A urinary biomarker for monitoring exposures to 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate in rats.

2,2,4-Trimethyl-1,3-pentanediol monoisobutyrate (TMPD-MB) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TMPD-DB) are widely used primarily as surface stabilizers for water-based paints and plasticizers, respectively. Exposure to these compounds has been suspected as being associated with sick building syndrome and allergic diseases such as asthma in general populations. Therefore, it is very important to be able to know the amounts of these compounds absorbed into the body in order to evaluate its adverse effects on humans in living environments. In the present study, the urinary excretion kinetics of TMPD-MB and TMPD-DB were studied in animals to establish for urinary metabolites suitable as biomarkers for monitoring exposure. A single dose (48-750 mg/kg body weight) of TMPD-MB or TMPD-DB was administered intraperitoneally to male Sprague-Dawley rats, and their urine was collected periodically for a week. Two major metabolites, 2,2,4-trimethyl-1,3-pentanediol (TMPD) and 3-hydroxy-2,2,4-trimethylvaleric acid (HTMV), were measured in the urine samples. Their kinetics were evaluated by moment analysis of the urinary excretion rates of the metabolites versus time curves. The urinary excretion amounts of HTMV were suggested to be proportional to the absorption amounts over a wide exposure range of both TMPD-MB and TMPD-DB. The amounts of HTMV accounted for almost the same level, i.e., 4-5% of the dose at the lowest dosage, in rats tested for both TMPD-MB and TMPD-DB. Urinary HTMV was considered to be an optimal biomarker for monitoring exposure to mixtures of these compounds.

Changes in disease characteristics of primary biliary cholangitis: An observational retrospective study from 1982 to 2016.

AIM: Disease characteristics of primary biliary cholangitis have changed recently. However, detailed studies on the subject have been limited. Therefore, we aimed to clarify disease characteristics of patients with recent primary biliary cholangitis using the cohort from Niigata University and 21 affiliated hospitals. METHODS: Overall, 508 patients were enrolled in this study from 1982 to 2016, divided into three cohorts according to their year of diagnosis: ≤1999, 2000-2009 and ≥2010. We compared differences in clinical characteristics, response to ursodeoxycholic acid and prognosis. RESULTS: The male-to-female ratio increased incrementally from 1:16.4 (≤1999) to 1:3.8 (≥2010) (P < 0.001). In women, the median age at diagnosis increased incrementally from 54.0 years (≤1999) to 60.5 years (≥2010) (P < 0.001) and serum albumin decreased gradually (P = 0.001), which might have affected the increase in the Fibrosis-4 Index and albumin-bilirubin score. The ursodeoxycholic acid response rate according to the Barcelona criteria increased incrementally from 26.7% (≤1999) to 78.4% (≥2010) (P < 0.010), and those according to other criteria (Paris-I, Rotterdam and Toronto) were approximately ≥80% in all cohorts. Ten-year survival rate in the ≤1999 and 2000-2009 cohorts were 98.6% and 95.6%, respectively. These earlier cohorts were also characterized by a higher rate of asymptomatic state and mild histology (83.5% [≤1999] and 84.7% [2000-2009], and 93.6% [≤1999] and 91.1% [2000-2009]). CONCLUSIONS: Patients with primary biliary cholangitis were characterized by older age at diagnosis and an increase in male to female ratio as well as higher response rates of ursodeoxycholic acid and longer survival, resulting from the early recognition of primary biliary cholangitis.

Efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation in patients with recurrent hepatocellular carcinoma and thrombocytopenia.

AIMS: Thrombocytopenia is often associated with chronic liver disease. Lusutrombopag is a small molecule thrombopoietin receptor agonist designed to temporarily increase the platelet count in patients with chronic liver disease for whom elective invasive procedures are planned. In the present study, the efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma were examined. METHODS: Eight patients with hepatocellular carcinoma who had a platelet count <50 000/µL prior to both initial and repeat RFA at the time of recurrence received lusutrombopag (3 mg/day) orally for 7 days between March 2016 and August 2018. The following were compared: the effect of lusutrombopag to increase the platelet count as determined by the platelet count after the initial and repeated use of lusutrombopag, the rate of avoiding platelet transfusion, and the presence of any complications. RESULTS: The platelet count increased to 103 100 ± 22 800/µL 14 days after the first treatment and to 110 700 ± 17 800/µL 14 days after the repeated use. None of the patients required platelet transfusion. None of the patients developed clinical symptoms such as thrombosis, fever, rash, portal vein thrombosis, bleeding, or any other serious adverse events. CONCLUSIONS: Repeated use of lusutrombopag increased the platelet count. It did not cause any serious adverse events and led to avoidance of platelet transfusion. Radiofrequency ablation was carried out safely in all patients. Future studies with more cases of repeated use are needed to examine the long-term efficacy and safety of lusutrombopag.

