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Background Endoscopic ultrasound (EUS)-guided gallbladder drainage (GBD) has gained increasing popularity as an alternative treatment approach for acute cholecystitis in high-risk patients. We report the procedural and long-term outcomes of elective EUS-GBD using self-expandable metallic stents (SEMSs) after percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis. Methods Between April 2015 and January 2017, 15 patients at the study institution underwent elective EUS-GBD after PTGBD. SEMSs were placed in all patients, and the external gallbladder catheter was removed one week after the procedure. Procedural and long-term outcomes were measured retrospectively. Results Both the technical and clinical success rates were 93.3% (14/15). Two patients (13.3%) developed adverse events, with distal stent migration in one patient (6.7%) and asymptomatic pneumoperitoneum in the other patient (6.7%). Cholecystitis recurred only in patients who experienced stent migration. None of the patients underwent elective cholecystectomy. The median duration of stent patency was 544 days (18-1006 days), without any deaths. The overall stent patency rate was 86.7% (13/15). Conclusion Thus, elective EUS-GBD using SEMSs after PTGBD exhibited favorable long-term outcomes, indicating that this approach is effective for patients with severe comorbidities that preclude open surgical cholecystectomy.

Malignant bowel obstruction is a complication of colorectal carcinoma or metastasis from other carcinoma, and it causes significant damage on the condition of elderly patients; however, the self-expandable metallic stents (SEMSs) have been effectively used either for palliation or for bridging to the surgical procedure for this condition. The aim of this study was to investigate the factors influencing long-term outcomes of old-aged patients with SEMS for large bowel obstruction to develop the strategy for those patients in the community medicine. We performed a retrospective review of 42 patients with a median age of 83.0 years (range, 65–99 years), who underwent SEMS placement for malignant colorectal obstruction between 2006 and 2015 in our hospital. Univariate and multivariate logistic regressions were performed on data from the patients to assess the factors affecting 6-month survival without stent dysfunction. The study population comprised 24 females (57.1%) and 18 males (42.9%). Of these, 38 patients (90.5%) received SEMS as palliation, whereas 4 patients (9.5%) underwent subsequent surgery. SEMSs were successfully inserted in 97.6% of patients. The median duration of follow-up was 205.0 days (range, 20–1377 days). On multivariate analysis, shorter stents (

Giant hepatic hemangiomas, though often asymptomatic, may require intervention if rapid growth occurs. The imaging studies including the computed tomography, magnetic resonance imaging, and ultrasonography, and so on are effective for the diagnosis and the management of this tumor; however, due to its size and various patterns of these studies, we need to carefully consider the therapeutic methods. Compared to the cost needed for these modalities, recently developed and approved Perflubutane- (Sonazoid-) based contrast agent enhanced ultrasonography is reasonable and safe. The major advantage is the real-time observation of the vascular structure and function of the Kupffer cells. By this procedure, we can carefully follow the tumor growth or character change in a hemangioma and decide the timing of therapeutic intervention, since abdominal pain, abdominal mass, consumptive coagulopathy, and hemangioma growth are the signs for the therapeutic intervention. We reviewed recent reports about Sonazoid-based enhancement and also showed the representative images collected in our department. This is the first review showing the detailed findings of the giant hemangiomas using Perflubutane (Sonazoid). This review will help the physician in making the decision, and we hope that Sonazoid will gain widespread acceptance in the near future.

Administration of chemotherapy treating hepatocellular carcinoma (HCC) is divided into hepatic arterial infusion chemotherapy (HAIC) which delivers chemotherapeutic agents directly using a catheter, and systemic chemotherapy including oral treatment. Evidence for treatment with sorafenib has emerged indicating it is an effective drug for advanced HCC. HAIC can provide high anticancer efficacy, and it is often performed on patients with advanced HCC in our country. Since various HAIC regimens exist, the efficacy of HAIC using a reservoir system was tested in patients with advanced HCC. The overall response rate was 36%, with a median survival time of 11.9 months. Patients with controlled disease at 8 weeks had Child-Pugh classification A, and no increase in AFP levels when starting early stage in treatment, which were considered to be factors that influenced therapeutic efficacy. Comparison with other HAIC regimens, and consideration of combined treatments using sorafenib and HAIC will be needed.

