Diagnostic accuracy of real-time tissue elastography for the staging of liver fibrosis: a meta-analysis.

OBJECTIVE: To evaluate the overall accuracy of real-time tissue elastography (RTE) for the staging of liver fibrosis. METHODS: We systematically reviewed 15 studies (1,626 subjects) in which sensitivity and specificity of RTE for liver fibrosis are available. For each cut-off stage of fibrosis, i.e., F ≥ 1, F ≥ 2, F ≥ 3, and F ≥ 4, summary sensitivity and specificity were estimated using a bivariate random-effects model. Publication bias was assessed using funnel plots and Egger's test. RESULTS: Summary sensitivity and specificity were 0.79 and 0.76 for F ≥ 2, 0.82 and 0.81 for F ≥ 3, and 0.74 and 0.84 for F ≥ 4, respectively. Meta-regressions revealed scoring methods of RTE and liver diseases in the samples might not influence sensitivity and specificity of RTE. However, the estimated accuracy of RTE might be overestimated due to publication bias (p = 0.004 for F ≥ 2, p < 0.001 for F ≥ 3, and p = 0.002 for F ≥ 4). CONCLUSIONS: RTE is not highly accurate for any cut-off stage of fibrosis. Compared with findings of meta-analyses on Transient Elastography and Acoustic Radiation Force Impulse imaging, the overall accuracy of RTE seems to be nearly identical for the evaluation of significant liver fibrosis, but less accurate for the evaluation of cirrhosis. KEY POINTS: • Non-invasive methods for evaluating liver fibrosis are necessary to replace liver biopsy. • ARFI is as accurate as TE for evaluating liver fibrosis. • RTE may be as accurate as TE and ARFI for fibrosis. • RTE may be less accurate than TE and ARFI for cirrhosis. • The estimated accuracy of RTE may be overestimated by publication bias.

Neurolytic celiac plexus block reduces occurrence and duration of terminal delirium in patients with pancreatic cancer.

PURPOSE: WHO's three step ladder sometimes cannot provide adequate pain relief for pancreatic cancer. Some patients develop terminal delirium (TD). The aim of this study was to test if the addition of a celiac plexus block (CPB) to pharmacotherapy could reduce the incidence of TD. METHODS: Pancreatic cancer patients under the care of our palliative-care team were investigated with regard to the duration and occurrence of TD, pain scores [numerical rating score (NRS)] and daily opioid dose. Between August 2007 to September 2008, 17 patients received only pharmacotherapy (control group). Then, we modified our guideline for analgesia, performing CPB 7 days after the first intervention of our team. Between October 2008 to September 2009, 19 patients received CPB. RESULTS: The opioid doses in CPB group were significantly lower both at 10 days after the first intervention (3 days after CPB) (27 ± 11 vs. 66 ± 82 mg; p = 0.029) and 2 days before death (37 ± 25 vs. 124 ± 117 mg; p = 0.009). NRS in the CPB group were significantly lower both at 10 days after the first intervention (0 [0-2] vs. 3 [2-5], p < 0.0001) and 2 days before death (1 [0-2] vs. 3 [1-4.5], p = 0.018). The occurrence and duration of TD in CPB group were both reduced (42 vs. 94 %, p = 0.019; and 1.8 ± 2.9 vs. 10.4 ± 7.5 days, p = 0.0003). CONCLUSION: The duration and occurrence of TD and the pain severity were significantly less in pancreatic cancer patients who underwent neurolytic CPB.

Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine.

PURPOSE: Painful neuropathic conditions of cancer pain often show little response to nonopioid and opioid analgesics but may be eased by antidepressants and anticonvulsants. Although gabapentin is effective in the treatment of neuropathic pain in patients with cancer, some patients experience intolerable side effects sufficient to warrant discontinuation. The aim of this study was to see whether low-dose gabapentin is effective in treating cancer-related neuropathic pain when combined with low-dose imipramine. METHODS: Fifty-two cancer patients diagnosed as having neuropathic pain were allocated into four groups: G400-I group took gabapentin 200 mg and imipramine 10 mg every 12 h orally; G400 group took gabapentin 200 mg every 12 h orally; G800 group took gabapentin 400 mg every 12 h orally; I group took imipramine 10 mg every 12 h orally. RESULTS: Low-dose gabapentin-imipramine significantly decreased the total pain score and daily paroxysmal pain episodes. Several patients developed mild adverse symptoms in the four groups, and three patients discontinued treatment due to severe adverse events in the G800 group. CONCLUSION: Low-dose gabapentin-antidepressant combination with opioids was effective in managing neuropathic cancer pain without severe adverse effects.

