During the EVEDA (engineering validation and engineering design activities) phase of the International Fusion Materials Irradiation Facility (IFMIF) project, a 125 mA/9 MeV linear prototype accelerator (LIPAc) has to be built, tested and operated in Rokkasho-mura (Japan). Involved in this project for several years, CEA-Saclay designed the injector of this accelerator which is composed of an electron cyclotron resonance ion source, delivering a 140 mA deuteron beam at 100 keV, and a low energy beam transport (LEBT) line to match the beam for the injection into the radio-frequency quadrupole. In this paper, the components of the LIPAc injector are described. The commissioning of the ion source and LEBT with beam started in November 2014. The different phases of the commissioning are explained and some noticeable experimental results obtained with a D+ beam at 100 keV are presented.

The objective of linear IFMIF prototype accelerator is to demonstrate 125 mA/CW deuterium ion beam acceleration up to 9 MeV. The injector has been developed in CEA Saclay and already demonstrated 140 mA/100 keV deuterium beam [R. Gobin et al., Rev. Sci. Instrum. 85, 02A918 (2014)]. The injector was disassembled and delivered to the International Fusion Energy Research Center in Rokkasho, Japan. After reassembling the injector, commissioning has started in 2014. Up to now, 100 keV/120 mA/CW hydrogen and 100 keV/90 mA/CW deuterium ion beams have been produced stably from a 10 mm diameter extraction aperture with a low beam emittance of 0.21 π mm mrad (rms, normalized). Neutron production by D-D reaction up to 2.4 × 10(9) n/s has been observed in the deuterium operation.

Ion species ratio of high current positive hydrogen/deuterium ion beams extracted from an electron-cyclotron-resonance ion source for International Fusion Materials Irradiation Facility accelerator was measured by the Doppler shift Balmer-α line spectroscopy. The proton (H+) ratio at the middle of the low energy beam transport reached 80% at the hydrogen ion beam extraction of 100 keV/160 mA and the deuteron (D+) ratio reached 75% at the deuterium ion beam extraction of 100 keV/113 mA. It is found that the H+ ratio measured by the spectroscopy gives lower than that derived from the phase-space diagram measured by an Allison scanner type emittance monitor. The H+/D+ ratio estimated by the emittance monitor was more than 90% at those extraction currents.

Introduction: We have performed straight laparoscopic total proctocolectomy for ulcerative colitis, in which all procedures, including transection of the rectum and anastomosis, were performed in the abdominal cavity. The primary objective of this study was to evaluate whether straight laparoscopic total proctocolectomy is technically feasible and safe.Methods: A retrospective database identified 22 consecutive patients who underwent straight laparoscopic total proctocolectomy for ulcerative colitis between March 1998 and September 2007. Patients were excluded if they required emergency surgery. First, to create a stoma site, a minilaparotomy to insert a 15mm trocar was performed. Seven other trocars, 5mm in diameter, were then inserted. Mobilization and dissection of the colorectum and anastmosis were performed completely intracorporeally under laparoscopic guidance. Anastomosis of an ileal J-pouch to the anal canal was performed using the double-stapling technique.Results: Nineteen patients were underwent ileal pouch anal canal anastomosis; two underwent ileorectal anastomosis; and one underwent abdominoperineal resection. The median operation time was 355 min (range 255-605); the median blood loss was 50 g (range 0-800); and the median postoperative hospital stay was 24.5 d. Postoperative complications occurred in eight patients, including three (13.6%) with bowel obstruction, two (9.1%) with portal vein thrombosis, one (4.5%) with anastomotic leakage, and one (4.5%) with postoperative hemorrhage. The morbidity rate was 36.4%. There were no intraoperative complications or conversions to conventional surgery.Conclusion: In the context of this study, we have shown that straight laparoscopic total proctocolectomy is technically feasible and safe in patients with ulcerative colitis.

