Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.     

ASO Author Reflections: Perspectives of Laparoscopic Hepatectomy with Venous Tumor Thrombectomy for Hepatocellular Carcinoma

Annals of Surgical Oncology -     

ASO Author Reflections: Laparoscopic Arantius’ Approach as Shortcut Access for Major Hepatic Veins

Annals of Surgical Oncology -     

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.     

Cytotoxic properties of eosinophil granule major basic protein for tumor cells

BACKGROUND: Eosinophil granule major basic protein (MBP) mediates many eosinophil-associated immune functions and it adheres eosinophils to parasite targets. METHODS: We compared the toxicities of MBP and melittin to K562 and HL-60 cells using five cytotoxicity methods. RESULTS: Trypan blue staining, propidium iodide/ CellTrackertrade markGreen staining and incorporation of 14C-leucine assays indicated that MBP damages most cells by 1 h. In contrast, 51Cr and lactic dehydrogenase (LDH) release assays indicated that MBP damages most cells only at 20 h. All five methods indicated that melittin damages nearly all cells by 1 h. To resolve these discrepancies, the procedures were modified. Without cell transfer, dye staining methods showed that MBP produces very little cytotoxicity at 4 h. 51Cr and LDH assays, modified to mimic cell transfer, showed increased cytotoxicities at 4 h. The 14C-leucine assay modified by solubilization of cells with SDS and by trichloroacetic acid precipitation showed increased recovery of labeled protein and, thus, lower cytotoxicity, about 50%, at 4 h. CONCLUSION: Overall, MBP's ability to cause molecular and cellular adhesion confounds cytotoxicity measurements. A modified 14C-leucine assay overcame MBP's adhesiveness and provided an accurate measure of cytotoxicity.     

Hip fracture mortality and morbidity in Switzerland and Japan: A cross-cultural comparison

Summary Based on national mortality data, the frequency of hip fractures in elderly people was compared between Switzerland and Japan. Age-adjusted annual incidence rates per 100 000 population estimated for Swiss persons over 60 years were around 150 and 200 in males and around 450 in females, while for the Japanese they were only 132 in males and 285 in females. Age-adjusted death rates from hip fracture for the Swiss over 60 were 20.0 in males and 28.9 in females, while for the Japanese they were only 1.6 in males and 2.7 in females. The inclination of the age-dependent slope in hip fracture mortality rates was substantially the same in both countries, but there was a lag time of approximately 10 years in Japan. Remarkably, the proportion of deaths due to falls among all accidental deaths was several times greater in both sexes for the Swiss than for the Japanese. This differential might be an important underlying reason for the observed difference between death rates of hip fracture in Switzerland and Japan. Other known behavioral risk factors for hip fracture such as diet, exercise, estrogen use etc. are unlikely to explain the observed difference in hip fracture mortality and morbidity between Switzerland and Japan. However, given the doubts on the reliability and thus comparability of the available data on mortality and morbidity, the present findings should be regarded as preliminary. In conclusion, we believe that the unexplained and large difference in the burden of hip fracture between Switzerland and Japan merits further studies, including new aetiological hypotheses.

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Zusammenfassung Gestützt auf nationale Sterbedaten wird die Häufigkeit von Hüftfrakturen bei Betagten in der Schweiz und Japan verglichen. Alterskorrigierte jährliche Inzidenzraten (bezogen auf 100 000 Einwohner) bezifferten sich bei den Schweizer Personen über 60 Jahren auf ca. 150–200 bei den Männern sowie ca. 450 bei den Frauen, während bei den Japanern die entsprechenden Inzidenzen lediglich 132 bei den Männern und 285 bei den Frauen betrugen. Die alterskorrigierte durch Hüftfrakturen bedinte Mortalität (pro 100000) betrug bei den Schweizern über 60 Jahren 20,0 bei den Männern und 28,9 bei den Frauen, während bei den Japanern die entsprechenden Werte bei 1,6 für Männer und 2,7 für Frauen lagen. Die Gerade, die das Verhältnis zwischen Alter und Hüftfraktur-Mortalität charakterisiert, zeigte in beiden Ländern ungefähr die gleiche Steigung, war in Japan jedoch um ca. 10 Jahre rechtsverschoben. Bemerkenswerterweise war der Anteil sturzbedingter Todesfälle unter allen unfallbedingten Todesfällen bei beiden Geschlechtern in der Schweiz wesentlich höher als in Japan. Dieser Unterschied könnte eine wichtige, zurgrundeliegende Ursache für die Differenz in der Hüftfrakturmortalität zwischen der Schweiz und Japan darstellen. Andere verhaltensabhängige Risikofaktoren für Hüftfraktur wie Ernährung, körperliche Bewegung, Oestrogenzufuhr usw. vermögen die beobachteten Unterschiede in der Mortalität und Morbidität an Hüftfraktur zwischen der Schweiz und Japan kaum zu erklären Angesichts der ungewissen Reliabilität und Vergleichbarkeit der zur Verfügung stehenden Daten müssen die vorliegenden Ergebnisse allerdings mit Vorsicht interpretiert werden. Zusammenfassend glauben wir, dass der grosse und weitgehend unerklärte schweizerisch-japanische Unterschied im Auftreten von Hüftfrakturen weiter abgeklärt werden sollte, unter Einschluss neuer ätiologischer Hypothesen.