Rationale: Endoscopic ultrasound (EUS)-guided treatment has been recently described for internalizing refractory pancreaticocutaneous fistulas (PCFs). However, the existing techniques are limited because of the difficulty in accessing nondilated pancreatic ducts or fistulas. In an attempt to overcome this limitation, we present a case where a EUS-guided intervention utilizing a balloon-target technique was employed to internalize a PCF into the stomach. Patient concerns: A 78-year-old woman underwent percutaneous drainage and 4 percutaneous endoscopic necrosectomies for walled-off pancreatic necrosis (WOPN) after severe acute pancreatitis due to choledocholithiasis. Although the WOPN was resolved, refractory PCFs remained. Diagnosis: Pancreaticocutaneous fistulas. Interventions: An echoendoscope was introduced into the stomach, but the narrow PCF lumen made visualization of the fistula by EUS difficult. Subsequently, a balloon catheter was percutaneously inserted into the fistula, and then the inflated balloon was visualized by EUS from the stomach. The balloon was punctured with a 19-gauge fine needle through the posterior wall of the upper body of the stomach (balloon-target technique). A guidewire was then passed through the fistula to the outside of the body through the EUS scope. After dilating the gastro-fistula space with an 8-mm balloon dilation catheter, a 7-French double pigtail catheter was placed from the stomach into the PCF. Outcomes: The percutaneous drainage tube was removed after one week, and the patient was discharged 6 months after admission. No adverse outcomes have been observed in the 2 years since the procedure. Lessons: PCFs can be successfully managed using EUS-guided internalization with a balloon-target technique.

重症型アルコール性肝炎患者に対して，早期よりの持続性血液濾過透析およびステロイドホルモン併用療法が著効し，極めて短い入院日数で退院できた症例を経験した。本症例において，短期間で症状の改善が認められかつ早期に退院できたことについては，年齢が若かったことによる強い肝再生力の存在と急性腎不全は合併していたが感染症，消化管出血などの合併症を認めなかったことで，ステロイドホルモンが非常に有効だったことおよび早期から強力に血液浄化療法を併用したことが考えられた。今回のような重症疾患に対する集中治療には，医師，看護師，臨床工学技士間の緊密に連携したチーム医療が極めて重要であることを改めて実感した。

A 56-year-old Japanese man with hypertension presented with a 10 days history of high fever, right and left upper quadrant tenderness. An abdominal ultrasonography and computerized tomographic scan revealed a large collection in the right lobe of the liver that was consistent with an abscess. A drainage catheter was placed and purulent fluid was drained. Cultures of the fluid and blood were positive for a strain of ampicillin-resistant Klebsiella pneumoniae. Six days after admission, paraplegia and urinary retention were found. On the neurological examination, deep tendon reflexes of the lower extremities were absent bilaterally. Magnetic resonance imaging scan detected thoracic spinal epidural abscess and paraspinal abscess. He received the emergent decompressive laminectomy. Culture of surgical specimen grew ampicillin-resistant K. pneumoniae. The patient was treated with biapenem intravenously. Thereafter, clinical symptoms improved gradually and he was removed to the professional hospital to continue rehabilitation for gait disturbance on hospital day 147.

