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Protozoan parasites infect humans and many warm-blooded animals. Toxoplasma gondii, a major protozoan parasite, is commonly found in HIV-positive patients, organ transplant recipients and pregnant women, resulting in the severe health condition, Toxoplasmosis. Another major protozoan, Neospora caninum, which bears many similarities to Toxoplasma gondii, causes serious diseases in animals, as does Encephalomyelitis and Myositis-Polyradiculitis in dogs and cows, resulting in stillborn calves. All these exhibited similar nucleoside triphosphate hydrolases (NTPase). Neospora caninum has a NcNTPase, while Toxoplasma gondii has a TgNTPase-I. The enzymes are thought to play crucial roles in propagation and survival. In order to establish compounds and/or extracts preventing protozoan infection, we targeted these enzymes for drug discovery. The next step was to establish a novel, highly sensitive, and highly accurate assay by combining a conventional biochemical enzyme assay with a fluorescent assay to determine ADP content. We also validated that the novel assay fulfills the criteria to carry out high-throughput screening (HTS) in the two protozoan enzymes. We performed HTS, identified 19 compounds and six extracts from two synthetic compound libraries and an extract library derived from marine bacteria, respectively. In this study, a detailed explanation has been introduced on how to carry out HTS, including information about the preparation of reagents, devices, robot arm, etc.

Repressor element-1 (RE-1) or neural restrictive silencer element (NRSE) bound with a zinc finger transcription repressor, RE-1 silencing transcription factor (REST, also known as neural restrictive silencer factor, NRSF) has been identified as a fundamental repressor element in many genes, including neuronal genes. Genes regulated by REST/NRSF regulate multifaceted neuronal phenotypes, and their defects in the machinery cause neuropathies, disorders of neuron activity), autism and so on. In REST repressions, the N-terminal repressor domain recruits Sin3B via its paired amphipathic helix 1 (PAH1) domain, which plays an important role as a scaffold for histone deacetylase 1 and 2. This machinery has a critical role in maintaining neuronal robustness. In this study, in order to establish protein–protein interaction assays mimicking a binding surface between Sin3B and REST, we selected important amino acids from structural information of the PAH1/REST complex and then tried to reconstitute it using recombinant short peptides derived from PAH1/REST. Initially, we validated whether biotinylated REST interacts with glutathione S-transferase (GST)-tagged PAH1 and whether another PAH1 peptide (PAH1-FLAG) competitively binds with biotinylated REST using surface plasmon resonance (SPR). We observed a direct interaction and competitive binding of two PAH1 peptides. Secondly, in order to establish a high-throughput and high-dynamic-range assay, we utilized an easily performed novel time-resolved fluorescence energy transfer (TR-FRET) assay, and closely monitored this interaction. Finally, we succeeded in establishing a novel high-quality TR-FRET assay and a novel interaction assay based on SPR.

Background: Transcriptional regulation is a very important and pivotal function in myriad biological responses. Thus, methods to determine transcriptional activity are required in not only basic medical research but also in drug discovery. We established novel reporter constructs using human secreted embryonic alkaline phosphatase (SEAP) and Epstein-Barr virus nuclear antigen (EBNA) 1, which can maintain constructs synchronized to host cell replication. Methods: We established nuclear factor-kappa B (NFkB) or interferon regulatory factor (IRF) driven SEAP expression constructs and then, introduced them into culture cells. Results: The cells maintain reporter constructs for a long period in the culture and produce SEAP into culture supernatant in response to each specific ligand such as lipopolysaccharide (LPS) and inter-feron-beta. Measuring SEAP with chemiluminescence makes it possible to get high standard dynamic range applying to high-throughput screening in drug discovery in both 96 and 384 well format. We can also use it to determine transcriptional activity in the cells transfected with expression plasmid or treated with various toll-like receptor (TLR) ligands in a concentration-dependent manner and time-dependent manner. Finally, we demonstrated drug screening using a number of natural products library. Conclusion: We for the first time established the two novel reporter cells and validated their quality and accuracy enough to carry out drug screening., Current Pharmaceutical Biotechnology, 19(3), pp.224-231; 2018

