Thermodynamic study on hydrated bilayers of ether-linked phosphatidylcholines with terminal perfluorobutyl group.

Novel terminally perfluorobutyl group-containing ether-linked phosphatidylcholines with different alkyl chain lengths (di-O-F4-Cn-PCs, n = 14,16 and 18) were developed as possible materials for stable liposomes aiming at applications of structural and functional analyses of membrane proteins. Differential scanning calorimetric investigations of the thermotropic transition of hydrated di-O-F4-Cn-PC bilayers demonstrated that the transition temperature of every di-O-F4-Cn-PC decreases by ~20 °C compared to their corresponding non-fluorinated PCs, di-O-Cn-PCs. With the elongation of the hydrophobic chain, on the other hand, the transition enthalpy (ΔH) and entropy (ΔS) increased in a linear manner. Comparison of ΔH and ΔS values against the net hydrocarbon chain length between di-O-F4-Cn-PCs and di-O-Cn-PCs strongly suggests that in the thermotropic transition of the di-O-F4-Cn-PC membrane, the perfluorobutyl segments undergo very limited structural changes; therefore, the hydrocarbon segments are mainly responsible for the phase transition.

Significance of Early Postoperative Magnetic Resonance Imaging following Intracranial Meningioma Resection.

The significance of early postoperative magnetic resonance imaging (MRI) for meningioma resection has not yet been evaluated. We retrospectively reviewed patients with intracranial meningiomas resected at our institute between 2011 and 2021. Early postoperative MRI with contrast enhancement was routinely performed within 48 h after surgery while first follow-up MRI was performed approximately after 6 months. MRI findings were reviewed, and the risk factors for postoperative infarction and early recurrence were analyzed. Among the 245 resections performed, early postoperative MRI was performed in 200 cases. Postoperative radiological and symptomatic infarctions occurred in 54 (27%) and 17 patients (9%), respectively. Diameter > 5 cm (p = 0.015) and skull base location (p = 0.010) were independent risk factors for radiological infarctions. Follow-up postoperative MRI performed in 180 patients (90%) detected early recurrence in 24 patients (13%). Non-gross total resection was an independent risk factor for early recurrence (p < 0.0001). Additionally, early recurrence after gross total resection occurred significantly more frequently in meningiomas with dural sinus involvement than in those without (8.3% vs. 0%, p = 0.018). Thus, early postoperative MRI may enable the timely assessment of postoperative neurological deficits, especially after large skull base meningioma resections along with accurate detection of early recurrence, which is critical for meningiomas with dural sinus involvement.

Conventional or Drug-Eluting Beads? Randomized Controlled Study of Chemoembolization for Hepatocellular Carcinoma: JIVROSG-1302.

Introduction: With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients with hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads (DEB-TACE) loaded with epirubicin or selective conventional TACE (cTACE) with epirubicin-ethiodized oil might be more effective for obtaining complete response(CR) in patients with HCC. Methods: Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events. Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, p = 0.0001), fatigue (5.1% vs. 15.8%, p = 0.0194), malaise (11.1% vs. 25.7%, p = 0.0103), appetite loss (12.1% vs. 28.7%, p = 0.0048), abdominal pain (12.1% vs. 23.8%, p = 0.0423), increased serum bilirubin (22.2% vs. 48.5%, p = 0.0002), hypoalbuminemia (43.4% vs. 60.3%, p = 0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, p < 0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, p < 0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm. Conclusions: Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of postembolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate postembolization syndrome.

Lysosome­targeted drug combination induces multiple organelle dysfunctions and non­canonical death in pancreatic cancer cells.

