[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.

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.

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.

Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment.

Gemcitabine in arterial injection chemotherapy for pancreatic cancer does not cause catheter obstruction or any other complication.

BACKGROUND/AIMS: Intra-arterial injection therapy is performed to ensure more localized administration; however, this approach has led to more cases of catheter obstruction during the course of treatment for pancreatic cancer than in any other type of cancer. Therefore, the purpose of this study was to verify the resistance of catheters to gemcitabine. METHODOLOGY: The catheters were prepared by injecting gemcitabine into the lumen, which was subsequently closed by clipping both ends. After incubation, the gemcitabine in the lumen of the catheter was removed, the breaking strength was measured by pulling 1 side of the catheter at a speed of 500 mm/min to test the tensile strength. To verify the surface of the lumen, the lumen was observed with an electron microscope. RESULTS: Soaking the lumen revealed no significant differences in breaking strength due to abusive treatment conditions. Electron microscopy revealed residual microscopic amounts of gemcitabine in the lumen but with no marked deterioration or alteration in the quality of the tube surface. CONCLUSIONS: Gemcitabine had no chemical effect on the intra-arterial injection catheter. It is possible that a thrombotic tendency in pancreatic cancer patients may be responsible for the high frequency of catheter occlusion in patients with this disease.

[Multiple liver metastases due to sigmoid colon cancer successfully treated by degradable starch microspheres (DSM)-TAE, radiofrequency ablation therapy, and Uzel/UFT].

A69-year-old man was diagnosed with sigmoid colon cancer and underwent resection of the sigmoid colon. He was later diagnosed with multiple liver metastases 11 months after resection of the sigmoid colon cancer. He was treated by intraarterial chemoembolization using degradable starch microspheres (DSM) and radiofrequency ablation therapy. As a systemic therapy, combined oral administration of tegafur/uracil (UFT) and Leucovorin(Uzel) was started (UFT 450 mg/day, Leucovorin 75 mg/day, 4 weeks of therapy followed by a 1-week treatment break). Two months after 4 courses, the liver metastases had markedly diminished and CEA was within the normal range. The metastases had almost disappeared and tumor markers decreased to within normal limits. This treatment was very safe and effective. Such a strategic multidisciplinary treatment can lead to a better prognosis for colorectal cancer with liver metastases.

Fitness consequences of reciprocally asymmetric hybridization between simultaneous hermaphrodites.

Depending on fitness consequences, hybridization may rescue Inbred populations; generate premating barriers, reproductive Interference, or hybrid species; or extinguish a species. However, the fitness of hybrids is unpredictable without direct quantification of their performance in fitness components across multiple generations. The land snails Bradybaena pellucida and B. similaris, which are Indigenous and non-Indigenous in Japan, respectively, copulate with each other simultaneously and reciprocally. However, only B. pellucida produces hybrids, because it ends mating by removing the penis before transferring a spermatophore, while B. similaris Inseminates B. pellucida. To evaluate the strength of an Intrinsic postzygotic barrier against the hybrids produced by B. pellucida, we conducted breeding experiments in the laboratory and measured six life-history traits: (1) growth rate, (2) body weight at maturity, (3) number of days to first oviposition after being permitted to mate, (4) clutch size, (5) fecundity, and (6) hatchability. We also calculated the relative intrinsic fitness based on five of these trait values (excluding clutch size). F(1) hybrids exhibited heterosis in growth rate, body weight at maturity and relative intrinsic fitness. F(2) hybrids also showed heterosis in body weight at maturity. Nevertheless, the F(2) hybrids produced significantly fewer progeny than the mid-point value of the parental species. Thus, the F(2) hybrids exhibited weak out-breeding depression in reproduction, offsetting their vigor in body size. These results indicate that only a weak postzygotic barrier, contrasting with strong F(1) heterosis, has evolved during genetic divergence of the two sibling species in allopatry.

Oral branched-chain amino acids administration improves impaired liver dysfunction after radiofrequency ablation therapy for hepatocellular carcinoma.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is a new modality for hepatocellular carcinoma (HCC). However, the effects of RFA on hepatic reserve have not yet been thoroughly studied. In the present study, it was evaluated the effect of branched chain amino acid (BCAA) administration after RFA. METHODOLOGY: Fifty-seven patients with initial, single HCC lesions measuring not more than 30mm in whom RFA was selected in first-line therapy were enrolled. Twenty-eight patients with the Child-Pugh B/C grade who received RFA therapy were divided into two groups: 11 who received a BCAA-enriched nutrient mixture, and 17 who did not. Changes in serum albumin were evaluated before RFA and 1, 6 and 12 months after RFA. RESULTS: Multivariate analysis showed that the Child-Pugh grading is the most important factor related to intrahepatic distant recurrence following by RFA. Serum albumin levels decreased 1 month after RFA. Although a tendency toward recovery was noted 6 months after RFA, a decreasing tendency was noted again one year after RFA compared to the pre-RFA baseline. However, a tendency toward improvement was noted in Child-Pugh B grade patients who received BCAA mixture. CONCLUSIONS: BCAA mixture made it possible to maintain serum albumin levels and hepatic reserve.

Therapeutic efficacy of continuous arterial infusion of the protease inhibitor and the antibiotics and via celiac and superior mesenteric artery for severe acute pancreatitis--pilot study.

