Plasma Cholesteryl Ester Transfer Protein (CETP) in Relation to Human Pathophysiology

Plasma CETP was initially isolated as a highly purified 74 kD protein. The human CETP gene is located at chromosome 16q13, near the locus of the lecithin cholesterol acyltransferase (LCAT) gene. The CETP gene consists of 16 exons, spanning 25 kb. The CETP mRNA encodes 476 amino acids. The mature CETP contains four N-linked sugars with a variable glycosylation site of 341Asn. CETP mRNA is expressed in various tissues, but liver cells, adipocytes, and macrophages are abundant sources. One of the determinants of high density lipoprotein (HDL) neutral lipid composition is plasma CETP. In incubated human plasma, transfer and equilibration of (LCAT)-generated cholesteryl ester (CE) is found. Humans, hamsters, guinea pigs, and chickens belong to a group with intermediate CETP activity. Plasma CETP binds neutral lipids CE or triglyceride (TG), and phospholipid (PL) on HDL3, but CETP selectively promotes an exchange of CE and TG among lipoproteins. On the one hand, HDL-TG can be hydrolyzed by hepatic lipase, and on the other hand, plasma CETP decreases HDL particle size via CE/TG exchange between chylomicron/VLDL and HDL. Thus, CETP thereby accelerates the catabolic rate of HDL apolipoproteins. CETP enhances HDL remodeling from large HDL to small subclasses including pre-HDL. However, CETP deficiency would decrease cholesterol esterification rate, thereby inhibiting maturation of preb-HDL to α-migrating spherical HDL. Therefore, in CETP deficiency, large-to-small HDL remodeling is decreased and preb-HDL catabolism is also decreased. © 2010 Elsevier Inc. All rights reserved.[Book Chapter

Structural and Functional Hierarchy in Photosynthetic Energy Conversion—from Molecules to Nanostructures

Basic principles of structural and functional requirements of photosynthetic energy conversion in hierarchically organized machineries are reviewed. Blueprints of photosynthesis, the energetic basis of virtually all life on Earth, can serve the basis for constructing artificial light energy-converting molecular devices. In photosynthetic organisms, the conversion of light energy into chemical energy takes places in highly organized fine-tunable systems with structural and functional hierarchy. The incident photons are absorbed by light-harvesting complexes, which funnel the excitation energy into reaction centre (RC) protein complexes containing redox-active chlorophyll molecules; the primary charge separations in the RCs are followed by vectorial transport of charges (electrons and protons) in the photosynthetic membrane. RCs possess properties that make their use in solar energy-converting and integrated optoelectronic systems feasible. Therefore, there is a large interest in many laboratories and in the industry toward their use in molecular devices. RCs have been bound to different carrier matrices, with their photophysical and photochemical activities largely retained in the nano-systems and with electronic connection to conducting surfaces. We show examples of RCs bound to carbon-based materials (functionalized and non-functionalized single- and multiwalled carbon nanotubes), transitional metal oxides (ITO) and conducting polymers and porous silicon and characterize their photochemical activities. Recently, we adapted several physical and chemical methods for binding RCs to different nanomaterials. It is generally found that the P(+)(Q(A)Q(B))(−) charge pair, which is formed after single saturating light excitation is stabilized after the attachment of the RCs to the nanostructures, which is followed by slow reorganization of the protein structure. Measuring the electric conductivity in a direct contact mode or in electrochemical cell indicates that there is an electronic interaction between the protein and the inorganic carrier matrices. This can be a basis of sensing element of bio-hybrid device for biosensor and/or optoelectronic applications

A new prognostic scoring system using factors available preoperatively to predict survival after operative resection of perihilar cholangiocarcinoma

Background: Perihilar cholangiocarcinoma has one of the poorest prognoses of all cancers. However, mortality and morbidity rates after surgical resection are 0-15% and 14-66%, respectively. Additionally, the 5-year overall survival rates are reported at 22-40%. These findings indicate that only selected patients achieve satisfactory beneficial effects from operative treatment. This retrospective study sought to investigate preoperatively available prognostic factors and establish a new preoperative staging system to predict survival after major hepatectomy of perihilar cholangiocarcinoma. Patients and methods: We evaluated 121 consecutive patients who underwent operative exploration for perihilar cholangiocarcinoma. Results: Univariate and multivariate analysis using the identified preoperative factors revealed that 4 factors (platelet-lymphocyte ratio [PLR] > 150, serum C-reactive protein [CRP] levels > 0.5 mg/dL, albumin levels 7.0 ng/mL) were independent prognostic factors of postoperative survival. These 4 preoperative factors were allocated 1 point each. The total score was defined as the Preoperative Prognostic Score (PPS). Patients with a PPS of 0, 1, 2, or 3/4 had a 5-year survival of 84.3%, 51.3%, 46.4%, and 0%, respectively. There were also differences in the 5-year survival according to the PPS (0 vs 1 [P = .013] and 2 vs 3/4 [P < .001]). Patients with a total PPS of 3/4 had a dismal prognosis, with a median survival of 11.3 months. Conclusion: A new preoperative scoring system using PLR, serum CRP, albumin, and CEA levels could predict postoperative survival resection of perihilar cholangiocarcinoma

Survival benefit of conversion surgery for patients with initially unresectable pancreatic cancer who responded favorably to nonsurgical treatment