Pancreatic cancer is one of the leading causes of cancer­related mortality and has the lowest 5­year survival rate. Therefore, novel strategies are urgently required to treat pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) cells rely on enhanced lysosomal function for survival and proliferation to facilitate the degradation of contents accumulated via autophagy and macropinocytosis. Previously, we have reported that the combination of epidermal growth factor receptor/HER2 inhibitor lapatinib and sphingosine analog fingolimod (FTY720) confers a significant cytostatic effect in lung cancer cells. In the present study, the combined effects of these drugs on PDAC cell lines, BxPC­3, KP­4, PANC­1 and MIA PaCa­2, were examined. It was observed that FTY720 enhanced the lapatinib­induced cytotoxic effect and caused non­canonical and lysosome­dependent death in PDAC cells. Lapatinib and FTY720 induced lysosomal swelling and inhibited lysosomal acidification. Combination treatment with lapatinib and FTY720 increased lysosomal membrane permeability, induced mitochondrial depolarization, induced endoplasmic reticulum stress and disturbed intracellular calcium homeostasis. Additionally, the cytotoxic effect of lapatinib was enhanced by hydroxychloroquine or the CDK4/6 inhibitor abemaciclib, both of which induce lysosomal dysfunction. Collectively, these results indicated that the lysosome­targeted drug combination induces multiple organelle dysfunction and exerts a marked cytotoxic effect in PDAC cells.

Patients' radiation dose in computed tomography-fluoroscopy-guided percutaneous cryoablation for small renal tumors.

PURPOSE: This study aimed to evaluate patients' radiation dose in computed tomography (CT)-fluoroscopy-guided cryoablation for small renal tumors and assess the possible factors affecting it. METHODS: In our institution, cryoablation was performed in 152 patients between 2013 and 2020. Procedures that were not for renal tumors and did not have radiation dose records and detailed information were excluded from the analysis. The size-specific dose estimates (SSDE), volume CT dose index (CTDIvol), dose-length product (DLP), and entrance skin dose (ESD) were evaluated for both spiral scan and CT-fluoroscopy. The effects of the number of cryoneedle punctures; combined use of hydro- and/or pneumodissection procedures; patients' characteristics, such as body-mass index (BMI); and the tumor-related factors, such as tumor location, were determined by the univariate and multivariate analyses. RESULTS: In the 72 included procedures, the median SSDE was 658 mGy and the median CTDIvol was 456 mGy. The median percentage dose of CT-fluoroscopy to the total procedure dose was estimated as 89.8% (591/658 mGy) with SSDE and 41.4% (611/1,475 mGy cm) with DLP. The combined use of hydro- and/or pneumodissection and number of cryoneedle punctures were significantly associated with the total ESD, and the maximum total ESD was 863 mGy in our cases. CONCLUSIONS: Using SSDE as an index, 89.8% of patients' radiation dose was attributed to CT-fluoroscopy, and ESD for the total procedure did not exceed 1 Gy. The increased number of cryoneedle punctures and combined use of hydro- and/or pneumodissection increased the total ESD.

Multimodal approach to portal hypertension and gastric varices before hepatic resection for hepatocellular carcinoma: a case report.

BACKGROUND: Liver cirrhosis occurs in approximately 80-90% of patients with hepatocellular carcinoma (HCC), and hepatic resection may be dangerous because of well-documented liver cirrhosis, which may be accompanied by portal hypertension (PH). Here we report a patient with advanced HCC with gastric varices and PH who experienced a good clinical course after undergoing balloon-occluded retrograde transvenous obliteration (BRTO), percutaneous transhepatic portal vein embolization (PTPE), hand-assisted laparoscopic (HALS) splenectomy, and right lobectomy of the liver. CASE PRESENTATION: A 72-year-old man had two HCCs with gastric varices. CT revealed one tumor (4.5 cm) located in segment 7, involving the right hepatic vein, adjacent to the middle hepatic vein. Another tumor (2.7 cm) was located in segment 6. He first underwent BRTO for gastric varices and PTPE for planned right lobectomy of the liver. To reduce PH, HALS splenectomy was performed, and uncomplicated right lobectomy of the liver was performed 10 weeks after the first visit. He has remained free of recurrence for at least 1 year. CONCLUSIONS: Our patient underwent uncomplicated BRTO, PTPE, HALS splenectomy, and right lobectomy of the liver for advanced HCC with PH. Controlling portal pressure is important when hepatic resection is required to treat HCC with PH.

