Multicenter prospective trial of total gastrectomy versus proximal gastrectomy for upper third cT1 gastric cancer.

BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.

Understanding the asymmetry between advancing and receding microscopic contact angles.

By means of molecular dynamics simulation, the advancing and receding microscopic contact angles were analyzed for a shear flow of two mono-atomic fluids confined between parallel non-polar solid walls. We defined the microscopic dynamic contact angle based on the coarse-grained microscopic density distribution of the fluids (the instantaneous interface method [Willard and Chandler, J. Phys. Chem. B, 2010, 114, 1954-1958]) near the moving contact line. We have found that the asymmetric change of fluid density near the wall with respect to the moving contact line results in a different dependence between the advancing and receding contact angles on the contact line velocity in a system where the two fluids across the interface have unequal wettability to the solid wall. This difference between the advancing and receding contact angles leads to different flow resistance caused by the advancing and receding contact lines, which should have impact on the industrial applications of the fine fluid transportation with contact lines.

Clinical significance of plasma fibrinogen level as a predictive marker for postoperative recurrence of esophageal squamous cell carcinoma in patients receiving neoadjuvant treatment.

Among multidisciplinary therapies developed for advanced esophageal cancer, neoadjuvant chemotherapy and chemoradiotherapy have been established as standard treatments. To deliver cautious follow up and intense treatment for high-risk patients, a simple and instructive biomarker for the postoperative recurrence needs to be identified. Fibrinogen, a common component of hemostasis, has been suggested to not only play an important role in cancer metastasis, but also correlate with tumor recurrence. We aim to clarify the validity of plasma fibrinogen as a marker for predicting the postoperative recurrence of esophageal squamous cell carcinoma patients who received neoadjuvant treatment. We reviewed 72 consecutive patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy or chemoradiotherapy, followed by esophagectomy at the Keio University Hospital from 2001 to 2010. Of them, we retrospectively examined 68 patients who underwent plasma fibrinogen examination before and after neoadjuvant treatment and underwent transthoracic radical esophagectomy. We investigated patient characteristics, clinicopathological factors, neoadjuvant treatment effects, postoperative course, and plasma fibrinogen levels. We investigated pretreatment and preoperative (postneoadjuvant treatment) plasma fibrinogen levels, as well as changes in fibrinogen levels before and after neoadjuvant treatment. Patients with preoperative hyperfibrinogenemia (>350 mg/dL) and patients with increased plasma fibrinogen levels during neoadjuvant treatment showed significantly shorter postoperative disease-free survival (DFS) (P = 0.002 and P = 0.037, respectively). Moreover, we classified these patients into three classes on the basis of their preoperative fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment. Patients who had both high preoperative plasma fibrinogen and increased fibrinogen levels showed significantly shorter DFS than others. In contrast, patients who had normal preoperative plasma fibrinogen and decreased fibrinogen levels showed significantly longer DFS. Based on this fibrinogen classification, we could differentiate between significantly favorable and poor prognosis patients group. Overall, this classification (hazard ratio = 1.812, P = 0.013) and the response to neoadjuvant treatment (hazard ratio = 0.350, P = 0.007) were found to be significant determining factors for postoperative DFS. With the validity of preoperative plasma fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment, the plasma fibrinogen level was found to be a possible biomarker for postoperative recurrence in advanced esophageal cancer patients who received neoadjuvant treatment. Moreover, plasma fibrinogen classification could be a simple and valuable predictive marker for postoperative follow up.

Clinical utility of preoperative evaluation of bronchial arteries by three-dimensional computed tomographic angiography for esophageal cancer surgery.

