Hypoxic hepatitis with marked elevation of serum ferritin probably due to activation of intrahepatic macrophages: another form of hypoxic hepatitis hitherto not reported?

BACKGROUND AND STUDY AIMS: Hypoxic hepatitis (HH) is an acute liver injury that develops in patients with underlying diseases, such as heart failure, respiratory failure, septic/toxic shock. However, some patients do not have underlying diseases or episodes which are known to result in HH. Here, we analyzed the clinical characteristics of this particular patient group (called 'unknown HH' hereafter) to understand its pathogenesis. PATIENTS AND METHODS: Between October 2010 and January 2016, 157 consecutive patients with acute liver injury were admitted to our hospital. Among these patients, 15 patients were categorized as unknown HH. Medical histories and blood test results of unknown HH were analyzed. RESULTS: Among 15 patients of unknown HH, 11 were habitual drinkers and all experienced one of digestive symptoms which might result in mild hypovolemia such as vomiting, diarrhea, appetite loss, and epigastralgia. All patients of unknown HH presented marked elevation of serum ferritin concentration paralleled with aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) concentrations. The serum levels of ferritin, ALT, LDH, and prothrombin time-international normalized ratio (PT-INR) were rapidly decreased during hospitalization and all 15 patients of unknown HH recovered without any complication. CONCLUSIONS: We found the particular group of HH with marked elevation of serum ferritin probably due to intrahepatic macrophage activation. Anti-inflammatory treatments might be effective for this group of hypoxic hepatitis.

A new application of the phase-field method for understanding the mechanisms of nuclear architecture reorganization.

Specific features of nuclear architecture are important for the functional organization of the nucleus, and chromatin consists of two forms, heterochromatin and euchromatin. Conventional nuclear architecture is observed when heterochromatin is enriched at nuclear periphery, and it represents the primary structure in the majority of eukaryotic cells, including the rod cells of diurnal mammals. In contrast to this, inverted nuclear architecture is observed when the heterochromatin is distributed at the center of the nucleus, which occurs in the rod cells of nocturnal mammals. The inverted architecture found in the rod cells of the adult mouse is formed through the reorganization of conventional architecture during terminal differentiation. Although a previous experimental approach has demonstrated the relationship between these two nuclear architecture types at the molecular level, the mechanisms underlying long-range reorganization processes remain unknown. The details of nuclear structures and their spatial and temporal dynamics remain to be elucidated. Therefore, a comprehensive approach, using mathematical modeling, is required, in order to address these questions. Here, we propose a new mathematical approach to the understanding of nuclear architecture dynamics using the phase-field method. We successfully recreated the process of nuclear architecture reorganization, and showed that it is robustly induced by physical features, independent of a specific genotype. Our study demonstrates the potential of phase-field method application in the life science fields.

Analysis of individual differences in radiosensitivity using genome editing.

Current standards for radiological protection of the public have been uniformly established. However, individual differences in radiosensitivity are suggested to exist in human populations, which could be caused by nucleotide variants of DNA repair genes. In order to verify if such genetic variants are responsible for individual differences in radiosensitivity, they could be introduced into cultured human cells for evaluation. This strategy would make it possible to analyse the effect of candidate nucleotide variants on individual radiosensitivity, independent of the diverse genetic background. However, efficient gene targeting in cultured human cells is difficult due to the low frequency of homologous recombination (HR) repair. The development of artificial nucleases has enabled efficient HR-mediated genome editing to be performed in cultured human cells. A novel genome editing strategy, 'transcription activator-like effector nuclease (TALEN)-mediated two-step single base pair editing', has been developed, and this was used to introduce a nucleotide variant associated with a chromosomal instability syndrome bi-allelically into cultured human cells to demonstrate that it is the causative mutation. It is proposed that this editing technique will be useful to investigate individual radiosensitivity.

Increased RP105-Negative B Cells in IgG4-Related Disease.

Four patients with IgG4-related disease (IgG4-RD) showed increased percentages of RP105-negative B cells in the peripheral blood. Case 1: A 66-year-old man having retroperitoneal fibrosis had 18.8% of RP105-negative B cells. Oral prednisolone improved the affected lesions and the percentage of RP105-negative B cells decreased (3.2%) after the treatment. Case 2: A 53-year-old man with retroperitoneal fibrosis had 27.9% of RP105-negative B cells. Case 3: A 38-year-old man with follicular hyperplasia showed increased percentage of RP105-negative B cells (8.3%). Case 4: A 60-year-old man with interstitial nephritis had 27.5% of RP105-negative B cells. The treatment decreased the numbers of RP105-negative B cells. Increased numbers of RP105-negatvie B cells is possibly associated with disease activity of IgG4-RD. Analysis of expression of RP105 on B cells may be helpful in evaluation of disease activity of IgG4-RD.