Toxoplasma gondii is a major protozoan parasite and infects human and many other warm-blooded animals. The infection leads to Toxoplasmosis, a serious issue in AIDS patients, organ transplant recipients and pregnant women. Neospora caninum, another type of protozoa, is closely related to Toxoplasma gondii. Infections of the protozoa in animals also causes serious diseases such as Encephalomyelitis and Myositis-Polyradiculitis in dogs or abortion in cows. Both Toxoplasma gondii and Neospora caninum have similar nucleoside triphosphate hydrolases (NTPase), NcNTPase and TgNTPase-I in Neospora caninum and Toxoplasma gondii, respectively. These possibly play important roles in propagation and survival. Thus, we targeted the enzymes for drug discovery and tried to establish a novel high-standard assay by a combination of original biochemical enzyme assay and fluorescent assay to determine ADP content. We then validated whether or not it can be applied to high-throughput screening (HTS). Then, it fulfilled criterion to carry out HTS in both of the enzymes. In order to identify small molecules having inhibitory effects on the protozoan enzyme, we also performed HTS using two synthetic compound libraries and an extract library derived from marine bacteria and then, identified 19 compounds and 6 extracts. Nagasaki University collected many extracts from over 18,000 marine bacteria found in local Omura bay, and continues to compile an extensive collection of synthetic compounds from numerous drug libraries established by Japanese chemists., Marine Drugs, 18(3), art.no.161; 2020

Very recently, the immunotherapies against cancer, autoimmune diseases, and infection have been feasible and promising. Thus, we have examined the possibility whether or not human gamma delta T cells can be applied for the novel immunotherapies. We previously established the cells stably maintaining NFkB-driven human secreted embryonic alkaline phosphatase (SEAP) expression. The cells can be used to determine the transcription activity of NFkB with high-standard dynamic range and accuracy. Because IL-18 is a kind of cytokines that enhances cytotoxicity and activity of human gamma delta T cells through NFkB activation, we have focused on the activity and signaling of IL-18. In this study, we modified the previous reporter cell that can determine the transcription activity of NFkB to express two subunits consisted of human IL-18 receptor. The modified cells secreted SEAP in response to treatment with human recombinant IL-18 in a concentration-dependent manner. We also observed the concentration-dependently enhancement of NFkB activity in the cells treated with mouse recombinant IL-18 although the affinity was lower compared to human recombinant IL-18. We also previously established the cells stably expressing and secreting human recombinant IL-18 and then validated whether or not the conditioned medium from the cells activate NFkB transcription activity using this assay. Our university has kept collecting many extracts from over 18,000 marine bacteria in our local sea around Omura bay&mdash, fungi, plants for Chinese herbal medicine, and so on&mdash, and also have kept gathering synthetic compounds from many Japanese chemists as drug libraries. Finally, in order to identify drugs mimicking IL-18 biological activity or possessing inhibitory effects on IL-18-induced NFkB, we demonstrated drug screening using number of extracts derived from marine bacteria and synthetic compounds.

Background:The immunotherapies against cancer, autoinmmune diseases or infection are remarkable development. These days programmed cell death (PD)-1 antibody-induced immune checkpoint blockade or chimeric antigen receptor-T cells (CAR-T) have been shown to have eminent therapeutic effects on tumor development. We have focused on adoptive transfer with human gamma delta T cells for novel immunotherapies. Additionally, IL-18 is one of the cytokines that enhances cytokine secretion and cytotoxicity of human gamma delta T cells.Method:Thus, we established novel cell lines stably expressing and secreting various types of human recombinant IL-18 proteins to their culture supernatants using episomal vector. We also differentiated primary cultured human gamma delta T cells from peripheral blood mononuclear leukocytes to validate biological activity of the IL-18 proteins using measuring IFN-γ by ELISA.Results and Conclusion:Finally, we demonstrated that the supernatant could activate human gamma delta T cells using monitoring interferon gamma in culture medium.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy has not been well established. Preoperative neutrophil-to-lymphocyte ratio (NLR) is a biomarker of the malignant potential in patients with several types of malignancy. We explored malignant potential in patients with IPMN. The present study included 56 patients aged of 73 ± 9 years (mean ± standard deviation) who underwent curative resection for IPMN from 1996 to 2017. We analyzed the relationship between the characteristics including NLR and malignant component for predicting pathological results. The nonmalignant IPMN group (N = 21) included patients with low-grade dysplasia (LGD) and intermediate-grade dysplasia (IGD), and the malignant IPMN group (N = 35) included patients with high-grade dysplasia (HGD) and invasive carcinoma. In a univariate analysis, NLR ⩾ 2.2 ( P = .001), prognostic nutritional index (PNI) 37 U/mL ( P = .039), and cystic diameter ⩾ 30 mm ( P = .010), and mural nodule ( P = .010) were significantly different between the malignant IPMN and the nonmalignant IPMN groups. Multivariate analysis showed that high NLR (⩾2.2) (odds ratio 9.79; 95% confidence interval: 2.06-45.6), cystic diameter ⩾ 30 mm (4.65; 1.14-18.9), and mural nodule (4.91; 1.20-20.1) were independently predictive of malignant IPMN. These results suggest that preoperative NLR is a useful predictive biomarker for evaluating malignant potential in patients with IPMN.1