An identification of bronchial arteries (BAs) is critical in esophageal cancer surgery to avoid tracheobronchial ischemia and unexpected massive bleeding during surgical procedure particularly in thoracoscopic video-assisted esophagectomy. We describe the efficacy of three-dimensional computed tomographic angiography (3D-CTA) of BAs for preoperative evaluation in esophageal cancer surgery. Sixty-four patients with esophageal cancer who preoperatively underwent multidetector computed tomography examination were included in this study. We evaluated the number, origin, and intraoperative preservation rate of BAs, and we compared the number of thoracic paratracheal lymph nodes harvested between two groups comprising patients who either underwent preoperative 3D-CTA of BAs (3D-CTA group) or did not (non-3D-CTA group). The right and left BAs were preoperatively identified in 62 patients (97%) and 55 patients (86%), respectively, using 3D-CTA. In 34 patients (53%), the right BA originated as a common trunk with the right intercostal artery. In 48 patients (75%), the left BA originated from the descending aorta as a single or double branch. Some anomalies such as the right BA originated from the left subclavian artery were observed. In all patients, either the right or the left BA was preserved. The number of harvested lymph nodes in left side of paratrachea was significantly increased in 3D-CTA group, than those in non-3D-CTA group. 3D-CTA clearly revealed BA anatomy, contributing to BA preservation and safe and precise lymphadenectomy in esophageal cancer surgery. 3D-CTA of BAs is useful for preoperative evaluation in esophageal cancer surgery.

Self-sustaining oscillation of two axonemal microtubules based on a stochastic bonding model between microtubules and dynein.

The motility of cilia and flagella plays important physiological roles, and there has been a great deal of research on the mechanisms underlying the motility of molecular motors. Although recent molecular structural analyses have revealed the components of the ciliary axoneme, the mechanisms involved in the regulation of dynein activity are still unknown, and how multiple dyneins coordinate their movements remains unclear. In particular, the mode of binding for axonemal dynein has not been elucidated. In this study, we constructed a thermodynamic stochastic model of microtubule-dynein coupling and reproduced the experiments of Aoyama and Kamiya on the minimal component of axonemal microtubule-dynein. We then identified the binding mode of axonemal dynein and clarified the relationship between dynein activity distribution and axonemal movement. Based on our numerical results, the slip-bond mechanism agrees quantitatively with the experimental results in terms of amplitude, frequency, and propagation velocity, implying that axial microtubule-dynein coupling may follow a slip-bond mechanism. Moreover, the frequency and propagation velocity decayed in proportion to the fourth power of microtubule length, and the critical load of the trigger for the oscillation agreed well with Euler's critical load.

Intracellular Localization of Mycoplasma bovis in the Bronchiolar Epithelium of Experimentally Infected Calves.

Lung tissues from calves infected experimentally with Mycoplasma bovis were examined by immunohistochemistry and electron microscopy. All inoculated calves had dark red areas of consolidation affecting both left and right lungs, which were characterized microscopically by subacute purulent bronchiolitis with hyperplasia of the surrounding lymphoid tissue. Immunohistochemically, M. bovis antigen was detected on the surface and inside the cytoplasm of bronchiolar epithelial cells in the pneumonic foci. The antigen was also found in the cytoplasm of phagocytes at the margin of bronchiolar exudates. Electron microscopically, numerous organisms were demonstrated in the immunohistochemically-positive sites. These findings suggest that M. bovis organisms adhere to the bronchiolar epithelium and at least some of them invade the epithelium.

Proteus syndrome complicated by multiple spinal meningiomas.

Proteus syndrome is a complex and highly variable disorder comprising malformations and overgrowth of multiple tissues. We present a 65-year-old Japanese man who had multiple spinal meningiomas and accompanying neural symptoms. His right leg showed hypertrophy with cerebriform connective-tissue naevus on the sole, and macrodactyly. Chest computed tomography imaging revealed mild cystic and emphysematous lung changes, which were possibly related to Proteus syndrome. Otherwise, he had no particular cutaneous, musculoskeletal or visceral involvements. Because of the rather insignificant clinical features, he had not been accurately diagnosed in the past and yet had survived to this age. In particular, the presence of spinal meningiomas as an exceptional complication was sufficiently confusing to consider that he had neurofibromatosis. Doctors should be familiar with the diverse clinical pictures of this rare syndrome for its correct diagnosis and proper management.

Neural correlates of auditory feedback control in human.