Both loss of heterozygosity (LOH) and replication error (RER) are considered to be phenotypes of genomic instability. To unveil the role of the genomic instability in hepatocarcinogenesis, frequencies of LOH and RER were simultaneously determined in 15 hepatocellular carcinomas (HCCs), surrounding nontumorous liver tissues (SL), and 13 liver tissues with chronic viral hepatitis void of cancer (NC) by referencing peripheral blood leukocytes (PBLs) from the corresponding donor using 18 microsatellite markers spread throughout the genome. LOH was significantly frequent in HCC compared with that in SL or NC (P = .005, P = .0003, respectively) and observed preferentially at particular microsatellite loci, D1S204, D2S123, D8S1106, D9S266, D16S748, and D19S601. Although the higher prevalence of RER was also significant in HCC compared with that in NC (P = .03), in most cases the errors were detected at very low frequencies and random loci. Both LOH and RER tended to appear more prevalently in SL than in NC. The occurrence rate of LOH was higher in the tissues associated with hepatitis B virus (HBV) than with hepatitis C virus (HCV) infection especially in HCC (P = .03). When referencing SL instead of PBLs, the prevalence of LOH and RER in HCC significantly decreased (P = .02 and P = .03, respectively). These results suggest that LOH is closely associated with multistep hepatocarcinogenesis especially under HBV infection, but RER is imperceptibly associated. The quantitative evaluation of the frequency of LOH by referencing PBLs may be a useful predictor for HCC development in chronic liver diseases.

原発性胆汁性肝硬変に対してウルソデオキシコール酸治療中に, 自己免疫性肝炎を発症した2例を経験した. 原発性胆汁性肝硬変と診断されウルソデオキシコール酸投与後, 症例1は約1年半後, 症例2は約半年後に自己免疫性肝炎を発症した. 2例共ステロイドが投与され, 症例1は8カ月, 症例2は2年の間再燃していない. かかる報告は我々の2例を含めて5例のみであるが, 原発性胆汁性肝硬変の経過観察中には自己免疫性肝炎の発症をみることがあることに注意する必要がある.

BACKGROUND The aim of this study was to elucidate the usefulness of measuring the fucosylation index (FI) of α-fetoprotein (AFP) before the initiation of therapy as a new prognostic indicator for patients with hepatocellular carcinoma (HCC). METHODS One hundred twelve patients with HCC who underwent transcatheter arterial embolization, chemoembolization, and/or percutaneous ethanol injection were examined in the current study. FI was determined by crossed immunoaffinoelectrophoresis in the presence of Lens culinaris agglutinin. RESULTS When the tentative discriminating value of FI was set at 18%, the mean survival rate for the group whose FI was higher than 18% was significantly lower than that for the group whose FI was equal to or less than 18%, according to the generalized Wilcoxon test (P = 0.0117) and the log rank test (P = 0.0183). The survival rate for HCC patients with AFP concentrations of more than 200 ng/mL was also significantly lower than that for patients with AFP in the range of 21-200 ng/mL, according to the generalized Wilcoxon test (P = 0.0017) and the log rank test (P = 0.0018). When FI was combined with AFP concentration, a highly significant difference was observed between the group with FI >18% and AFP >200 ng/mL and another group with FI ≤18% and AFP ≤200 ng/mL, as determined by the generalized Wilcoxon test (P < 0.0001) and the log rank test (P = 0.0003). An analysis of multiple covariates in the prognostic factors with the Cox proportional hazards model showed that FI was one of the independent prognostic factors. CONCLUSIONS The current study indicates that measuring FI from sera before the initiation of treatment serves as a new prognostic factor and may improve prognostic estimates and appraisal of therapeutic outcomes for patients with HCC. Cancer 1998;83:2076-2082. © 1998 American Cancer Society.

Because telomerase activity is necessary for cell immortality and probably associated with tumor progression, we have evaluated a possible aid for quantitation of the activity to predict intrahepatic recurrences after surgery in patients with hepatocellular carcinoma (HCC). HCC tissues obtained by surgical resection from 20 patients were studied. Telomerase activity was expressed as peaks with a periodicity through a fluorescence-based telomeric repeat amplification protocol using an autosequencer, and the quantity of activity was calculated from peak areas. A ratio of fluorescence intensity depending on telomerase to that of an internal standard was used as a value of relative telomerase activity (RTA). RTA in serially diluted S100 extracts from HepG2 cells was well correlated with the amount of the extracts. The mean RTA value of 36.4 +/- 27.8 (mean +/- SD, 3.21 to 105) in 9 patients suffering from early recurrences after surgery was significantly higher than that (9.84 +/- 7.65; mean +/- SD, 3.00 to 29.0) in 11 patients without intrahepatic recurrences during the early period (P = .004). These results indicate that RTA value can be a useful predictor for intrahepatic recurrences during the early period after surgical resection of HCC.

