Prevention of biliary fistula after partial hepatectomy by transcystic biliary drainage: randomized clinical trial.

BACKGROUND: Biliary fistula is one of the most common complications after hepatectomy. This study evaluated the effect of transcystic biliary drainage during hepatectomy on the occurrence of postoperative biliary fistula. METHODS: This multicentre RCT was carried out from 2009 to 2016 in nine centres. Patients were randomized to transcystic biliary drainage or no transcystic drainage (control). Patients underwent hepatectomy (more than 2 segments) of non-cirrhotic livers. The primary endpoint was the occurrence of biliary fistula after surgery. Secondary endpoints were morbidity, postoperative mortality, duration of hospital stay, reoperation, readmission to hospital, and complications caused by catheters. Intention-to-treat and per-protocol analyses were performed. RESULTS: A total of 310 patients were randomized. In intention-to-treat analysis, there were 158 patients in the transcystic group and 149 in the control group. Seven patients were removed from the per-protocol analysis owing to protocol deviations. The biliary fistula rate was 5·9 per cent in intention-to-treat and 6·0 per cent in per-protocol analyses. The rate was similar in the transcystic and control groups (5·7 versus 6·0 per cent; P = 1·000). There were no differences in terms of morbidity (49·4 versus 46·3 per cent; P = 0·731), mortality (2·5 versus 4·7 per cent; P = 0·367) and reoperations (4·4 versus 10·1 per cent; P = 1·000). Median duration of hospital stay was longer in the transcystic group (11 versus 10 days; P = 0·042). The biliary fistula risk was associated with the width and length of the hepatic cut surface. CONCLUSION: This randomized trial did not demonstrate superiority of transcystic drainage during hepatectomy in preventing biliary fistula. The use of transcystic drainage during hepatectomy to prevent postoperative biliary fistula is not recommended. Registration number: NCT01469442 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La fístula biliar es una de las complicaciones más comunes después de la hepatectomía. Este estudio evalúa el efecto del drenaje biliar transcístico durante la hepatectomía en la aparición de una fístula biliar postoperatoria. MÉTODOS: Este ensayo prospectivo aleatorizado y multicéntrico (Clinical Trial NCT01469442) con dos grupos de estudio (grupo transcístico versus grupo control) se llevó a cabo de 2009 a 2016 en 9 centros. Los pacientes fueron sometidos a una hepatectomía (≥ 2 segmentos) en hígados no cirróticos. El resultado principal fue la aparición de una fístula biliar después de la cirugía. Los resultados secundarios fueron la morbilidad, la mortalidad postoperatoria, la duración de la estancia hospitalaria, la reintervención, la necesidad de reingreso y las complicaciones causadas por los catéteres. Se realizaron análisis por intención de tratamiento y por protocolo. RESULTADOS: Un total de 310 pacientes fueron randomizados. Por intención de tratamiento, 158 pacientes fueron aleatorizados al grupo transcístico y 149 al grupo control. Siete pacientes fueron excluidos del análisis por protocolo por desviaciones del protocolo. La tasa de fístula biliar fue del 5,9% en el análisis por intención de tratamiento y del 6,0% en el análisis por protocolo. Esta tasa fue similar para el grupo transcístico y para el grupo control: 5,7% versus 6,0% (P = 1). No hubo diferencias en términos de morbilidad (49,4% versus 46,9%, P = 0,731), mortalidad (2,5% versus 4,7%, P = 0,367) y reintervenciones (4,4% versus 10,1%, P = 1). La mediana de la duración de la estancia hospitalaria fue mayor para el grupo transcístico (11 versus 10 días, P = 0,042). El riesgo de fístula biliar se correlacionó con el grosor y la longitud de la transección hepática. CONCLUSIÓN: Este ensayo aleatorizado no demuestra la superioridad del drenaje transcístico durante la hepatectomía para prevenir la fístula biliar. No se recomienda el uso de drenaje transcístico durante la hepatectomía para prevenir la fístula biliar postoperatoria.

Major abdominal surgery for cancer: does epidural analgesia have a long-term effect on recurrence-free and overall survival?