[A case of a hepatic arterial pseudoaneurysm that occurred after acute cholangitis due to choledocholithiasis].

We describe a 52-year-old male who underwent endoscopic retrograde biliary drainage for acute cholangitis associated with common bile duct stones. Endoscopic papillary balloon dilatation was performed, and the stones were removed using a balloon catheter. Simultaneously, we initiated edoxaban for portal vein thrombosis. Approximately one month later, he visited our hospital complaining of tarry stools and dizziness. Contrast-enhanced computed tomography revealed a pseudoaneurysm in the hepatic artery (A7), and he was diagnosed with hemobilia from bile duct perforation associated with the hepatic arterial pseudoaneurysm. We performed an emergent transcatheter arterial embolization. Notably, re-bleeding has not occurred to date. Hepatic arterial pseudoaneurysms can occur after acute cholangitis;therefore, careful follow-up is essential.

[Unresectable combined hepatocellular-cholangiocellular carcinoma treated with transcatheter arterial chemoembolization and gemcitabine: a case study].

A 76-year-old female was referred to our hospital because of liver dysfunction. Abdominal contrasted computed tomography (CT) revealed a tumor of 7.5cm in the hepatic hilar area. Based on the biopsy, the tumor was diagnosed by as combined hepatocellular-cholangiocellular carcinoma (with stem-cell features). The tumor was considered unresectable;hence, the patient underwent transcatheter arterial chemoembolization (TACE). However, a CT scan revealed the treatment to be ineffective. Subsequently, systemic gemcitabine (GEM) chemotherapy was administered and tumor shrinkage was observed with reperfusion of the umbilical portion of the left portal vein. The patient's condition is currently stable 17 months after diagnosis, with no tumor regrowth on account of repeated TACE and GEM therapy. The present case of unresectable combined hepatocellular-cholangiocellular carcinoma was successfully treated using TACE and systemic GEM chemotherapy.

Hemodynamic Changes on Cone-Beam Computed Tomography during Balloon-Occluded Transcatheter Arterial Chemoembolization Using Miriplatin for Hepatocellular Carcinoma: A Preliminary Study.

BACKGROUND/AIM: Balloon-occluded transcatheter arterial chemoembolization (B-TACE) using miriplatin (MPT) is anticipated as a new strategy for hepatocellular carcinoma (HCC). This study was aimed at evaluating the hemodynamic changes with/without balloon occlusion of the hepatic artery, correlation of cone-beam CT (CBCT) pixels, and CT value after B-TACE for HCC. METHODS: A total of 52 patients with HCC, who underwent B-TACE using MPT in addition to the balloon-occluded CBCT hepatic arteriography, were studied. RESULTS: After balloon occlusion, CBCT pixel values increased in 37 lesions, whereas it decreased in 15 lesions. Intratumoral CT values after B-TACE were lower with decreased CBCT pixel values than with increased CBCT pixel values. CONCLUSION: Hemodynamic changes on CBCT during balloon occlusion can be used to predict the efficacy of B-TACE using MPT.

Analytical method for urinary metabolites as biomarkers for monitoring exposure to phthalates by gas chromatography/mass spectrometry.