症例は58歳女性で, 左肺癌肉腫の診断のもと左肺全摘術を施行した. 術後1年経過して突然腹痛, 嘔吐が出現し当院内科を受診した. 腹部単純X線検査で鏡面像を認め, 腹部造影CTでtarget signが右側腹部に認められた. 腸重積の診断で入院, イレウス管で保存的治療が行われ, イレウス管造影検査では上部空腸に9cm大の透亮像が認められた. 以上より腸重積をともなう小腸腫瘍と診断され, 腹腔鏡下手術が施行された. 術中所見では, トライツ靱帯から20cmの部位に空腸―空腸型の腸重積が認められ, 整復後トライツ靱帯から34cmの空腸に径10cmの腫瘍が認められたため小腸部分切除を施行した. 切除標本上, 10×6cm大の隆起性腫瘍が認められ, 病理組織検査では, 異型の強い紡錘形細胞束の増生があり, 肺癌肉腫の肉腫成分の空腸転移と診断した.肺癌肉腫の小腸転移はまれな疾患であり, 本邦では5例の報告があるが, 腸重積で発症した症例は2例のみであった. 腹腔鏡下手術は腸重積の診断に引き続き癒着剥離や整復などの治療も行える, したがって減圧された腸重積は本法の良い適応と考えられた.

潰瘍性大腸炎に対する大腸全摘術後に生じた小網異常裂孔ヘルニアを経験したので報告する.症例は21歳女性で,2002年5月潰瘍性大腸炎に対して腹腔鏡下大腸全摘術を施行した.2005年6月激しい上腹部痛と嘔気を主訴に受診し,腹部単純X線で術後腸閉塞と診断,イレウス管による保存的治療を開始した.しかし改善傾向なく第9病日手術を施行した.開腹所見では,空腸が網嚢腔から胃背側を通り,小網の異常裂孔を介して胃の前面へ脱出し嵌頓していた.手術は,ヘルニア解除およびヘルニア門の閉鎖,他の部位の癒着剥離と狭窄部位に対する狭窄形成術を行い,患者は術後14日目に退院した.このような内ヘルニアは,本邦では自験例を含め9例の報告をみるにすぎない.術前診断に難渋することが多いが,激しい上腹部痛をともなう腸閉塞でかつて胃結腸間膜を切除している症例では小網異常裂孔ヘルニアを念頭におき早期診断治療が重要であると考えられた.

PURPOSE:We devised a new method for the safe introduction of the first trocar and induction of pneumoperitoneum for laparoscopic excision of the large intestine.METHODS:With this method, a small laparotomy is first conducted according to the size of the exposed affected intestinal tract or tumor size, prior to the application of a LAP DISC (LD) to the wound and introduction of a 12-mm trocar for the establishment of pneumoperitoneum. The method is advantageous in that organ injury and vessel injury are avoided when the small laparotomy is conducted first, and prompt transition to a conventional laparotomy is possible. The diaphragm of the iris bulb can be controlled in a non-stepwise manner. In addition, trocars, the stapler, and other instruments, can be inserted under the pneumoperitoneum. Furthermore, the use of a 5-mm flexible scope allows surgical maneuvers, except for application of LD, to be conducted via 5-mm trocars. In addition, the 5-mm scope can be inserted through any trocar, allowing multidirectional avoidance of dead space and intraperitoneal observation. When only 5-mm trocars are used, it is not necessary for the sites of trocar puncture to be closed by sutures, and this minimizes the risk of adhesions and port-site herniation. The method is also considered to be excellent from the point of view of esthetics.RESULTS:We employed this surgical approach in 50 patients with colorectal cancer at our hospital. None of the patients developed any traumatic complications associated with the insertion of trocars, and none of the patients, even those with a past history of abdominal operation, required conversion to conventional laparotomy.CONCLUSIONS:Based on these results, this method involving a small laparotomy prior to the application of an LD and introduction of a 12-mm trocar for establishing pneumoperitoneum, with the efficient use of a 5-mm flexible camera, is considered to be safe and useful for laparoscopic excision of the large intestine.