Diffusion-weighted MR imaging of ameloblastomas and keratocystic odontogenic tumors: differentiation by apparent diffusion coefficients of cystic lesions.

BACKGROUND AND PURPOSE: Ameloblastomas and keratocystic odontogenic tumors are major aggressive odontogenic tumors in the maxillomandibular regions, but the differentiation between these 2 tumors is frequently ineffective based on only conventional CT and MR imaging findings. Here, we evaluated diffusion-weighted MR imaging for the differentiation of these 2 odontogenic tumors. MATERIALS AND METHODS: We prospectively studied 9 patients with ameloblastoma and 7 patients with keratocystic odontogenic tumor using diffusion-weighted MR imaging. Apparent diffusion coefficients (ADCs) of the nonenhancing and solid lesions in these tumors were determined with use of 2 b factors (500 and 1000). RESULTS: Two types of nonenhancing lesions were identified; one with high signal intensity on fat-suppressed T2-weighted images (type A) and the other with low or intermediate intensity (type B). The type A nonenhancing lesions were observed in all the ameloblastomas, but they were evident in only 2 keratocystic odontogenic tumors. It is interesting to note that the ADCs of the nonenhancing lesions in the ameloblastomas were significantly higher than those of the nonenhancing lesions in the keratocystic odontogenic tumors (2.48 +/- 0.20 x 10(-3) mm(2)/s vs 1.13 +/- 0.56 x 10(-3) mm(2)/s; P < .001). The ADCs of the solid lesions in the ameloblastomas (1.39 +/- 0.15 x 10(-3) mm(2)/s) were significantly lower than those of the nonenhancing lesions in the ameloblastomas and were similar to those of the nonenhancing lesions in the keratocystic odontogenic tumors. CONCLUSION: ADC determination may be used as an adjunct tool for differentiation between ameloblastomas and keratocystic odontogenic tumors.

Radiological landmarks for placement of the tunnels in single-bundle reconstruction of the anterior cruciate ligament.

There is little evidence examining the relationship between anatomical landmarks, radiological placement of the tunnels and long-term clinical outcomes following anterior cruciate ligament (ACL) reconstruction. The aim of this study was to investigate the reproducibility of intra-operative landmarks for placement of the tunnels in single-bundle reconstruction of the ACL using four-strand hamstring tendon autografts. Isolated reconstruction of the ACL was performed in 200 patients, who were followed prospectively for seven years with use of the International Knee Documentation Committee forms and radiographs. Taking 0% as the anterior and 100% as the posterior extent, the femoral tunnel was a mean of 86% (sd 5) along Blumensaat's line and the tibial tunnel was 48% (sd 5) along the tibial plateau. Taking 0% as the medial and 100% as the lateral extent, the tibial tunnel was 46% (sd 3) across the tibial plateau and the mean inclination of the graft in the coronal plane was 19 degrees (sd 5.5). The use of intra-operative landmarks resulted in reproducible placement of the tunnels and an excellent clinical outcome seven years after operation. Vertical inclination was associated with increased rotational instability and degenerative radiological changes, while rupture of the graft was associated with posterior placement of the tibial tunnel. If the osseous tunnels are correctly placed, single-bundle reconstruction of the ACL adequately controls both anteroposterior and rotational instability.

Activation of the SIRT1 pathway and modulation of the cell cycle were involved in silymarin's protection against UV-induced A375-S2 cell apoptosis.

Silymarin, derived from the milk thistle plant, Silybum marianum, has been traditionally used in the treatment of liver disease. Our previous study demonstrated that silymarin has an anti-apoptotic effect against UV irradiation. In this study, SIRT1, a human deacetylase that was reported to promote cell survival, was activated by silymarin (5 x 10(- 4) mol/L) in UV-irradiated human malignant melanoma, A375-S2 cells, followed by down-regulated expression of Bax and decreased release of cytochrome c. Cleavage of procaspase-3 and digestion of its substrates, the inhibitor of caspase-activated DNase (ICAD) and poly(ADP-ribose) polymerase (PARP), were also reduced. Consistent with its protective effect on UV-induced apoptosis, silymarin (5 x 10(- 4) mol/L) also increased G(2)/M phase arrest, possibly providing a prolonged time for efficient DNA repair. Consequently, that silymarin protected A375-S2 cell against UV-induced apoptosis was partially through SIRT1 pathway and modulation of the cell cycle distribution.

