Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility.

BACKGROUND: Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial. METHODS: Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL). RESULTS: A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3·1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was -111 ml (P = 0·456). Among patients at high risk of transfusion, the median EBL difference was -448 ml (P = 0·069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7·6(1·9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0·326). CONCLUSION: Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La resección hepática mayor se asocia con pérdida de sangre y necesidad de transfusión. Datos observacionales sugieren que la flebotomía hipovolémica (hypovolaemic phlebotomy, HP) puede reducir estos riesgos. Este ensayo clínico aleatorizado (randomised clinical trial, RCT) de factibilidad comparó HP con el tratamiento estándar con el fin de proporcionar información para un futuro ensayo multicéntrico. MÉTODOS: Se reclutaron pacientes sometidos a resecciones hepáticas mayores entre junio 2016 y enero 2018. La aleatorización se realizó durante el intraoperatorio y los cirujanos eran ciegos al resultado de la asignación. Para la HP, se extrajeron 7-10 mL/kg de sangre total, sin reposición de líquidos intravenosos. Los resultados primarios fueron la factibilidad y la pérdida de sangre estimada (estimated blood loss, EBL). RESULTADOS: Un total de 62 pacientes se aleatorizaron a HP (n = 31) y a tratamiento estándar (n = 31), a un ritmo de 3,1 pacientes/mes, cumpliendo el co-objetivo primario de la factibilidad. La mediana de la diferencia de EBL fue 11 mL (P = 0,46). Entre los pacientes con alto riesgo de transfusión, la mediana de la diferencia de EBL fue 448 mL (P = 0,069). Los objetivos secundarios de factibilidad se consiguieron: reclutamiento (89%), cegamiento (98%), y objetivo de la flebotomía (7,6 ± 1,9 mL/kg). Los cirujanos que fueron cegados percibieron que la resección fue más fácil con la HP (52% versus 32%) y acertaron el uso de HP con una exactitud del 65%. No hubo diferencia significativa en las complicaciones globales (32% versus 48%), complicaciones mayores y transfusión. Entre aquellos pacientes de alto riesgo, la trasfusión se realizó en un 13% versus 33% (P = 0,33). CONCLUSIÓN: Se cumplieron los objetivos, pero no se identificó diferencia en EBL en este estudio de factibilidad. Ello justifica un ensayo multicéntrico (PRICE-2) con poder estadístico para identificar una diferencia en la transfusión de sangre perioperatoria.

Hepatocellular carcinoma tumour burden score to stratify prognosis after resection.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. METHODS: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. RESULTS: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). CONCLUSION: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

ANTECEDENTES: Aunque el sistema de estadificación del Barcelona Clinic Liver Cancer (BCLC) ha sido adoptado en gran medida en la práctica clínica, estudios recientes han enfatizado la necesidad de un mayor refinamiento y subclasificación del sistema BCLC. MÉTODOS: Los pacientes con carcinoma hepatocelular (hepatocellular cancer, HCC) BCLC-0, A y B que se sometieron a una hepatectomía con intención curativa entre 2000 y 2017 fueron identificados utilizando una base de datos multi-institucional. Se calculó la puntuación de carga tumoral (tumour burden score, TBS) y se examinó la supervivencia global (overall survival, OS) en relación con la TBS y los estadios BCLC. RESULTADOS: En la serie de 1.053 pacientes, 63 (6%) tenían HCC BCLC-0, 826 (78,4%) HCC BCLC-A y 164 (15,6%) HCC BCLC-B. La OS disminuyó de forma incremental en función de la mayor TBS (OS a 5 años; TBS baja: 77,9% versus TBS media: 61% versus TBS alta: 39%, P < 0,001). No se observaron diferencias en la OS entre pacientes con una puntuación TBS similar, independientemente del estadio BCLC (BCLC-A/TBS media: 61,6% versus BCLC-B/TBS media: 58,9%, P = 0,93; BCLC-A/TBS alta: 45,1% versus BCLC-B/TBS alta: 12,8%, P = 0,175). Los pacientes con BCLC-B/TBS media tuvieron una mejor OS que los pacientes con BCLC-A/TBS alta (58,9% versus 45,1%, P = 0,005). En el análisis multivariable, la TBS se mantuvo asociada a la OS en el caso de BCLC-A (TBS media: cociente de riesgos instantáneos, hazard ratio, HR = 2,07, i.c. del 95%: 1,42-3,02, P < 0,001; TBS alta: HR = 4,05, i.c. del 95%: 2,40-6,82, P < 0,001) y BCLC-B pacientes (TBS alta: HR = 3,85, i.c. del 95%: 2,03-7,30, P < 0,001). La TBS también pudo estratificar el pronóstico entre pacientes en una cohorte de validación externa (OS a 5 años; TBS baja: 78,7% versus TBS media: 51,2% versus TBS alta: 27,6%, P = 0,01). CONCLUSIÓN: El pronóstico de los pacientes con HCC varió según el estadio BCLC, pero dependió en gran medida de la TBS.

Historical epidemiology of hepatitis C virus in select countries-volume 4.

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

Excessive Daytime Sleepiness among Hypertensive US-Born Blacks and Foreign-Born Blacks: Analysis of the CAATCH Data.

Background. Evidence shows that blacks exhibit greater daytime sleepiness compared with whites, based on the Epworth Sleepiness Scale. In addition, sleep complaints might differ based on individuals' country of origin. However, it is not clear whether individuals' country of origin has any influence on excessive daytime sleepiness (EDS). Study Objectives. We tested the hypothesis that US-born blacks would show a greater level of EDS compared with foreign-born blacks. The potential effects of sociodemographic and medical risk were also determined. Design. We used the Counseling African-Americans to Control Hypertension (CAATCH) data. CAATCH is a group randomized clinical trial that was conducted among 30 community healthcare centers in New York, yielding baseline data for 1,058 hypertensive black patients. Results. Results of univariate logistic regression analysis indicated that US-born blacks were nearly twice as likely as their foreign-born black counterparts to exhibit EDS (OR = 1.87, 95% CI: 1.30-2.68, P < 0.001). After adjusting for effects of age, sex, education, employment, body mass index, alcohol consumption, and smoking habit, US-born blacks were 69% more likely than their counterparts to exhibit EDS (OR = 1.69, 95% CI: 1.11-2.57, P < 0.01). Conclusion. Findings demonstrate the importance of considering individuals' country of origin, in addition to their race and ethnicity, when analyzing epidemiologic sleep data.