Mutations in the hepatocyte nuclear factor (HNF) 4alpha gene cause a form of maturity-onset diabetes of the young (MODY1), which is a monogenic form of type 2 diabetes characterized by impaired insulin secretion by pancreatic beta-cells. HNF4alpha is a transcription factor expressed in the liver, kidney, intestine, and pancreatic islet. Multiple splice variants of the HNF4alpha gene have been identified and an isoform of HNF4alpha8, an N-terminal splice variant, is expressed in pancreatic beta-cells. However, expression levels of HNF4alpha protein in pancreatic beta-cells and the transcriptional activity of HNF4alpha8 are not yet understood. In the present study, we investigated the expression of HNF4alpha in beta-cells and examined its functional properties. Western blotting and immunohistochemical analysis revealed that the expression of HNF4alpha protein in pancreatic islets and INS-1 cells was much lower than in the liver. A reporter gene assay showed that the transactivation potential of HNF4alpha8 was significantly weaker than that of HNF4alpha2, which is a major isoform in the liver, suggesting that the total level of HNF4alpha activity is very weak in pancreatic beta-cells. We also showed that the N-terminal A/B region of HNF4alpha8 possessed no activation function and C-terminal F region negatively regulated the transcriptional activity of HNF4alpha8. The information presented here would be helpful for the better understanding of MODY1/HNF4alpha diabetes.

Background/Aims: Liver and lymph node metastasis is the major prognostic factor in patients with colorectal carcinoma. The aim of this work was to search for tumor parameters which can be employed to predict whether this has occurred.Methodology: A total of 211 patients with a colorectal carcinoma (Dukes' B group, 83; Dukes' C, 94; Dukes' D, 34) were investigated for 10 clinicopathological variables, as well as apoptotic activity, expression of Ki-67, p21(WAF1)/(CIP1), p53, bcl-2 and DCC proteins, and the c-K-i-ras mutations. Data were analyzed by univariate and multivariate statistics.Results: Lymph node metastasis-predictive models were developed using the venous involvement index (the number of vascular involvements per elastica van Gieson-stained slide; Odds ratio [OR], 2.38; 95% confidence interval [CI], 1.52-3.71;p=0.0001), tumor size (OR, 0.82; 95% CI, 0.70-0.97; p=0.0179), and p21(WAF1/CIP1) immunolabeled index (the percentages of positive tumor cells; OR, 0.76; 95% CI, 0.64-0.90; P=0.0011). Liver metastasis-predictive models were developed using the venous involvement index (OR, 2.40; 95% CI, 1.71-3.37; p = 0.0000) and tumor location (rectum vs. colon; OR, 9.31; 95% CI, 2.41-36.01; p=0.0012).Conclusions: Down-regulation of p21(WAF1/CIP1) as well as marked venous involvement, small tumor size and colonic tumor are associated with lymph node and/or liver metastasis. Criteria for assessment of metastasis risk provide a basis for additional treatment guidelines.

BACKGROUND/AIMS:Serrated adenomas (SAs) of the colorectum can be broadly divided into two subtypes: type I more closely mimicking hyperplastic polyps, and type II unequivocal traditional adenomas. The aim of this study was to clarify their differential clinicopathologic and colonoscopic features.METHODOLOGY:A total of 127 SAs (53 type I, 52 type II and 22 admixed type I+II) were investigated and colonoscopic surface patterns were divided into three categories: speckled, granular and cerebriform.RESULTS:The cerebriform pattern was most frequently observed in all SA types. Types I+II (median size, 7.5 mm) or type II SAs (median size, 10 mm) were generally sessile or pedunculated polyps in the rectosigmoid colon whereas some type I lesions (median size, 5 mm) demonstrated a flat-elevated morphology and were found in the ascending colon and cecum. Co-existing (2/127: 1.6%) invasive carcinomas were only detected with type II SAs. In contrast, synchronous invasive carcinomas distant from SAs were more frequently observed with type I (31%) than types I+II (5%) or II (12%).CONCLUSIONS:Clinicopathologic differences are apparent among the types of SAs. A type II SA-invasive carcinoma sequence might exist. We stress recognition of type I SA as a neoplastic, rather than a hyperplastic lesion, often accompanying invasive carcinomas at a distance from the SA.