症例は42歳，女性．下腹部腫瘤を主訴に，当科を紹介された．既往歴，家族歴に特記事項はなく，来院時現症では，軽度の貧血と腹部に小児頭大の可動性腫瘤を認めた．各種画像検査と内視鏡検査より，消化管間葉系腫瘍（胃GIST）が疑われ手術を行った．手術所見では，胃体上部後壁大彎側から壁外性に巨大発育する多結節性黄白色調の充実性腫瘤がみられ，周囲組織への浸潤はなく，腫瘤を含めた胃部分切除術を行った．病理組織所見は，脱分化型脂肪肉腫と判明した．胃脂肪肉腫の報告は少なく，これまで26例の報告（2009年）があるのみである．われわれの症例は，徐々に自覚された無痛性可動性腹部腫瘤が主訴で，切除標本での最大径は22cm，重量は1,300gであり，これまでの報告例の中でも3番目に大きなものであった．胃原発の脂肪肉腫は極めて稀であるが，本疾患を念頭に入れ，画像診断および手術をすすめることが重要と考えられた．

症例は65歳, 男性. 食欲低下, 全身倦怠感, 下血を主訴に2006年5月15日近医を受診, 貧血, 血圧低下を認め, 同日当科紹介となった. 来院時血圧70mmHg前後であり, 血液検査にて高度貧血, 代謝性アシドーシスを認めた. 緊急胃内視鏡検査を施行したところ, コーヒー残渣様の貯留液および黒色調の巨大な胃石を認めた. 全身状態改善後, 精査をしたが胃石の他には著変なく, 6月6日, 開腹胃切開胃石除去術を施行した. 胃石は13×10cm大で胃の鋳型を呈していた. 結石分析では一部タンニン酸と類似の吸収がみられた.本症例は巨大胃石により胃粘膜が損傷され, 出血さらには高度貧血をきたし, また通過障害により栄養障害等きたし, ショック, 代謝性アシドーシスをきたしたと思われた. 胃石の合併症として胃潰瘍, 腸閉塞等があるが, 本症例のように重篤な経過を辿るものもあり, 消化管出血の際には本症の可能性も念頭におくべきと思われた.

Ehlers-Danlos症候群(以下EDS)は皮膚の過伸展性,弛緩性,関節の過伸展性,皮膚血管の脆弱性を3主徴とする結合組織疾患である.全部で10型あるが,特にIV型では動脈破裂,動脈解離,大腸穿孔などの生命を脅かす合併症がある.われわれEDS IV型で腸間膜内に出血をきたし外科的に切除した症例を経験したので報告する.症例は29歳,女性で下腹部痛を主訴に受診となった.造影CTなどで膿瘍を疑い手術となった.開腹所見では上行結腸肝彎曲部の腸間膜側に鶏卵大の嚢胞様病変を認め,右半結腸切除を行った.切除標本では腸間膜に被胞化された血腫を認めた.組織学的には血管の平滑筋構造の消失を認め血管の脆弱性を示唆した.術後経過は良好であり現在再発などを認めていない. EDS IV型では血管脆弱性のために多くの合併症が報告されており手術の際には十分な注意が必要である.