Sequestosome 1 (p62) accumulation in breast cancer cells suppresses progesterone receptor expression via argonaute 2.

Sequestosome 1 (p62) is a multifunctional adapter protein involved in various physiological functions, such as selective autophagy and oxidative stress response. Hence, aberrant expression and defective regulation of p62 are thought to lead to the onset of various diseases, including cancer. The expression of p62 has been shown to be increased in breast cancer tissues, and is correlated with a poor prognosis. However, the role of p62 in the breast cancer pathophysiology is still unclear. Here, we aimed to analyze the effect of changes in p62 expression on breast cancer cell lines. DNA microarray analysis revealed that the expression of progesterone receptor (PR), which is one of the indices for the classification of breast cancer subtypes, was markedly suppressed by forced expression of p62. The protein expression of PR was also decreased by forced expression of p62, but increased by knockdown of p62. Moreover, we found that p62 knockdown induced the protein expression of argonaute 2 (AGO2). Luciferase reporter assay results showed that the gene expression of PR was promoted by AGO2. Furthermore, results revealed that overexpression of AGO2 partially rescued the decrease in PR expression induced by forced expression of p62. Collectively, our findings indicated that p62 accumulation suppressed the expression of AGO2, which in turn decreased the expression of PR, suggesting that p62 may serve as a marker of aggressive breast cancer and poor prognosis. Moreover, the p62-AGO2-PR axis was identified as a crucial signaling cascade in breast cancer progression.

Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin.

Tyrosine kinase inhibitors (TKIs) induce autophagy in many types of cancer cells. We previously reported that gefitinib (GEF) and imatinib (IMA) induce autophagy in epidermal growth factor receptor (EGFR) knock-out A549 and non-BCR-ABL-expressing leukemia cell lines, respectively. This evidence suggests that TKI-induced autophagy is independent of the original target molecules. The present study compared the autophagy-inducing abilities of various TKIs, regardless of their targets, by quantitative autophagy flux assay. We established stable clones expressing the GFP-LC3-mCherry-LC3ΔG plasmid in A549, PC-9, and CAL 27 cell lines and assessed autophagy inducibility by monitoring the fluorescent ratios of GFP-LC3 to mCherry-LC3ΔG using an IncuCyte live cell imaging system during exposure to TKIs viz; GEF, osimertinib (OSI), lapatinib (LAP), lenvatinib (LEN), sorafenib (SOR), IMA, dasatinib (DAS), and tivantinib (TIV). Among these TKIs, DAS, GEF, and SOR exhibited prominent autophagy induction in A549 and PC-9 cells. In CAL 27 cells, IMA, SOR, and LEN, but not GEF, TIV, or OSI, exhibited autophagy induction. In the presence of azithromycin (AZM), which showed an inhibitory effect on autophagy flux, TKIs with prominent autophagy inducibility exhibited enhanced cytotoxicity via non-apoptotic cell death relative to effects of TKI alone. Therefore, autophagy inducibility of TKIs differed in the context of cancer cells. However, once induced, they appeared to have cytoprotective functions. Thus, blocking TKI-induced autophagy with AZM may improve the therapeutic effect of TKIs in cancer cells.

Bowel injury complicating percutaneous cryoablation of large renal cell carcinoma.

We report the case of a bowel injury, which occurred after the percutaneous cryoablation (PCA) of large renal cell carcinoma (RCC). A 50-year-old man with RCC measuring 47 mm in diameter. First, we performed transarterial embolization for the tumor, followed by PCA with hydrodissection, which displaced the small intestine from the iceball. The procedure was completed without any complication on the procedural day; however, the patient complained of appetite loss and abdominal pain 2 days after PCA. Computed tomography revealed a bowel injury at the small intestine adjacent to the tumor. After 7 days, ileus tube insertion, and fasting, the patient recovered from the bowel injury and was discharged 10 days after PCA. He underwent a second PCA because of a small recurrent renal tumor 5 months after the first PCA without complications. This case indicated that a bowel injury after PCA for RCC could be treated conservatively.