BACKGROUND: Retrospective studies have suggested that regional analgesia combined with general anaesthesia could decrease cancer recurrence. The purpose of this study was to assess the influence of regional analgesia on recurrence-free (RFS) and overall survival in patients undergoing major intra-abdominal surgery for cancer. METHOD: Patients previously included in a prospective randomized study comparing two postoperative techniques of analgesia were retrospectively studied. The EP group received general anaesthesia with bupivacaine thoracic epidural analgesia and the SC group received general anaesthesia with fentanyl followed by continuous subcutaneous morphine. RESULTS: One hundred and thirty-two patients were analyzed (63 and 69 in SC and EP group, respectively) with a 17-year-median follow-up. After 5 years, RFS was 43% [95% CI: 32%-55%] in EP group and 24% [95% CI: 15%-36%] in SC group, but the difference did not reach statistical significance for RFS nor for overall survival (P=0.10 and 0.16 respectively). Using multivariable analysis over the whole follow-up period, the type of analgesia was not a statistically significant predictive factor for RFS (EP/SC, HR=1.3 [95% CI: 0.8-2.0%]). The anaesthesia effect changed moderately over the follow-up and HR for overall survival (EP/SC) reached statistical significance after 5, 6 and 8 years. CONCLUSION: Despite a trend in favour of the epidural, this retrospective review of patients included in a previous randomized study failed to demonstrate a statistically significant association between the perioperative analgesia and RFS after abdominal surgery for cancer. The duration of follow-up may have an impact on the analgesia effect on survival.

Levels of circulating CD45(dim)CD34(+)VEGFR2(+) progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors.

BACKGROUND: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45(dim)CD34(+)VEGFR2(+) progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). METHODS: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45(-)CD31(+)CD146(+)7-amino-actinomycin (7AAD)(-) cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1α and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells, plasma factors, as well as day 1-day 14 changes in CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined. RESULTS: No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cell levels were associated with PFS (P=0.01) and OS (P=0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P=0.03, P=0.002). Changes in VEGF and SDF-1α levels were associated with OS (P=0.02, P=0.007). CONCLUSION: Monitoring CD45(dim)CD34(+)VEGFR2(+) progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome.

Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer.

BACKGROUND: In patients with bone metastases from castration-resistant prostate cancer (CRPC) not pretreated with a bisphosphonate elevated N-telopeptide of type I collagen (uNTx), a marker of bone resorption, predicts skeletal-related events (SRE). The aim of this study was to assess the prognostic value of uNTx for overall survival (OS) and the incidence of SRE in patients with bone metastases from CRPC receiving zoledronic acid. METHODS: From 2004 to 2007, 94 patients with bone metastases from CRPC receiving zoledronic acid for at least 2 months were screened for uNTx. RESULTS: Median age was 66 years (range 46-88). Median serum prostate-specific antigen (PSA) was 66 ng/ml (0-3984) and median uNTx was 19 nmol/mM creatinine (3-489). During follow-up, 38 patients (40%) experienced an SRE. Median OS was 20 months [95% (CI) confidence interval 15-24). In the multivariate analysis, elevated uNTx [hazard ratio (HR) 2.2 (95% CI 1.2-4.0)], serum PSA [HR 2.8 (95% CI 1.6-5.1)], and ECOG performance status were the only independent prognostic factors for OS. Median OS was 12 months (10-16) and 25 months (21-34) in patients with uNTx > or =20 nmol/mM creatinine and in those with uNTx <20 nmol/mM creatinine, respectively. CONCLUSION: An elevated uNTx level is an independent prognostic factor for OS in patients with bone metastases from CRPC receiving a bisphosphonate.

Microvascular leakage and contrast enhancement as prognostic factors for recurrence in unfavorable low-grade gliomas.

Perfusion estimates and microvascular leakage (MVL) were recently correlated with glioma angiogenesis and aggressiveness, but their role in predicting outcome of patients (pts) with unfavorable low-grade gliomas (ULGG) is unclear. Their prognostic value was then investigated, versus conventional factors such as age, neurological status, tumor size, and contrast enhancement (CE). Clinical and anatomical magnetic resonance imaging (MRI) criteria of a cohort of ULGG pts were prospectively evaluated. A dynamic T2*-weighted MR sequence was included to detect high-perfusion areas, using the maximal value of the relative cerebral blood volume (rCBV) estimate, and MVL. Conventional and microvascular characteristics were correlated with progression-free survival (PFS). Among the 46 pts included, the following features were present in 61%, 26%, 67%, and 26%, respectively: age >or=40 years, neurological deficits, tumor size >or=6 cm, and CE. High perfusion value was noted in 30% of cases and MVL in 52%. With median follow-up of 22 months (range 4-46 months), median PFS was 32 months [95% confidence interval (CI) 17-45 months]. On univariate analysis, CE, rCBV, and MVL were significantly correlated with PFS. On multivariate analysis, only CE and MVL were unfavorable factors, with hazard ratio of 3.0 and 7.3 and P value of 0.04 and 0.02, respectively. Different prognostic subgroups were identified, with 2-year PFS of 86%, 57%, and 19% for pts with no MVL, MVL without CE, and MVL with CE, respectively. MVL and CE seem to predict short-term outcome in ULGG pts.