症例は75歳女性.バリウム注腸造影で直腸RsSに全周性の大腸癌を認めた.注腸検査4日後に突然の腹痛が生じ腹部CT検査でバリウム腹膜炎と診断した.腹膜内洗浄ドレナージ術と人工肛門造設術を施行し,術後39病日に高位前方切除術を施行した.経過観察造影CTで肝S6の腫瘍性病変を認めCT-APとCT-Aで増大傾向を認めたため大腸癌肝転移と診断し肝切除術を施行した. S6の腫瘍性病変は病理学的検索で異物性の炎症性肉芽腫と診断され,バリウムの肝内への侵入による炎症性肝肉芽腫と類推された.バリウム性腹膜炎後の肝の腫瘍性病変に対してはバリウム性肉芽腫をも念頭に置き慎重な対応が必要と考えられた.

We report new surgical techniques for intraopera-tive microwave coagulation therapy (IMCT), conducted in three patients with large liver neoplasms with poor liver function or difficult tumor location. Anterolateral thoracotomy was performed for tumors in the right lobe to obtain a good operative field. Four electrode needles were inserted for microwave irradiation, with settings of 60 W, 45 s for coagulation and 1 s for dissociation. Clamping of the hepatoduodenal ligament was performed during IMCT. We began the coagulation at the bottom of the tumor, irradiating the tumor and the surrounding parenchyma to create regional necrosis with a safe margin. With these methods, we treated two women diagnosed with large hepatocellular carcinoma with liver cirrhosis and a man with liver metastasis from rectal cancer. The postoperative course of these patients was uneventful. A marked low-density area was seen in the region of therapy and no enhanced findings were observed on enhanced computed tomography postoperatively. However, in one patient, transcatheter embolization (TAE) was performed 1 month postoperatively because recurrence was noted on the bottom of the tumor. Thus, IMCT destroys the peripheral part of the tumor that may remain viable after TAE, but combination therapy with TAE is preferable, especially when a viable part exists within tumors. IMCT is an active, safe, and nontoxic therapeutic modality for large hepatic tumors, and is particularly applicable in patients with large hepatocellular carcinomas and poor liver function.

The antiproliferative effects of somatostatin and its analogs on human pancreatic cancers were studied: (1) by evaluating the gene expression of somatostatin receptor (sstr) subtypes in human pancreatic cancer cell lines and cancer tissue specimens, (2) by evaluating the antiproliferative effects of somatostatin analogs, and (3) by evaluating the effect of sstr-2 cDNA transduction. Using a reverse transcriptase polymerase chain reaction (RT-PCR), the gene expression of five sstr subtypes (sstr-1 to -5) was examined in eight cell lines, and in ten pancreatic cancer tissues and in the normal surrounding pancreatic tissues. The antiproliferative effects of somatostatin (SS) -14 and its two analogs (SMS 201-995, RC-160) were examined by means of an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (thiazolyl blue)) assay on three cell lines and Panc-1 transfectants with human sstr (hsstr)-2A cDNA. Sstr-2 was expressed in all samples tested. All examined cell lines simultaneously expressed sstr-2 and -5, while most of the examined pancreatic cancer tissues did not express both of these subtypes simultaneously. Somatostatin analogs inhibited epidermal growth factor (EGF)-stimulated pancreatic cancer cell proliferation. The cell proliferation was further and significantly inhibited by 14% in stable transfectants of Panc-1 cells with hsstr-2A. Based on these findings, it is concluded that somatostatin analogs with their antiproliferative effects mediated by sstr-2 could be potentially useful in the treatment of pancreatic cancers.

