Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

Purpose

Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy.

Methods

We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens.

Results

According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p?=?0.116, and p?<?0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%.

Conclusion

RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

     

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II–V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III–V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model’s scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.     

Knee Flexion Angle Following Total Knee Arthroplasty Relates to a Preoperative Range of Motion of the Hip

BackgroundMany factors have been reported to affect postoperative range of knee flexion after total knee arthroplasty (TKA); however, no study has reported the impact of preoperative range of motion of the hip to the postoperative flexion angle of the knee thus far.MethodsOf 38 consecutive patients who underwent posterior-stabilized TKA, we assessed 21 patients after excluding 17 patients who met exclusion criteria. The range of motion of the knee and the hip, age, body-mass index, serum albumin level, HbA1c, Kellgren–Lawrence grade, knee extension strength and radiological femorotibial angle as well as postoperative knee flexion angle at three months were evaluated. The preoperative data and the knee flexion angle at three months after TKA were compared using Spearman''s rank correlation coefficient.ResultsKnee flexion angle at three months after TKA was positively correlated with preoperative flexion (ρ = 0.616, p = 0.007) and external rotation angle (ρ = 0.576, p = 0.012) of the hip as well as preoperative knee flexion angle (ρ = 0.797, p = 0.001). There were no correlations between postoperative knee flexion angle and other preoperative data.ConclusionsPatients with restricted flexion and/or external rotation of the hip may have contractures of Gluteus maximus, Gluteus medius and Tensor fasciae latae, which can cause hypertension of iliotibial tract. It may cause decreased internal rotation of the tibia when the knee is flexed, which affects postoperative knee flexion angle, thus limited flexion and/or external rotation of the hip might restrict knee flexion angle following TKA.     

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.     

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.     

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.

     

p53 status and prognosis in stage I-IIIa non-small cell lung cancer

To investigate the role of p53 abnormalities in predicting the survival of patients with non-small cell lung cancer (NSCLC), polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and immunohistochemical analyses were performed on 74 and 67 tumor samples, respectively, from patients with pathological stage I-IIIa NSCLC. An abnormally migrating SSCP band was observed in 21 of 74 (28%) tumor specimens. DNA sequence analysis revealed 23 intragenic mutations including 3 small deletions and 20 point mutations. Immunohistochemical analysis using the DO-7 monoclonal antibody showed abnormal expression of p53 in 27 of 67 (40%) patients. The concordance rate between immunohistochemical and PCRSSCP analyses was 73% (49/67) in this study. Univariate and multivariate analyses demonstrated that abnormal expression of p53 may be associated with prolonged survival (p=0.0997 and 0.0099, respectively). In contrast, no relationship was observed between p53 mutation and overall survival (0.6968). These results suggest that p53 status and the survival outcome changes between immunohistochemical and mutational analyses in stage I-IIIa NSCLC.