Efficacy of Superselective Conventional Transarterial Chemoembolization Using Guidance Software for Hepatocellular Carcinoma within Three Lesions Smaller Than 3 cm.

The indication of transarterial chemoembolization (TACE) has advanced to hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage A when surgical resection (SR), thermal ablation, and bridging to transplantation are contraindicated; however, TACE for small HCC is frequently difficult and ineffective because of less hypervascularity and the presence of tumor portions receiving a dual blood supply. Here, we report outcomes of superselective conventional TACE (cTACE) for 259 patients with HCCs within three lesions smaller than 3 cm using guidance software. Automated tumor feeder detection (AFD) functionality was applied to identify tumor feeders on cone-beam computed tomography during hepatic arteriography (CBCTHA) data. When it failed, the feeder was identified by manual feeder detection functionality and/or selective angiography and CBCTHA. Regarding the technical success in 382 tumors (mean diameter, 17.2 ± 5.9 mm), 310 (81.2%) were completely embolized with a safety margin (5 mm wide for HCC ≤25 mm and 10 mm wide for HCC >25 mm). In 61 (16.0%), the entire tumor was embolized but the safety margin was not uniformly obtained. The entire tumor was not embolized in 11 (2.9%). Regarding the tumor response at 2-3 months after cTACE in 303 tumors excluding those treated with combined radiofrequency ablation (RFA) or SR and lost to follow-up, 287 (94.7%) were classified into complete response, seven (2.3%) into partial response, and nine (3.0%) into stable disease. The mean follow-up period was 44.9 ± 27.6 months (range, 1-109) and the cumulative local tumor progression rates at 1, 3, 5, and 7 years were 17.8, 27.8, 32.0, and 36.0%, respectively. The 1-, 3-, 5-, and 7-year overall and recurrence-free survival rates in 175 patients, excluding those with Child-Pugh C class, who died of other malignancies, or who underwent combined RFA or hepatic resection, were 97.1 and 68.7, 82.8 and 34.9, 64.8 and 20.2, and 45.3 and 17.3%, respectively. Our results indicate the efficacy of superselective cTACE using guidance software for HCC within three lesions smaller than 3 cm.

[Hepatits B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy and effective prophylactic management: a prospective observational study in a hospital over an 8-year period].

We investigated the development of hepatits B virus (HBV) reactivation in patients receiving immunosuppressive therapy or chemotherapy at our hospital for 8 years. Using the automatic checking system for HBV reactivation coded using medical information that has been in operation in our hospital since October 2012, we prospectively observed the occurrence status of HBV reactivation in immunosuppressive/chemotherapy cases for 8 years. HBV reactivation occurred in 31 of 1516 patients with HBV infection. It occurred annually between 1 and 7 cases in multiple clinical departments, and in 8 of 59 patients treated with rituximab, 10 of 653 patients treated with antineoplastic agents, 10 of 399 patients treated with steroids, and 3 of 212 patients treated with direct-acting antivirals. The cumulative incidence of HBV reactivation was 1.2%, 2.3%, and 3.4% at 1, 2, and 3 years, respectively. The results of Cox regression analysis showed that the incidence of HBV reactivation was significantly higher in patients who received rituximab (odds ratio:12.841) or steroid (hazard ratio:4.264) or those who tested positive for HBc antibody alone (hazard ratio:11.005). We observed the occurrence of HBV reactivation in HBV-infected patients treated with immunosuppressive therapy or chemotherapy. HBV reactivation by immunosuppressive therapy or chemotherapy still occurs, and further safety management and caution are required in the hospital.

Effects of In-Hospital Exercise on Frailty in Patients with Hepatocellular Carcinoma.

Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise (n = 114) and non-exercise (n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20-40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI -0.17 vs. -0.02, p = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240-4.570, p = 0.0091) and females (OR 2.09; 95%CI, 1.062-4.109; p = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC.

Efficient Prophylactic Management of HBV Reactivation by an Information Technology Encoding System: Results of a 6-year Prospective Cohort Study.