Phthalates, widely used as plasticizers, have been detected in indoor air, but there have been few reports on methods of analyzing urinary metabolites as biomarkers to monitor exposure to di-n-pentyl phthalate or di-n-hexyl phthalate. Presented here is a cost-effective and sensitive analytical method for the determination of urinary metabolites of phthalates containing these two compounds. Nine urinary phthalate metabolites were enzymatically hydrolyzed and extracted with toluene: monomethyl phthalate, monoethyl phthalate, monoisobutyl phthalate, mono-n-butyl phthalate, mono-n-pentyl phthalate, mono-n-hexyl phthalate, monocyclohexyl phthalate, monobenzyl phthalate and mono(2-ethyl-5-carboxypentyl) phthalate. After transformation to their tert-butyldimethylsilyl derivatives, they were analyzed by gas chromatography/mass spectrometry in the electron impact ionization mode. The calibration curves for the metabolites were linear at urinary concentrations of up to 30 µg/L, showing that they could be determined accurately and precisely (detection limits 0.1-0.4 µg/L, quantification limits 0.3-1.3 µg/L). The urine samples collected could be stored for up to 1 month at -20°C. The proposed analytical method was used to examine urine samples from seven healthy volunteers. This method should be useful for monitoring phthalate exposure in the general population.

Discrepant diagnostic results using two genotyping methods in a chronic hepatitis C patient in serogroup 1.

We present the case of a chronic hepatitis C (CHC) patient who was originally diagnosed with genotype 2a on serogroup 1 CHC genotype testing, but who was subsequently confirmed to have genotype 1b when using the hepatitis C virus (HCV) monitor genotype assay. The genotype 2a diagnosis was attributed to the fact that the type 2a-specific primer used in Okamoto et al.'s method (HCV genotype primer kit) has relatively high homology, which caused the amplification reaction to proceed, rendering a HCV RNA genotype test result of 2a. Genotype testing is important in determining whether a patient is indicated for concomitant dual oral therapy; however, the potential for different diagnoses such as described in this report highlights the importance of serogroup confirmation.

4-Methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol as a urinary biomarker for monitoring of metofluthrin, a fluorine-containing pyrethroid, in exposed rats.

CONTEXT: A fluorine-containing pyrethroid metofluthrin is widely used recently in mosquito repellents. OBJECTIVE: The urinary excretion kinetics of its metabolites was evaluated in rats to establish an optimal biomarker for monitoring metofluthrin exposure of the general population. METHODS AND RESULTS: After metofluthrin had been administered intraperitoneally to rats, the urinary excretion kinetics of the major metofluthrin metabolites was evaluated by moment analysis. The urinary excretion amounts of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol were estimated to be proportional to the absorption amounts over a wide exposure range. CONCLUSION: Urinary 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol was considered to be an optimal biomarker for metofluthrin exposure.

Concurrent partial splenic embolization with transcatheter arterial chemoembolization for hepatocellular carcinoma can maintain hepatic functional reserve.

AIM: Hepatocellular carcinoma (HCC) is frequently complicated with cirrhosis, and it is not unusual for treatment options to be limited as a result of pancytopenia due to hypersplenism. Partial splenic embolization (PSE) has been performed for thrombocytopenia resulting from hypersplenism. We studied the efficacy in terms of hepatic functional reserve and safety in patients who underwent concurrent transcatheter arterial chemoembolization (TACE) with PSE for HCC. METHODS: The study population consisted of 101 HCC patients with thrombocytopenia. Fifty-three patients were treated with concurrent TACE/PSE (PSE group), and the remaining 48 TACE patients without PSE (non-PSE group) were investigated hepatic functional reserve. RESULTS: Platelet counts were significantly higher in the PSE group after 2 weeks, 2 months and 6 months after TACE than the non-PSE group. Child-Pugh score significantly deteriorated from 7.13 ± 1.16 to 7.60 ± 1.20 at 2 weeks, to 7.71 ± 1.25 at 2 months, and 7.71 ± 1.35 at 6 weeks after TACE in the non-PSE group. Hence, it worsened from 7.04 ± 1.05 to 7.21 ± 0.99 at 2 weeks temporally, but improved to 7.00 ± 1.17 after 2 months and 6.70 ± 1.16 at 6 weeks after TACE in the PSE group. CONCLUSION: Thrombocytopenia has been improved and treatment continued using concurrent PSE. In addition, hepatic functional reserve could be maintained even after treatment for HCC. Concurrent TACE and PSE for HCC with thrombocytopenia can be expected to help maintain hepatic reserve, and may contribute to improving the prognosis of HCC.

