Functional transition:Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUND Preoperative portal vein embolization(PVE)is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant.PVE induces hypertrophy of the future liver remnant(FLR)and a shift of the functional reserve to the FLR.However,whether the increase of the FLR volume(FLRV)corresponds to the functional transition after PVE remains unclear.AIM To investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional(3D)computed tomography(CT)and 99mTc-galactosyl-human serum albumin(99mTc-GSA)singlephoton emission computed tomography(SPECT)fusion images.METHODS Thirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I,Hokkaido University Hospital between October 2013 and March 2018 were enrolled.Three-phase dynamic multidetector CT and 99mTc-GSA SPECT scintigraphy were performed at pre-PVE,and at 1 and 2 wk after PVE;3D 99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system.Functional FLRV(FFLRV)was defined as the total liver volume×(FLR volume counts/total liver volume counts)on the 3D 99m Tc-GSA SPECT CT-fused images.The calculated FFLRV was compared with FLRV.RESULTS FFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE(P<0.01).The increase in FFLRV and FLRV was 55.1%±41.6%and 26.7%±17.8%(P<0.001),respectively,at 1 wk after PVE,and 64.2%±33.3%and 36.8%±18.9%(P<0.001),respectively,at 2 wk after PVE.In 3 of the 33 patients,FFLRV levels decreased below FLRV at 2 wk.One of the three patients showed rapidly progressive fatty changes in FLR.The biopsy at 4 wk after PVE showed macroand micro-vesicular steatosis of more than 40%,which improved to 10%.Radical resection was performed at 13 wk after PVE.The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSION The functional transition lagged behind the increase in FLRV after PVE in some cases.Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.

Outcomes of reduction hepatectomy combined with postoperative multidisciplinary therapy for advanced hepatocellular carcinoma

BACKGROUND The prognosis of advanced hepatocellular carcinoma(HCC)that is not indicated for curative hepatectomy remains poor,despite advances in the treatment of HCC,including the development of tyrosine kinase inhibitors(TKIs).The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy,including those of recently treated cases,should be investigated.AIM To examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy.METHODS Thirty cases of advanced HCC that were not indicated for curative hepatectomy,in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I,Hokkaido University Graduate School of Medicine,were divided into postoperative complete remission(POCR)(+)and POCR(-)groups,depending on whether POCR of all evaluable lesions was achieved through postoperative treatment.The cases in the POCR(-)group were subdivided into POCR(-)TKI(+)and POCR(-)TKI(-)groups,depending on whether TKIs were administered postoperatively.RESULTS The 5-year overall survival rate and mean survival time(MST)after reduction hepatectomy were 15.7%and 28.40 mo,respectively,for all cases;37.5%and 56.55 mo,respectively,in the POCR(+)group;and 6.3%and 14.84 mo,respectively,in the POCR(-)group(P=0.0041).Tumor size,major vascular invasion,and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival outcomes.The number of tumors in the remnant liver was the only factor that differed significantly between the POCR(+)and POCR(-)groups,and POCR was achieved significantly more frequently when≤3 tumors remained in the remnant liver(P=0.0025).The MST was 33.52 mo in the POCR(-)TKI(+)group,which was superior to the MST of 10.74 mo seen in the POCR(-)TKI(-)group(P=0.0473).CONCLUSION Reduction hepatectomy combined with multidisciplinary postoperative treatment for unresectable advanced HCC that was not indicated for curative hepatectomy was effective when POCR was achieved via multidisciplinary postoperative therapy.To achieve POCR,reduction hepatectomy should aim to ensure that≤3 tumors remain in the remnant liver.Even in cases in which POCR is not achieved,combined treatment with reduction hepatectomy and multidisciplinary therapy can improve survival outcomes when TKIs are administered.

Impact of comorbid renal dysfunction in patients with hepatocellular carcinoma on long-term outcomes after curative resection

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies worldwide.However,the number of patients with chronic kidney disease(CKD)is on the rise because of the increase in lifestyle-related diseases.AIM To establish a tailored management strategy for HCC patients,we evaluated the impact of comorbid renal dysfunction(RD),as stratified by using the estimated glomerular filtration rate(EGFR),and assessed the oncologic validity of hepatectomy for HCC patients with RD.METHODS We enrolled 800 HCC patients who underwent hepatectomy between 1997 and 2015 at our university hospital.We categorized patients into two(RD,EGFR<60 mL/min/1.73 m^(2);non-RD,EGFR≥60 mL/min/1.73 m^(2))and three groups(severe CKD,EGFR<30 mL/min/1.73 m^(2);mild CKD,30≤EGFR<60 mL/min/1.73 m2;control,EGFR≥60 mL/min/1.73 m^(2))according to renal function as defined by the EGFR.Overall survival(OS)and recurrence-free survival(RFS)were compared among these groups with the log-rank test,and we also analyzed survival by using a propensity score matching(PSM)model to exclude the influence of patient characteristics.The mean postoperative observation period was 64.7±53.0 mo.RESULTS The RD patients were significantly older and had lower serum total bilirubin,aspartate aminotransferase,and aspartate aminotransferase levels than the non-RD patients(P<0.0001,P<0.001,P<0.05,and P<0.01,respectively).No patient received maintenance hemodialysis after surgery.Although the overall postoperative complication rates were similar between the RD and non-RD patients,the proportions of postoperative bleeding and surgical site infection were significantly higher in the RD patients(5.5%vs 1.8%;P<0.05,3.9%vs 1.8%;P<0.05,respectively),and postoperative bleeding was the highest in the severe CKD group(P<0.05).Regardless of the degree of comorbid RD,OS and RFS were comparable,even after PSM between the RD and non-RD groups to exclude the influence of patient characteristics,liver function,and other causes of death.CONCLUSION Comorbid mild RD had a negligible impact on the prognosis of HCC patients who underwent curative hepatectomy with appropriate perioperative management,and close attention to severe CKD is necessary to prevent postoperative bleeding and surgical site infection.

Intravenous immunoglobulin suppresses IL-10 production by activated B cells in vitro

A therapeutic preparation of polyclonal human IgG, i.e., intravenous immunoglobulin (IVIg), has been employed to treat several inflammatory and autoimmune disorders. B cells are supposed to be a target of IVIg, but the molecular mechanism is elusive because of the lack of a suitable experimental system. To gain an insight into the beneficial effect of IVIg on B cells, we first established an experimental setting in which IVIg modulates a murine B cell function in vitro, and then aimed at identifying the mechanistic features at the molecular level. Here we show that IVIg down-regulates IL-10 production by CpG-activated B cells in vitro. The responsible component of IVIg was identified as the F(ab’)2 portion, whose polyclonality is mandatory for the suppressive effect. IVIg, bound to the surface of activated B cells, was found to be co-localized with intracellular SHP-1 on confocal laser microscopy, suggesting that B cell-surface immunoreceptor tyrosine-based inhibitory motif-harboring receptors that recruit SHP-1 are target molecules for IVIg in our experimental setting. Overall, we postulate a scenario in which IVIg attenuates B cells by suppressing IL-10 production, a B cell growth factor, and thus down-regulates the production of pathogenic antibodies.