RESUMO
Oxygen is considered a key element in the complex tissue repair process. O3-Oil antiseptics are obtained from the chemical reaction between ozone and unsaturated fatty acids of vegetable oils. The purpose of this study was to assess the effectiveness of a commercially available O3-Oil in the management of recalcitrant burn wounds. This study involved 20 patients with mid-deep and deep burn wounds (average TBSA approximately 23%, range 7-35%). Patient average age was 47 years (range 26-74 years), 8 were male. The presence of exudate, pain and delayed re-epithelialization, absence of tissue necrosis and/or sepsis were the inclusion criteria for the topical use of O3-Oil. In each patient two clinically similar areas were identified and treated every 48 hours with O3-Oil (Group 1) and conventional medication (Group 2). All the patients had positive bacterial culture results before treatment. A quicker reduction of exudates and pain and a progressive and faster bacterial load reduction was observed in Group 1. Negative cultures were obtained after 4 days on average in Group 1 (range 1-7 days) and 8 days in Group 2 (range 5-11 days). The present study demonstrated that Novox® provides a significant antibacterial effect, while stimulating reparative processes. According to our experience, the use of gel or pad is useful for re-epithelializing lesions, while the impregnated gauzes, which tend to adhere to the wound, are better used on lesions with granulation tissue.
L'oxygène est un élément- clé du processus complexe de réparation tissulaire. Les antiseptique O3-huile sont obtenus par réaction chimique entre l'ozone et des acides gras polyinsaturés d'origine végétale. Cette étude avait pour but d'évaluer l'efficacité d'un tel produit sur les brûlures d'évolution torpide. Elle a concerné 20 patients (dont 8 hommes) de 47 ans d'âge moyen (26- 74) ayant des brûlures intermédiaires à profondes sur 23% de SCT (7 à 35). Les indications de mise sous O3- huile pouvaient être la persistance d'exsudation, la douleur, l'absence d'épithélialisation, l'absence de séparation de l'escarre, l'infection (tous les patients ayant d'ailleurs une bactériologie cutanée positive avant le début du traitement). Chez chaque patient, deux zones similaires recevaient toutes les 48 h soit de l'huile ozonée (groupe 1) soit un traitement conventionnel (groupe 2). La réduction des exsudats, de la douleur et de la charge bactérienne était plus rapide dans le groupe 1, les cultures se négativant à J4 (1 à 7) dans ce groupe contre J8 (5 à 11) dans le groupe 2. Cette étude montre que le Novox® a un effet antibactérien significatif et stimule la cicatrisation. Dans notre expérience, l'utilisation de gel ou de plaques imprégnées sont plus efficaces pour promouvoir l'épithélialisation quand les compresses saturées, qui adhèrent à la plaie, sont préférables sur des tissus hyperbourgeonnants.
RESUMO
BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Idoso , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Laparoscopia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Hipertensão Portal/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/mortalidade , Tempo de Internação/estatística & dados numéricos , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The range of procedures with documented feasibility by laparoscopic approach is widening in the setting of liver resections. Many technical limits have been overcome in the attempt to reduce the biological impact of major procedures [1-8]. Similarly, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS)-which could be assumed as the paradigm of maxi-invasiveness-has recently been proposed in a minimally invasive fashion to reduce the impact of this procedure [9-12]. Technical insights to perform laparoscopic ALPPS are provided. METHODS: Perioperative and intraoperative tips for laparoscopic ALPPS are provided within a SMART (Strategy to Minimize ALPPS Risks by Targeting invasiveness) protocol. Stage 1: After volumetric and functional assessment, partial liver transection is performed, keeping intact both the hilum and the caval plane (to prevent adhesions), therefore avoiding portal ligation. No inert material is left inside the abdominal cavity at the end of procedure to keep the liver surfaces apart. Radiologic portography with portal vein embolization is scheduled on postoperative day (POD) 1. Liver volume (pre-PVE: 29%; post-PVE: 52%) and liver function measured through a Technetium-99 hepatobiliary scintigraphy [13] (pre-PVE: 2.15%/min/sqm; post-PVE: 3.67%/min/sqm) of the future remnant liver are reassessed within 10 days to verify whether size and function are adequate. Stage 2: After 2 weeks from the first stage, laparoscopic right hepatectomy is performed following an anterior approach. RESULTS: No conversion to open was required. Operative time was 100 and 300 minutes for stage 1 and 2, respectively. Intraoperative blood loss was 50 and 300 ml for the two procedures. Postoperative course was uneventful; patient was discharged on POD 6 of the second operation. CONCLUSIONS: The implementation of a perioperative protocol to prevent the risk of liver failure by both assessing volume and function of FLR and targeting the invasiveness of the surgical procedure may allow to minimize and control risks of a maximally invasive procedure, such as ALPPS.