Percutaneous transhepatic portal vein stent placement can improve prognosis for hepatocellular carcinoma patients with portal vein tumor thrombosis.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has an extremely poor prognosis. One reason is that portal hypertension may progress rapidly and intractable gastric/esophageal variceal hemorrhage may occur in PVTT cases. We studied whether a percutaneous transhepatic portal vein stent placement could improve the prognosis for HCC with PVTT. METHODOLOGY: Five cases of HCC with PVTT where portal hypertension had rapidly progressed were performed portal vein stenting. RESULTS: All cases had been classified into Child-Pugh class C. Only one of them died of liver failure five months after stent placement, but two of the cases successfully avoided dying of liver failure and the other two cases are still alive with a hepatic functional reserve maintained. CONCLUSIONS: Although portal vein stent placement for HCC with PVTT is not by itself a therapy for PVTT, portal vein stent placement plays a prominent role in improving hepatic function reserve preventing fatal hepatic failures due to PVTT and gastric/esophageal variceal hemorrhage associated with portal hypertension. This leads to prolonged survival for HCC patients with PVTT. Further prospective trials including the appropriate timing of portal vein stent placement treatment will be needed for larger numbers of HCC patients with PVTT.

Improved method for transjugular liver biopsy using imaging sheaths developed for balloon-occluded retrograde transvenous obliteration.

BACKGROUND/AIMS: Patients with ascites or coagulation abnormalities and requiring a liver biopsy may undergo transjugular liver biopsy (TJLB) rather than percutaneous liver biopsy. Currently, the difficulty in maneuvering the sheath towards the hepatic vein keeps this procedure from being widely used. Therefore, the utility of imaging sheaths, typically used for balloon-occluded retrograde transvenous obliteration, during TJLB was examined. METHODOLOGY: TJLB was conducted on 41 patients using conventional, Teflon vascular sheaths (9 Fr, 45 cm) and on 60 patients using S1 sheaths (8 Fr, 50 cm). The duration of TJLB procedures, and their associated complications were compared. RESULTS: The mean duration of the procedure was 26.9±7.94 minutes in the group undergoing TJLB with Teflon sheaths, significantly longer (p <0.01) than 20.1±4.52 minutes in the patients using S1 sheaths. However, in two (3.3%) of the S1 sheath patients, the sheaths had to be replaced with Teflon TJLB sheaths. CONCLUSIONS: This study demonstrates that liver biopsies can be successfully collected by TJLB using S1 sheaths instead of the Teflon sheaths. This substitution for a more flexible material allows for a shorter invasive intervention time for patients for which percutaneous liver biopsy is not an option.

Branched-chain amino acids to tyrosine ratio (BTR) predicts intrahepatic distant recurrence and survival for early hepatocellular carcinoma.

BACKGROUND/AIMS: The Child-Pugh classification system is the most widely used system for assessing hepatic functional reserve in HCC treatment. In the Child-Pugh classification system, serum albumin levels are used to accurately assess the status of protein metabolism and nutrition. To date, a lack of attention has been given to amino acid metabolism. In the present study, we investigated whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of amino acid metabolism can serve as both a prognostic factor for early HCC and a predictive factor for recurrence. METHODOLOGY: We conducted a cohort study of 50 patients with stage I/II HCC enrolled between May 2002 and December 2010. It was investigated whether BTR can serve as both a prognostic factor and a predictive factor for HCC recurrence. RESULTS: Overall survival rates were significantly higher in patients with high baseline BTR than in those with low BTR. Multivariate analysis showed that both BTR and serum albumin were prognostic factors, and that BTR was the best predictive factor for recurrence. CONCLUSIONS: BTR was a prognostic factor for early HCC and the most predictive factor for intrahepatic distant recurrence and contributing factors for survival.

Combination PEG-IFN a-2b/ribavirin therapy following treatment of hepatitis C virus-associated hepatocellular carcinoma is capable of improving hepatic functional reserve and survival.