Dracorhodin perchlorate induces apoptosis in HL-60 cells.

Dracorhodin perchlorate, an anthocyanin red pigment, induces human premyelocytic leukemia HL-60 cell death through apoptotic pathway. Caspase -1, -3, -8, -9, and -10 inhibitors partially reversed the cell death induced by dracorhodin perchlorate. Caspase-3 and -8 were activated followed to the degradation of caspase-3 substrates, inhibitor of caspase-activated DNase (ICAD) and poly-(ADP-ribose) polymerase (PARP). Dracorhodin perchlorate up-regulated the expression ratio of mitochondrial proteins, Bax/Bcl-XL. The cell death was accompanied with phosphorylation of ERK, JNK and p38 MAPK and partially reduced by MEK inhibitor (PD98059), JNK MAPK inhibitor (SP600125) and p38 MAPK inhibitor (SB 203580). Taken together, dracorhodin perchlorate-induced apoptosis in HL-60 cells via up-regulation of Bax, activation of caspases and ERK/p38/JNK MAPKs.

Significance of administration of fat emulsion: hepatic changes in infant rats receiving total parenteral nutrition with and without fat.

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present animal study focused on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. Thirty infant (3-week-old) male SD rats weighing 60-70 g were randomly allocated to five groups (n = 6): the OD group received an oral diet, the FT group received an oral diet and was fasted overnight on the last day of experiment before sacrifice, the 0% fat group received TPN without fat, the 20% fat group received TPN with 20% of calories from fat emulsion, and the 40% fat group received TPN with 40% of calories from fat emulsion. All TPN regimens were isocaloric, isonitrogenic, and administered for 4 days. In the 0% fat group, plasma levels of liver enzymes were significantly higher than in the other groups. Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the 0% fat group. The results of this study in infant rats indicate the importance of including fat in the TPN regimen in order to prevent the abnormal hepatic changes associated with the excessive administration of fat-free TPN.

A new system for laser-UVA-microirradiation of living cells.

Local nuclear irradiation of living cells has been used to gain insight into the dynamic changes that cell nuclei undergo in response to DNA damage. In particular, the effects of DNA double-strand breaks (DSBs), a major threat to the genomic integrity of cells, have been studied by local nuclear irradiation with ionizing radiation. This method has the disadvantage that it requires expensive equipment to generate a sufficiently high density of focused or collimated ionizing radiation. After appropriate sensitization of the cellular DNA, nuclear microirradiation with UVA can also produce DSBs. In this communication we present a semi-automatic system for laser-UVA-microirradiation based on a commercial laser scanning microscope. The system allows the convenient selection and precise irradiation of living cells, and could provide the basis for a more widespread availability of microirradiation facilities for DNA-repair research.

Differential diagnosis of small hepatocellular carcinoma and borderline lesions and therapeutic strategy.

BACKGROUND/AIMS: To investigate imaging characteristics and surgical results of adenomatous hyperplasia and early-stage hepatocellular carcinoma. METHODOLOGY: A retrospective study set in the First Department of Surgery, University of Tokushima, Japan. From 1994 to 1997, 33 patients with 55 small hepatocellular carcinomas (< or = 3 cm) and 10 borderline lesions (3 adenomatous hyperplasia, 5 atypical adenomatous hyperplasia, 2 atypical adenomatous hyperplasia with focal malignancy) were enrolled for this study. The detectability of these lesions on imaging was evaluated. Cumulative survival and disease-free survival rates were also calculated. RESULTS: Twenty-eight patients were incidentally diagnosed on ultrasonography during follow-up study for chronic disease. In the conventional studies, detection rates of ultrasonography, computed tomography and angiography for small hepatocellular carcinomas and borderline lesions were 76% 80%, 33% 10% and 36% 20%, respectively. Magnetic resonance imaging, intraoperative ultrasonography, helical computed tomography and portal angiographic computed tomography showed better results of 67% 20%, 100% 90%, 70% 50% and 74% 56%, respectively. On differential diagnosis, the ratio of echo level in small hepatocellular carcinomas was significantly higher than that in borderline lesions. The 3-year and 5-year survival rates for all patients were 61% and 41%, while disease-free survival rates at the corresponding times were 15% and 7%, respectively. A total of 25 patients (76%) developed intrahepatic recurrence during a mean follow-up of 33.8 months, although there was no recurrent lesion in 4 adenomatous hyperplasia patients treated with microwave coagulation therapy and ethanol injection intraoperatively. CONCLUSIONS: For tumors larger than 1 cm in diameter, the detection rates with various diagnostic modalities were rather high. However, the differential diagnosis of borderline lesions from small hepatocellular carcinomas could be based on pathologic studies only. Early detection of small hepatic lesions and treatment by methods such as resection or ethanol injection are of critical importance in improving long-term survival.