Hepatic Arterial Infusion Chemotherapy of 5-Fluorouracil for Patients with Unresectable Liver Metastases from Colorectal Cancer Refractory to Standard Systemic Chemotherapy: A Multicenter Retrospective Study.

INTRODUCTION: Hepatic arterial infusion chemotherapy (HAIC) is a feasible treatment for patients with colorectal cancer (CRC) with unresectable liver metastases. OBJECTIVE: The aim of this retrospective study was to assess HAIC of 5-fluorouracil (5FU) in patients with unresectable liver metastases from CRC refractory to standard systemic chemotherapy. METHODS: A total of 137 patients (85 men, 52 women; median age, 62 years; with KRAS mutation, n = 57) were recruited from seven institutions from September 2008 to December 2015. These patients were refractory to systemic chemotherapy including three cytotoxic agents (fluoropyrimidine, oxaliplatin, and irinotecan) with two molecular-targeted agents (bevacizumab and epidermal growth factor receptor antibody [cetuximab or panitumumab]). All patients underwent HAIC of continuous 5FU for unresectable liver metastases. Overall survival time, time to treatment failure, objective response rate, disease control rate, and incidence of adverse events to HAIC were assessed retrospectively. RESULTS: The median overall survival time was 4.8 months (95% confidence interval [CI], 4.0-5.7 months), whereas time to treatment failure was 2.4 months (95% CI, 2.0-2.8 months). The objective overall response rate and disease control rate were 12.4 and 64%, respectively. Grade 3 or 4 adverse events were observed in 2.9% of the patients (hyperbilirubinemia in 2, liver abscess in 1, and myelosuppression in 1). CONCLUSIONS: There were few incidences of severe adverse events to HAIC of 5FU for liver metastases from CRC refractory to standard systemic chemotherapy. Therefore, it might present as a treatment option as last-line chemotherapy.

Radiation Exposure of Interventional Radiologists during Computed Tomography Fluoroscopy-Guided Percutaneous Cryoablation.

Purpose: The principal aim of this study was to evaluate radiation exposure of interventionalists during computed tomography (CT) fluoroscopy-guided percutaneous cryoablation (PCA) using radiophotoluminescent glass dosimeters (RPLDs). The radioprotective effects of safety glasses and lead apron were also evaluated. Materials and Methods: Radiation exposure of interventionalists during 46 CT fluoroscopy-guided PCA procedures was evaluated. Entrance surface dose (ESD) was measured using RPLDs on multiple sites: five sites, representing eye lens exposure; five sites, representing body exposure; and four sites, representing skin exposure. The ESD values on multiple sites were compared between different PCA procedures (renal, liver, and bone). Results: The mean ESD on the X-ray-side hand exhibited the highest value (358.8 µGy). Regarding evaluation sites representing exposure to the eye lens, the highest ESD inside the radiation protective glasses was detected on the X-ray-side cheek (167.1 µGy). Most ESD values among multiple sites (10/14) were linearly correlated with CT fluoroscopy time. Among them, the ESD values measured during renal and liver PCA were relatively higher than those measured during bone PCA, especially on the chest area outside the lead apron, and on the X-ray tube-side elbow and hand during renal and bone PCA. Radioprotective effects of safety glasses and lead apron ranged from 44.6 to 50.6% and from 30.2 to 79.6%, respectively, on each evaluation site. Conclusion: The site with the highest radiation exposure on interventionalists during CT fluoroscopy-guided PCA was the X-ray tube-side hand. Radiation exposure of interventionalists was at acceptable levels and consistent with the recommended dose limits.

