Regulatory mechanisms of C4b‐binding protein (C4BP)α and β expression in rat hepatocytes by lipopolysaccharide and interleukin‐6

Summary. Background: C4b‐binding protein (C4BP), a multimeric protein structurally composed of α chains (C4BPα) and a β chain (C4BPβ), regulates the anticoagulant activity of protein S (PS). Patients with sepsis have increased levels of plasma C4BP, which appears to be induced by interleukin (IL)‐6. However, it is not fully understood how lipopolysaccharide (LPS) and IL‐6 affect the plasma C4BP antigen level and C4BPα and C4BPβ expression in hepatocytes. Objectives: To assess the effect of LPS and IL‐6 on plasma C4BP, PS–C4BP complex levels, PS activity, and C4BP expression by rat liver in vivo and on C4BP expression by isolated rat hepatocytes in vitro. Results: Plasma C4BP antigen level transiently decreased from 2 to 12 h after LPS (2 mg kg^?1) injection, and then it abruptly increased up to 24 h after LPS injection. Plasma C4BP antigen level increased until 8 h after IL‐6 (10 μg kg^?1) injection, and then gradually decreased up to 24 h after IL‐6 injection. LPS significantly decreased the protein and mRNA expression of both C4BPα and C4BPβ in rat hepatocytes, and this effect was inhibited by NFκB and MEK/ERK inhibitors. IL‐6 mediated increase in C4BPβ expression in rat hepatocytes, which leads to increased plasma PS–C4BP complex level and to decreased plasma PS activity, was inhibited by inhibition of STAT‐3. Conclusion: LPS decreases both C4BPα and C4BPβ expression via the NFκB and MEK/ERK pathways, whereas IL‐6 specifically increases C4BPβ expression via the STAT‐3 pathway, causing an increase in plasma PS–C4BP complex, and thus decreasing the anticoagulant activity of PS.     

Pipeline Flex with Shield Technology Placement for Small- and Medium-sized Aneurysms Achieves Early Complete Occlusion

The flow diverter has been shown to be a safe and effective device for large cerebral aneurysms in the proximal internal carotid artery (ICA). Recently, its indication has been expanded to small- and medium-sized cerebral aneurysms in the distal segment of the ICA. In this study, we report a single-center, retrospective investigation of the safety and efficacy of the Pipeline Flex device to treat these aneurysms. Of the patients who underwent Pipeline implantation for small- and medium-sized ICA aneurysms (≤12 mm) at our hospital between July 2013 and October 2021, 102 patients with 104 aneurysms were included in this study. The mean age of the patients was 57.7 ± 12.1 years, and 94 (90.4%) were female. The mean aneurysmal dome diameter was 9.2 ± 2.3 mm, the mean neck diameter was 5.3 ± 1.6 mm, and the mean dome-to-neck ratio was 1.8 ± 0.5. Twenty-five patients (24.0%) had incorporated vessels from the aneurysm. Complete occlusion of the aneurysms was obtained in 96 patients (92.3%). There were no cases of parent artery stenosis or major stroke after the procedure. Absence of incorporated vessel from the aneurysm dome and adjunctive coil embolization are statistically significant factors indicating complete occlusion in multivariate analysis. The time to complete occlusion was determined earlier with the use of the Pipeline Shield (p = 0.0386) and with adjunctive coils (p = 0.0025). We showed that Pipeline implantation for small- and medium-sized aneurysms was safe and highly effective.     