Assuntos
Neoplasias Hepáticas , Hepatectomia , Humanos , Ligadura , Fígado , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Veia Porta/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Laparoscopic liver resection demands expertise and a long learning curve. Resection of the posterosuperior segments is challenging, and there are no data on the learning curve. The aim of this study was to evaluate the learning curve for laparoscopic resection of the posterosuperior segments. METHODS: A cumulative sum (CUSUM) analysis of the difficulty score for resection was undertaken using patient data from four specialized centres. Risk-adjusted CUSUM analysis of duration of operation, blood loss and conversions was performed, adjusting for the difficulty score of the procedures. A receiver operating characteristic (ROC) curve was used to identify the completion of the learning curve. RESULTS: According to the CUSUM analysis of 464 patients, the learning curve showed an initial decrease in the difficulty score followed by an increase and, finally, stabilization. More patients with cirrhosis or previous surgery were operated in the latest phase of the learning curve. A smaller number of wedge resections and a larger number of anatomical resections were performed progressively. Dissection using a Cavitron ultrasonic surgical aspirator and the Pringle manoeuvre were used more frequently with time. Risk-adjusted CUSUM analysis showed a progressive decrease in operating time. Blood loss initially increased slightly, then stabilized and finally decreased over time. A similar trend was found for conversions. The learning curve was estimated to be 40 procedures for wedge and 65 for anatomical resections. CONCLUSION: The learning curve for laparoscopic liver resection of the posterosuperior segments consists of a stepwise process, during which accurate patient selection is key.
ANTECEDENTES: La resección hepática laparoscópica exige experiencia y una larga curva de aprendizaje. La resección de los segmentos posterosuperiores (PS) es un reto, y no hay datos acerca de la curva de aprendizaje (learning curve, LC). El objetivo de este estudio fue evaluar la LC de la resección laparoscópica de los segmentos PS. MÉTODOS: Se realizó un análisis CUSUM de la puntuación de dificultad (difficulty score, DS) de la resección en pacientes de 4 centros especializados. La técnica CUSUM se ajustó al riesgo (risk-adjusted CUSUM, RA-CUSUM) para el tiempo operatorio, la pérdida de sangre y las conversiones a cirugía abierta ajustando según la DS de los procedimientos. Se utilizó una curva ROC para identificar el momento en el que se consideró que la LC había sido completada. RESULTADOS: De acuerdo con el análisis CUSUM de los 464 pacientes incluidos, se observó una DS baja al inicio, que posteriormente se fue incrementando hasta llegar a una estabilización. En la última fase de la LC se operaron más pacientes con cirrosis o cirugía previa. De forma progresiva se fueron reduciendo el número de resecciones hepáticas en cuña y aumentando el de resecciones anatómicas. A lo largo del tiempo se introdujo el CUSA y la maniobra de Pringle con mayor frecuencia. El RA-CUSUM mostró una reducción progresiva del tiempo operatorio. La pérdida de sangre inicialmente aumentó ligeramente, luego se estabilizó y finalmente disminuyó con el tiempo. Una tendencia similar se observó para las conversiones. La LC se estimó en 40 casos para las resecciones en cuña y en 65 casos para las resecciones anatómicas. CONCLUSIÓN: La LC de la resección hepática laparoscópica de los segmentos PS es un proceso paso a paso durante el cual la selección del paciente es clave.