本邦では,大腸癌の病期分類として日本大腸癌取扱い規約(以下JGR),欧米ではAmerican Joint Committee on Cancer and the Union Internationale Contrele Cancer(AJCC/UICC)TNM(以下TNM)分類が広く用いられている.本研究はDukesC大腸癌患者においてJGRとTNMのリンパ節分類と予後との関係を明らかにし,いずれの分類が妥当であるかを検証することを目的とした.治癒切除が施行されたDukesC大腸癌患者386例を対象とした.転移リンパ節の解剖学的位置にもとずいたJGRによるn-stage,リンパ節転移個数による新TNM分類のN-stage,そして,既存の臨床病理学的因子(性別,年齢,腫瘍径,占居部位,組織型,深達度,リンパ管侵襲,静脈侵襲)について,多変量解析を用いて予後規定因子につき検討した.単変量解析では,腫瘍径,深達度,リンパ管侵襲,静脈侵襲,JGR(n-stage),TNM(N-stage)の6因子で5年生存率に有意差を認めたが.多変量解析ではTNMのリンパ節転移分類のみが,DukesC大腸癌患者の独立した予後規定因子であった(p<0.0001,odds比:2.876).系統的リンパ節郭清を施行したDukesC大腸患者において,TNMのN-stage分類は,解剖学的な位置によるJGRのn-stage分類より予後を予測する上で,妥当な分類と考えられた.

Mutations in the hepatocyte nuclear factor (HNF) 4a gene cause a form of maturity-onset diabetes of the young (MODY1), which is a monogenic form of type 2 diabetes characterized by impaired insulin secretion by pancreatic b-cells. HNF4a is a transcription factor expressed in the liver, kidney, intestine, and pancreatic islet. Multiple splice variants of the HNF4a gene have been identified and an isoform of HNF4a8, an N-terminal splice variant, is expressed in pancreatic b-cells. However, expression levels of HNF4a protein in pancreatic b-cells and the transcriptional activity of HNF4a8 are not yet understood. In the present study, we investigated the expression of HNF4a in b-cells and examined its functional properties. Western blotting and immunohistochemical analysis revealed that the expression of HNF4a protein in pancreatic islets and INS-1 cells was much lower than in the liver. A reporter gene assay showed that the transactivation potential of HNF4a8 was significantly weaker than that of HNF4a2, which is a major isoform in the liver, suggesting that the total level of HNF4a activity is very weak in pancreatic b-cells. We also showed that the N-terminal A/B region of HNF4a8 possessed no activation function and C-terminal F region negatively regulated the transcriptional activity of HNF4a8. The information presented here would be helpful for the better understanding of MODY1/HNF4a diabetes.

Cerebral dominance for language function was investigated with synthetic aperture magnetometry (SAM). The results were compared with those of the Wada test. SAM is a spatial filtering technique that enables demonstration of the spatiotemporal distribution of oscillatory changes (synchronization and desynchronization) in magnetoencephalography (MEG) signals elicited by specific brain activation. MEG was conducted during a silent reading task in 20 consecutive preoperative neurosurgical patients who also underwent a Wada test. The spatial distribution of oscillatory changes related to silent reading was shown tomographically with SAM as statistical images. Language dominance was estimated by the laterality index, which scales the lateralization of the beta (13–25 Hz) and low gamma (25–50 Hz) band desynchronizations in the inferior frontal gyrus (IFG) or middle frontal gyrus (MFG). Oscillatory changes were distributed multifocally and bilaterally in the occipital cortex, IFG or MFG, and temporo-parieto-occipital border regions. In 19 patients (95%), language lateralization estimated by the laterality index was congruent with the result of the Wada test. In left-handed patients, SAM analysis clearly differentiated language dominance (left, right, or bilateral), and the findings were confirmed by the Wada test. Lateralization of beta or low gamma band desynchronizations in the IFG or MFG is a good indicator of the side of language dominance. Reliability of MEG imaging with SAM is sufficient to evaluate language dominance preoperatively in neurosurgical patients.