Clarification of risk factors for hepatectomy in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatic resection is still associated with a higher morbidity than other major abdominal surgery. The aim of this study was to define risk factors for postoperative morbidity, and to evaluate the plasma cytokine pattern to detect early postoperative infection in patients with hepatocellular carcinoma. METHODOLOGY: One hundred and thirty-nine hepatic resections for hepatocellular carcinoma over a 10-year period from 1987 to 1997 were performed. Preoperative and intraoperative predictors of morbid outcomes were analyzed using multiple regression in a stepwise, logistic model. The postoperative concentrations of interleukin-6, interleukin-8, granulocytecolony stimulating factor, endotoxin and hepatocyte growth factor were measured in 32 patients following hepatic resection. RESULTS: Mortality rate within 30 postoperative days was 2.2%, with morbidity occurring in 40.2%. Significant pre- and intraoperative predictors for morbidity were ICGR15 and the presence of liver cirrhosis. Changes of interleukin-6, interleukin-8, granulocytecolony stimulating factor and endotoxin levels were not consistent with the occurrence of postoperative complications. However, the postoperative peak hepatocyte growth factor levels were positively correlated with morbidity. CONCLUSIONS: ICGR15 and presence of liver cirrhosis had a marked effect on the incidence of postoperative complications after hepatectomy for hepatocellular carcinoma. An increase of serum hepatocyte growth factor level could be used to detect complications in the early postoperative period, but the inflammatory cytokine response after hepatectomy did not relate to an increased complication rate.

Experimental study of combined treatment with tacrolimus and donor splenocytes via the portal vein in small bowel transplantation.

We previously reported that the combined treatment of perioperative administration of donor splenocytes via the recipient's portal vein (DSPV) and a short-course Tacrolimus significantly prolonged the survival of fully allogenic grafts in rat small bowel transplantation (SBTX). In the present study we examined whether this effect depended on the quantity of the administered alloantigens in DSPV. In addition, we examined the expression of the surface antigen on T cells of the splenocytes and the induced toleragenic factor, according to the tolerant recipients which in our previous report had shown the prolongation of allogenic transplant small bowel graft survival by the combined treatment of DSPV (1 x 10(8) donor splenocytes) and a short-course Tacrolimus. Donor splenocytes were prepared from Brown-Norway (BN (RT1n)) rat spleens for Lewis (LEW (RT1l)) recipients. The recipients (n = 10), treated with a short course of Tacrolimus (0.5 mg/kg, 0 to 3 days postoperatively) only showed graft rejection with an average of 6.3 +/- 1.0 days postoperatively. However, the combined treatment, consisting of DSPV of 1 x 10(8) donor splenocytes and a short course Tacrolimus significantly prolonged graft survival to 12.7 +/- 2.1 days (n = 12, P < 0.01). DSPV of less than 1 x 10(8) donor splenocytes (5 x 10(7) cells and 2.5 x 10(7)) could not prolong the graft or animal survival under a short-course Tacrolimus treatment. In the tolerant recipients, the CD4 and CD8 percentages of splenocytes were not significantly different from those of control rats or recipients that were treated with short-course Tacrolimus alone. Nevertheless, the percentage of Tcr-alpha beta+ cells expressing IL-2 receptor (R) was significantly lower than in either control rats or the recipients with short-course Tacrolimus. In the suppression assay to one-way mixed lymphocyte response, a toleragenic factor was suggested to the present in the serum of the tolerant recipients. In the present study, it was suggested that the effects of the combined treatment of DSPV and short-course Tacrolimus for the prolongation of graft survival in the rat allogenic SBTX should depended on the quantity of the antigens administered into the portal vein. The beneficial effects of this treatment were reflected in the suppression of IL-2R on the recipient's splenocytes, and tolerogenic factor(s) might subsequently be induced in the tolerant recipient's serum.