Auditory feedback plays an important role in natural speech production. We conducted a functional magnetic resonance imaging (fMRI) experiment using a transformed auditory feedback (TAF) method to delineate the neural mechanism for auditory feedback control of pitch. Twelve right-handed subjects were required to vocalize /a/ for 5 s, while hearing their own voice through headphones. In the TAF condition, the pitch of the feedback voice was randomly shifted either up or down from the original pitch two or three times in each trial. The subjects were required to hold the pitch of the feedback voice constant by changing the pitch of original voice. In non-TAF condition, the pitch of the feedback voice was not modulated and the subjects just vocalized /a/ continuously. The contrast between TAF and non-TAF conditions revealed significant activations; the supramarginal gyrus, the prefrontal area, the anterior insula, the superior temporal area and the intraparietal sulcus in the right hemisphere, but only the premotor area in the left hemisphere. This result suggests that auditory feedback control of pitch is mainly supported by the right hemispheric network.

Nodal cilia-driven flow: Development of a computational model of the nodal cilia axoneme.

Cilia-driven nodal flow is important in the determination of left-right asymmetry in the body. Several theoretical and computational models have been proposed to explain the mechanics of ciliary motion, although the full mechanism remains unknown. Here, we developed a three-dimensional nodal cilia axoneme model using a finite element-boundary element coupling method, and investigated the mechanics of nodal ciliary motion. We found that the rotational orbit was strongly dependent on the dynein activation frequency. We also investigated flow field generated by the ciliary rotation, and the flow strength decayed as r-3 at the far field from the cilium. Our numerical results also suggest that experimentally observed tilt angle θ=2π/9 is sufficiently large to make a leftward flow. These findings are helpful in better understanding ciliary motion and nodal flow.

FDG-PET predicts treatment efficacy and surgical outcome of pre-operative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: The efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectable and borderline resectable pancreatic cancer is important for predicting outcomes after radical surgery, but few clinical indicators predict outcome before resection. This study examined the utility of FDG-PET in predicting the efficacy of NACRT and outcome after radical surgery. METHODS: Eighty-three pancreatic cancer patients who underwent FDG-PET before and after NACRT and had positive standard uptake values (SUVs) before NACRT were enrolled in this study. Peri-operative clinical factors, including FDG-PET findings, were examined to predict the efficacy of NACRT and outcome after surgery. RESULTS: Evans grade I, IIA, IIB, III, and IV was determined in 11, 31, 27, 11, and 3 patients, respectively. The maximum SUVs after NACRT (post SUV-max) and tumor size were significantly decreased compared to pretreatment values (p < 0.001 and p = 0.007, respectively). The post SUV-max and regression index were significantly related to grade III/IV (p = 0.04 and p < 0.001, respectively), but only the regression index predicted NACRT efficacy (p = 0.002). The AUC of the regression index for the detection of grade III/IV was 0.822, and 13 of 14 grade III/IV patients were picked up using 50% as the threshold (p < 0.001). Patients with a regression index >50% had a significantly better prognosis after radical resection than patients with <50% (p = 0.032). Regression index as well as pathological lymph node status and resectability status were independent prognostic factors in multivariate analysis (exp 2.086, p = 0.043). CONCLUSION: The regression index is potentially a good indicator of the efficacy of NACRT and outcome after radical resection for pancreatic cancer.

Laparoscopically assisted total gastrectomy with jejunal pouch interposition.

BACKGROUND: Jejunal pouch interposition (JPI) is known as a useful gastric replacement procedure after total gastrectomy. The JPI procedure, however, has not been applicable to laparoscopically assisted total gastrectomy (LATG) because of its technical complexity and difficulty. This study aimed to describe our modified LATG/JPI technique, and to evaluate its feasibility, safety, and early postoperative functional outcome. METHODS: Between September 2002 and August 2003, LATG/JPI was attempted for five patients (3 men and 2 women) with early gastric cancers in the upper portion of the stomach. The mean age of the patients was 57 years, and their BMI was 21 kg/m2. Using a 5-port technique, the gastric arteries were laparoscopically clipped and divided with adequate lymphatic dissection. After completion of gastric resection, the anvil of a circular stapling device was placed in the esophageal stump. An 8-cm minilaparotomy then was performed, and the 12-cm pouch was created extracorporeally in the "reverse U" fashion. The stapled pouch-esophagostomy was performed under laparoscopic monitoring. The remainder of the procedure was accomplished under direct vision. RESULTS: All cases were managed laparoscopically without any complications. The mean operating time was 407 min, and the blood loss was 279 ml. All the patients showed rapid and uneventful recovery. Postoperative studies, including dual scintigraphy, showed that all jejunal pouches were satisfactorily functioning. CONCLUSIONS: This study showed LATG/JPI to be feasible and safe. With technical modifications, LATG/JPI can become a potentially effective option for improving patients' quality of life after total gastrectomy.