The imminent healthcare and emergency care crisis in Japan.

OBJECTIVES: Japan has a universal healthcare system, and this paper describes the reality of the healthcare services provided, as well as current issues with the system. METHODS: Academic, government, and press reports on Japanese healthcare systems and healthcare guidelines were reviewed. RESULTS: The universal healthcare system of Japan is considered internationally to be both low-cost and effective because the Japanese population enjoys good health status with a long life expectancy, while healthcare spending in Japan is below the average given by the Organization for Economic Corporation and Development (OECD). However, in many regions of Japan the existing healthcare resources are seriously inadequate, especially with regard to the number of physicians and other health professionals. Because healthcare is traditionally viewed as "sacred" work in Japan, healthcare professionals are expected to make large personal sacrifices. Also, public attitudes toward medical malpractice have changed in recent decades, and medical professionals are facing legal issues without experienced support of the government or legal professionals. Administrative response to the lack of resources and collaboration among communities are beginning, and more efficient control and management of the healthcare system is under consideration. CONCLUSION: The Japanese healthcare system needs to adopt an efficient medical control organization to ease the strain on existing healthcare professionals and to increase the number of physicians and other healthcare resources. Rather than continuing to depend on healthcare professionals being able and willing to make personal sacrifices, the government, the public and medical societies must cooperate and support changes in the healthcare system.

Issues and Solutions in Introducing Western Systems to the Pre-hospital Care System in Japan.

OBJECTIVE: This report aims to illustrate the history and current status of Japanese emergency medical services (EMS), including development of the specialty and characteristics adapted from the U.S. and European models. In addition, recommendations are made for improvement of the current systems. METHODS: Government reports and academic papers were reviewed, along with the collective experiences of the authors. Literature searches were performed in PubMed (English) and Ichushi (Japanese), using keywords such as emergency medicine and pre-hospital care. More recent and peer-reviewed articles were given priority in the selection process. RESULTS: The pre-hospital care system in Japan has developed as a mixture of U.S. and European systems. Other countries undergoing economic and industrial development similar to Japan may benefit from emulating the Japanese EMS model. DISCUSSION: Currently, the Japanese system is in transition, searching for the most suitable and efficient way of providing quality pre-hospital care. CONCLUSION: Japan has the potential to enhance its current pre-hospital care system, but this will require greater collaboration between physicians and paramedics, increased paramedic scope of medical practice, and greater Japanese societal recognition and support of paramedics.

Diagnosis of the "large medial meniscus" of the knee on MR imaging.

Although several quantitative magnetic resonance (MR) diagnostic criteria for discoid lateral meniscus (DLM) have been described, there are no criteria by which to estimate the size of the medial meniscus. We define a medial meniscus that exceeds the normal size as a "large medial meniscus" (LMM), and the purpose of this study is to establish the quantitative MR diagnostic criteria for LMM. The MR imaging findings of 96 knees with arthroscopically confirmed intact semilunar lateral meniscus (SLM), 18 knees with intact DLM, 105 knees with intact semilunar medial meniscus (SMM) and 4 knees with torn LMM were analyzed. The following three quantitative parameters were measured: (a) meniscal width (MW): the minimum MW on the coronal slice; (b) ratio of the meniscus to the tibia (RMT): the ratio of minimum MW to maximum tibial width on the coronal slice; (c) continuity of the anterior and posterior horns (CAPH): the number of consecutive 5-mm-thick sagittal slices showing continuity between the anterior horn and the posterior horn of the meniscus on sagittal slices. Using logistic discriminant analysis between intact SLM and DLM groups and using descriptive statistics of intact SLM and SMM groups, the cutoff values used to discriminate LMM from SMM were calculated by MW and RMT. Moreover, the efficacy of these cutoff values and three slices of the cutoff values for CAPH were estimated in the medial meniscus group. "MW> or =11 mm" and "RMT> or =15%" were determined to be effective diagnostic criteria for LMM, while three of four cases in the torn LMM group were true positives and specificity was 99% in both criteria. When "CAPH> or =3 slices" was used as a criterion, three of four torn LMM cases were true positives and specificity was 93%.

Comparison of response to 17 beta-estradiol and 17 beta-trenbolone among three small fish species.