Simultaneous resection of pancreas and liver metastases from different metachronous primary cancers.

Resection of a pancreatic head tumor and partial resection of the liver for metastatic lesions were carried out simultaneously in a 72-year-old woman. The patient had a history of two previous operations, right nephrectomy for renal cell carcinoma (clear cell type), done 14 years previously, and an Autincloss procedure for cancer of the left breast (solid tubular carcinoma); (T1N0M0; stage I) done 7 years previously. At the current presentation, preoperative radiographic examination showed a hypervascular tumor in each of the pancreatic and hepatic lesions, but with different patterns. On the basis of histological findings in the two resected specimens, it was difficult to establish whether the hepatic tumor originated from the renal cell carcinoma or the breast cancer, but postoperative immunohistochemical studies for carcinoembryonic antigen (CEA), estrogen receptors, and gross cystic disease fluid protein (GCDFP)-15 showed that the pancreatic tumor had metastasized from the renal cell carcinoma, and the liver tumor from the breast cancer. The immunohistochemical investigation of different markers thus proved to be useful in making the final diagnosis of metastatic lesions from different and metachronous cancers.

Evaluation of the acetaminophen absorption test for early detection of orthotopic small bowel transplant rejection.

We evaluated the efficiency of the acetaminophen (AC) absorption test as a marker of graft rejection in orthotopic small bowel transplantation (SBTX) in rats. Brown Norway (BN) rats were used as donors and Lewis (LEW) rats as recipients. Orthotopic allogenic SBTX was accomplished using a cuff technique for vessel anastomosis. Animals were divided into: group A (n = 9), untreated; group B (n = 15), extended small bowel resection; group C (n = 12), syngeneic SBTX without immunosuppressants; group D (n = 15), allogenic SBTX with tacrolimus (0.1 mg/kg per day); group E (n = 15), allogenic SBTX with tacrolimus (0.5mg/kg per day). Serum AC was measured 15 min following the instillation of 0.15 g/kg AC into the stomach on postoperative days (POD) 1, 3, and 7. Grafts were examined histologically. The group D grafts showed progressive acute rejection histologically, from normal on POD 1, to moderate on POD 3, and severe on POD 7. Serum AC in group D decreased significantly from 53.1 +/- 3.9 microg/ml on POD 1, to 35.0 +/- 12.0 microg/ml on POD 3, and 10.9 +/- 5.6 microg/ml on POD 7. No remarkable change was observed in the other groups. Serum AC correlated well with histological changes in rats subjected to SBTX, resulting in acute rejection. The AC absorption test could be useful for detection of progressive graft rejection in clinical SBTX.

[A case of nonresectable scirrhous type gastric cancer treated by hypertensive subselective chemotherapy with pharmacokinetic modulating chemotherapy].

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. A 62-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the upper gastric body. Histologic study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography revealed swollen paraaortic lymph nodes and peritonitis carcinomatosa. The patient was diagnosed as having a nonresectable scirrhous type gastric cancer with peritonitis carcinomatosa and paraaortic lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously implanted port system placed into the thoracic aorta. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as a pharmacokinetic modulating chemotherapy (PMC). After eight courses of treatment of PMC, paraaortic lymph node swelling and ascites decreased. This chemotherapy produced a partial response in the peritonitis carcinomatosa and paraaortic lymph nodes. This chemotherapy was repeated preoperatively. We reconsidered this case to show indications for operation. The patient died suddenly of acute heart failure before the operation. This therapy was considered an effective treatment for nonresectable gastric cancer.

A non-toxic heat shock protein 70 inducer, geranylgeranylacetone, suppresses apoptosis of cultured rat hepatocytes caused by hydrogen peroxide and ethanol.