A comparison of carbon ion radiotherapy and transarterial chemoembolization treatment outcomes for single hepatocellular carcinoma: a propensity score matching study.

BACKGROUND: We compared clinical outcomes of carbon ion radiotherapy and transarterial chemoembolization in the treatment of hepatocellular carcinoma. METHODS: Data of 477 patients with hepatocellular carcinoma who had undergone carbon ion radiotherapy or transarterial chemoembolization between April 2007 and September 2016 were retrospectively reviewed. Treatment naïve patients with single HCC, who underwent carbon ion radiotherapy or transarterial chemoembolization as a primary treatment were included. Clinical outcomes of the treatments were compared after utilizing propensity score matching. RESULTS: Of 124 patients who received carbon ion radiotherapy and 353 patients who received transarterial chemoembolization, 31 and 23 patients met our inclusion criteria, respectively. After utilizing propensity score matching, 17 matched pairs of patients from each treatment group were analyzed. The median follow-up durations after carbon ion radiotherapy and transarterial chemoembolization were 43 and 32 months, respectively. The 3-year overall survival, local control, and progression-free survival rates in the carbon ion radiotherapy versus transarterial chemoembolization groups were 88% versus 58% (p < 0.05), 80% versus 26% (p < 0.01), and 51% versus 15% (p < 0.05), respectively. CONCLUSIONS: Carbon ion radiotherapy showed more favorable clinical outcomes than did transarterial chemoembolization for patients with single hepatocellular carcinoma after matching patient characteristics utilizing propensity score matching. Further studies with larger patient numbers are required to confirm our results. TRIAL REGISTRATION: UMIN000036455 : date of registration 22 March 2019, retrospectively registered.

Hepatic pleomorphic leiomyosarcoma after surgery for gastric gastrointestinal stromal tumor: a case report.

BACKGROUND: Pleomorphic leiomyosarcomas (PLMSs) are extremely rare tumors. We present the first case of hepatic primary PLMS after surgery for gastric gastrointestinal stromal tumor (GIST). CASE PRESENTATION: The patient was a 62-year-old man who was referred to our hospital for resection of a hepatic tumor arising after gastric GIST surgery that was resistant to imatinib and sunitinib. A 40-mm tumor in the left lobe of the liver and three small nodules in the right lobe were detected. We performed hepatic left lobectomy and partial resections for three lesions. According to the histopathological and immunohistochemical findings and c-kit gene mutations analysis, the main tumor was diagnosed as a PLMS. CONCLUSION: It is necessary to consider the possibility that imatinib-resistant GIST recurrence lesions are a different kind of soft-tissue sarcoma. Accurate diagnosis is required to not miss the opportunity for radical excision of PLMS.

The Feature of Solitary Small Nodular Type of Hepatic Epithelioid Hemangioendothelioma.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor. Preoperative diagnosis of HEHE is difficult because it does not manifest specific symptoms or tumor markers. We report a resected case of small and solitary HEHE. The patient, a 74-year-old man, had undergone surgical resection for left renal cell carcinoma 20 years ago. During follow-up, a tumor approximately 1.3 cm in diameter was detected by computed tomography (CT) at liver segment VIII. It showed isodensity in the arterial phase, low density in the portal venous phase, and homogeneous enhancement in the late phase on CT and magnetic resonance imaging (MRI). We performed hepatic resection of the right hepatic vein drainage area. A pathological diagnosis of HEHE was made. Although small and solitary HEHE is rare, an enhancement pattern in each phase on CT and MRI, using contrast media, can yield clues for the diagnosis of HEHE.

Phase I clinical trial of percutaneous cryoablation for osteoid osteoma.