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Résumé Basée sur les données de mortalité nationales, la fréquence des fractures de hanche des personnes âgées est comparée entre la Suisse et le Japon. Les taux d'incidence annuels corrigés pour l'effet de l'âge chez les personnes suisses âgées de plus de 60 ans sont d'environ 150–200 chez les hommes (par rapport à 100 000 habitants), ainsi qu'environ 450 chez les femmes, tandis qu'au Japon les incidences correspondantes s'élèvent à 132 chez les hommes et 285 chez les femmes. La mortalité des fractures de hanche, corrigée pour l'effet de l'âge s'élève chez les Suisses âgés de plus de 60 ans à 20,0 (par 100 000) chez les hommes et à 28,9 chez les femmes, alors que chez les Japonais les taux correspondants sont 1,6 chez les hommes et 2,7 chez les femmes. La proportion de décès faisant suite à des chutes parmi l'ensemble des accidents mortels est remarquablement plus élevée en Suisse qu'au Japon, pour les femmes comme pour les hommes. Cette différence pourrait expliquer le taux élvé de décès suite à une fracture de hanche observé en Suisse. D'autres facteurs de risque pour la fracture de hanche liés au style de vie ne sont apparemment pas en mesure d'expliquer les différences de mortalité et de morbidité par fracture de hanche observées entre la Suisse et le Japon. Face aux doutes qui concernent la fiabilité et la comparabilité des données à disposition, ces résultats doivent être interprétés avec prudence. Toutefois, nous pensons que la différence substantielle des taux de fractures de hanche entre Suisse et Japon, qui reste inexpliquée, devrait être examinée plus en détail, également en ce qui concerne de nouvelles hypothèses étiologiques.

     

Studies on function of the upper urinary tract. XXIX. Canine ureteral electromyogram isolated from "so-called Pacemaker"

Many workers have reported that ureteral peristaltic movement is controlled by the "so-called Pacemaker". But, in our recent studies, it was revealed that the existence of pacemaker is not always necessary for the peristaltic movement. In this study, we made isolated and non-isolated prototype models, using 18 mongrel dogs, to explore the influential factors on ureteral peristaltic discharge. Bilateral kidney and ureter were exposed transperitoneally. Unilateral upper urinary tract was prepared to preserve the pacemaker without renal blood supply, and contralateral one was prepared not to preserve the pacemaker by cutting at the proximal portion of the ureter. Vesico-ureteral reflux (VUR) was caused on these two models. A luminal pressure and ureteral electromyogram was recorded. In the result, there is spontaneous peristaltic discharges of the ureter which had the tendency to increase peristaltic frequency according to the increase of the luminal pressure. It was suggested that adequate expanding stimulation is the factor of peristaltic discharge to increase, and the peristaltic discharge under this condition propagates from upper to lower portion of the ureter.     

Anti-inflammatory activity of ginsenoside ro

Ginsenoside Ro, an oleanane-type saponin has been screened for activity in experimental models of inflammation. Ginsenoside Ro (10,50, and 200 mg/kg, P. O.) inhibited an increase in vascular permeability in mice induced by acetic acid and reduced an acute paw edema in rats induced by compound 48/80 or carrageenin. Ginsenoside Ro did not suppress a developing adjuvant-induced edema in arthritic rats. However, ginsenoside Ro was found to be effective in hypercoagulable state, increase of connective tissue in the artery and calcium effluence from the bone in adjuvant-induced arthritic rats.     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.