BACKGROUND/AIMS: A stress-inducible heat shock protein 70 (HSP70) is one of the best-known endogenous factors protecting cell injury under various pathological conditions. The aim of this study was to examine anti-apoptotic actions of a non-toxic HSP70 inducer, geranylgeranylacetone (GGA), on hepatocytes exposed to hydrogen peroxide (H2O2) or ethanol. METHODS: Primary cultures of rat hepatocytes were treated with different concentrations of GGA and exposed to 0.5 mM H202 or 100 mM ethanol. The heat shock response was assessed by measuring the activation of heat shock factor 1 (HSF1), HSP70 mRNA expression, and accumulations of HSP70, HSP90, and HSP27. Apoptosis was evaluated by DNA fragmentation. RESULTS: Pretreatment with 1 microM GGA for 2 h enhanced nuclear translocation and phosphorylation of HSF1, HSF1-DNA binding, HSP70 mRNA expression, and its accumulation, when the cells were exposed to H202 or ethanol. In association with this accelerated response, GGA suppressed the insult-induced activation of c-Jun N-terminal kinases, caspase 9, and caspase 3-like proteases, leading to significant inhibition of apoptosis. CONCLUSIONS: GGA exerted anti-apoptotic actions, at least in part, by priming hepatocytes for enhanced HSP70 induction. Our results suggest that GGA may have a potential benefit for the treatment of alcoholic and ischemia-reperfusion liver injuries.

Neonatal ketosis is not rare: experience of neonatal screening using gas chromatography-mass spectrometry.

The causes and effects of transient neonatal ketosis, discovered during a pilot study of screening for abnormalities in neonatal metabolism using gas chromatography-mass spectrometry, were investigated. Of the 21,342 neonates that were screened, 47 had significant ketosis. The organic acid profile accompanying ketosis in the urine of neonates followed the pattern of ketotic dicarboxylic aciduria in approximately half of the cases. Ketosis was more often found in neonates nourished by breast feeding (33 out of 47). Over half of the neonates showing ketosis (28 out of 47) were asymptomatic. When normal neonates and neonates testing positive for ketosis were compared, no statistically significant correlations were found with regard to birth mass, gestational period, or gender. However, neonates with ketosis tended to have low mass gain rates in the 5 days from birth and a statistically significant difference was found in this regard in comparison to normal neonates (P<0.0001). From the above results, development of ketosis in neonates was found to be possible even in normal subjects. Most ketosis in neonates was also found to depend largely on nourishment after birth. Existence of an asymptomatic ketosis category was also suggested.

Effect of intrahepatic omental implantation on angiogenesis in rat liver with hepatic artery ligation.

Despite early surgical intervention, the results of treating hepatic artery thrombosis remain poor. The use of omental flaps is well documented for its angiogenic potential in promoting neovascularization in ischemic tissues. This experimental study evaluated the formation of new blood-vessels after omental implantation (OI) in rats after ligation of the hepatic artery. Wistar rats were used and divided into the following groups: I OI with HAL, II OI without HAL, III hepatic artery ligation (HAL). For angiography, measurements were made of liver tissue blood flow by the laser Doppler method and of hepatic artery flow by the colored microsphere method (CMS), and immunohistochemical study was done for vascular endothelial growth factor (VEGF). The rats were killed at 1, 3, 7 or 30 days after laparotomy. Relative arterial hepatic blood flow in the implanted lobe of group I, as determined by CMS, reached 50% of control values 7 days after surgery. Angiography and microscopic studies of the excised liver revealed distinct angiogenesis surrounding the omental implant in the liver for 7 days postoperatively. The formation of new blood-vessels after OI was not observed in livers without HAL. Omental implantation appears to be useful in preventing organ anoxia after hepatic artery thrombosis.

[A case of successful management of nonresectable pancreas cancer with liver metastasis by intra-arterial infusion chemotherapy with angiotensin-II and administration of tegafur/uracil].

Nontypical chemotherapy regimens exist for advanced pancreatic cancer. We herein report a 62-year-old man whose nonresectable pancreatic cancer was treated effectively with a new method of intra-arterial regional chemotherapy with angiotensin-II (AT-II). The patient was admitted to our hospital with obstructive jaundice and anorexia. He was diagnosed as having inoperable advanced pancreatic cancer with liver metastasis. Enteric-coated tegafur/uracil (400 mg) was administered for 3 weeks. Simultaneously, intraarterial infusion with 5-fluorouracil (500 mg) and infusion of methotrexate (100 mg) with 50 micrograms of AT-II was given every week. A catheter connected to a subcutaneously implanted port system was placed into the common hepatic artery. As a result of this treatment, the maximum diameter of the pancreatic tumor decreased from 3 cm to 2 cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 24,000 U/ml to 186 U/ml. Moreover, the performance status of patient also improved, and he was discharged from our hospital despite his terminal cancer. This regimen could well be effective in cases of advanced pancreatic cancer.