A 22-year-old female with origin unknown liver cirrhosis in the absence of serological markers for hepatitis B (HBV) except for HBV-DNA developed fulminant hepatitis with HBV after liver transplantation. The donor was her father with Gilbert’s syndrome who showed anti-HBs and low titer anti-HBc positive. Severe hepatitis developed in the grafted liver due to HBV at 11 months postoperatively. HBsAg and HBeAg became positive, while anti-HBs, anti-HBe, anti-HBc, and hepatitis C were negative. After hepatitis B infection was confirmed by a liver biopsy, treatment with HB immunoglobulin and prostaglandin E1 were initiated. Despite intensive-care support including frequent plasma exchange and continuous hemofiltration, the patient died at 16 months postoperatively. Pre-transplant serum HBV-DNA was positive in the recipient but negative in the donor, while immunopathologic studies for HBsAg and HBV-DNA were negative in the liver of both the recipient and donor. Therefore, acquisition of HBV in the recipient would be due to occult pre-transplant infection. In conclusion, the pre-transplant evaluation of HBV-DNA in the liver tissue and serum should be examined when liver transplantation is attempted in patients with origin unknown liver cirrhosis.

It has been proved that antibiotics binding to penicillin-binding protein 3 (PBP3) are associated with the greater release of endotoxin than those that bind to PBP2 in both in vitro and animal models. The aim of this study is to evaluate the potential clinical implications of antibiotic-induced endotoxin release after hepatic resection. Forty-five patients who underwent hepatic resection in our clinic were enrolled. The patients were divided into two groups. Group A (n = 26): antibiotics that bind primarily to PBP3, including cefmetazole (CMZ), latamoxef (LMOX), flomoxef (FMOX), were used. Group B (n = 19); antibiotics that bind to both PBP2 and PBP3, including cefazolin (CEZ), cefoperazone (CPZ), cefotiam (CTM). Postoperative complications, liver functional tests, and chemical mediators [endotoxin, interleukins (IL-6, IL-8), tumor necrosis factor alpha (TNFalpha), granulocyte colony-stimulating factor (G-CSF), hepatotrophic growth factor (HGF) were examined after hepatic resection. There were no significant differences in the backgrounds of the two groups. Eight patients in each group developed postoperative complications; in particular, 9 of 13 patients with biliary tract carcinoma developed postoperative complications. No significant elevation of peripheral blood endotoxin was noted by the endospecy method, in any of the patients, although six died following sepsis. Pre- and postoperative levels of cytokines showed no significant difference between the two groups. Our data suggest that clinical antibiotic-induced endotoxin release would not occur after hepatic resection regardless of the antibiotic, probably owing to continuous scavenging of endotoxin from peripheral blood.

肝細胞癌手術症例の初回術式について関連肝炎別に検討した.対象は遺残例を除くHBs抗原陽性例 (B群) 24例, HCV抗体陽性例 (C群) 67例で, B群で若年者に多く腫瘍径が大きかった.門脈侵襲, 肝内転移など予後に与える因子の陽性率は腫瘍径5cm以上の群で有意に高かったので, B群18例, C群63例の腫瘍径5cm未満症例について検討した.再発例はB群が4例 (22.2%), C群が36例 (57.1%) で, 再発様式はB群は2例 (50.0%) が残肝多発再発であったが, C群では多発再発は5例 (13.9%) のみで, 同側葉, 対側葉の別で差は見られなかった.[結論] 1.B群では肝機能が良好で再発様式も遺残再発が多く, 初回手術時に病巣をできるだけ大きく系統的に治癒切除すべきである, 2.C群では初回, 再発ともに多中心性発生と考えられる症例が多く局所のコントロールを目的とした支配グリソンを処理した部分切除で良いと考えられた.

A space-occupying lesion in the right hepatic lobe, with dilated peripheral bile ducts, was observed by ultrasonography and computed tomography in a 50-year-old man with right upper quadrant abdominal pain. One month later, this lesion evidenced rapid growth and a tumor thrombus, which completely occluded the main trunk and the left primary branch of the portal vein, had developed. The tumor was diagnosed as a cholangiocellular carcinoma with an unusual pattern of intravascular extension. The primary tumor and the portal tumor thrombus were resected via a right hepatic trisegmentectomy combined with resection of the portal vein and extrahepatic bile duct, using a superior mesenteric vein—left femoral vein catheter bypass (SMV—FV bypass). The SMV—FV bypass was found to effectively reduce intraoperative hemorrhage.