PURPOSE: This prospective phase I trial was conducted to evaluate the safety of percutaneous cryoablation for osteoid osteoma (OO). MATERIALS AND METHODS: Nine patients with OO (mean tumor size: 5.9 mm; tibia, n = 5; femur, n = 2; lumbar spine, n = 2) were enrolled and treated with percutaneous cryoablation. The primary endpoint was the evaluation of the treatment safety as determined using step-by-step registration. The secondary endpoints were the incidence and grade of adverse events by CTCAE version 4.0, and the short-term efficacy of this treatment. Based on a decrease in the numerical rating scale (NRS) score, efficacy was classified as significantly effective (SE ≥ 5 or reached 0-2), moderately effective (ME 2-4), or not effective (NE < 2 or increase). RESULTS: Cryoablation procedures were completed in all patients. Major adverse events (≥ grade 3) related to the procedure were not observed. Minor adverse events (≤ grade2) were observed in 22-67%. The mean NRS score was 7 before treatment, 0.6 at 4-week, 0.1 at 6-month, and 0 at 1-year post-treatment. All procedures were classified as SE. CONCLUSION: Percutaneous cryoablation is a safe treatment for OO. Future phase II trials with large patient cohorts are warranted.

Radiofrequency ablation versus cryoablation for T1b renal cell carcinoma: a multi-center study.

PURPOSE: To compare the clinical outcomes between radiofrequency ablation (RFA) and cryoablation for the treatment of clinical T1b (cT1b) renal cell carcinoma (RCC). MATERIALS AND METHODS: The data of 46 patients [(39 men and 7 women, median age; 73 years, range 39-87 years)] were gathered from 3 institutions. RFA and cryoablation were performed on 23 patients each. The median number of ablation needle was 2 (range 1-4) and 4 (range 3-5, p < 0.0001) in RFA and cryoablation, respectively. Technique efficacy defined as coverage of the tumor by ablative zone, adverse events, local tumor progression, and survival were compared between the RFA and cryoablation groups. RESULTS: The primary technique efficacy rate was significantly higher in the cryoablation group (96%, 22/23) than in the RFA group (65%, 15/23, P = 0.02). There was no significant difference in the secondary technique efficacy rate after additional RFA and cryoablation [21/23 (91%) vs. 23/23 (100%); P = 0.24]. The incidence of grade 3 or higher adverse events was similar between the 2 groups (P > 0.99). There was no significant difference between local tumor progression rate after RFA and cryoablation [3/21 (14%) vs. 2/23 (9%); P = 0.66]. The 5-year overall survival rates were comparable between RFA and cryoablation (78 vs. 82%; P =0.82). CONCLUSION: Other than primary technique efficacy, the clinical outcomes between RFA and cryoablation were similar in patients with cT1b RCC.

Bioluminescence Image as a Quantitative Imaging Biomarker for Preclinical Evaluation of Cryoablation in a Murine Model.

PURPOSE: To employ bioluminescence imaging (BLI) as a quantitative imaging biomarker to assess preclinical evaluation of cryoablation in a murine model. MATERIALS AND METHODS: In vitro, Colon26-Luc (C26-Luc) cells were seeded at 6 different concentrations in 35-mm dishes. These were divided into 6 groups: group 0 (G0), a control group without treatment; and groups 1-5 (G1-G5) according to the number of freeze-thaw cycles, with each cycle consisting of freezing at -80°C for 10 min followed by thawing at room temperature for 5 minutes. BLI and flow-cytometric analysis were performed after cryotherapy. In vivo, 20 tumor-bearing mice with C26-Luc cells were divided into 4 groups: group 0 (G0), a control group; and groups 1-3 (G1-G3) according to the number of freeze-thaw cycles. Each cryoablation procedure was performed for 30 seconds with liquid nitrogen (-170°C) applied with cotton-tipped applicators. BLI was acquired at 6 hours and 1, 3, and 7 days after treatments. RESULTS: In vitro, BLI signal showed a negative correlation with the number of freeze-thaw cycles (r = -0.86, P = .02). In vivo, there was no difference in tumor volume at 1 day after cryoablation among all groups, but the BLI signals were significantly different between G0 and G2/G3 (P = .03 and P = .02, respectively) and between G1 and G3 (P = .04). BLI signals reflected tumor growth speed and survival ratio. CONCLUSIONS: This study demonstrates the direct validation of BLI as a quantitative tool for the early assessment of therapeutic effects of cryoablation.