Renal cell carcinoma in dialysis patients: A single center experience

AIM: Renal cell carcinoma (RCC) is a life-threatening complication of end-stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis. METHODS: In 2624 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis at our hospital between July 1993 and March 2004, we performed annual screening for RCC using abdominal computed tomography and ultrasonography. Patients diagnosed with RCC underwent radical nephrectomy as well as clinical and pathologic evaluation. RESULTS: RCC was detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients was 55.5 +/- 11.1 years. Dialysis duration before RCC diagnosis was 11.2 +/- 7.2 years. Most RCC were early stage and low stage by TNM classification, 43 patients had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9 +/- 1.9 cm. The predominant histological type of RCC was common or conventional cell-type carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients, 5(11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in 13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease of the kidney. These patients had longer dialysis durations (P = 0.01) and smaller tumors (P = 0.048). RCC metastasized postoperatively in 4 patients (9.1%), while one (2.3%) died of cancer. CONCLUSIONS: Our dialysis patients showed a higher incidence of RCC than the general population. Prognosis was favorable because tumors were detected by screening when they were small. Therefore, periodical screening for RCC seems very important in dialysis patients.     

Clinical trials of new antibiotics in children in Japan

Japan is the most advanced of the industrialized nations in the development of antibiotics. Compared to the United States and countries of the European Union, there is a rich selection and availability of new and appropriate antibiotics for patients with infectious diseases in Japan that is unchallenged under a medical system where its people are all covered by a national health insurance plan. This can also be said in the area of antimicrobial treatment of children and newborns. In Japan, the turning point (T-point), which the author defines as the point when the average life expectancy of newborns equals that of 1 year olds, was in 1970. Keeping infant deaths from infectious diseases under control was indispensable for this achievement, to which antibiotics had greatly contributed. After the T-point, another methodology was needed in pediatrics. The situation in Japan, where most newly developed antibiotics are equipped with statements concerning methods of administration, dosage and safety for children or newborns, differs considerably from overseas situations. The procedures and methods of the clinical trials on children that were performed in strict compliance with good clinical practice are described. Trial studies cannot be performed easily in Japan. Next, the reason why the clinical trials of the antibiotics in pediatrics were performed and accurately evaluated without incident over 50 years by comparatively small numbers of specialists and facilities is described historically and retrospectively. During the 30 years since modern methods were established, clinical trials of antibiotics with children and newborns have been performed only on essential agents; about one-half and one-third, respectively, of the 91 new antibiotics on which clinical trials with adults were conducted. The author has recently published evaluation criteria for clinical studies on antibiotics in the pediatric field. In addition, as the trial's director/administrator, the author states his concept for future clinical development of new antibiotics for children.     

The Role of Surgical Resection in the Management of Small Cell Carcinoma of the Lung

To assess the role of surgical resection in the management ofsmall cell carcinoma of the lung, experience with 118 patientswho were treated between 1973 and 1985 was reviewed. Twenty-fivepatients underwent surgical resection followed by combinationchemotherapy in all except one. The remaining 93 pa tients weretreated by combined chemotherapy and radiation therapy. The 5-year survival rate for patients with stage I disease undergoingsurgical resection was 50.8%. For all 25 patients operated on,the 5-year survival rate was 30.7%. In the patients not operated on, only those with complete responsehad long-term survival, for whom the 5-year survival rate was11.9% We consider that surgical resection is definitely indicatedin patients with stage I disease. If the response to initialchemotherapy is very good, patients with stage 11 or T3N0M0disease also probably should receive resection. Patients withN2 disease are not candidates for resection, unless distantmetastases are controlled completely by intensive chemotherapy.     

Renin-angiotensin system component gene polymorphisms in Japanese maintenance haemodialysis patients

Summary: The renin-angiotension system (RAS) component gene polymorphisms was examined in 216 patients undergoing maintenance haemodialysis (HD) therapy and in 208 control subjects. the RAS polymorphisms selected for analysis were angiotensin I converting enzyme (ACE) I/D, angiotensinogen (Agt) T235/M235, angiotensin II type 1 receptor (AGT1R) A1166/C1166. the control allelic frequencies was ACE I/D (0.63/0.37), Agt T235/M235 (0.16/0.84), and AGT1R A1166/C1166 (0.94/0.06). Recently, relationships between ACE I/D and the progression of renal disease attract great attention in Japanese and Caucasian populations. ACE D allele was expected to be more frequent in HD population. However, no accumulation of ACE D allele or Agt T235 allele, AFT1R C1166 allele in Japanese end-stage renal disease (ESRD) subjects was detected. to explain the paradoxical result of positive association of ACE D allele with progression of renal disease and no bias of ACE genotype in ESRD subjects, further investigation with systematic prospective study regarding the change of ACE genotype distribution around the period of entering dialysis therapy is required.     