We studied whether the maximal excretion rate of indocyanine green (ICG Bmax) and the 2-h ICG excretion rate in the bile could be used to estimate the separate functions of the left and right liver in 20 patients with biliary obstruction at the hepatic hilus. ICG Bmax was measured after biliary decompression. An operative procedure that preserved the side of the liver with a positive ICG Bmax value was selected. Eighteen patients tolerated extensive hepatic resection, such as right trisegmentectomy, extended right lobectomy, extended left lobectomy, or left lobectomy. However, prolonged jaundice was observed postoperatively in five of the six patients with 2-h excretion rates of less than 25% and who had undergone extended right lobectomy. One patient on whom extended right lobectomy had been performed died because of postoperative hepatic failure. His ICG Bmax value was +0.6 and his 2-h excretion rate was very low (3%). ICG Bmax and the 2-h excretion rate in the bile reflected well the degree of separate hepatic dysfunction in patients with biliary obstruction at the hepatic confluence. If ICG Bmax value is more than +1.0, resection of more than two segments, such as trisegmentectomy or extended hepatic lobectomy, may be tolerated, and if the ICG Bmax value is positive, hepatic lobectomy may be tolerated. ICG Bmax and 2-h excretion rate in bile are useful indicators of hepatic functional reserve of the separate lobes of the liver in patients with biliary obstruction at the hepatic hilus.

肝切除後早期の腹水発生関連因子につき検討した.1985年1月から1993年12月までの肝細胞癌肝切除例中77例を対象とし, 術後腹腔ドレーンからの1日最大総排液量が500ml未満をA群 (53例, 68.8%), 500ml以上をB群 (24例, 31.2%) に分類した.両群間 (A vs B) で有意差を認めたものは, 術前因子でChE (0.58±0.21 vs 0.45±0.15ΔpH), ICGRmax (1.15±1.01 vs 0.78±0.42mg/kg/min), 総合的Risk (2.35±0.64 vs 2.65±0.43), 術中因子で手術時間, 出血量, 輸血・輸液量, 術後因子で組織学的肝硬変度であった.両群間で, アプローチ法, 肝阻血法, 阻血時間, 脱転操作の有無, 切除部位・範囲, 切除重量に有意差はなかった.術後大量腹水の発生にはChE, ICGRmax, 総合的Risk, 肝組織の硬変度が重要であり, 長時間手術や術中出血量, 輸血・輸液量の多い症例に好発した.術後管理は, 体液バランスと肝機能保護, 術後合併症予防とその治療が重要と考えられた.

The adhesion of biofilm to the microscopic part, or the thermal microhabitat on the heated media was studied to establish an effective water purification process at low water temperature. The circular tube was used as filter media for simplicity of both the experimental operation and the theoretical development to which the theory of the convection heat transfer at laminar flow was applied. Major conclusions obtained in this study were as follows : (1) The rise of water temperature by the heated media was a function of the surface area of media, the heat flux from media surface and the flow rate. (2) It was confirmed that the adhesion of the biofilm was brought about on the surface of the heated media, where the raw water at low temperature flew at laminar flow and the microscopic part was kept at higher temperature. (3) The mean thickness of the biofilm was computed using the water temperature in influent and effluent, and the flow rate. The calculated value was found to agree approximately with the result observed using the scanning electron microscope at the end of the experimental period. (4) It was found that there were few differences in the surface temperature of the heated media and the biofilm which thickness was about 35μm. Thus, the temperature in the biofilm was considered to be constant.

The therapeutic outcome after hepatic resection for hepatocellular carcinomas (HCC) smaller than 5cm in diameter was examined in 65 patients followed up for more than 6 months postoperatively. Patients were divided into two groups: patients with solitary tumors (ST, n=46) and those with two or more tumors (n=19). The latter group was subdivided into an intrahepatic metastasis (IM) group (n=10), and multicentric occurrence (MT) group (n=9). There was one perioperative death (1.5%), and 21 patients suffered from postoperative complications (32.3%). The overall 1-year, 3-year, and 5-year survival rates were 86.1%, 72.3%, and 44/7%, respectively. The 3-year survival rate was significantly higher in the MT than IM group (86% versus 42%, p

