Angiomyolipoma (AML) is a benign mesenchymal tumor that is frequently found in the kidney and, rarely, in the liver. The natural history of hepatic AML has not been clarified, and, because of the similar patterns in imaging studies, such as ultrasonography, computed tomography, and magnetic resonance imaging, some of these tumors have been overdiagnosed as hepatocellular carcinoma in the past. With an increase in the number of case reports showing detailed imaging studies and immunohistochemical staining of the tumor with human melanoma black-45, the diagnostic accuracy is also increasing. In this paper, we focused on the role of noninvasive imaging studies and histological diagnosis showing distinctive characteristics of this tumor. In addition, because several reports have described tumor progression in terms of size, recurrence after surgical resection, metastasis to other organs, and portal thrombosis, we summarized these cases for the management and discussed the indications for the surgical treatment of this tumor.

Background

There is no standard therapeutic procedure for the hepatocellular carcinoma (HCC) in patients with poor hepatic reserve function. With the approval of newly developed chemotherapeutic agent of miriplatin, we have firstly conducted the phase I study of CDDP powder (DDP-H) and miriplatin combination therapy and reported its safety and efficacy for treating unresectable HCC in such cases. To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for the combination of transarterial oily chemoembolization (TOCE) and transarterial chemotherapy (TAC) using miriplatin and DDP-H for treating unresectable hepatocellular carcinoma (HCC).

Methods

Transarterial chemotherapy using DDP-H was performed through the proper hepatic artery targeting the HCC nodules by increasing the dose of DDP-H (35–65 mg/m2) followed by targeting the HCC nodules by transarterial oily chemoembolization with miriplatin.

Results

A total of nine patients were enrolled in this study and no DLT was observed with any dose of DDP-H in all cases in whom 80 mg (median, 18–120) miriplatin was administered. An anti-tumour efficacy rating for partial response was obtained in one patient, while a total of four patients (among eight evaluated) showed stable disease response, leading to 62.5% of disease control rate. The pharmacokinetic results showed no further increase in plasma platinum concentration following miriplatin administration.

Conclusion

Our results suggest that a combination of DDP-H and miriplatin can be safely administered up to their respective MTD for treating HCC.

Trial registration

This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003541).

The effects of acute (AR) and chronic rejection (CR) on intestinal smooth muscle that are responsible for the dysmotility following small bowel transplantation (SBTX) are incompletely understood. Jejunal and ileal specimens from normal control dogs (n=7), and auto-transplanted dogs were examined at 7 days (n=6) and 1 (n=7), 3 (n=6), 6 (n=6), and 12 months (n=6). Allo-transplanted dogs that developed AR (n=8) and CR (n=5) were examined for gross and microscopic morphology (muscle thickness, the number and size of myocytes, and inflammatory infiltrate), and for contractile and intracellular electrical function in vitro. Auto-SBTX did not alter morphology at any period, but contractile function was impaired at 7 days (73.6%) compared with normal intestine. Acute rejection did not influence myocyte number or size, but was associated with a prominent infiltrate of neutrophils and lymphocytes, and severely impaired contractile function (20.6%) compared with auto-SBTX controls. Acute rejection also significantly inhibited the amplitude of slow waves and of inhibitory junction potentials. Chronic rejection caused thickening of muscularis propria by both hyperplasia (175.5%) and hypertrophy (202.6%) accompanied by moderate inflammatory cell infiltrate compared with auto-SBTX controls. We conclude that the marked inflammatory infiltrate into the muscularis propria indicates that the graft muscle is injured by both acute and chronic rejection; impaired function of intestinal smooth muscle following SBTX results from both rejection and the injury associated with transplantation, and chronic rejection following SBTX is associated with both hyperplasia and hypertrophy of the muscularis propria.

AIM: To reveal the manner of hepatocellular carcinoma (HCC) development in patients with nonalcoholic steatohepatitis (NASH) focusing on multicentric occurrence (MO) of HCC.

METHODS: We compared clinicopathological characteristics between patients with and without MO of HCC arising from NASH background. The clinical features were implicated with reference to the literature available.