症例は49歳,男性.約2年前より下血を繰り返すため近医で精査するも,原因不明であった.今回,当院に下血の原因精査目的で入院中に突然の大量下血を認め,腹部血管造影を施行したところ,空腸枝末端に出血源を同定し得た.超選択的に出血部近傍の動脈に留置したマイクロカテーテルより術中に色素を注入,腸管漿膜の色調の変化を確認した上で,腹腔鏡下に小腸切除を施行した.切除標本では,肉眼的に出血源は2mm大の血まめ様の腫瘤として認められ,病理組織学的にpyogenic granulomaと診断された.術後経過は良好で,術後8日目に退院した.小腸のpyogenic granulomaは極めてまれであるが,小腸出血の原因の1つとして念頭におく必要がある.また術中に病変部の確認が困難な小腸出血例における術中の動脈内留置カテーテルからの色素注入法は,切除範囲を決定するために有効な手段の1つと考えられた.

We performed magnetic stimulation at the level of foramen magnum in healthy subjects to evaluate the long latency response in lower limb muscle. Subjects assumed an upright stance and we recorded electromyographic activities in soleus muscle. A late response at the onset latency of approximately 40 ms was elicited. The late response wasn't induced in other lower limb muscles; anterior tibial muscle, quadriceps femoris muscle, and biceps femoris muscle. Additionally, magnetic stimulation to foot motor cortex, basal occiput and cervical nerve roots did not evoke the response with latency of 40 ms. These results reveal the late response in soleus muscle that has not been previously reported. We speculate that it is involved with the long-loop reflex.

In healthy subjects, we studied the late electromyographic response elicited by transcranial magnetic stimulation (TMS) applied at the level of the foramen magnum in the left soleus muscle in an upright and supine posture. The late response at the latency of approximately 40 ms was constantly elicited during both postures. It was elicited during planter flexion, but not dorsi flexion. Additionally, no response appeared in the relaxed muscle. Those behaviours are the same as that of the long-loop reflex (LLR). We believe that the late response may be a long-loop reflex.

The aim of this study was to verify the relation between gamma-band activity and process of function words. We recorded the neuromagnetic signals in six healthy volunteers during silent reading of verbs (verb task) and forming of the past tenses (past-tense task) and investigated the spatio-temporal distribution of event-related desynchronization (ERD) and synchronization using synthetic aperture magnetometry. In both tasks, ERDs were observed simultaneously at multiple language-related areas. The left junctional area of inferior frontal sulcus and precentral sulcus and the left supramarginal gyrus showed stronger and/or longer-lasting ERDs in past-tense task than in verb task. This result suggests that the gamma-activities reflect the syntactic process of words.

To evaluate the gamma-band activity related to somatosensory processing, we recorded neuromagnetic signals from seven healthy subjects. The source power changes evoked by electrical stimulation of the median nerve were estimated with synthetic aperture magnetometry (SAM). Source power in the low gamma band (40 Hz) decreased in the contralateral primary somatosensory cortex (SI) for a few hundred milliseconds (i.e. middle and long latency) and then increased inversely. Source power in the high gamma band (70-90 Hz) increased simultaneously both in the contralateral SI and contra/ipsilateral secondary somatosensory cortex (SII) in 80-180 ms. These results suggest that low and high gamma oscillations work under independent mechanisms during somatosensory processing. In particular, high gamma oscillations may play an essential role in making a functional connection between SI and SII.

Transcranial magnetic stimulation (TMS) with a double cone coil placed over the left lateral side of the basal occiput was able to elicit late electromyographic (EMG) responses at the bilateral soleus muscles (SOL) averaged over 30 stimulation events, with a mean latency of approximately 100 ms. These EMG responses were detected using a low frequency bandpass filter with 0.05 Hz magnetic stimulation on ten healthy subjects in standing posture. As magnetic stimulation over the left basal occiput with a double cone coil can stimulate cerebellar structure, this late response seems to be conducted from the cerebellar structure to the SOL via an as yet unknown descending pathway. Here, we report new late EMG responses in relation to cerebellum or cerebellum related structures.