Assuntos
Hepatectomia/educação , Laparoscopia/educação , Curva de Aprendizado , Hepatopatias/cirurgia , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Conversão para Cirurgia Aberta/estatística & dados numéricos , Feminino , Hepatectomia/métodos , Hepatectomia/normas , Humanos , Laparoscopia/normas , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Seleção de Pacientes , Curva ROCRESUMO
BACKGROUND: Laparoscopic major hepatectomy is expanding, but little data exist comparing surgical approaches. The aim of this study was to test the hypothesis that pure laparoscopic liver resection (PLAP) has advantages over hand-assisted (HALS) or hybrid (HYB) resection for major hemi-hepatectomy at two western centers. METHODS: Using propensity score matching, 65 cases of HALS + HYB (18 hand-assisted and 47 hybrid) were matched to 65 cases of PLAP. Baseline characteristics were well matched for gender, age, ASA score, Childs A cirrhosis, right/left hepatectomy, malignancy, tumor size, and type between the groups. RESULTS: The HALS + HYB group had 27 right and 38 left major hepatectomies (n = 65) versus 29 right and 36 left (n = 65) in the PLAP group (p = NS). The median number of lesions resected was 1 in each group, with median size 5.6 cm (HALS + HYB) versus 6.0 cm (PLAP), (p = NS). The HALS + HYB group had shorter OR time (240 versus 330 min, p < 0.01), and less blood loss (EBL 150 ml vs. 300 ml, p < 0.01) versus the PLAP group, respectively. Median length of stay (LOS) was 4 days with HALS + HYB versus 5 days in the PLAP group (p = 0.02). There were no significant differences in use of the Pringle maneuver, transfusion rate, ICU stay, post-op morbidity, liver-specific complications, or R0 resection. Pain regimen/usage in each group is provided. There were no 30/90-day deaths in either group. CONCLUSION: This is the first reported series of propensity score matching of HALS + HYB versus PLAP for major hepatectomy. The HALS + HYB group had non-inferior OR time, blood loss, and LOS versus the PLAP group, while the other perioperative parameters were comparable. We conclude that minimally invasive liver resection with either PLAP or HALS + HYB technique yields excellent results.
Assuntos
Laparoscopia Assistida com a Mão , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Feminino , Laparoscopia Assistida com a Mão/efeitos adversos , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pontuação de Propensão , Carga TumoralRESUMO
BACKGROUND: Repeat liver resection is often the best treatment option for patients with recurrent colorectal liver metastases (CRLM). Repeat resections can be complex, however, owing to adhesions and altered liver anatomy. It remains uncertain whether the advantages of a laparoscopic approach are upheld in this setting. The aim of this retrospective, propensity score-matched study was to compare the short-term outcome of laparoscopic (LRLR) and open (ORLR) repeat liver resection. METHODS: A multicentre retrospective propensity score-matched study was performed including all patients who underwent LRLRs and ORLRs for CRLM performed in nine high-volume centres from seven European countries between 2000 and 2016. Patients were matched based on propensity scores in a 1 : 1 ratio. Propensity scores were calculated based on 12 preoperative variables, including the approach to, and extent of, the previous liver resection. Operative outcomes were compared using paired tests. RESULTS: Overall, 425 repeat liver resections were included. Of 271 LRLRs, 105 were matched with an ORLR. Baseline characteristics were comparable after matching. LRLR was associated with a shorter duration of operation (median 200 (i.q.r. 123-273) versus 256 (199-320) min; P < 0·001), less intraoperative blood loss (200 (50-450) versus 300 (100-600) ml; P = 0·077) and a shorter postoperative hospital stay (5 (3-8) versus 6 (5-8) days; P = 0·028). Postoperative morbidity and mortality rates were similar after LRLR and ORLR. CONCLUSION: LRLR for CRLM is feasible in selected patients and may offer advantages over an open approach.
Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Reoperação/métodos , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The accessibility to posterosuperior segments of the liver has traditionally constituted a restrain to adopt the laparoscopic approach in this setting. To overcome this challenge, multiple approaches have been reported in literature. Total transabdominal approach has been previously described for this purpose, even though the rationale to standardly adopt it and a technical depiction of how to achieve an optimal mobilization has never been specifically addressed. METHODS: Total transabdominal purely laparoscopic approach to posterosuperior segments of the liver is presented, with detailed emphasis to the rotational motions targeted in laparoscopy. A literature review is presented to summarize all other possible accesses to posterosuperior area of the liver. The institutional series for the laparoscopic approach to Sg 7, Sg 6+7, and Sg8 is retrospectively described. RESULTS: Three rotational motions of the liver are specifically addressed in a video presentation and described for the laparoscopic total-transabdominal approach; the local institutional series using this approach is presented. Other miscellaneous approaches identified from literature encompassing variations in operative position, transabdominal, transthoracic, and combined approaches are described. CONCLUSIONS: Complete mobilization of the ligaments of the liver leads to a rotation of the transection line in front of the operator's view, allowing to achieve a safe total trans-abdominal laparoscopic approach to the posterosuperior ligaments of the liver, without compromising the vascular inflow control, the possibility to convert to open approach, nor requiring potentially harmful decubitus.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/secundário , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Previous studies have demonstrated that patient, surgical, tumour and operative variables affect the complexity of laparoscopic liver resections. However, current difficulty scoring systems address only tumour factors. The aim of this study was to develop and validate a predictive model for the risk of intraoperative complications during laparoscopic liver resections. METHODS: The prospectively maintained databases of seven European tertiary referral liver centres were compiled. Data from two-thirds of the patients were used for development and one-third for validation of the model. Intraoperative complications were based on a modified Satava classification. Using the methodology of the Framingham Heart Study, developed to identify risk factors that contribute to the development of cardiovascular disease, factors found to predict intraoperative complications independently were assigned points, and grouped into low-, moderate-, high- and extremely high-risk groups based on the likelihood of intraoperative complications. RESULTS: A total of 2856 patients were included. Neoadjuvant chemotherapy, lesion type and size, classification of resection and previous open liver resection were found to be independent predictors of intraoperative complications. Patients with intraoperative complications had a longer duration of hospital stay (5 versus 4 days; P < 0·001), higher complication rates (32·5 versus 15·5 per cent; P < 0·001), and higher 30-day (3·0 versus 0·3 per cent; P < 0·001) and 90-day (3·8 versus 0·8 per cent; P < 0·001) mortality rates than those who did not. The model was able to predict intraoperative complications (area under the receiver operating characteristic (ROC) curve (AUC) 0·677, 95 per cent c.i. 0·647 to 0·706) as well as postoperative 90-day mortality (AUC 0·769, 0·681 to 0·858). CONCLUSION: This comprehensive scoring system, based on patient, surgical and tumour factors, and developed and validated using a large multicentre European database, helped estimate the risk of intraoperative complications.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Complicações Intraoperatórias/diagnóstico , Laparoscopia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Carcinoma Hepatocelular/diagnóstico , Seguimentos , Humanos , Incidência , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Neoplasias Hepáticas/diagnóstico , Pessoa de Meia-Idade , Duração da Cirurgia , Prognóstico , Estudos Prospectivos , Curva ROC , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: A dramatic spread of laparoscopic liver surgery has been experienced over the last years. The approach to paracaval liver segments 1 and 9 is still poorly described in literature, mainly due to its technical demands. OBJECTIVE: The aim of this article was to introduce a safe and effective approach to paracaval liver segments through laparoscopy. METHODS: A minimally invasive approach to resection of Segments 1 and 9 is presented, and an operative set-up is depicted. A step-by-step technique describing the inferior vena cava (IVC) with left and right hepatic venous junction exposure, segmental pedicle isolation, and parenchymal transection is shown through a video document. RESULTS: Postoperative courses were uneventful, and patients were discharged on postoperative day 3. DISCUSSION: The approach to paracaval liver segments requires accurate preoperative case selection, technical, surgical, and anesthesiological expertise in laparoscopic liver surgery, and adequate instrumentary. CONCLUSION: Paracaval segments of the liver can be approached safely through laparoscopy by teams with extensive expertise in the field of laparoscopic liver surgery; however, suspected malignant infiltration of the IVC or unclear preoperative anatomy still contraindicate this approach.