小腸近位側2/3切除術後の胃酸分泌動態を分泌促進系因子面から検討するため, 実験犬を用い酸分泌能, 右胃大網静脈 (RGEV) 血漿ガストリン値とヒスタミン値, 幽門洞G細胞数, 壁細胞数を経時的に測定した.1) 術後3～4週: BAO, MAO (mEq/h), 壁細胞数 (個/0.2mm幅垂直切片柱) はそれぞれ48.5%, 28.2%, 16.4%増加し, RGEV血漿ガストリン値 (pg/ml), ヒスタミン値 (nM), G細胞数 (個/mm幅垂直切片柱) はそれぞれ57.8%, 32.2%, 10.9%減少した.2) 術後11～12週: BAOは術前値にほぼ回復したが, MAOは減少傾向を示すものの高値を持続した.RGEV血漿ガストリン値とヒスタミン値は増加し術前値に回復する傾向を示した.壁細胞数はやや減少したのに対しG細胞数は増加した.以上から, 術後の胃酸分泌能の亢進は壁細胞数の増加と機能亢進が直接関与しており, RGEV血漿ガストリンおよびヒスタミンの変動は,酸分泌量の増減に伴うfeedback作用の結果であると考えられた.

653 Background: The impact of previous abdominal surgeries on the need for conversion to open surgery and on short-term outcomes during/after laparoscopic colorectal surgery was retrospectively investigated. This retrospective cohort study was conducted from May 2004 through October 2012. This study was conducted at Tokushima University Hospital and Ehime Prefectural Central Hospital. Methods: A total of 145 consecutive patients who had undergone laparoscopic resection of the sigmoid colon and upper rectum were classified as not having previous abdominal surgery (NPAS group, n = 123) or as having previous abdominal surgery (PAS group, n = 22). Short-term outcomes were assessed between the two groups. Results: The population of previous abdominal surgery consisted of 6 appendectomy, 3 gastrectomy for gastric ulcer, 2 nephrectomy, 2 peritonitis and 11 others (2 duplication). There were no significant differences in age, gender, BMI, tumor location, tumor size, Stage, operating time, blood loss and number of lymph node harvest between the two groups. The conversion to open surgery was performed in 1 patient (4.5%) in the PAS group and 6 patients (4.9%) in the NPAS group. The intraoperative inadvertent enterotomy occurred in 1 patient in the NPAS group. There was no difference in postoperative morbility between the two groups. In the NPAS group, anastomotic leakage was observed in 3 cases. Ileus was observed in one case in the NPAS and none in the PAS. Postoperative hospital stay was 14 days in the PAS group and 16 days in the NPAS group. Conclusions: Short-term outcomes following laparoscopic surgery for sigmoid colon and upper rectal cancer with previous abdominal surgery are acceptable.

643 Background: Safety and validity of performing laparoscopic surgery after preoperative lavege using the self-expandable metallic stent (SEMS) for left-sided obstructive colorectal cancer were examined. We evaluated the short-term outcome of SEMS insertion compared with laparoscopic surgery without SEMS. Methods: Patients with left-sided colorectal cancer treated by either laparoscopic surgery with stent placement (n = 8) or laparoscopic surgery only (n = 42) in our hospital between April, 2012 and January, 2013 were registered. Short-term outcomes were compared with the two groups about patient characteristics (sex, age, American Society of Anesthesiologists Physical Status, body mass index, prior abdominal surgery), pathological data of patients (tumor location, size of tumor , tumor differentiation, number of harvested lymph nodes, pTNM classification, UICC pathological stage), and operative and post operative results (procedures, conversion, operative time, blood loss, morbidity, solid food intake, postoperative hospital stay, total hospital stay). Results: Except for tumor size in the patient characteristic parameters, there were no statistically significant difference between the two groups. Conversion rate to laparotomy was higher in the stent group (2 versus 1, p = 0.013). There was no difference in operation time, blood loss and postoperative complications between the two groups. Conclusions: Although the long-term oncological result requires further investigation, laparoscopic surgery after self-expandable metallic stent is a safe and feasible treatment as a “brige to surgery” for left-sided obstructive colorectal cancer.