Background: Conversion surgery (CS) is expected as a new therapeutic strategy for patients with unresectable pancreatic cancer (UR-PC). We analyzed outcomes of CS for patients with UR-PC and evaluated the survival benefit of CS. Methods: Thirty-four patients diagnosed with UR-PC according to the National Comprehensive Cancer Network guideline underwent CS in our hospital. Resectability was considered by multimodal images in patients who underwent nonsurgical treatment (NST) for more than 6 months. CS was performed only in patients who were judged to be able to undergo R0 resection. Results: Twenty-six patients had locally advanced PC, and eight had distant metastases. The median duration of NST was 9 (range 5-44) months. R0 resection was achieved in 30 patients (88.2%). Six patients (17.6%) showed Evans grade ≥III. Three- and 5-year overall survival (OS) rates from initial treatment were 74% and 56.9%, respectively, with median survival time (MST) of 5.3 years. The actual 5-year OS rate in 19 patients was 47.4% with an MST of 4.0 years. Patients with Evans grade ≥III had a better prognosis than those with Evans grade <III (P = 0.0092, log-rank test). Conclusions: Conversion surgery might have survival benefits to patients with UR-PC who responded favorably to NST

Risk factors for dysfunction of preoperative endoscopic biliary drainage for malignant hilar biliary obstruction

Background Few studies have focused on the risk factors for dysfunction of endoscopic biliary drainage (EBD) in preoperative patients with malignant hilar biliary obstruction (MHBO). Methods We searched the database between February 2011 and December 2018 and identified patients with MHBO who underwent radical operation. The rate of dysfunction of the initial EBD, risk factors for dysfunction of the initial EBD and survival after surgery were retrospectively evaluated. Results We analyzed a total of 131 patients [95 males (72.5%); mean age, 69.5 (+/- 7.3) years; Bismuth-Corlette classification (BC) I/II/IIIa/IIIb/IV, 50/26/22/17/16; hilar cholangiocarcinoma/gall bladder cancer, 115/16]. Dysfunction of the initial EBD occurred in 28 patients (21.4%). The cumulative incidences of dysfunction of the initial EBD in all patients were 18.4%, 38.2% and 47.0% at 30, 60 and 90 days, respectively (Kaplan-Meier method). The rate of dysfunction of the initial EBD increased in patients with BC-IV (P = .03). Multivariate analysis showed that BC-IV and pre-EBD cholangitis were significantly associated with the occurrence of dysfunction of the initial EBD. Survival rates were not significantly different according to the initial biliary drainage methods and presence/absence of the initial EBD dysfunction. Conclusions Dysfunction of the initial EBD frequently occurs in patients with the BC-IV and those with pre-EBD cholangitis

Hilar cholangiocarcinoma with intratumoral calcification : A case report

This report describes a rare case of hilar cholangiocarcinoma with intratumoral calcification that mimicked hepatolithiasis. A 73-year-old man presented to a local hospital with a calcified lesion in the hepatic hilum. At first, hepatolithiasis was diagnosed, and he underwent endoscopic stone extraction via the trans-papillary route. This treatment strategy failed due to biliary stricture. He was referred to our hospital, and further examination suggested the existence of cholangiocarcinoma. He underwent left hepatectomy with caudate lobectomy and extrahepatic bile duct resection. Pathological examination revealed hilar cholangiocarcinoma with intratumoral calcification, while no stones were found. To the best of our knowledge, only one case of calcified hilar cholangiocarcinoma has been previously reported in the literature. Here, we report a rare case of calcified hilar cholangiocarcinoma and reveal its clinicopathologic features

Totally LG for gastric cancer after ESD

Purpose: A recently developed endoscopic mucosal resection (EMR) procedure, endoscopic submucosal dissection (ESD), makes en-bloc resection possible for mucosal cancer regardless of lesion size. ESD involves deeper and wider dissection of the gastric wall, and may therefore increase the difficulty of subsequent totally laparoscopic gastrectomy (TLG) and the risk of complications. However, the influence of ESD on subsequent TLG has yet to be demonstrated. The purpose of the present study was to clarify the influence of ESD on subsequent TLG. Methods: Between March 2006 and December 2013, we retrospectively collected data of 38 patients undergoing TLG with ESD (ESD Group) and propensity score matched 38 patients undergone TLG without ESD (non-ESD Group) for treatment of gastric cancer at Tonan Hospital and Hokkaido University Hospital. The covariates for propensity score matching were: age, sex, American Society of Anesthesiologists score, body mass index, and type of surgery. Clinicopathologic characteristics and surgical outcomes were compared between the two groups. Results: Operative times for TLG in ESD group and non-ESD group were 228.2 ± 53.9 and 228.1 ± 52.7 min (P=0.989), and blood loss was 45.7 ± 83.0, 71.3 ± 74.5 g, respectively (P=0.161). There were no significant differences between the groups of ESD and non-ESD in postoperative recovery and postoperative complications. In totally laparoscopic distal gastrectomy (TLDG), the patients with ESD-resected specimens of more than 50 mm in diameter had significantly longer operative times (P=0.009). Conclusions: In this study, TLG is feasible procedure treatment of gastric cancer regardless of ESD. However, TLDG is more difficult in cases where the ESD-resected specimen is more than 50 mm in diameter