Late relapse of stage I testicular seminoma metastatic to just a para-ureteropelvic region

A follow-up ultrasonography study 43 months after an operation for left stage I testicular seminoma in a 39-year-old man revealed left hydronephrosis. Serum beta-human chorionic gonadotropin (beta-hCG) levels were slightly increased. Computed tomography scans of the abdomen showed a bulky tumor around the ureteropelvic region without para-aortic lymph node enlargement, but did not show a clear distinction between a recurrence of the testicular tumor and an invasive ureteral tumor. After the patient underwent two cycles of chemotherapy with cisplatin and etoposide, the tumor mass decreased by approximately 60% and beta-hCG levels returned to normal. We then performed a resection of the residual tumor involving the upper ureter and left kidney and a retroperitoneal lymph node dissection under a clinical diagnosis of recurrence of the testicular tumor. Histologically, no viable cancer cells remained. The patient has been well with no evidence of recurrence for more than two years.     

Radio-frequency ablation of renal cell carcinoma in patients who were at significant risk

OBJECTIVE: Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia. METHODS: Radio-frequency ablation was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in nine patients with biopsy proven RCC (mean diameter, 38 mm; range, 20-53 mm), who were at significant operative or anesthetic risk for invasive surgery. Follow-up enhanced CT scans or magnetic resonance images were evaluated every 3-6 months and an evaluation of metastasis was performed every 6 months. RESULTS: At a mean follow-up of 17 months, seven (78%) of the nine patients with renal tumor showed no tumor enhancement. The renal function of all patients was well preserved. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment. No distant metastasis, urine leakage were reported and one case of temporary hematuria and one case of peri-renal hemorrhage not requiring blood transfusion were encountered. Intra-operative ultrasonography was useful in the real-time monitoring of the minimally excessive extension of ablation into the normal parenchyma. CONCLUSION: Radio-frequency ablation appears to be an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.     

Laparoscopic pyeloplasty for ureteropelvic junction obstruction: Outcome of initial 12 procedures

BACKGROUND: Open pyeloplasty has been the gold standard for surgical treatment of ureteropelvic junction (UPJ) obstruction, enjoying a long-term success rate exceeding 90%. Unfortunately, this procedure requires a muscle incision that entails some degree of morbidity. We have, therefore, investigated the feasibility of laparoscopic pyeloplasty for UPJ obstruction and report here the outcomes of our early cases. The median follow up is 25 months (range, 12-42 months). METHODS: Between March 1999 and September 2001 we performed laparoscopic pyeloplasty on 12 ureters in 11 patients presenting with symptomatic hydronephrosis, secondary to a short stenosis of the UPJ or to ventrally crossing vessels; bilateral pyeloplasty was performed as a single procedure in one patient. We performed dismembered Anderson-Hynes pyeloplasty, Fenger plasty and Y-V plasty in eight, two and two ureters, respectively. All procedures were carried out transperitoneally. RESULTS: The procedure was completed successfully in all cases. Crossing vessels were noted in six of 12 ureters (50.0%). Mean operative time and blood loss in 11 patients (including one bilateral case) were 272.8 min (range, 175-480 min) and 96.4 mL (range, 20-340 mL), respectively. Postoperative complications were noted in two patients (18.2%): one instance of prolonged urine leakage and one anastomotic re-stricture. Eleven of 12 ureters (91.6%) demonstrated a patent UPJ on excretory urography and/or improvement of renal function on diuretic renography at a minimum follow up of 12 months. CONCLUSION: Although the procedure requires advanced laparoscopic skills, it can be safely and successfully completed as frequently as the conventional open procedure. Laparoscopic pyeloplasty seems to be a valuable alternative to open pyeloplasty for UPJ obstruction.