BACKGROUND/AIMS: Hepatitis C virus (HCV) associated HCC shows a high rate of recurrence even after curative treatment. Outcomes of pegylated interferon PEGIFN a-2b/ribavirin (RBV) therapy for HCV-associated HCC have yet to be elucidated. We investigated therapeutic response and hepatic functional reserve improvement in patients receiving PEG-IFN a-2b/RBV after curative HCC treatment. METHODOLOGY: We investigated survival rate, metachronous recurrence and hepatic functional reserve in 54 patients with initial HCV-associated Stage I/II HCC; 29 patients were administered a preparation of PEG-IFN a-2b/RBV after HCC treatment (Secondary IFN group) and 25 were not (Non-secondary IFN group). RESULTS: A significant difference was observed in cumulative survival rates among HCV-associated HCC patients with rates of 100% after 1 year and 90.2% after 3 years in the secondary IFN group compared to 96.0% and 61.2%, respectively, in the non-secondary IFN group. Univariate analysis identified secondary IFN treatment, alanine aminotransferase and albumin levels as factors contributing to survival. Serum albumin level decreased temporarily but subsequently increased and improved hepatic functional reserve was observed in PEG-IFN a-2b/RBV therapy. CONCLUSIONS: PEG-IFN a-2b/RBV therapy after HCC treatment can improve hepatic functional reserve and may therefore represent a therapeutic option in the event of recurrence. PEG-IFN a-2b/ RBV therapy following HCC treatment shows promise for improving the prognosis of HCC.

Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C.

BACKGROUND/AIMS: To examine the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein-D (SP-D) as markers of interstitial pneumonitis. Many antiviral therapies have become available for chronic hepatitis C, including pegylated interferon (PEGIFN) plus ribavirin. Since interstitial pneumonitis is a serious adverse drug reaction during interferon therapy, interferon treatment requires caution in respiratory disease patients. Hence, the predictors of interstitial pneumonitis have not been elucidated. METHODOLOGY: Fifty-two chronic hepatitis C patients who received PEG-IFN plus ribavirin were studied; 14 patients received PEGIFN-α 2a, and 38 received PEG-IFN-α 2b. Serum KL-6 and SP-D levels were measured during treatment. Time changes in serum KL-6 and SP-D levels, as well as the presence of interstitial pneumonitis, were investigated. RESULTS: No cases of pneumonitis in which both markers were below the standard values were seen. Interstitial pneumonitis developed in 1 of the 5 patients in whom both markers were above standard values. Patients whose KL-6 levels alone exceeded the standard value had bacterial pneumonia and emphysema, not interstitial pneumonitis. Though no correlation between SP-D and KL-6 levels was observed, KL-6 levels tended to increase after interstitial pneumonitis was detected on imaging, but SP-D levels increased before imaging detection. CONCLUSIONS: It is important to monitor changes in levels of serum markers and other factors to avoid interstitial pneumonitis during PEG-IFN therapy. SP-D in particular may be important for early detection of interstitial pneumonitis.

Exposure to organophosphorus compounds of Japanese children and the indoor air quality in their residences.

Several organophosphorus compounds such as organophosphate pesticides (OPPs) and trialkylphosphates (TAPs) are suspected to inhibit cholinesterase activities, to affect endocrine systems or to possibly be carcinogenic. To evaluate their adverse effects on health with chronic exposure in the general population, especially in children, we measured the household exposure to OPPs and TAPs by Japanese children via all exposure pathways and the contribution of indoor air quality. First-morning void urine was collected from subjects aged 6 to 15 years (n = 132), and airborne organophosphorus compounds were sampled in the subject's bedroom for 24 h. Airborne levels of nine OPPs and three TAPs and their urinary metabolites were determined. No significant correlations were detected for any compounds between their airborne concentrations and the urinary excretion amounts of their corresponding metabolites. The estimated daily intakes were as follows (median, µg/kg b.w./d): chlorpyrifos, 0.042; diazinon, 0.067; tri-n-butylphosphate, 0.094. The 95th percentiles of the intakes for fenthion, fenitrothion and the above three compounds did not exceed their reference limit values, although one subject had a daily intake of tri-n-butylphosphate that was about twice its reference limit value. The concentration levels of the urinary metabolite of tri-n-butylphosphate in our subjects tended to be higher than those for children in many other countries. The fractions of the amounts absorbed by inhalation to the amounts absorbed via all of the exposure pathways was only 2.3 % (median) for tri-n-butylphosphate. Inhalation did not seem to contribute very much as an absorption pathway of the organophosphorus compounds in these Japanese children while they were at home. The exposure amounts of OPPs were not suggested to be high enough to adversely affect the health of these children at present on the basis of their daily intakes compared to their reference limit values.

Impact of COVID-19 Countermeasures on Pediatric Infections.