Three small fish species, medaka (Oryzias latipes), fathead minnow (Pimephales promelas), and zebrafish (Danio rerio), were exposed to an estrogen, 17 beta-estradiol (E2), and an androgen, 17 beta-trenbolone (TB), for 21 d under flow-through conditions to compare the susceptibility among these three small fish species to the substances. Effects on gross morphology, including secondary sex characteristics and gonadosomatic index, as well as on blood or liver vitellogenin (VTG) levels were assessed. In E2 exposures, significant increases in estrogenic activity were observed in both sexes of all three fish species. The lowest-observed-effect concentrations (LOECs) of E2 for VTG induction in males of medaka, fathead minnow, and zebrafish were less than or equal to 8.94, 28.6, and 85.9 ng/L, respectively. In TB exposures, we observed masculinization of secondary sex characteristics in females as a result of the androgenic activity of TB in medaka with a LOEC of 365 ng/L and in fathead minnow with a LOEC of 401 ng/ L. We also found VTG reduction in females of all three fish species. These results suggest that the susceptibility of medaka to estrogenic chemicals may be higher than those of fathead minnow and zebrafish and that the susceptibility of medaka to androgenic chemicals may be almost equal to that of fathead minnow in the 21-d fish assay.

Fish full life-cycle testing for 17beta-estradiol on medaka (Oryzias latipes).

We studied the chronic effects of 17beta-estradiol (E2) on the reproductive status of medaka (Oryzias latipes) over two generations under continuous exposure to assess its hazard on this species. The exposure of parental (F0) medaka to E2 was begun on embryos within 12 h postfertilization and continued for up to 101 d; the assessment endpoints included embryological development, hatching, posthatch survival, growth, sexual differentiation, reproduction, and hepatic vitellogenin (VTG) levels under flow-through exposure to E2 at each mean measured concentration of 0.939, 2.86, 8.66, 27.9, and 92.4 ng/L. Eggs (F1) spawned from the F0 fish at 98, 99, and 100 d posthatch were also examined for hatchability, survival after hatching, growth, sexual differentiation, and hepatic VTG level until 59 d posthatch. In the F0 medaka, no concentration-related effect of E2 was observed on hatching, posthatch mortality, and growth. However, we observed abnormal sex differentiation, induction of VTG, and reproductive impairment in a dose-dependent manner. The lowest-observed-effect concentration and no-observed-effect concentration of E2 for these effects were 8.66 and 2.86 ng/L, respectively. In the F1 medaka treated with E2 at < or = 8.66 ng/L, however, dose-dependent effects were not observed in any parameter. The results indicate that E2 can have significant effects on reproductive potential of medaka at concentrations as low as 8.66 ng/L, suggesting that the ecological risk of E2 is higher than that of weak estrogens, such as nonylphenol and octylphenol.

Prognostic implications of inhalation injury in burn patients in Tokyo.

Inhalation injury has recently emerged as the major cause of mortality in burn patients. However, the prognostic value of inhalation injury has not been thoroughly assessed in Japanese burn facilities. The aim of the present study was to evaluate the impact of inhalation injury on burn patients' mortality in Tokyo. Of 6416 patients admitted to 13 burn facilities of the Tokyo Burn Unit Association between 1984 and 2002; the 5560 eligible patients were included in this study (mean age, 40+/-20 years; male, 61.6%; mean partial- and full-thickness burn size, 10.7+/-13.0% and 9.6+/-20.5%). Of the 5560 patients, 1690 patients (30.4%) had experienced inhalation injury. The overall in-hospital mortality rate of the patients with inhalation injury was higher than that of those without inhalation injury (33.6% versus 8.1%, odds ratio, 5.72 [95% CI, 4.91-6.67]). The results of the multivariate analysis indicated that inhalation injury; full- and partial-thickness burn size, and age were independent predictors of outcome (relative risk, 2.58 [2.03-3.29], 1.10 [1.09-1.11], 1.06 [1.06-1.07], 1.05 [1.05-1.06], respectively). In conclusion, inhalation injury was the most important predictor of overall mortality among burned patients in Tokyo.

Fish full life-cycle testing for androgen methyltestosterone on medaka (Oryzias latipes).