Successful treatment of isolated bile leakage after hepatectomy combination therapy with percutaneous transhepatic portal embolization and bile duct ablation with ethanol: a case report.

BACKGROUND: Bile leakage after hepatectomy still causes relatively serious problems, and some types of bile leakage are intractable. CASE PRESENTATION: We report a case of postoperative isolated bile duct leakage managed successfully by combination therapy of percutaneous transhepatic portal vein embolization (PTPE) and bile duct ablation with ethanol. A 61-year-old man diagnosed with hepatocellular carcinoma underwent partial hepatectomy. On postoperative day 1, bile leakage was detected at the drainage tube. Simple drainage treatment did not improve the situation. He was diagnosed with isolated bile leakage based on fistulogram from the drainage tube that showed the bile duct at segments V and VIII but not the common bile duct. A volume of drainage fluid of 200 mL/day was observed. Combination therapy with PTPE and bile duct ablation with ethanol was planned. After the percutaneous transhepatic cholangiography, the drainage tube was inserted into the bile duct, and PTPE was performed to segments V and VIII. The amount of drainage fluid decreased, and bile duct ablation with ethanol was performed to the isolated bile duct. No complication was found following combination therapy. CONCLUSION: In this case, we successfully treated a patient with isolated bile leakage by combination therapy with PTPE and bile duct ablation.

Phase I/II Study of Radiofrequency Ablation for Painful Bone Metastases: Japan Interventional Radiology in Oncology Study Group 0208.

PURPOSE: A prospective multicenter phase I/II trial was performed to evaluate the clinical safety and efficacy of radiofrequency ablation (RFA) for metastatic bone tumors. MATERIALS AND METHODS: Thirty-three patients (27 men, 6 women, mean age 61 years) with metastatic bone tumors were enrolled. In phase I, nine patients were enrolled, and the safety of RFA was evaluated. In phase II, 23 patients were included, and an intent-to-treat analysis was performed. The primary endpoint was to evaluate the treatment's safety. The secondary endpoint was to evaluate the efficacy of pain relief at 1 week after RFA. RESULTS: RFA was performed in 32 of 33 enrolled patients. No serious complications were observed during the phase I, so phase II was performed. Four patients exhibited adverse events, including one case each of Grade 3 pain and, Grade 2 hypotension, and one patient developed Grade 1 burns at the grounding pad and puncture site. One patient died of liver failure on day 7 after RFA due to the progression of the primary lesion. The efficacy was excellent (no increase in analgesic dosage, post-RFA VAS score of 0-2 or decreased by not less than 5 compared to before RFA) in 20 patients (60.6%), good (no increase in analgesic dosage, post-RFA VAS score decreased by not less than 2 but by < 5 compared to before RFA) in 3 (9.1%), and poor in 10 patients (30.3%). Thus, the response rate was 69.7%. CONCLUSION: RFA is a safe and effective method for treating painful metastatic bone tumors.

Multimodality Therapy Including Proton Beam Therapy for AFP Producing Esophageal Cancer with Multiple Liver Metastases.

A 50-year-old man who presented with a fever and epigastralgia was diagnosed to have esophageal carcinoma which was identified as poorly differentiated adenocarcinoma producing alpha-fetoprotein (AFP) with Barrett's esophagus. Computed tomography revealed multiple liver metastases and lymph node metastases surrounding the stomach. We first performed chemotherapy for the systemic lesions and proton beam therapy for the local control of lesions without complete remission and we were able to successfully control the frequently recurring lesions by proton beam therapy, cryotherapy and chemotherapy. A complete response has been maintained for 16 months and the overall survival time is 4 years and 2 months. Proton beam therapy for primary esophageal cancer and metastatic lesions was thus found to be an effective therapeutic option for such cases.