Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment.

BACKGROUND: With the development of direct-acting anti-virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR). AIM: To evaluate the short-term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC. METHODS: This large-scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon-free sofosbuvir-based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan-Meier method and Cox proportional hazard analysis were used to calculate the cumulative HCC incidence and related factors of HCC. RESULTS: During the follow-up period (median: 17 months), 46 (2.7%) patients developed HCC. The 1-year cumulative rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P < 0.001). For cirrhotic patients, serum α-fetoprotein level at the end of treatment (EOT-AFP) was the strongest predictor of de novo HCC. The 1-year cumulative de novo HCC rates were 1.4% and 13.1% in the EOT-AFP < 9.0 ng/mL and ≥ 9.0 ng/mL groups (cut-off value) respectively (log-rank test: P < 0.001). The 1-year cumulative rates of HCC recurrence were 6.5% and 23.1% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P = 0.023). For cirrhotic patients, previous HCC characteristics were significantly associated with HCC recurrence. In contrast, sex, age and metabolic features did not influence de novo HCC or recurrence. CONCLUSIONS: For cirrhotic patients after elimination of HCV, serum EOT-AFP level and previous HCC characteristics would be useful markers for predicting de novo HCC or recurrence.

Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure.

Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG-IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study was carried out to evaluate the effectiveness of simeprevir-based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir-based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG-IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve [3/4 (75.0%)] or with prior relapse [1/1 (100%)] or partial response [5/6 (83.3%)] to PEG-IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct-acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG-IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir-based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG-IFNα and ribavirin. For patients with prior null response to PEG-IFNα and ribavirin, retreatment with simeprevir-based triple therapy is not a useful option.

Ulnar nerve strain at the elbow in patients with cubital tunnel syndrome: effect of simple decompression.

Simple decompression of the ulnar nerve at the elbow has not been shown to reduce nerve strain in cadavers. In this study, ulnar nerve strain at the elbow was measured intraoperatively in 11 patients with cubital tunnel syndrome, before and after simple decompression. Statistical analysis was performed using a paired Student's t-test. Mean ulnar nerve strain before and after simple decompression was 30.5% (range 9% to 69%) and 5.5% (range -2% to 11%), respectively; this difference was statistically significant (p < 0.01) with a statistical power of 96%. Simple decompression reduced ulnar nerve strain in all patients by an average of 24.5%. Our results suggest that the pathophysiology of cubital tunnel syndrome may be multifactorial, being neither a simple compression neuropathy nor a simple traction neuropathy, and simple decompression may be a favourable surgical procedure for cubital tunnel syndrome in terms of decompression and reduction of strain in the ulnar nerve.

Blind subxiphoid pericardiotomy to relieve critical acute hemopericardium: a final report.

PURPOSE: Percutaneous catheter drainage (PCD) has been considered a standard method of relieving acute cardiac tamponade. Although conventional subxiphoid pericardiotomy is useful even for clotted hemopericardium, it has been believed to be unsuitable for emergency treatment because it is a time-consuming procedure. We report our modified pericardiotomy technique that can be used for emergency management. METHODS: We designed a prospective observational study to evaluate blind subxiphoid pericardiotomy (BSP) for critical cardiac tamponade due to hemopericardium. Emergency patients (n = 148) with acute hemopericardium secondary to trauma (n = 12), acute aortic disease (n = 122), or cardiac rupture following acute myocardial infarction (n = 14) were the subjects. Early results were compared between the BSP group (n = 53) and the PCD group (n = 95). RESULTS: BSP was effective at relieving cardiac tamponade in all 53 cases, but PCD was ineffective in 12 cases (12.6 %, p = 0.008). Procedure-related complication rates of BSP and PCD were 0 and 16.8 %, respectively (p = 0.002). Survival rates for the BSP and PCD groups were 18.9 and 6.3 %, respectively (p = 0.018). Since 2005, when we discarded the restriction that only board-certified surgeons should perform BSP, acute care physicians (including trainees) have performed BSP for 22 patients without procedure-related complications. CONCLUSIONS: BSP was safe and effective for cardiac tamponade due to acute hemopericardium. Critical complications during PCD for hemopericardium could not be avoided in some cases because of clots in the pericardium.

Pyrosequencing survey of the microbial diversity of 'narezushi', an archetype of modern Japanese sushi.