Abstract-We studied the chronic effects of methyltestosterone (MT) on reproductive status of medaka (Oryzias latipes) over two generations under continuous exposure to verify the applicability of the fish full life-cycle test (FFLC) for this androgen with this species. The exposure of parental (F0) medaka to MT was begun on embryos within 12 h postfertilization and continued for up to 101 d; assessment endpoints included embryological development, hatching, posthatch survival, growth, sexual differentiation, reproduction, and hepatic vitellogenin (VTG) levels under flow-through exposure to MT at each mean measured concentration of 0.35, 1.09, 3.29, 9.98, and 27.75 ng/L. Eggs (F1) spawned from the F0 fish at 98, 99, and 100 d posthatch were examined for hatchability, survival after hatching, growth, sexual differentiation, and hepatic VTG level until 60 d posthatch. In the FFLC with medaka, MT induced masculinization of both secondary sex characteristics and gonads. We observed that all F0 fish in the 27.75-ng/L treatment group showed male secondary sex characteristics in which no fish with ovary could be discerned. Several fish with ovaries in F0 and F1 generations treated with 9.98 ng/L showed male secondary sex characteristics. We also observed swollen abdomens in the F0 and F1 female fish in the 9.98-ng/L treatment group. These swollen abdomens were induced by enlarged ovaries and were accompanied with declined fecundity and fertility in the F0 generation. These results indicate that MT reduces the reproductive potential of medaka and that the FFLC with this species is applicable to the evaluation of androgens.

[Suppression of neutrophil immune function in rabbit models of hemorrhagic shock complicated by intra-abdominal hypertension].

OBJECTIVE: To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)- kappaB. METHODS: Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A), a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-kappaB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization. RESULTS: Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-kappaB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-kappaB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation. CONCLUSIONS: Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.

Development of vitellogenin assay for endocrine disrupters using medaka (Oryzias latipes).

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of the egg yolk precursor vitellogenin (VTG) in the liver of medaka (Oryzias latipes) and was employed to establish an in vivo testing system for estrogen and estrogenic compounds using liver homogenates. Results of 3-month-old fish exposed to three reference chemicals (ethynylestradiol, methyltestosterone and flutamide) recommended by Organisation for Economic Co-operation and Development (OECD) for the validation showed the induction and decrease of vitellogenic responses, making the assay using the liver VTG of medaka a possible screening method for not only estrogens but also androgens. In addition, 21-day exposure of male fish to 4-tert-octylphenol and 4-nonylphenol produced concentration-dependent inductions of liver vitellogenin, with the lowest observed effect concentrations of 64.1 microg/L and 22.5 microg/L, respectively, while no significant VTG responses were observed in male and female fish exposed to tributyltin chloride and dibutyl phthalate. This study demonstrates that the VTG assay using liver homogenates from small fish such as medaka can be used as a screening method for environmental estrogens. This is because the sensitivity of the VTG response in medaka may be almost the same as that of other fish using blood samples.

Fish full life-cycle testing for the weak estrogen 4-tert-pentylphenol on medaka (Oryzias latipes).

We studied the chronic effects of 4-tert-pentylphenol (4-PP) on reproductive status of medaka (Oryzias latipes) over two generations under continuous exposure, with the goal of verifying the applicability of the fish full life-cycle test (FFLC) for this weak estrogen with this species. The exposure of parental (F0) medaka to 4-PP was begun on embryos within 12 h after fertilization and continued for up to 101 d, with monitoring of embryological development, hatching, posthatch survival, growth, sexual differentiation, reproduction, and hepatic vitellogenin (VTG) levels under flow-through exposure to 4-PP at mean measured concentrations of 51.1, 100, 224, 402, and 931 microg/L. Eggs (F1) spawned from the F0 fish at 99, 100, and 101 d after hatch also were examined for hatchability, survival after hatching, growth, sexual differentiation, and hepatic VTG levels, until 61 d after hatch. In the FFLC with the F0 medaka, the lowest-observed-effect concentration (LOEC) of 4-PP for lethal and sublethal toxicity (as shown by growth inhibition) was 931 microg/L. The LOECs for estrogenic effects (as shown by abnormal sexual differentiation and VTG induction) were 224 and < or = 51.1 microg/L, respectively, and the LOEC for reproductive impairment was 224 microg/L. Therefore, the effective concentrations of 4-PP for abnormal sexual differentiation and reproductive impairment were about four times lower than those for lethal and sublethal toxicity. In the F1 medaka, the LOECs for sublethal toxicity and estrogenic effects were 224 and < or = 51.1 microg/L, respectively. This finding suggests that the continuous exposure to 4-PP over two generations induced these adverse effects at lower concentrations in the F1 generation than those in the F0 generation. Thus, 4-PP has estrogenic effects that reduce the reproductive potential of medaka. The results indicate that the FFLC with medaka is applicable to the evaluation of weak estrogens.

Effects of 4-nonylphenol and 4-tert-octylphenol on sex differentiation and vitellogenin induction in medaka (Oryzias latipes).