Assuntos
Neoplasias do Colo/patologia , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Veia Cava Inferior/cirurgia , Dissecação , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: Adeno-associated virus type 2 (AAV) is a nonpathogenic parvovirus that is a promising tool for gene therapy. We aimed to construct plasmids for optimal expression and assembly of capsid proteins and evaluate adenovirus (Ad) protein effect on AAV single-stranded DNA (ssDNA) formation in Saccharomyces cerevisiae. METHODS AND RESULTS: Yeast expression plasmids have been developed in which the transcription of AAV capsid proteins (VP1,2,3) is driven by the constitutive ADH1 promoter or galactose-inducible promoters. Optimal VP1,2,3 expression was obtained from GAL1/10 bidirectional promoter. Moreover, we demonstrated that AAP is expressed in yeast and virus-like particles (VLPs) assembled inside the cell. Finally, the expression of two Ad proteins, E4orf6 and E1b55k, had no effect on AAV ssDNA formation. CONCLUSIONS: This study confirms that yeast is able to form AAV VLPs; however, capsid assembly and ssDNA formation are less efficient in yeast than in human cells. Moreover, the expression of Ad proteins did not affect AAV ssDNA formation. SIGNIFICANCE AND IMPACT OF THE STUDY: New manufacturing strategies for AAV-based gene therapy vectors (rAAV) are needed to reduce costs and time of production. Our study explores the feasibility of yeast as alternative system for rAAV production.
Assuntos
Proteínas do Capsídeo/genética , DNA de Cadeia Simples/genética , Dependovirus/genética , Saccharomyces cerevisiae/genética , Capsídeo , Proteínas do Capsídeo/metabolismo , DNA de Cadeia Simples/metabolismo , Expressão Gênica , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Humanos , Plasmídeos/genética , Plasmídeos/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMO
BACKGROUND: Laparoscopic resection of posterosuperior (PS) segments of the liver is hindered by limited visualization and curvilinear resection planes. The aim of this study was to compare outcomes after open and laparoscopic liver resections of PS segments. METHODS: Patients who underwent minor open liver resection (OLR) and laparoscopic liver resection (LLR) between 2006 and 2014 were identified from the institutional databases of seven tertiary referral European hepatobiliary surgical units. Propensity score-matched analysis was used to match groups for known confounders. Perioperative outcomes including complications were assessed using the Dindo-Clavien classification, and the comprehensive complication index was calculated. Survival was analysed with the Kaplan-Meier method. RESULTS: Some 170 patients underwent OLR and 148 had LLR. After propensity score-matched analysis, 86 patients remained in both groups. Overall postoperative complication rates were significantly higher after OLR compared with LLR: 28 versus 14 per cent respectively (P = 0·039). The mean(s.d.) comprehensive complication index was higher in the OLR group, although the difference was not statistically significant (26·7(16·6) versus 18·3(8·0) in the LLR group; P = 0·108). The mean(s.d.) duration of required analgesia and the median (range) duration of postoperative hospital stay were significantly shorter in the LLR group: 3·0(1·1) days versus 1·6(0·8) days in the OLR group (P < 0·001), and 6 (3-44) versus 4 (1-11) days (P < 0·001), respectively. The 3-year recurrence-free survival rates for patients with hepatocellular carcinoma (37 per cent for OLR versus 30 per cent for LLR; P = 0·534) and those with colorectal liver metastases (36 versus 36 per cent respectively; P = 0·440) were not significantly different between the groups. CONCLUSION: LLR of tumours in PS segments is feasible in selected patients. LLR is associated with fewer complications and does not compromise survival compared with OLR.
Assuntos
Carcinoma Hepatocelular/cirurgia , Laparoscopia/métodos , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/mortalidade , Tempo de Internação , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: There is a need for high-level evidence regarding the added value of laparoscopic (LLR) compared with open (OLR) liver resection. The aim of this study was to compare the surgical and oncological outcomes of patients with colorectal liver metastases (CRLM) undergoing LLR and OLR using propensity score matching to minimize bias. METHODS: This was a single-centre retrospective study using a prospective database of patients undergoing liver resection for CRLM between August 2004 and April 2015. Co-variates selected for matching included: number and size of lesions, tumour location, extent and number of resections, phase of surgical experience, location and lymph node status of primary tumour, perioperative chemotherapy, unilobar or bilobar disease, synchronous or metachronous disease. Prematching and postmatching analyses were compared. Surgical and oncological outcomes were analysed. RESULTS: Some 176 patients undergoing LLR and 191 having OLR were enrolled. After matching, 133 patients from each group were compared. At prematching analysis, patients in the LLR group showed a longer overall survival (OS) and higher R0 rate than those in the OLR group (P = 0·047 and P = 0·030 respectively). Postmatching analyses failed to confirm these results, showing similar OS and R0 rate between the LLR and OLR group (median OS: 55·2 versus 65·3 months respectively, hazard ratio 0·70 (95 per cent c.i. 0·42 to 1·05; P = 0·082); R0 rate: 92·5 versus 86·5 per cent, P = 0·186). The 5-year OS rate was 62·5 (95 per cent c.i. 45·5 to 71·5) per cent) for OLR and 64·3 (48·2 to 69·5) per cent for LLR. Longer duration of surgery, lower blood loss and morbidity, and shorter postoperative stay were found for LLR on postmatching analysis. CONCLUSION: Propensity score matching showed that LLR for CRLM may provide R0 resection rates and long-term OS comparable to those for OLR, with lower blood loss and morbidity, and shorter postoperative hospital stay.