Adenoviral-mediated overexpression of membrane-bound human FasL and human decoy Fas protect pig islets against human CD8+ CTL-mediated cytotoxicity.

Pig islets are considered to be most suitable source of islets for xenotransplantation into patients with type 1 diabetes mellitus. However, cellular rejection, especially CD8+ CTL-mediated cytotoxicity, remains a formidable barrier preventing long-term xenograft survival. Our previous study demonstrated that human CD8+ CTLs were highly detrimental to xenograft cells and that this strong cytotoxicity of human CTLs was mediated mainly by the Fas/FasL apoptotic pathway. Furthermore, we exploited novel methods for inhibiting human CD8+ CTL-mediated xenocytotoxicity with overexpression of membrane-bound human FasL and human decoy Fas antigen in xenografted cells. In the present study, we assessed the cytoprotective effects of these novel inhibitory molecules overexpressed by an adenoviral-mediated system in pig islets. Isolated pig islets were transfected with adenovirus vector encoding either human decoy Fas or membrane-bound human FasL genes. Thirty percent to 60% of transfected pig islets expressed these molecules producing 60% to 88% suppression of CTL killing compared with parental pig islets. These data indicated that pig islet grafts isolated from transgenic pigs with either membrane-bound human FasL or human decoy Fas antigen genes may control the innate cellular response to xenografts, and creating a window of opportunity to facilitate xenograft survival.

Cross-species function of the pig C1 esterase inhibitor.

BACKGROUND: The use of a bioartificial liver with pig cells for the treatment of fulminant hepatic failure will require research on the plasma complement regulatory proteins of the pig, because the liver produces most of the complement components and plasma complement regulatory proteins. In our previous study, the pig C1 esterase inhibitor (C1-INH), which functions as an inhibitor of the complement reaction in the first step of the classical pathway in the fluid phase, was cloned and some relevant features of the molecule were characterized, especially its cross-species regulation, in comparison with human C1-INH. In a further analysis, the species specificity of C1-INH was examined, using pig endothelial cells (PEC) and several types of sera. MATERIALS AND METHODS: The cDNA of pig C1-INH was used to produce the membrane type pC1-INH, pC1-INH-PI, and inserted into the cloning site of pCXN2 (chicken beta actin promoter). The pCX/pCl-INH-PI plasmid was then transfected into PEC to establish stable PEC with pCl-INH-PI. The expression of the pCl-INH-PI was evaluated by a FACS analysis, and complement-dependent cell lysis with human, dog, rabbit, and mouse sera was then assessed. RESULTS: The transfectant with pig Cl-INH-PI showed a high level of expression on PEC. The PEC transfectants showed an inhibitory effect on complement-dependent PEC lysis. Pig Cl-INH did not show the same suppressive effect for each serum. However, considering the alternative pathway activation of each serum on the pig cell membrane, it can be concluded that pCl-INH has a relatively small species restriction. CONCLUSION: Pig Cl-INH, having a similar structure to human Cl-INH, shows a strong complement regulatory function on other species sera.

High flux circularly polarized gamma beam factory: coupling a Fabry-Perot optical cavity with an electron storage ring.