Objective We started an information technology (IT) system that encodes the medical treatment status of hepatitis B virrus (HBV) with a 9-digit number, automatically checks for inappropriate situations occurring due to immunosuppression and chemotherapy that do not comply with the flowchart of the hepatitis B countermeasure guideline, and promotes correct HBV medical treatment in our hospital. We conducted a prospective study of HBV reactivation using this system. Methods Among 21,607 cases that were managed using this system, 1,206 patients who were HBs antigen-negative, HBc antibody- and/or HBs antibody-positive and in whom HBV DNA quantification was performed two times or more were examined for the occurrence of HBV reactivation. The study population included: malignant lymphoma patients using rituximab (n=40), patients with malignant tumors using anticancer agents (n=546), patients treated with steroids (n=274), rheumatoid arthritis (RA) patients (n=144), patients using immunosuppressants/biologics (n=26), and patients undergoing hepatitis C direct acting antiviral (DAA) treatment (n=176). Results HBV reactivation was observed in 27 cases undergoing treatment with the following agents: rituximab (n=6), anticancer agents (n=8), steroids (n=10), anti-RA agents (n=1), and hepatitis C DAA (n=2). Among the 40 patients who were using rituximab, 6 (18.2%) showed a high rate of reactivation. In 10 in which HBV reactivation occurred at a median of 10 (range, 4-32) months after steroid administration, 6 occurred after the 7th month, and 1 patient showed HBs antigen positivity and severe hepatitis. Conclusion Continuing of the operation of an automatic check system using coded medical information to check for the reactivation enabled this prospective study of HBV reactivation. Careful attention should be paid to patients using steroids, as well as malignant lymphoma patients who are treated with rituximab. The results of the present study suggest that the present IT encoding system would be useful for preventing HBV reactivation.

Outcomes of conventional transarterial chemoembolization for hepatocellular carcinoma ≥10 cm.

AIM: To retrospectively evaluate the outcomes of conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) ≥10 cm. METHODS: Twenty-five patients with naïve HCC ≥10 cm (mean maximum tumor diameter, 130 ± 27.6 mm; single [n = 12], 2-9 [n = 6], and ≥10 [n = 7]) without extrahepatic spread treated with cTACE were eligible. Five (20%) had vascular invasion. Two to three stepwise cTACE sessions using iodized oil ≤10 mL in one cTACE session were scheduled. When the tumor recurred, additional cTACE was repeated on demand, if possible. Overall survival (OS) rates were calculated using the Kaplan-Meier method. The prognostic factors were evaluated using uni- and multivariate analyses. RESULTS: Stepwise cTACE sessions were completed for 20 (80%) patients, but could not be completed for four (16%). In the remaining (4%) patient, the whole tumor was embolized in one session. Additional treatment, mainly cTACE, was undertaken for 19 (76%) patients. The OS rates at 1, 3, and 5 years were 68, 34.7, and 23.1%, respectively. A tumor number of three was a significant prognostic factor (P = 0.020) and the 1-, 3-, and 4-year OS rates in patients with ≤3 and ≥4 tumors were 81.3 and 33.3, 55.6 and 11.1, and 38.9% and 0%, respectively. Whole tumor embolization and the serum level of protein induced by vitamin K absence or antagonist-II were also significant prognostic factors (P < 0.001 and P = 0.042, respectively). Bile duct complications requiring additional interventions developed in two (8%) patients. CONCLUSION: Conventional TACE is safe and effective for huge HCCs, but has limited effects in cases with four or more tumors.

Prognosis of type 1 autoimmune pancreatitis after corticosteroid therapy-induced remission in terms of relapse and diabetes mellitus.

BACKGROUND AND AIM: Relapse and diabetes mellitus (DM) are major problems for the prognosis of autoimmune pancreatitis (AIP). We examined the prognosis of type 1 AIP after corticosteroid therapy (CST)-induced remission in terms of relapse and DM. METHODS: The study enrolled 82 patients diagnosed with type 1 AIP who achieved remission with CST. We retrospectively evaluated the relapse rate in terms of the administration period of CST, clinical factors associated with relapse, and the temporal change in glucose tolerance. RESULTS: During follow-up, 32 patients (39.0%) experienced relapse. There was no significant clinical factor that could predict relapse before beginning CST. AIP patients who ceased CST within 2 or 3 years experienced significantly earlier relapse than those who had the continuance of CST (p = 0.050 or p = 0.020). Of the 37 DM patients, 15 patients (40.5%) had pre-existing DM, 17 (45.9%) showed new-onset DM, and 5 (13.5%) developed CST-induced DM. Patients with new-onset DM were significantly more likely to show improvement (p = 0.008) than those with pre-existing DM. CONCLUSIONS: It was difficult to predict relapse of AIP based on clinical parameters before beginning CST. Relapse was likely to occur within 3 years after the beginning of CST and maintenance of CST for at least 3 years reduced the risk of relapse. The early initiation of CST for AIP with impaired glucose tolerance is desirable because pre-existing DM is refractory to CST.

Excretion of necrotic hepatocellular carcinoma tissues into the biliary system after transcatheter arterial chemoembolization.