Assuntos
Neoplasias Colorretais , Laparoscopia/estatística & dados numéricos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Hepatectomia/métodos , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/métodos , Laparoscopia/mortalidade , Tempo de Internação/estatística & dados numéricos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pontuação de Propensão , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
UNLABELLED: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. INTRODUCTION: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. METHODS: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out. RESULTS: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). CONCLUSION: In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.
Assuntos
Fibrilação Atrial/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Administração Oral , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Difosfonatos/administração & dosagem , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Distribuição por SexoRESUMO
AIM: An accurate and noninvasive tool to predict Chemotherapy Associated Liver Injury (CALI) still lacks. Study aimed to evaluate chronic liver disease scores (Aspartate aminotransferase to Platelet Ratio Index, APRI and Fibrosis-4, FIB-4) as Postoperative Liver Failure (PLF) predictors in patients treated with Oxaliplatin for Colorectal Liver Metastases (CLM). METHODS: 8 patients who developed PLF after major hepatectomy (Group B) were compared to 24 patients who did not develop PLF (Group A) in a case-matched analysis for patients and disease characteristics. ROC curves analysis was performed to assess score accuracy. RESULTS: In Group A number of CT cycles was lower, (6 vs 9, p NS), interval between treatment and surgery was longer (11 vs 7 weeks, p < 0.05) and bevacizumab was more frequently administered (66.7% vs 37.5%, p < 0.05). In Group B median APRI score was 0.53 (range: 0.86-4.26) whereas in Group A was 0.30 (range: 0.06-2.21, p < 0.05). Median FIB-4 score was 2.46 (range: 0.86-13.65) in Group B and 1.58 (range: 0.27-7.68) in Group A (p < 0.001). Multivariate analysis showed a significant correlation between APRI and the onset of PLF. A good accuracy of APRI score was evident in ROC curves with an area under the curve of 0.72 (p 0.003). CONCLUSIONS: APRI score is calculated considering both liver damage and platelet count, it is cost effective and easily available. This study demonstrates that there is a good accuracy in PLF prediction and consequently in CT induced liver damage evaluation.
Assuntos
Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Neoplasias Hepáticas/terapia , Terapia Neoadjuvante , Idoso , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Aspartato Aminotransferases/sangue , Bevacizumab , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Crônica , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Contagem de Plaquetas , Curva ROC , Estudos Retrospectivos , Fatores de RiscoRESUMO
SUMMARY: There is evidence that the use oral bisphosphonates can lead to osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare among oral bisphosphonates (BPs) users, it is important to know that it exists and can be opportunely minimized. INTRODUCTION: The purpose of this study is to evaluate the association between BPs prescribed for the secondary prevention of osteoporotic fractures and the occurrence of ONJ. METHODS: An Italian record linkage claims database with a target population of around 18 million individuals (6 million over 55 years of age) constituted the data source. We conducted a nested case-control study within a cohort of individuals aged 55+ years old, who were discharged from hospitals with a primary diagnosis of incident osteoporotic fracture. The date related to the discharge diagnosis of ONJ was the index date. Conditional logistic regression for matched data was fitted to estimate the odds ratio (OR) along with 95 % confidence intervals (95 % CI) for the likely association between use of BPs and the risk of ONJ. RESULTS: Any one of the 61 ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was matched to 20 controls for a total of 1120 controls. When the exposure to BPs was modeled according to recency (i.e., exposure time window prior to the index date) of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against never users. The cumulative use of BPs has shown to increase the incidence of ONJ among patients with primary osteoporotic fractures, although not statistically significant risk has been observed. CONCLUSIONS: Although the risk of BP-related ONJ appears low in non-oncological indications, it is important to be aware that it exists and to know how it may be predicted and possibly minimized.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Fraturas por Osteoporose/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Casos e Controles , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Feminino , Humanos , Itália/epidemiologia , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Medição de Risco/métodosRESUMO
