Structural elements influencing von Willebrand factor (vWF) binding affinity for platelet glycoprotein Ib within a dispase-digested vWF fragment

We investigated the structural elements in human von Willebrand factor (vWF) that influence binding affinity for platelet glycoprotein (GP) Ib using a dispase-digested vWF fragment as a prototype (residues Leu480/Val481-Gly718 of the vWF subunit; Andrews et al, Biochemistry 28:8326, 1989). The major structural features of this fragment are a large A1-loop formed by an intrachain disulfide bond between Cys509 and Cys695 and six O-linked sugar chains. The fragment was chemically modified by (1) reduction and S-carboxyamido-methylation (R/A), (2) desialylation (DS), or (3) a combination of both (R/A-DS). The GPIb binding affinity of these fragments was basically evaluated by competitive binding assay with anti-GPIb monoclonal antibody (LJ-Ib1), a receptor blocker for vWF (Sugimoto et al, Biochemistry 30:5202, 1991). Both the prototype and the R/A fragments were also assessed for their function in shear-induced platelet aggregation. Results unambiguously demonstrated that the presence of a disulfide bridge (Cys509-Cys695) within this domain downregulates the affinity of vWF to GPIb. In addition, it was also demonstrated that the terminal sialic acids attached to six o-linked sugar chains within this domain contribute to optimal functional modulation by the antibiotic ristocetin, but not by snake venom botrocetin.     

Management under anesthesia of a patient with renal cell carcinoma extending into the retrohepatic inferior vena cava with the aid of partial cardiopulmonary bypass]

A 70-year-old male with renal cell carcinoma extending into the retrohepatic inferior vena cava was scheduled for radical nephrectomy with vena caval resection under general anesthesia. He had received partial gastrectomy for gastric cancer twelve years before. Computed tomography and inferior vena cavography confirmed that the vena cava was almost completely occluded and that a collateral venous network was well established. It was considered that the surgical approach to the retrohepatic cavals area was technically very difficult, and that there was a high possibility of a pulmonary embolus during the surgical manipulation. To prevent a pulmonary embolus and get good control of the vena cava above the tumor and below the hepatic vein, we decided to use a partial cardiopulmonary bypass (CPB) until the vena cava was clamping above the tumor. Anesthesia was induced with propofol and fentanyl, and maintained with fentanyl and isoflurane-N2O-O2. In the partial CPB blood from the hepatic vein was drained from the inferior vena cava cannula through right atrium, oxygenated by microporus membrane oxygenator, and returned to the left femoral artery. Cannulation to drain the venous circulation entering the vena cava below the tumor was abandoned because the extensive collateral venous network ultimately drains into the superior vena cava. The partial CPB time was 90 min, and the bladder temperature during the CPB was 35-36 degrees C. During the 7.3 hr procedure, the pulmonary embolus did not occur and the total blood loss was 5515 ml. The patient made an uncomplicated recovery and was discharged 30 days after the operation. This newly reported partial-CPB method may be safe and effective for the management under anesthesia of other patients.     

Salvage Hepatectomy for Local Recurrent Hepatocellular Carcinoma After Ablation Therapy

Background

The results of salvage hepatectomy for local recurrent hepatocellular carcinoma after incomplete percutaneous ablation therapy are still unclear.

Methods

We conducted a retrospective analysis of 197 consecutive patients with hepatocellular carcinoma who underwent either salvage hepatectomy after prior incomplete percutaneous ablation therapy (salvage group; n?=?23) or primary hepatectomy as the initial treatment (primary group; n?=?174). The two groups were compared with respect to intraoperative data, operative mortality and morbidity, and long-term survival.

Results

The salvage group showed a significantly longer operation time (385 vs. 300?min; P?=?0.006) and a significantly greater intraoperative blood loss volume (402 vs. 265?ml; P?=?0.024). The postoperative mortality rate was zero in both groups, and the morbidity rates were similar. Although the 1-, 3-, and 5-year disease-free survival rates after hepatectomy were significantly worse in the salvage group than in the primary group (65%, 41%, and 33% vs. 81%, 51%, and 45%, respectively; P?=?0.031), the overall survival rates after hepatectomy did not differ significantly (91%, 91%, and 67% vs. 96%, 79%, and 65%, respectively; P?=?0.790). The 1-, 3-, and 5-year overall survival and disease-free survival rates after percutaneous ablation therapy were also not different from those in the primary group (100, 96, and 83%, P?=?0.115; and 96, 60, and 45%, P?=?0.524, respectively).