Resection of a pancreatic head tumor and partial resection of the liver for metastatic lesions were carried out simultaneously in a 72-year-old woman. The patient had a history of two previous operations, right nephrectomy for renal cell carcinoma (clear cell type), done 14 years previously, and an Autincloss procedure for cancer of the left breast (solid tubular carcinoma); (T1N0M0; stage I) done 7 years previously. At the current presentation, preoperative radiographic examination showed a hypervascular tumor in each of the pancreatic and hepatic lesions, but with different patterns. On the basis of histological findings in the two resected specimens, it was difficult to establish whether the hepatic tumor originated from the renal cell carcinoma or the breast cancer, but postoperative immunohistochemical studies for carcinoembryonic antigen (CEA), estrogen receptors, and gross cystic disease fluid protein (GCDFP)-15 showed that the pancreatic tumor had metastasized from the renal cell carcinoma, and the liver tumor from the breast cancer. The immunohistochemical investigation of different markers thus proved to be useful in making the final diagnosis of metastatic lesions from different and metachronous cancers.

We report a rare case of hepatocellular carcinoma (HCC) for which intravenous administration of cisplatin (CDDP) was effective. A 48-year-old woman with recurrent HCC was admitted to our hospital. She had undergone right hepatectomy 1 year previously. A large tumor in the liver and multiple lung metastases were found by computed tomography in June 1995. She was icteric, and titers of serum alpha-fetoprotein (AFP; 214 ng/ml) and protein induced vitamin K absence or antagonist-II (PIVKA-II; 80 AU/ml) were high. According to these findings, she was diagnosed as having nonresectable recurrent HCC with extrahepatic lesions. She was treated by intravenous administration of CDDP. The dose of CDDP was 50 mg and it was infused once a week. One kur of CDDP was 4 weeks, and a total of four kur were administered. We noted that the lung metastases and primary liver tumor resolved after 1 kur of chemotherapy. The levels of serum AFP and PIVKA-II decreased markedly, to 26 ng/ml and0.07 AU/ml, respectively. A complete response was obtained, and she maintained a good state of health for the next 6 months, until brain metastases occurred. She died 13 months after the initiation of treatment with CDDP. In general, intravenous CDDP cannot be recommended as a single agent for HCC therapy, but CDDP showed good antineoplastic activity in our patient.

A total of 902 surgical patients with peptic ulcer disease were evaluated to clarify the effects of H2-receptor antagonists and endoscopic hemostasis on surgical treatment. Following the introduction of these treatments to our institute in 1982, the number of operations performed annually decreased by 40%, or 36 cases per year. However, a remarkable increase in the frequency of surgical emergency intervention since 1982 was concurrently observed, with the ratio of emergency procedures to the total number of operated cases increasing to 72.5% in the last 5 years of the study. Moreover, intractability as an indication for surgery decreased to 34.1%, compared with an increase in the number of patients with bleeding and perforated ulcers requiring operation. There were 13 postoperative deaths recorded (1.4%). All of the deaths were in patients who had undergone emergency surgery in poor health. Of these 13 patients, 10 had bleeding ulcers. A study of bleeding ulcers for which endoscopic hemostasis had been unsuccessful revealed that shock on admission and a concomitant medical condition had been evident in all the patients who died, and in 52.2% and 30.4% of the survivors, respectively. The current study suggests that the frequency of high-risk patients requiring surgery is increasing since the introduction of H2-receptor antagonists and endoscopic hemostasis, and thus, prompt surgical treatment and intensive management for such patients is essential.

Multifocal or continuous pancreatic lesion is identified frequently but finding an appropriate surgical approach is quite challenging. Total pancreatectomy is a useful procedure. However, postoperative endocrine and exocrine disturbance is inevitable. Recently, the safety and feasibility of parenchyma preserving pancreatectomy, including middle-preserving pancreatectomy (MPP), have been reported. MPP is a combined procedure of pancreaticoduodenectomy and distal pancreatectomy, while preserving the body of the pancreas, for cases of multifocal pancreatic lesions. So far, there have only been a few reports that have described MPP. We report a case of MPP for multifocal intraductal papillary mucinous neoplasms of the pancreas, describe the surgical procedure, and discuss the feasibility of MPP as parenchyma-preserving pancreatectomy with reference to the literature.

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書誌情報のみ, Bibliographic data Only