Comparison of Local Recurrence in Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma with Or Without Accumulation of Iodized Oil Beyond Corona Enhancement Area: Short-term Results

BackgroundLocal tumor recurrence of hepatocellular carcinoma (HCC) often occurs in blood drainage areas. Corona enhancement is determined by computed tomography during hepatic arteriography (CTHA) and is considered to represent the blood drainage area. This study aimed to investigate the relationship between embolization of corona enhancement area and local tumor recurrence of patients with HCC who underwent transcatheter arterial chemoembolization (TACE).Patients and methodsThe study retrospectively selected 53 patients with 60 HCC nodules that showed corona enhancement area on late-phase CTHA and showed homogenous accumulation of iodized oil throughout the nodule on non-contrast-enhanced CT performed immediately after TACE. We divided the nodules into two groups, according to whether the accumulation of iodized oil covered the entire corona enhancement area (group A) or not (group B). Local tumor recurrence was compared between the two groups.ResultsThe cumulative local tumor recurrence rates for group A (n = 36) were 2.8%, 2.8%, 8.3% at 3, 6, and 12 months, respectively, whereas the recurrence rates for group B (n = 24) were 20.8%, 45.8%, 75% at 3, 6, and 12 months, respectively. The cumulative local tumor recurrence rates for group A were significantly lower than those for group B (hazard ratio, 0.079; 95% confidence interval, 0.026–0.24; p < 0.001).ConclusionsThe results of the study suggest that the corona enhancement area may be an accurate safety margin in TACE which should be performed until the embolic area covers the entire corona enhancement area.Key words: corona enhancement, transcatheter arterial chemoembolization, computed tomography during hepatic arteriography, hepatocellular carcinoma     

Protective effect of geranylgeranylacetone against loxoprofen sodium-induced small intestinal lesions in rats

We studied the effect of the selective serotonin reuptake inhibitor (SSRI) paroxetine on the immobility time in the forced swimming test using different strains of mice (ICR, ddY, C57BL/6, BALB/c and DBA/2). There was a difference between strains in the response to paroxetine (although it induced anti-immobility effects in all strains of mice used). The mouse strain most sensitive to paroxetine was DBA/2; the ICR strain showed the lowest sensitivity. We previously demonstrated variations in the responses to another SSRI, fluvoxamine, in different strains of mice, which was in agreement with the present findings. In DBA/2 and ICR mice, the anti-immobility effects of paroxetine were significantly antagonized by the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). The noradrenergic α(1)-adrenoceptor antagonist prazosin significantly reduced the anti-immobility effects elicited by a high dose (5mg/kg) of paroxetine in DBA/2 and ICR mice. However, prazosin did not affect the anti-immobility effects of a lower dose of paroxetine (1mg/kg) in DBA/2 mice. This suggests that the anti-immobility effects of a higher dose of paroxetine in mice are associated with serotonergic and noradrenergic neurons. Prazosin did not the affect anti-immobility effects of fluvoxamine. These results suggest that there are differences between mice strains in the antidepressant-like effects of paroxetine (which are similar to those elicited by fluvoxamine). Moreover, involvement of the noradrenergic system was partly related to the anti-immobility effects of paroxetine (which are different to those elicited by fluvoxamine).     

Combined arsenic trioxide-cisplatin treatment enhances apoptosis in oral squamous cell carcinoma cells

Background

Oral squamous cell carcinoma (OSCC) accounts for the majority of oral cancers. Despite recent advances in OSCC diagnostics and therapeutics, the overall survival rate still remains low. Here, we assessed the efficacy of a combinatorial arsenic trioxide (ATO) and cisplatin (CDDP) treatment in human OSCC cells.

Methods

The combinatorial effect of ATO/CDDP on the growth and apoptosis of OSCC cell lines HSC-2, HSC-3, and HSC-4 was evaluated using MTT and annexin V assays, respectively. Chou–Talalay analyses were preformed to evaluate the combinatorial effects of ATO/CDDP on the dose-reduction index (DRI). To clarify the mechanism underlying the ATO/CDDP anticancer effect, we also examined the involvement of reactive oxygen species (ROS) in ATO/CDDP-induced apoptosis.

Results

Combination index (CI) analyses revealed that a synergistic interaction of ATO and CDDP elicits a wide range of effects in HSC-2 cells, with CI values ranging from 0.78 to 0.90, where CI?<?1 defines synergism. The CI values in HSC-3 and HSC-4 cells ranged from 0.34 to 0.45 and from 0.60 to 0.92, respectively. In addition, ATO/CDDP yielded favorable DRI values ranging from 1.6-fold to 7.71-fold dose reduction. Compared to mono-therapy, ATO/CDDP combinatorial therapy significantly augmented the loss of mitochondrial potential, caspase-3/7 activity and subsequent apoptosis. These changes were all abrogated by the antioxidant N-acetylcysteine.

Conclusions

This study provides the first evidence for a synergistic ATO/CDDP anticancer (apoptotic) activity in OSCC cells with a favorable DRI, thereby highlighting its potential as a combinational therapeutic regime in OSCC.     