RESULTS: MO of HCC was identified with histological proof in 4 out of 12 patients with NASH-related HCC (2 males and 2 females). One patient had synchronous MO; an advanced HCC, two well-differentiated HCCs and a dysplastic nodule, followed by the development of metachronous MO of HCC. The other three patients had multiple advanced HCCs accompanied by a well-differentiated HCC or a dysplastic nodule. Of these three patients, one had synchronous MO, one had metachronous MO and the other had both synchronous and metachronous MO. There were no obvious differences between the patients with or without MO in terms of liver function tests, tumor markers and anatomical extent of HCC. On the other hand, all four patients with MO of HCC were older than 70 years old and had the comorbidities of obesity, type 2 diabetes mellitus (T2DM), hypertension and cirrhosis. Although these conditions were not limited to MO of HCC, all the conditions were met in only one of eight patients without MO of HCC. Thus, concurrence of these conditions may be a predisposing situation to synchronous MO of HCC. In particular, old age, T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the literature.

CONCLUSION: The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this study. Further investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.

In normal rats, the xenobiotic K76 inhibited the C5 and probably the C2 and C3 steps of complement and effectively depressed classical complement pathway activity, alternative complement pathway activity, and the C3 complement component during and well beyond the drug’s 3-hr half-life. It was tested alone and with intramuscular tacrolimus (TAC) and/or intragastric cyclophosphamide (CP) in rat recipients of heterotopic hearts from guinea pig (discordant) and hamster (concordant) donors. Single prevascularization doses of 100 and 200 mg/kg increased the median survival time of guinea pig hearts from 0.17 hr in untreated controls to 1.7 hr and 10.2 hr, respectively; with repeated injections of the 200-mg dose every 9–12 hr, graft survival time was increased to 18.1 hr. Pretreatment of guinea pig heart recipients for 10 days with TAC and CP, with or without perioperative splenectomy or infusion of donor bone marrow, further increased median graft survival time to 24 hr. Among the guinea pig recipients, the majority of treated animals died with a beating heart from respiratory failure that was ascribed to anaphylatoxins. Hamster heart survival also was increased with monotherapy using 200 mg/kg b.i.d. i.v. E76 (limited by protocol to 6 days), but only from 3 to 4 days. Survival was prolonged to 7 days with the addition to K76 of intragastric CP at 5 mg/kg per day begun 1 day before operation (to a limit of 9 days); it was prolonged to 4.5 days with the addition of intramuscular TAC at 2 mg/kg per day beginning on the day of transplantation and continued indefinitely. In contrast to the limited efficacy of the single drugs, or any two drugs in combination, the three drugs together (K76, CP, and TAC) in the same dose schedules increased median graft survival time to 61 days. Antihamster antibodies rapidly increased during the first 5 days after transplantation, and plateaued at an abnormal level in animals with long graft survival times without immediate humoral rejection. However, rejection could not be reliably prevented, and was present even in most of the xenografts recovered from most of the animals dying (usually from infection) with a beating heart. Thus, although effective complement inhibition with K76 was achieved in both guinea pig- and hamster-to-rat heart transplant models, the results suggest that effective interruption of the complement cascade will have a limited role, if any, in the induction of xenograft acceptance.

Background

Although much is known about the mucosal damage that occurs after intestinal warm ischemia and reperfusion and its recovery, little is known about the effect of cold preservation and transplantation on the mucosa. We studied the electrophysiological, biochemical, and histological changes of the intestinal mucosa after preservation for 24 hr and subsequent transplantation.

Methods

The small intestines from adult mongrel dogs were harvested. The intestines were orthotopically autotransplanted immediately (control group) or after preservation for 24 hr (preservation group). Jejunal and ileal tissues were taken before harvesting, at the end of preservation, 1 hr after reperfusion, and on postoperative days 3, 7, 14, and 28. The Ussing chamber method was used to study the electrophysiologic changes. Tissue maltase, diamine oxidase, and ornithine decarboxylase were measured. A histological analysis was also performed.