This study evaluates the risk of mortality in a cohort of Italian alcoholics resident in a rural area characterised by traditional drinking habits. Individual vital status of the 1,037 patients enrolled at the Centro Alcologico in Arezzo during the 1979-1997 period has been traced. Causes of death (ICD-IX) have been retrieved from the Regional Mortality Register. Standardised mortality ratios (SMR) have been computed according to gender and 5-year age group mortality rates of the general population resident in Tuscany during the same period. This cohort is representative of the traditional rural alcoholism of the Tuscany region based on wine consumption. Among the 9,190 person-years followed-up, 333 deaths have occurred, corresponding to approximately 2.6 fold the expected number of deaths (SMR males: 2.6; females: 2.4). In both genders, significantly high SMRs for liver cirrhosis, oesophagus and liver cancer are reported, while SMRs of cancers at all sites, oral and respiratory cancers, injuries as a whole, road and traffic accidents, and suicides are significantly elevated only among males. No relevant variation between expected and observed deaths for pancreatic diseases, colon cancer, female breast cancer, and, despite a large proportion of heavy smokers, for cardiovascular diseases (hypertension, cerebrovascular diseases, coronary heart diseases) has been recorded. This research confirms the high mortality among a cohort of Italian alcoholics. However, causes of death related with violence and trauma are proportionally less represented, in accordance with the social pattern of Mediterranean alcoholism. The absence of cardiovascular mortality risk in a wine-based cohort of alcoholics is an unexpected finding that requires to be further examined. Finally, to prevent smoking related deaths, alcohol addiction services should begin to introduce smoking cessation practices among treatment protocols.
Assuntos
Alcoolismo/mortalidade , Adulto , Idoso , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: In a population-based multicenter case-control study of diet, life-style, and gastric cancer a large series of adults, aged 30-75 years (mean 58.9 years), were randomly sampled from the general population in 3 areas of Central-Northern Italy. AIM OF THE STUDY: To evaluate the relationship between plasma levels of antioxidant vitamins and cholesterol, and sociodemographic characteristics, life-style factors, and dietary intake of selected nutrients in a sample of the Italian population. METHODS: A fasting blood sample was available for 945 subjects (553 men, 392 women). The plasma concentrations of ascorbic acid, carotene, retinol, alpha-tocopherol, and cholesterol were determined by a centralized laboratory. All participants answered to a detailed questionnaire collecting information on sociodemographic and anthropometric characteristics, smoking, alcohol drinking, and dietary habits. Covariance analysis models, with post hoc Dunnett tests, including terms for age, sex, study center, and period of blood drawing, were used for selected multiple-way comparisons of mean values of plasma nutrients. RESULTS: Mean plasma values of retinol were higher among men while women had higher levels of plasma carotene, ascorbic acid, alpha-tocopherol, and cholesterol. Plasma carotene levels showed an inverse association with body mass index, alcohol consumption, and smoking and a positive association with social class. Carotene concentrations were higher in plasma samples obtained in spring/summer, while ascorbic acid levels were higher in autumn/winter. Partial correlation co-efficients between plasma vitamin levels showed a strong correlation between carotene and ascorbic acid (0.69 in men; 0.74 in women), between carotene and alpha-tocopherol (0.44; 0.37), and between alpha-tocopherol and ascorbic acid (0.45; 0.41). Plasma alpha-tocopherol and retinol correlated with plasma cholesterol. On the other hand, plasma carotene and ascorbic acid were correlated with their estimated dietary intakes, while the intakes of other nutrients, as expected, correlated rather poorly with the respective plasma concentrations. CONCLUSIONS: Socio-economic factors, life-style, and specific nutrient intake, in addition to gender, are related to nutrient plasma levels in Italian adults and may provide specific suggestions for the prevention of chronic diseases.