Conclusions

The short-term and long-term results of salvage hepatectomy after incomplete percutaneous ablation therapy are equivalent to those of primary hepatectomy. Salvage hepatectomy is an acceptable treatment for patients with local recurrence of hepatocellular carcinoma after ablation therapy.     

Surgical Treatment for Biliary Carcinoma Arising After Pancreatoduodenectomy

The clinicopathological features and surgical treatment of biliary carcinoma around the major hepatic duct confluence arising after pancreatoduodenectomy (PD) due to initial bile duct carcinoma are described in three patients. Occurrence of biliary carcinoma more than 12 years after initial surgery and a histological finding of cholangiocellular carcinoma mixed with hepatocellular carcinoma suggested metachronous incidence of biliary carcinoma after PD. Extended right hemihepatectomy with complete removal of the residual extrahepatic bile duct and segmental, resection of the jejunal loop were carried out safely without operative death or severe postoperative complications. Two patients died of tumor recurrence 6 months after surgery, and the remaining patient is currently living a normal life without evidence of recurrence 17 months after surgery. These surgical procedures are a therapeutic option in patients with biliary carcinoma around the major hepatic duct confluence arising after PD.     

Intraluminal lavage to remove exfoliated tumor cells after colorectal endoscopic submucosal dissection

Background

Endoscopic submucosal dissection (ESD) involves dissection of tumors and manipulation of them in an exposed condition for prolonged periods. A large number of tumor cells are exfoliated into the intestinal lumen after colorectal ESD. The aim of this study was to determine whether lavage volume has an influence on tumor cell clearance after colorectal ESD.

Methods

Twenty patients who underwent colorectal ESD at our hospital between July 2013 and December 2014 were studied. Cytological examination of intraluminal lavage samples associated incremental increases in lavage volume was collected. This prospective study was approved by the ethics committee of our hospital.

Results

No patients had exfoliated tumor cells in their samples before ESD. Four patients (20 %) had exfoliated tumor cells in their samples after lavage with 500 ml, while one patient (5 %) had exfoliated tumor cells after lavage with 1000 or 1500 ml.

Conclusion

Tumor cells are exfoliated into the intestinal lumen by tumor manipulation during colorectal ESD. There seems to be a risk for implantation after ESD, as well as rectal surgery. Sufficient intraluminal lavage of more than 1000 ml may be desirable to remove exfoliated tumor cells after colorectal ESD.

     

Morphologic Features of Carotid Plaque Rupture Assessed by Optical Coherence Tomography

BACKGROUND AND PURPOSE:Rupture of the plaque fibrous cap and subsequent thrombosis are the major causes of stroke. This study evaluated morphologic features of plaque rupture in the carotid artery by using optical coherence tomography in vivo.MATERIALS AND METHODS:Thirty-six carotid plaques with high-grade stenosis were prospectively imaged by optical coherence tomography. “Plaque rupture” was defined as a plaque containing a cavity that had overlying residual fibrous caps. The fibrous cap thickness was measured at its thinnest part for both ruptured and nonruptured plaques. The distance between the minimum fibrous cap thickness site and the bifurcation point was also measured. Optical coherence tomography identified 24 ruptured and 12 nonruptured plaques.RESULTS:Multiple ruptures were observed in 9 (38%) patients: Six patients had 2 ruptures in the same plaque, 2 patients had 3 ruptures in the same plaque, and 1 patient had 5 ruptures in the same plaque. Most (84%) of the fibrous cap disruptions were identified at the plaque shoulder and near the bifurcation point (within a 4.2-mm distance). The median thinnest cap thickness was 80 μm (interquartile range, 70–100 μm), and 95% of ruptured plaques had fibrous caps of <130 μm. Receiver operating characteristic analysis revealed that a fibrous cap thickness of <130 μm was the critical threshold value for plaque rupture in the carotid artery.CONCLUSIONS:Plaque rupture was common in high-grade stenosis and was located at the shoulder of the carotid plaque close to the bifurcation. A cap thickness of <130 μm was the threshold for plaque rupture in the carotid artery.