AIMS: This study aimed to analyse microbiota of the fermented food 'narezushi', an archetype of modern Japanese sushi. The pyrosequencing technique was used to analyse sequences of 16S ribosomal DNA contained in six narezushi products. METHODS AND RESULTS: The V1-V2 regions of the 16S ribosomal DNA were amplified from different narezushi products using PCR, and approximately 120,000 sequences were phylogenetically assigned at the genus level, using the Ribosomal Database Project classifier. In all samples, the microbial populations consisted of more than 90% Lactobacillales, mainly Lactobacillus or Pediococcus, reflecting their crucial role in narezushi fermentation. There were more than 700 operational taxonomy units in all samples, with Shannon-Wiener index varying from 1.69 to 2.60. CONCLUSIONS: The microbiota of all narezushi products were shown to consist largely of Lactobacillales populations. Interestingly, different species were found to be dominant in each product. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an insight into the bacterial composition of fermented fish-based foods, which are consumed worldwide. Significant differences in the dominant species were observed between products, possibly because of the starter-free production process.

[Case with cardiac myxoma causing cerebral metastasis after cardiac tumor resection].

We report a case of cardiac myxoma causing cerebral metastasis after cardiac tumor resection. A 68-year-old man with a cerebral infarction was admitted to our hospital. A cardioembolic source was suspected and echocardiography was performed. In that examination, a cardiac tumor was found in the left atrium. Tumor resection was performed urgently and his postoperative course was uneventful. After the operation he had no new episodes of cerebral deficit. However 6 months after the operation, he complained of headaches. The brain computed tomography (CT) showed there were multiple high-density areas. One of the tumors was resected and the tumor was diagnosed pathologically as metastasis of cardiac myxoma. Brain metastases were treated with 40.8 Gy whole-brain radiation therapy. As the result the tumors were effectively treated and reduced.

Competitive inhibitors and allosteric activators of protein kinase C isoenzymes: a personal account and progress report on transferring academic discoveries to the clinic.

PKC (protein kinase C) isoenzymes are related protein kinases, involved in many signalling events in normal state and in disease. Basic research into identifying the molecular basis of PKC selectivity led to simple strategies to identify selective competitive inhibitor peptides and allosteric agonist peptides of individual PKC isoenzymes. The strategies and rationale used to identify these peptide regulators of protein-protein interaction may be applicable to other signalling events. Importantly, the PKC-regulating peptides proved to be useful pharmacological tools and may serve as drugs or drug leads for a variety of human diseases.

[Mitral valve plasty for acute infective endocarditis; report of a case].

A 68-year-old woman was admitted with congestive heart failure and septic shock associated with suspected mitral valve acute infective endocarditis. Echocardiography revealed vegetations attached to both mitral leaflets, prolapse of the posterior mitral leaflet and severe mitral regurgitation. Emergent surgery was performed. The anterior mitral leaflet displayed multiple vegetations. The entire anterior leaflet of mitral valve was replaced with pericardium. The posterior mitral leaflet of the middle scallop was prolapsed with an attached vegetation. Quadrangular resection was performed. A commissural reconstruction by sliding commissuroplasty for a prolapse of both anterior and posterior leaflets in the paracommissural area and autologous pericardial mitral annuloplasty was performed. Mitral regurgitation disappeared postoperatively, and the patient is now doing well as of 5 years postoperatively.

[Lung cancer in patients with idiopathic interstitial pneumonia].

The purpose of this study was to determine the outcome of surgical treatment for lung cancer concomitant with idiopathic interstitial pneumonia (IIP). Between 1994 and 2003, 673 patients with primary lung cancer were treated. Forty-four patients (6.54%) of 673 patients were complicated with IIP. Their data were retrospectively reviewed. There were 37 male and 7 female with an average age of 67 years. They underwent 7 wedge resections of the lung, 3 segmentectomies, 32 lobectomies and 2 bi-lobectomies as surgical treatment for lung cancer. Five of these 44 patients died of acute exacerbation of IIP after the operation. The exacerbation occurred in an average postoperative day of 5 (range, 3 to 7) day. Preoperative values of serum CRP, LDH, SP-D and KL-6 failed to predict the occurrence of the exacerbation of IIP after the surgery. The preoperative value of %DLCO was lower in patients with the exacerbation than patients without the exacerbation (42.3+/-9.6% versus 66.8+/-18.8%, p=0.018). The postoperative 5-year survival rate for pathological stage I lung cancer were 84.9% and 70.2% (p=0.134) for patients without IIP and patients with IIP, respectively. Although the acute exacerbation of IIP after the surgery caused catastrophic outcomes, the long-term results in surgical treatment for stage I lung cancer simultaneously concomitant with IIP were not so poor. It is very important to avoid the postoperative exacerbation and further effort and research are required to avoid the exacerbation.

Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production.

OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5). RESULTS: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.

[Reoperation for double-outlet right ventricle (SDL type) following the Rastelli procedure: report of a case].

The relationship of the conduit to the sternum is crucial in the Rastelli operation. Right-sided conduits are more greatly affected by sternal compression than left, since the position of the right ventricular infundibulum is more anterior. A 37-year-old woman developed right ventricular outflow tract obstruction, left ventricular outflow tract obstruction, and aortic valve regurgitation secondary to infective endocarditis 15 years after Rastelli repair for double-outlet right ventricle (SDL). We enlarged the ventricular septal defect, performed intraventricular rerouting and aortic valve replacement, and reconstructed the valved conduit using a Carpentier-Edwards conduit. The old conduit was densely adherent to the sternum. Subaortic stenosis was caused by a narrow fibromuscular ridge associated with a bulge of the underlying septal muscle. The patient's recovery was uneventful. She is alive and well without any complaints 1 year after surgery.

[Recurrent right atrial myxoma five years after removal of left atrial myxoma; report of a case].

A 41-year-old man had undergone resection of a left atrial myxoma 5 years previously. Echocardiography revealed a new mass in the right atrium. Because of had increased in size gradually, removal of the right atrial mass involving full-thickness resection of the fossa ovalis was performed. Cardiac myxoma has the potential for heterotopic recurrence.

Afferent fibers of the hypogastric nerves are involved in the facilitating effects of chemical bladder irritation in rats.

To evaluate the role of bladder afferent fibers in the hypogastric nerves (HGN) in modulation of the micturition reflex induced by chemical bladder irritation, voiding behavior, continuous cystometry, and spinal c-fos expression following intravesical acetic acid instillation were investigated in rats with or without HGN transection. Voiding behavior and continuous cystometry were examined in unanesthetized conscious rats. Following chemical bladder irritation, a significant increase in urinary frequency associated with a marked decrease in the voided volume per micturition, was noted in control rats with the intact HGN, but not in HGN-transected rats. Continuous infusion of acetic acid in control rats elicited irritative bladder responses characterized by a marked decrease in the intercontraction interval and a marked increase in maximal vesical pressure, both of which were absent in capsaicin-desensitized rats. HGN transection prevented the decrease in the intercontraction interval but not an increase in maximal vesical pressure following chemical bladder irritation. Compared with saline infusion, acetic acid infusion caused a significant increase in c-fos expression at L(1) and L(6) of the spinal cord, and HGN transection significantly reduced c-fos expression in the dorsal horn of the spinal cord at L(1) but not at L(6). These results suggest that capsaicin-sensitive bladder afferent fibers in the HGN, which travel through the rostral lumbar spinal cord, have a role in urinary frequency caused by chemical bladder irritation.

Repair of double-chambered right ventricle: surgical results and long-term follow-up.

BACKGROUND: We reviewed the outcomes of double-chambered right ventricle repair. METHODS: Between 1969 and 1998, 40 patients underwent surgical repair of a double-chamber right ventricle. The patients ranged in age from 3 months to 52 years (mean, 12.8 +/- 11.6 years). Right ventricular outflow tract pressure gradients were from 20 to 170 mm Hg (mean, 65.0 +/- 38.5 mm Hg) An associated ventricular septal defect was present in 27 patients (67.5%). Four patients were older than 30 years of age. RESULTS: There were no hospital or late deaths. Mean postsurgical follow-up was 16.5 +/- 8.9 years (range, 2.5 to 31 years). No patient required further surgery to relieve obstruction of right ventricular outflow tract. CONCLUSIONS: Surgical repair of a double-chambered right ventricle yields excellent hemodynamic and functional results over both the short and long term.

Reoperative minimally invasive axillocoronary artery bypass to the obtuse marginal branch.

A 73-year-old man was admitted with unstable angina, having severe coronary artery disease involving 3 vessels. He had undergone coronary artery bypass grafting to the left anterior descending artery and the obtuse marginal branch using saphenous vein grafts in 1979. Computed tomography showed severe calcium deposition and atherosclerosis in the ascending and descending aorta. We conducted axillocoronary artery bypass to the obtuse marginal branch and left internal thoracic artery as an in situ graft to the left anterior descending artery without cardiopulmonary bypass. Grafts were satisfactory and clinical results good.

Clinical and endocrinological features of adrenocorticotropic hormone- independent bilateral macronodular adrenocortical hyperplasia.