Results

Control group grafts showed no evident deterioration in electrophysiology, biochemistry, or morphology. In contrast, preservation group grafts exhibited electrophysiological and biochemical degradation, complete denudation of the villi, and crypt injury (especially in the ileum) after reperfusion. Electrophysiologic function and the mucosa biochemical marker recovered within 3 days in the jejunum and within 7–14 days in the ileum; however, histological recovery of mucosal injury required 28 days in the jejunum and more than 28 days in the ileum.

Conclusions

Our study showed that despite severe destruction of mucosal integrity by prolonged preservation and transplantation, the intestinal mucosa has an enormous regenerative capacity. Our study also showed that regeneration was more pronounced in the jejunum than in the ileum.

AIM: To investigate whether a noninvasive measurement of tissue strain has a potential usefulness for management of nonalcoholic steatohepatitis (NASH).

METHODS: In total 26 patients, 23 NASHs and 3 normal controls were enrolled in this study. NASH was staged based on Brunt criterion. At a region of interest (ROI), a shear wave was evoked by implementing an acoustic radiation force impulse (ARFI), and the propagation velocity was quantified.

RESULTS: Shear wave velocity (SWV) could be reproducibly quantified at all ROIs in all subjects except for 4 NASH cases, in which a reliable SWV value was not calculated at several ROIs. An average SWV of 1.34 ± 0.26 m/s in fibrous stage 0-1 was significantly slower than 2.20 ± 0.74 m/s and 2.90 ± 1.01 m/s in stages 3 and 4, respectively, but was not significantly different from 1.79 ± 0.78 m/s in stage 2. When a cutoff value was set at 1.47 m/s, receiver operating characteristic analysis showed significance to dissociate stages 3 and 4 from stage 0-1 (P = 0.0092) with sensitivity, specificity and area under curve of 100%, 75% and 94.2%, respectively. In addition, the correlation between SWV and hyaluronic acid was significant (P < 0.0001), while a tendency toward negative correlation was observed with serum albumin (P = 0.053).

CONCLUSION: The clinical implementation of ARFI provides noninvasive repeated evaluations of liver stiffness at an arbitrary position, which has the potential to shed new light on NASH management.

Paraneoplastic syndromes of hepatocellular carcinoma (HCC) are not uncommon. However, the prognosis is poor and follow-up and improvement of paraneoplastic syndromes with treatment have been reported rarely. We report a successful case in an aged man of a massive HCC with paraneoplastic syndrome, treated by combined intraarterial chemotherapy and hepatic resection. Paraneoplastic syndrome (erythrocytosis and hyperlipidemia) was monitored throughout the treatment and erythropoietin (EPO) mRNA also was analyzed in the resected liver. The hemoglobin level and serum levels of EPO and total cholesterol (T-cho) decreased dramatically with treatment, along with a decrease in serum levels of α-fetoprotein and protein induced by vitamin vitamin K absence II (PIVKA-II). Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that the residual cancer expressed EPO RNA but the nontumor tissue did not. This was a rare case of paraneoplastic syndrome of HCC that was treated successfully. This case indicates that paraneoplastic syndrome reflected tumor progression and that serum levels of both EPO and T-cho might be used as tumor markers.

We have previously shown that Y box-binding protein-1 (YB-1) binds preferentially to cisplatin-modified Y box sequences. Based on structural and biochemical data, we predicted that this protein binds single-stranded nucleic acids. In the present study we confirmed the prediction and also discovered some unexpected functional features of YB-1. We found that the cold shock domain of the protein is necessary but not sufficient for double-stranded DNA binding while the C-tail domain interacts with both single-stranded DNA and RNA independently of the cold shock domain. In an in vitro translation system the C-tail domain of the protein inhibited translation but the cold shock domain did not. Both in vitro pull-down and in vivo co-immunoprecipitation assays revealed that YB-1 can form a homodimer. Deletion analysis mapped the C-tail domain of the protein as the region of homodimerization. We also characterized an intrinsic 3′→5′ DNA exonuclease activity of the protein. The region between residues 51 and 205 of its 324-amino acid extent is required for full exonuclease activity. Our findings suggest that YB-1 functions in regulating DNA/RNA transactions and that these actions involve different domains.