos adversos , Sobreviventes , Resultado do Tratamento , Gencitabina
17.
Eur Urol ; 55(3): 546-51, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18649992

RESUMO

BACKGROUND: Chemotherapy is emerging in the management of advanced penile cancer. OBJECTIVE: To evaluate the therapeutic activity of taxanes (T) in combination with cisplatin-fluorouracil (PF) for salvage of primarily unresectable or relapsed nodal metastases from squamous cell carcinoma (SCC) of the penis. DESIGN, SETTING, AND PARTICIPANTS: Six consecutive patients were treated at Istituto Nazionale Tumori (INT), Milano, with neoadjuvant paclitaxel, cisplatin, and 5-fluorouracil (TPF) for unresectable (two cases) or recurrent nodal metastases (four cases) from SCC of the penis from 2004 to 2006. Informed consent was given by all patients. INTERVENTION: Four courses of neoadjuvant TPF were to be given before salvage surgery. MEASUREMENTS: Patients underwent computed tomography (CT) scans before starting chemotherapy, after two courses, and at the end of chemotherapy. Lymph node dissection was to be performed in responsive patients. RESULTS AND LIMITATIONS: Two patients received more than four courses: Both had pathologically documented complete remission, and they are alive and disease free >2 yr after chemotherapy. The other four patients received only two courses. The first patient had subjective intolerance to TPF: He underwent early postchemotherapy radical lymph node dissection, which documented >90% tumour necrosis: He is alive and disease free 46 mo after starting chemotherapy. Of the other three patients, one was not responsive, changed therapy, and died within 4 mo. The other two had a clinical complete remission after the first two courses. Both refused to complete chemotherapy, and they relapsed after 10 and 4 mo. Limitations are the small number of patients and protocol violation in three cases. CONCLUSIONS: TPF chemotherapy for unresectable or recurrent nodal metastases from SCC of the penis is promising, and the standard four courses of therapy are to be completed in responding patients. A larger series is necessary to confirm preliminary results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Penianas/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Neoplasias Penianas/patologia , Taxoides/uso terapêutico
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