PURPOSE: We report clinical findings in 5 patients with adrenocorticotropic hormone independent bilateral macronodular adrenocortical hyperplasia. MATERIALS AND METHODS: In 4 males and 1 female 32 to 61 years old (median age 50) we evaluated clinical symptoms, endocrinological and radiological characteristics, treatment modality and postoperative clinical course. RESULTS: All cases presented with some features of Cushing's syndrome. Endocrinological examination revealed autonomous adrenal cortisol production with suppressed adrenocorticotropic hormone and a loss in the diurnal circadian rhythm of plasma cortisol. Abdominal computerized tomography showed bilateral enlargement of the adrenal glands with multiple nodules. 131Iodine labeled adosterol scintigraphy demonstrated remarkable bilateral uptake by the adrenal glands. The pituitary gland appeared normal on magnetic resonance imaging. Open unilateral complete adrenalectomy and contralateral partial adrenalectomy were performed in patient 1, open bilateral complete adrenalectomy was done in patients 2 and 3, and 2 and 1-stage laparoscopic bilateral complete adrenalectomy was performed in patients 4 and 5. Single removed adrenal glands weighed 32 to 108 gm. (median 60). The histological diagnosis was macronodular adrenocortical hyperplasia in all cases. Postoperative followup was 3 to 90 months. Clinical symptoms of Cushing's syndrome disappeared or improved after surgery in all cases. CONCLUSIONS: Although adrenocorticotropic hormone independent bilateral macronodular adrenocortical hyperplasia is a rare form of Cushing's syndrome, physicians are advised to consider it when diagnosing and treating cases of Cushing's syndrome with enlarged bilateral adrenal glands. Bilateral complete adrenalectomy is currently recommended as the treatment of choice.

Intravenous digital subtraction angiography and helical computed tomography in evaluation of living renal donors.

OBJECTIVES: The present study was carried out to evaluate the accuracy of helical computed tomography (CT) and intravenous digital subtraction angiography (IV-DSA) on anatomical assessment of renal vasculature for living renal donors. METHODS: Forty-two healthy potential renal donors were prospectively evaluated and 35 subsequently underwent donor nephrectomy after helical CT and IV-DSA evaluation. The vascular and non-vascular findings were compared between the findings on helical CT, IV-DSA and surgery. RESULTS: Ten prehilar branches and five accessory renal arteries were found at nephrectomy. Overall, operative findings agreed with the findings by IV-DSA in 89% and by helical CT in 83%. In delineating accessory arteries, IV-DSA had a sensitivity of 60% and specificity of 97%, whereas helical CT had a sensitivity of 40% and specificity of 100%. In delineating prehilar branches, IV-DSA had a sensitivity of 90% and specificity of 100%, whereas helical CT had a sensitivity of 70% and specificity of 100%. Accessory arteries and prehilar branches that were not detected by helical CT or IV-DSA, were less than 2 mm in diameter and did not require vascular reconstruction. Renal veins were delineated in 63% by IV-DSA, whereas they were clearly imaged by helical CT in all cases, including a case with a circumaortic renal vein. Non-vascular findings were obtained in 64% by helical CT, including two renal tumors. None of these findings were obtained by IV-DSA. CONCLUSION: Helical CT and IV-DSA provide comparably sufficient information on renal artery vasculature. However, helical CT provides significantly more information on venous and non-vascular findings as a single-imaging modality.

[The feasibility of a limited operation for primary lung cancer].

We reviewed 33 patients who underwent a limited operation for primary lung cancer between 1980 and 1998. These cases were divided into three groups; a poor risk group consisting of 18 patients who had a high risk such as pulmonary or cardiac dysfunction and who underwent partial resection of a lung, a reduction group consisting of 9 patients who had advanced lung cancer or uncontrolled cancer of an organ other than the lung and who underwent partial resection, and an active limited operation group consisting of 6 patients who underwent segmentectomy with lymphoadenectomy for the treatment of early lung cancer. The 1 and 3-year survival rates in the poor risk group, reduction group and active limited operation group were 73.9, 60.0, 100%, and 63.4, 0.0, 100%, respectively. The results of limited operations performed for poor risk cases were satisfactory in terms of both functional state and prognosis. Limited operations performed to reduce tumor in advanced lung cancer cases did not improve the prognosis. Although an active limited operation for a case of early lung cancer remains controversial with respect to indication, it is thought that this operation is not inferior to a standard radical operation (lobotomy with mediastinal lymphoadenectomy) in selective cases in which the maximum tumor diameter is 2 cm or less. The indication for a limited operation must be further examined from aspects of tumor size, tumor histology and the other factors of the tumor.