The hepatic cyst is a common benign liver tumor, and no surgical treatment is necessary. However, it is difficult to correctly diagnose the giant hepatic cyst containing the solid septal structures inside, from the malignant cystadenocarcinomas. The various imaging modalities such as computed tomography, magnetic resonance imaging, and ultrasonography, have been developed and are useful for the diagnosis of these liver tumors. Reviewing the other reports in this paper, the combination of more than 2 modalities will help to diagnose these tumors; however, the malignant potential is unable to be excluded if the tumor is huge. Therefore, the surgical resection should be considered for the huge hepatic cysts with septal structures if the correct diagnosis is unable to be made. For example, when the hemorrhages cause the granulation in the septa which often shows neovascularization, the imaging modalities are unable to define this situation from the malignant tissue with hypervascularity. Therefore, with the careful review of other reports, we conclude that if the imaging studies show the possible malignant potential or the sizing-up is marked, the surgical treatment should be considered with the consent from the patients.

Heterogeneous reactivity of human serum transferrin (Tf) with lectins was analysed using patient sera to determine whether it can be used to distinguish patients with hepatocellular carcinoma (HCC) from those with liver cirrhosis (LC). Microheterogeneity of Tf was analysed by crossed immunoaffinity electrophoresis (CIAE) with concanavalin A (Con A) and Lens culinaris agglutinin (LCA). Sample sera from 58 patients with HCC, 43 patients with LC and 10 normal controls were used in this study and the results were evaluated statistically. The increments of Con A-non-reactive (C1) and -weakly reactive (C2) species of Tf were observed in HCC compared with those of LC and Norm. Significant increase in the combined percentage of Con A- C1 + C2 species was also revealed in HCC (35.5 +/- 8.5%, mean+/-s.d.) compared with those of LC (29.1 +/- 6.8%; P < 0.001) and normal controls (17.1 +/- 2.3%; P < 0.001). The elevation of LCA-reactive (L2) species of Tf was recognized in HCC (8.2 +/- 3.8%) in comparison with those of LC (4.8 +/- 3.1%; P < 0.001) and normal controls (1.3 +/- 1.7%; P < 0.001). The increment of C1 + C2 species and/or L2 species of Tf was observed in 78% (sensitivity) of patients with HCC. The specificity, the positive predictive value and the overall accuracy were 81, 88 and 72%, respectively. Positive ratio of C1 + C2 and/or L2 species was 77 and 70% in alpha-fetoprotein low and -high producing HCC patients, respectively. These results indicate that the microheterogeneity analysis of human serum Tf is useful for distinguishing patients with HCC from those with LC and normal controls.

N-acetylglucosaminyltransferase (GnT) III catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin-A-(ConA)-reactive glycan into the ConA-nonreactive one. In this study, we measured GnT III levels in serum, tumor, and surrounding normal tissues together with a glucosaminylation index of alpha-fetoprotein (AFP), which is defined as the percentage of the ConA-nonreactive species in total AFP, in a case of AFP-producing renal cell carcinoma. The glucosaminylation index was determined by affinoelectrophoresis in the presence of ConA. GnT III was measured by using a pyridylaminated asialoagalactobiantennary sugar chain as a substrate by high-performance liquid chromatography. The glucosaminylation index of serum AFP, the concentration of which was 68 ng/ml, was 60%. This value is much higher than observed in hepatocellular carcinomas. The tumor tissue level of GnT III was 55.34 pmol/mg/h which was about six fold higher (9.50 pmol/mg/h) than in normal surrounding tissues. The serum level of this enzyme before surgery was 27.65 pmol/ml/h and decreased to 5.38 pmol/ml/h thereafter in association with a depression of serum AFP from 68 to 5.4 ng/ml. Thus, an increased level of GnT III in tumor tissues could account for the elevated conversion of a biantennary complex type sugar chain of AFP into a bisecting glucosaminylated biantennary one resulting from the addition of an N-acetylglucosamine residue at the trimannosyl core. This is, to our knowledge, the first report explaining the change in the carbohydrate structure of AFP with different affinity to ConA on the enzymatic basis in a renal cell carcinoma.