BACKGROUND/AIMS: Severe acute pancreatitis is poor prognosis. Continuous regional arterial infusion of protease inhibitors and antibiotics were developed in Japan. We evaluated whether arterial infusion both celiac artery and superior mesenteric artery for this disease would reduce mortality. METHODOLOGY: Seventeen patients were treated arterial infusion of protease inhibitor and antibiotics via both celiac artery and superior mesenteric artery. Changes of Acute Physiology and Chronic Health Evaluation II score and mortality were evaluated. RESULTS: Arterial infusion via two routes reduced the mortality rate and improved Acute Physiology and Chronic Health Evaluation II score. The overall mortality rate was 11.8%. The mortality rate in patients in whom were treated within 3days after the onset was significantly lower than that in patients in whom were treated without 3days after the onset. CONCLUSIONS: Arterial infusion via superior mesenteric artery might prevent both bacterial translocation and non-occlusive mesenteric ischemia. Continuous arterial infusion both celiac artery and superior mesenteric artery might be effective for reducing mortality and preventing the development of pancreatitis, especially when initiated within 3 days after the onset. Further prospective randomized studies using a larger number of patients are required.

Fluorescent pigment distinguishes between sibling snail species.

Traditional taxonomy of shell-bearing molluscs does not generally use soft-body coloration. However, the land snails Bradybaena pellucida and B. similaris have been distinguished only on the basis of the color of the soft-body visible through the shell. Thus, the taxonomic status of the two species has traditionally been questionable. We found that dense spots of pigments embedded in the dorsal mantle are responsible for the yellow coloration of B. pellucida . Similar spots in B. similaris are white and less densely aggregated in whorls further from the apex, and the brown color of the hepatopancreas is visible through the shell. The yellow pigments of B. pellucida seep out with mucus from the body in natural and laboratory conditions. The two species became externally indistinguishable after 30 days of laboratory feeding, because the yellow spots disappeared in B. pellucida and the color of the hepatopancreas changed from dark brown to pale brown in both species. Irradiation with ultraviolet A demonstrated that the yellow pigment of B. pellucida fluoresces. Adult specimens of the two species were distinct in penial microsculpture, with F(1) hybrids intermediate in form. Populations of the two species differed significantly in allelic frequencies at four allozyme loci. Therefore, B. pellucida and B. similaris are morphologically and genetically distinct. The fluorescent yellow pigment distinguishes B. pellucida from B. similaris under natural conditions despite its environmental dependence.

[Gemcitabine treatment in patients with stage IV pancreatic cancer and prognostic factors for survival of patients with stage IVb(a retrospective survey at 15 hospitals in Niigata Prefecture)].

We performed a retrospective survey at 15 hospitals in Niigata Prefecture to assess the effectiveness of gemcitabine in patients with stage IV pancreatic cancer and to analyze prognostic factors impacting survival in patients with stage IVb. The subjects were 244 unresectable or metastatic pancreatic cancer patients(IVa 68, IVb 176)who were treated with gemcitabine as first-line therapy. The overall response rate was 6.1% and the median survival time(MST)was 194 days. The MST of stage IVa(312 days)was double that of stage IVb(167 days). Prognostic factors for survival of patients with stage IVb were analyzed(performance status, response rate, liver metastasis, peritonitis carcinomatosa, paraaortic lymph node metastasis)with the Cox proportional hazards model. Performance status, response rate, and liver metastasis were significant factors influencing survival. When we compare an effect of other chemotherapy with GEM, we should treat stage IVa and stage IVb separately, and subdivision is necessary for stage IVb.

Eosinophilic esophagitis in Japanese patients: A mild and slow-progressing disorder.

BACKGROUND AND AIM: Awareness of eosinophilic esophagitis (EoE) has gradually increased in Japan, therefore the characteristics of this disease in the Japanese patient population need to be elucidated. This study aimed to investigate the features of EoE in the Japanese population. METHODS: During a 2-year period, all gastrointestinal endoscopies were performed with maximum attention being paid to identify EoE through endoscopic findings. Clinical features and findings were analyzed among this population. RESULTS: Among a total of 8589 patients (general gastrointestinal endoscopy, performed for evaluation of symptoms or disease follow-up: 3669; medical check-up endoscopy, routinely performed in asymptomatic patients: 4920), 17 patients (0.20%) were diagnosed with esophageal eosinophilia (mean age ± standard deviation: 44±11.9 years; 1 female). Only 6 patients with esophageal eosinophilia were diagnosed by general gastrointestinal endoscopy; among them, 3 patients had dysphagia and 3 were asymptomatic. The remaining 11 patients were diagnosed by medical check-up endoscopy. All patients were treated with a proton pump inhibitor (PPI); 5 were diagnosed with EoE and 12 with PPI responsive esophageal eosinophilia. Chronological endoscopy analysis showed that EoE findings could be observed for a mean of 6.1 years prior to diagnosis, and the disease did not significantly progress in severity. CONCLUSIONS: Most Japanese patients with EoE have mild and slowly progressing disease, which can be diagnosed when close attention is paid to the endoscopic findings. Medical check-up endoscopy in Japan could be a great opportunity for the early diagnosis of EoE.