Rupture of the fibrous cap and subsequent thrombosis are the major causes of cardiovascular events such as heart attack and stroke.^1–3 In a previous study of sudden coronary death, a fibrous cap thickness of 65 μm was chosen as a criterion of instability because for a cap to rupture, the average cap thickness was 23 ± 19 μm; 95% of caps measured <65 μm within a limit of only 2 SDs.¹ Therefore, the fibrous cap thickness of <65 μm is now widely accepted as the definition of in vivo coronary vulnerable plaque that is prone to rupture. Disruption of the fibrous cap is frequently observed in symptomatic carotid plaques^4,5 and is strongly associated with an ulceration appearance on angiography,⁶ which is considered an independent predictor of stroke on long-term follow-up in patients with symptomatic severe carotid stenosis.⁷ Redgrave et al⁸ examined the cross-sections of plaques with high-grade carotid stenosis and found that the optimum fibrous cap thickness for discriminating ruptured and nonruptured plaques was 200 μm; thus, it appears that there is no clear threshold for classifying plaques that are prone to rupture in vivo.Intravascular sonography, which is a widely used imaging method in the field of carotid artery intervention, has an axial resolution of 100–200 μm and a lateral resolution of 250 μm.⁹ Although it can visualize deep structures, intravascular sonography is not a suitable imaging technique for the detection of thin fibrous caps because its resolution is too low. Optical coherence tomography (OCT) has been introduced recently as a high-resolution imaging method.^10,11 The typical OCT image has an axial resolution of 10 μm, approximately 10 times higher than that of any other clinically available diagnostic imaging technique, such as intravascular sonography. OCT provides an accurate representation of the thickness of the fibrous cap that could not be measured by other imaging modalities.¹² In the present study, we evaluated the morphologic features of ruptured plaques in the carotid artery by using OCT.     

Work stress and workload of full-time anesthesiologists in acute care hospitals in Japan

Purpose  The number of anesthesiologists per population in Japan is small compared with that in Europe and North America. While there is a growing concern that hard work causes anesthesiologists’ fatigue and may compromise patient safety, the workload and physical stress, as well as the impact of staff support on physicians’ stress have not been assessed in detail. The goal of this study was to evaluate the working environment, anesthesia workload, and occupational stress of anesthesiologists in Japan. Methods  A questionnaire survey was performed targeting 1010 members of the Japanese Society of Anesthesiologists working as anesthesiologists affiliated with acute care hospitals in Japan. Data on background information, working environment, operation anesthesia duties, and stress were collected, and the relationship of work stress with background, environment, and anesthesia duties was evaluated by linear regression analysis. Results  Responses were obtained from 383 full-time anesthesiologists (response rate, 43.9%). The total anesthesia time per week was 23.6 h on average. The work stress score was 114.3 ± 30.2 (mean ± SD) when the average workers’ work stress score in Japan was 100. The work stress score was significantly associated with “years of experience” (with experience < 10 years considered as the reference; 10–19 years: β = −0.18, P = 0.02, ≥20 years: β = −0.15, P = 0.04), “hospital with ≥500 beds” (with a hospital with ≤ 299 beds considered as the reference; β = 0.15, P = 0.04), “total time of anesthesia per week” (β = 0.18, P.02), “estimated annual cases managed by an anesthesiologist” (β = 0.12, P = 0.04) and “no-support stress” (β = 0.21, P < 0.01) on linear regression analysis (R² = 0.12). Conclusion  Our results provide a quantitative assessment of the duties of anesthesiologists and show that work stress among anesthesiologists is related to workload and other factors. Summaries of this study were presented at the 53rd and 54th General Meetings of the Japanese Society of Anesthesiologists (JSA) at Kobe (2006) and Sapporo (2007).     

Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation

AIMS: Clinicopathological features were investigated to clarify the ultimate prognosis and prognostic indicators for patients with IgA nephropathy in Japanese children. METHODS: We evaluated the outcomes of 181 patients in whom IgA nephropathy was diagnosed before the age of 15 years since September 1979 and followed-up at least for three years with regard to clinical data at the onset of symptoms and renal histologic data. RESULTS: After mean follow-up of 7.3 years from onset, 91 patients of 181 (50.3%) were in clinical remission at the last examination, 24 (13.2%) had isolated hematuria, 59 (32.6%) had hematuria and proteinuria. Eighteen of 59 (9.9%) had proteinuria more than 1 g per 24 hours. Hypertension was observed in 12 cases and 7 (3.9%) developed end-stage renal disease. Except 7, no patient had reduced renal function and elevated serum creatinine at the final follow-up. Predicted renal survival rate from onset was 92.3% at 10 years and 89.1% at 20 years. In multivariable analysis, age at onset and chronic changes of tubulointerstitium were associated with poor outcome. CONCLUSIONS: Of 181 children with IgA nephropathy, 50% regressed, remaining 46% had hematuria and/or proteinuria and 4% of patients lapsed into end-stage renal disease. Our results indicate that childhood IgA nephropathy has a benign course and the risk for end-stage renal disease is lower than that of adults. Age at onset and tubulointerstitial lesions were the strong predictors of a progressive course of childhood IgA nephropathy.