The reactivity of transferrin (Tf) with concanavalin A (Con A) was examined by crossed immuno-affinity electrophoresis (CIAE) of the sera from patients with hepatocellular carcinoma (HCC). Serum Tf was separated into three species — Cl (Con A-nonreactive), C2 (-weakly reactive) and C3 (-reactive) —designated consecutively from the anode by CIAE. Nineteen pairs of serum samples were evaluated before and 1 month after therapies for HCC by transcatheter arterial embolization and/or percutaneous ethanol injection, and surgical resection. The significant decrease in the mean percentage of Tf-Cl species was observed after the above therapies, although there was no statistical difference between the serum Tf concentration before and after therapies. Thus, the present study suggests that the measurement of these species would be useful as an index of several therapeutic effects on HCC, especially in the case of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP)-non-producing HCC.

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.

A 56-year-old Japanese man with hypertension presented with a 10 days history of high fever, right and left upper quadrant tenderness. An abdominal ultrasonography and computerized tomographic scan revealed a large collection in the right lobe of the liver that was consistent with an abscess. A drainage catheter was placed and purulent fluid was drained. Cultures of the fluid and blood were positive for a strain of ampicillin-resistant Klebsiella pneumoniae. Six days after admission, paraplegia and urinary retention were found. On the neurological examination, deep tendon reflexes of the lower extremities were absent bilaterally. Magnetic resonance imaging scan detected thoracic spinal epidural abscess and paraspinal abscess. He received the emergent decompressive laminectomy. Culture of surgical specimen grew ampicillin-resistant K. pneumoniae. The patient was treated with biapenem intravenously. Thereafter, clinical symptoms improved gradually and he was removed to the professional hospital to continue rehabilitation for gait disturbance on hospital day 147.

Hepatocellular carcinoma (HCC) mainly arises from the liver with chronic inflammation. Because telomere reduction reflects replicative history in somatic cells, we analyzed the possibility that liver tissues surrounding HCC consist of the cells carrying substantial reduction of telomere. We studied 20 HCC and surrounding noncancerous liver tissues (SL) obtained by surgical resection, and 10 laparoscopically obtained needle biopsy specimens of the liver with chronic inflammation including no overt HCC (CI). Five liver tissues without chronic liver diseases (ND) were also examined. Extracted genomic DNAs were blotted on a nylon membrane, and probed at first with radio-labeled d(TTAGGG)(3) and reprobed with radio-labeled d(CCT)(7). The intensity caused by d(TTAGGG)(3) was divided by that of d(CCT)(7). The ratio was defined as telomeric repeats content (TC). Dilution experiments reproducibly revealed almost the same TC. The reduction rate of telomere length through aging estimated by regression analysis of TC was 0.62% per year. Concomitant analyses of TC and average telomere length revealed that both values were significantly correlated (r =.45; P =.009). To compare TC in the liver with respect to chronic inflammation, the value was divided by TC in peripheral blood leukocytes (PBL) from the same donor. The ratio was defined as relative TC (RTC). There was a statistically significant decrease of RTC in CI compared with that in ND (P =.03). Furthermore, RTC in SL was significantly lower than that in CI (P =.0001). These observations suggest that RTC value in liver tissues may digitally indicate a replicative history of hepatocytes under chronic inflammation, and a risk of HCC development.