A New Flavone C-glycoside from Scutelaria baicalensis

从黄芩根中首次分离出一个新黄酮碳糖甙，白杨素８ＣβＤ葡萄糖甙和一个已知苯乙醇甙，ａｃｔｅｏｓｉｄｅ。     

Unsuspected gallbladder cancer diagnosed by laparoscopic cholecystectomy: A clinicopathological study

Laparoscopic cholecystectomy (LC) for gallstones has become a popular treatment modality, but LC for gallbladder cancer is not yet established and its prognosis is still unknown. We clinicopathologically studied unsupected gallbladder cancer presenting at pathologic evaluation after LC. The entire cross section of gallbladders after 456 LCs was histologically examined. The presence of malignant lesions was confirmed in 13 (2.85%) of 456 cases. The preoperative diagnoses were gallstones in 5 patients, gallbladder polyps in 5, gallstones with gallbladder polyps in 2, and gallstones with adenomyomatosis in 1. The carcinoma had invaded the mucosa in 7, the proper muscle in 2, and the subserosa in 3; the serosa was exposed in 1. The tumor size ranged from 2 mm to the entire gallbladder. An additional resection was performed in 2 patients. During the mean follow-up period of 25.9 months, 1 patient died of recurrence at 8 months while 1 demonstrated recurrence at the port site 1 year after surgery. No other patients have had any recurrence to date. Since early gallbladder cancer removed laparoscopically can be expected to have a satisfactory outcome, diagnostic and therapeutic LC is recommended in cases where total biopsy is indicate. However, in every case, extreme caution needs to be exercised to prevent the dissemination and implantation of cancer cells at the port site. Portions of this paper were presented in 1995 at the 36th World Congress of Surgery in Lisbon, Portugal.     

Thoracic epidural clonidine and morphine for postoperative pain relief

This study was undertaken to evaluate the potentiation of the postoperative analgesic effect of thoracic epidural morphine by coadministration of thoracic epidural clonidine in a randomized double-blinded design. Twenty patients underwent radical gastrectomy under combined general anaesthesia (enflurane and nitrous oxide/oxygen) and epidural anaesthesia with local anaesthetics. They received a thoracic epidural bolus injection of either 0.05 mg · kg^?1 morphine plus 3 μg · kg^?1 clonidine (M+C group; n =10) or 0.05 mg · kg^?1 morphine alone, (M group; n = 10) immediately before completion of surgery. All patients received iv morphine via patient-controlled analgesia (PCA) equipment for 24 hr postoperative period, and the PCA iv consumption of morphine was the primary variable of efficacy of the analgesic regimen. In addition, data analyses included mean arterial blood pressure, heart rate, respiratory rate, arterial blood gas measurement, sedation score, and visual analogue pain scale score (VAS). The cumulative number of iv morphine injections via PCA was less in the M+C group than in the M group at each hour for 24 hr postoperative period (P < 0.05), while the numbers of PCA morphine injections per hour beyond nine hours after surgery were higher in the M group than in the M+C group (P < 0.05). Sedation score was higher, and VAS and mean blood pressure were lower in the M+C group only at one hour after surgery compared with the M group. We conclude that the combined single thoracic epidural administration of morphine plus clonidine produces a more potent and longer lasting analgesia than does morphine alone.     

Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer

The purpose of this study was to develop a new type of gene vector, polyamidoamine (PAMAM) dendriplex pharmaceutically modified, based on electrostatic interactions, by various anionic polymers. The γ-polyglutamic acid (γ-PGA)/PAMAM dendriplex and the α-PGA/PAMAM dendriplex formed a stable complex, although α-polyaspartic acid and heparin released pDNA from the complex. The addition of anionic polymer decreased the ζ-potential, although it did not greatly affect the size of the complex. As a result of an in vitro gene expression study of mouse melanoma cells, we found that the γ-PGA/PAMAM dendriplex showed high gene expression comparable to the PAMAM dendriplex, although the α-PGA/PAMAM dendriplex showed lower gene expression. Tail vein injection of the γ-PGA/PAMAM dendriplex into mice also led to high gene expression in the spleen and lung. The γ-PGA/PAMAM dendriplex showed no cytotoxicity and no agglutination, although severe cytotoxicity and agglutination were observed in the PAMAM dendriplex. Thus, we discovered that complexes of pDNA, PAMAM dendrimers, and γ-PGA showed higher gene expression in vitro and in vivo, and markedly lower toxicity. This complex is valuable and is expected to be a safe and effective gene vector.     

Cervical non-squamous carcinoma: an effective combination chemotherapy of taxane, anthracycline and platinum for advanced or recurrent cases

Objective

An effective salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. The aim of the present study was to analyze the safety and efficacy of a combination chemotherapy for this disease using taxane, anthracycline, and platinum.

Study design

This was a retrospective analysis of advanced and recurrent non-squamous cervical cancers treated at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during a 10 year study period from 2000 to 2009. Single agent chemotherapies and combination chemotherapies for advanced and recurrent cervical cancer cases of non-squamous histology which were reported in the English literature were also reviewed.

Results

Salvage chemotherapy, using taxane, anthracycline and platinum, was performed for 5 advanced and 14 recurrent cases. Prior to the salvage chemotherapy, 15 (79%) of the 19 patients had already received either radiation or chemotherapy. A complete or partial tumor response was achieved in 8 (42%) of the 19 cases. The response rate for recurrent disease in a previously irradiated field was 40%. The median progression-free survival (PFS) and overall survival (OS) were 8 months (1–108) and 13 months (5–108), respectively. Grade 4 and febrile grade 3 neutropenia was observed in 6 cases (32%), but there was no case in which salvage chemotherapy had to be cancelled due to toxicity. According to previous reports, the cumulative response rate of combination chemotherapy (35%) was significantly higher than that of single agent chemotherapy (17%) (p < 0.001). OS tended to be longer in the combination chemotherapy cases (8.7 months to 18 months) than that of single agent chemotherapy cases (7.3+ months to 9.1+ months).

Conclusion

Combination chemotherapy of taxane, anthracycline, and platinum was found to have a survival benefit for advanced and recurrent cervical cancer patients of non-squamous carcinoma histology, with a tolerable toxicity.