(1) Background: General infection control measures have been implemented at the societal level against COVID-19 since the middle of 2020, namely, hand hygiene, universal masking, and social distancing. The suppressive effect of the social implementation of general infection control measures on pediatric infections has not been systematically assessed. (2) Methods: We addressed this issue based on publicly available data on 11 pediatric infections reported weekly by sentinel sites in Osaka and Iwate prefectures in Japan since 2010. We obtained the 5-year average for 2015-2019 and compared it to the weekly report for 2020-2021. (3) Results: The rate of 6 of the 11 pediatric infections decreased significantly during 2020-2021, regardless of the magnitude of the prevalence of COVID-19 in both areas. However, only RSV infection, one of the six infections, was endemic in 2021. Exanthem subitum was not as affected by COVID-19 countermeasures as other diseases. (4) Conclusions: The social implementation of infectious disease control measures was effective in controling certain infectious diseases in younger age groups, where compliance with the countermeasures should not be as high as that of adults.

Effectiveness of different coils for endovascular coiling for intractable hepatic encephalopathy caused by a portosystemic shunt.

BACKGROUND: Interventional radiology (IVR), including balloon-occluded retrograde transvenous obliteration (BRTO) and percutaneous transhepatic obliteration (PTO), is performed for patients with intractable hepatic encephalopathy (HE). However, information on the appropriate coil for endovascular coiling for preventing recanalization is lacking. This study aimed to compare the different types of coils for endovascular coiling used in BRTO and PTO for cases of intractable HE. METHODS: This retrospective study included patients who underwent endovascular coiling with BRTO or PTO for HE caused by portosystemic shunts. The number of coils required for complete occlusion was compared among bare, fiber, and hydrogel-coated coils, and the expansion types that close the gap between and inside the hydrogel-coated coils were also compared. RESULTS: Of 38 patients (age range, 30-86 years), 16 and 22 underwent BRTO and PTO, respectively, using bare (19 patients), fiber (8 patients), and hydrogel-coated coils (10 patients; external expansion type, 4; internal expansion type, 6). No significant differences in the size of portosystemic shunts were observed according to the type of coil. The mean number of coils required for complete occlusion varied (bare coils, 19.32; fiber coils, 18.11; hydrogel-coated coils, 10.70). Significantly fewer coils were required for endovascular coiling with hydrogel-coated coils. In the internal expansion type, a mean of 8.5 coils was required for occlusion. CONCLUSIONS: In some patients who underwent portal vein embolization, complete occlusion was not achieved with the scheduled type of coil because of slight expansion of blood vessels due to coil pressure. The findings suggested that hydrogel-coated coils were effective in endovascular coiling for HE caused by a portosystemic shunt, and internal expansion-type hydrogel-coated coils may be effective for the first-line procedure.

Cumulative risk of developing a new symptom in patients with primary biliary cholangitis and its impact on prognosis.

Background and Aim: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma.

BACKGROUND: The effectiveness of additional chemotherapy in preventing intrahepatic distant tumor recurrence of hepatocellular carcinoma (HCC) has not been fully established. The authors compared the efficacy of 2 platinum-based chemotherapeutic agents in combination with radical local treatment for preventing intrahepatic distant recurrence (IDR). METHODS: Seventy-eight patients with stage I/II HCC aged 45 to 85 years underwent transcatheter arterial chemoembolization and/or radiofrequency ablation after they received hepatic arterial infusion (HAI) of platinum compounds. The HAI consisted of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) in 25 patients and cis-diamminedichloroplatinum (II) (cisplatin) in 53 patients. Multivariate analysis was used to identify independent factors that were associated with IDR. RESULTS: Cumulative IDR rates at 1 year, 2 years, and 3 years were 21.7%, 52.2% and 75.7%, respectively, in the carboplatin group and 8.1%, 22.7%, and 36.9%, respectively, in the cisplatin group. The cisplatin group had a significantly lower IDR rate compared with the carboplatin group. The selection of a platinum agent was 1 of the independent factors for IDR in a multivariate Cox proportional hazards model. CONCLUSIONS: HAI chemotherapy with cisplatin before radical local treatment was effective in patients with HCC. The authors concluded that radical local treatment with concurrent HAI using cisplatin may contribute to a longer progression-free period, which could be predicted with intrahepatic imaging in patients with stage I/II HCC.