Medaka (Oryzias latipes) were continuously exposed to various concentrations of two alkylphenols, 4-nonylphenol (NP) and 4-tert-octylphenol (OP), from fertilized eggs to 60 d posthatch. The effects on sexual differentiation and hepatic vitellogenin (VTG) induction in medaka were assessed to elucidate the lowest-observed-effect concentrations (LOECs) of NP and OP for these events during early life stages. The LOECs of NP and OP for these events were 11.6 and 11.4 microg/L, respectively. These results suggest that NP and OP may have adverse effects at similar concentrations during early life stage in medaka. Additionally, we investigated whether the abnormal sex differentiation induced by these alkylphenols would be permanent or reversible once the medaka were returned to clean water. The appearance of the secondary sex characteristics reverted from female to male when fish were returned to clean water. However, gonadal histology showed that intersex gonads still existed, even after the fish were transferred to clean water for two months. These results suggest that the induced feminization of secondary sex characteristics in medaka exposed to alkylphenols during the stage of sexual differentiation may not always be permanent, but the gonadal alteration (testis-ova) may continue much longer.

[Postgraduate trauma education for surgeon--from the veiwpoint of trauma and emergency physicians].

A recent important topic in the field of trauma care is the elimination of "preventable death." Since patients' satisfactory prognosis and good recovery mainly depend upon the success of the initial evaluation and care, the responsibility of physicians who first come into contact with trauma patients in the emergency room is especially heavy. Many general surgeons examine trauma patients, although, unfortunately they have few opportunities for training in how to deal with those patients in the present educational program. Traumatology should be one of the most important areas of surgery, and therefore this paper emphasizes that every surgeon needs to be educated and trained in an adequate curriculum of trauma care. The Japanese Association for Acute Medicine could help by offering the Japan Advanced Trauma Evaluation and Care (JATEC) training program. JATEC proposes standardized guidelines as well as a nationwide the educational program for trauma management.

Biliary cystadenocarcinoma followed up as benign cystadenoma for 10 years.

We describe a case of biliary cystadenocarcinoma that showed a longterm clinical course. A 69-year-old Japanese man was admitted to our hospital because of abdominal discomfort. The patient had been diagnosed with benign cystadenoma of the liver at another hospital in 1987 and had been followed up for 10 years. Abdominal ultrasonography (US) and computed tomography (CT) scan demonstrated a unilocular cystic lesion, which included multiple conspicuous papillary protrusions in the left hepatic lobe. Left lateral segmentectomy was performed, and intraoperative cholangiography revealed a communication between the cystic tumor and intrahepatic bile duct. The tumor contained clear mucinous fluid and enfolded multiple yellowish papillary projections on the cystic wall. Histological examination showed the tumor to be biliary cystadenocarcinoma. The patient is doing well 4 years after the operation.

Effect of ethinylestradiol on the reproduction and induction of vitellogenin and testis-ova in medaka (Oryzias latipes).

Mature medaka (Oryzias latipes) were exposed to ethinylestradiol (EE2) at measured concentrations of 32.6, 63.9, 116, 261, and 488 ng/L for 21 d under flow-through conditions. Effects on reproductive success of the fish as well as on gonadal condition and vitellogenin (VTG) induction were assessed. A significant decrease in fecundity was observed only at the highest EE2 concentration, whereas hepatic VTG concentration in males was increased at concentrations of 63.9 ng/L and greater. In addition, an intersex condition (testis-ova) of the gonad was observed in male medaka exposed to EE2 concentrations of > or = 63.9 ng/L. Overall, these results indicate that the lowest-observed-effect concentrations of EE2 based on reproduction versus induction of both VTG and testis-ova in the medaka were 488 and 63.9 ng/L, respectively. Thus, the physiological and histological measurements were approximately eightfold more responsive to the EE2 exposure than were overt reproductive effects. This suggests that the elevated VTG levels and testis-ova may not be definitely responsible for reproductive impairment of the fish.

[Damage control surgery--a historical view].

"Damage control surgery" is a surgical strategy to cope with the lethal triad of death, i.e., acidosis, hypothermia, and coagulopathy, often seen in severely injured patients. Perihepatic packing was attempted by some trauma surgeons during the 1970s as an alternative to hepatectomy for severe liver injury, with favorable results. The concept of bail-out surgery and reoperation was introduced during the 1980s as a treatment modality for severe abdominal trauma. This strategy of trauma care was named "damage control surgery" by Rotondo et al in 1993, which consists of initial laparotomy, secondary resuscitation, and definitive surgery. Angiography and TAE may be used during secondary resuscitation for hemostasis. The concept of damage control surgery is now applied not only to severely injured patients but also for other surgical patients in critical condition. Damage control surgery was introduced to Japan during the late 1990s. However, the Japanese experience has been limited because the volume of severe trauma cases is very small.