AIM: To evaluate the incidence and condition of necrotic tumor excretion into the biliary system in patients with hepatocellular carcinoma (HCC) >5 cm treated with conventional transcatheter arterial chemoembolization (TACE). METHODS: Eighty-three patients who underwent TACE for newly developed HCC >5 cm without an intraductal tumor thrombus and were followed-up by computed tomography for longer than 6 months were eligible. According to the location, the maximum tumors were divided into central (in contact with the left or right hepatic duct, n = 39) or peripheral (not in contact with them, n = 44). When high-density material in the biliary system that was not seen on pretreatment computed tomography was identified, it was determined as excreted necrotic tumor tissue containing iodized oil. The incidence, interval between TACE and occurrence of the necrotic tumor excretion, and clinical course were evaluated. RESULTS: Tumor excretion into the biliary system was identified in nine (10.8%) patients with a central tumor (mean diameter, 85.0 ± 29.6 mm) 28-433 days (mean, 219.3 ± 128.2) after the initial TACE. In one patient, the necrotic tumor cast caused cholangitis 1203 days after the initial TACE, and was endoscopically removed. Infection of the embolized tumor developed in two cases and percutaneous drainage was carried out 105 and 158 days later, respectively. CONCLUSIONS: Excretion of necrotic tumors into the biliary system after TACE was not rare in patients with centrally located HCC >5 cm. The detached tumor rarely caused symptoms and the communication between the tumor and bile duct caused the infection of tumors.

Sloughing of intraductal tumor thrombus of hepatocellular carcinoma after transcatheter arterial chemoembolization.

Transcatheter arterial chemoembolization (TACE) is effective for hepatocellular carcinoma (HCC) with intrabile duct thrombus. After TACE, intraductal tumor thrombi occasionally detach from the intrahepatic tumor and drop into the bottom of the common bile duct, causing clinical symptoms similar to the impaction of choledocholithiasis. The investigators describe three cases of sloughing of HCC intraductal tumor thrombi after selective TACE. In each of the three cases, the necrotic tumor cast was successfully removed endoscopically, and the patient's symptoms were dramatically improved. Two patients survived without recurrence of the intraductal tumor thrombus for 8 and 11 months after TACE, respectively.

Histopathological findings after ultraselective transcatheter arterial chemoembolization for hepatocellular carcinoma.

AIM: To evaluate the histopathologic findings in the surgical specimen of hepatocelluar carcinoma after transcatheter arterial chemoembolization (TACE) at the most distal portion of the sub-subsegmental artery of the liver (ultraselective TACE). METHODS: Histolopathologic findings from nine tumors with a mean diameter of 3.1 cm +/- 1.7 from patients who underwent hepatectomy after ultraselective TACE were evaluated, especially with regard to the relationship between peritumoral liver parenchymal necrosis and portal vein visualization during TACE. Portal vein visualization was classified into three grades by a spot digital radiograph obtained just after TACE: 0, no obvious portal vein visualization; 1, visualization of the portal vein adjacent to the tumor; and 2, visualization in the whole embolized area or extending into the surrounding non-embolized areas. Unenhanced computed tomography (CT) was obtained 1 week later and surgical resection was performed 37 +/- 6.3 days after ultraselective TACE. RESULTS: Portal vein visualization during TACE was classed as grade 1 in 5 tumors and grade 2 in 4. Histopathologically, complete tumor necrosis was observed in 7 tumors (77.8%). In 2 tumors (1 of grade 1, the other grade 2), a small viable portion or viable daughter nodule was seen. Macroscopic parenchymal necrosis adjacent to the tumor was observed in all 4 grade 2 tumors including gas-containing areas on CT obtained 1 week after TACE. CONCLUSIONS: Ultraselective TACE induces not only complete tumor necrosis but also peritumoral parenchymal necrosis, similar to that after radiofrequency ablation, when the portal veins are markedly visualized during the TACE procedure.

Acute cholecystitis caused by malignant cystic duct obstruction: treatment with metallic stent placement.

We report the successful management of acute cholecystitis using cystic duct stent placement in 3 patients with inoperable malignant cystic duct obstruction (2 cholangiocarcinoma and 1 pancreatic carcinoma). All patients underwent stent placement in the bile duct, using an uncovered stent in 2 and a covered stent in 1, to relieve jaundice occurring 8-184 days (mean 120 days) before the development of acute cholecystitis. The occluded cystic duct was traversed by a microcatheter and a stent was implanted 4-17 days (mean 12 days) after cholecystostomy. Acute cholecystitis was improved after the procedure in all patients. Two patients died 3 and 10 months later, while 1 has survived without cholecystitis for 22 months after the procedure to date.