We report and discuss high-flux generation of circularly polarized γ-rays by means of Compton scattering. The γ-ray beam results from the collision of an external-cavity-enhanced infrared laser beam and a low emittance relativistic electron beam. By operating a non-planar bow-tie high-finesse optical Fabry-Perot cavity coupled to a storage ring, we have recorded a flux of up to (3.5 ± 0.3) × 108 photons per second with a mean measured energy of 24 MeV. The γ-ray flux has been sustained for several hours. In particular, we were able to measure a record value of up to 400 γ-rays per collision in a full bandwidth. Moreover, the impact of Compton scattering on the electron beam dynamics could be observed resulting in a reduction of the electron beam lifetime correlated to the laser power stored in the Fabry-Perot cavity. We demonstrate that the electron beam lifetime provides an independent and consistent determination of the γ-ray flux. Furthermore, a reduction of the γ-ray flux due to intrabeam scattering has clearly been identified. These results, obtained on an accelerator test facility, warrant potential scaling and revealed both expected and yet unobserved effects. They set the baseline for further scaling of the future Compton sources under development around the world.

Involvement of Jasmonic Acid in Elicitor-Induced Phytoalexin Production in Suspension-Cultured Rice Cells.

It has been suggested that jasmonic acid (JA) could be an integral part of a general signal transduction system regulating inducible defense genes in plants. It was reported that treatment with an elicitor (N-acetylchitoheptaose) induced production of phytoalexin in suspension-cultured rice (Oryza sativa L.) cells. In this study, the role of JA in the induction of phytoalexin production by N-acetylchitoheptaose was investigated. Exogenously applied ([plus or minus])-JA (10-4 M) clearly induced the production of momilactone A, a major phytoalexin, in suspension-cultured rice cells. On the other hand, in rice cells treated with N-acetylchitoheptaose, endogenous JA was rapidly and transiently accumulated prior to accumulation of momilactone A. Treatment with ibuprofen, an inhibitor of JA biosynthesis, reduced production of momilactone A in the cells treated with N-acetylchitoheptaose, but the addition of ([plus or minus])-JA increased production of momilactone A to levels higher than those in the elicited rice cells. These results strongly suggest that JA functions as a signal transducer in the induction of biosynthesis of momilactone A by N-acetylchitoheptaose in suspension-cultured rice cells.

A simple technique for circular-stapled Billroth I reconstruction in laparoscopic gastrectomy.

A simple surgical technique that facilitates circular-stapled Billroth I gastroduodenostomy in laparoscopic distal gastrectomy is described. After standard laparoscopic mobilization of the distal stomach, a small duodenotomy is made just distal to the pyloric ring. The anvil of a circular-stapling device, secured with a Vicryl suture, is introduced via the duodenotomy. The Vicryl suture is advanced anteriorly so that a center rod penetrates the anterior duodenal wall. The duodenum is staple-transected at this point, and the center rod is wrapped with the stapled duodenal stump by approximation of both edges using a suturing device. The circular-stapled gastroduodenostomy then is completed in a standard fashion. The authors have used this technique for three patients, and their early outcomes are promising.

Shape matters: Near-field fluid mechanics dominate the collective motions of ellipsoidal squirmers.

Microswimmers show a variety of collective motions. Despite extensive study, questions remain regarding the role of near-field fluid mechanics in collective motion. In this paper, we describe precisely the Stokes flow around hydrodynamically interacting ellipsoidal squirmers in a monolayer suspension. The results showed that various collective motions, such as ordering, aggregation, and whirls, are dominated by the swimming mode and the aspect ratio. The collective motions are mainly induced by near-field fluid mechanics, despite Stokes flow propagation over a long range. These results emphasize the importance of particle shape in collective motion.

Demonstration of the stabilization technique for nonplanar optical resonant cavities utilizing polarization.

Based on our previously developed scheme to stabilize nonplanar optical resonant cavities utilizing polarization caused by a geometric phase in electromagnetic waves traveling along a twisted path, we report an application of the technique for a cavity installed in the Accelerator Test Facility, a 1.3-GeV electron beam accelerator at KEK, in which photons are generated by laser-Compton scattering. We successfully achieved a power enhancement of 1200 with 1.4% fluctuation, which means that the optical path length of the cavity has been controlled with a precision of 14 pm under an accelerator environment. In addition, polarization switching utilizing a geometric phase of the nonplanar cavity was demonstrated.

Cloning and characterization of genes encoding an enzyme which oxidizes dimethyl sulfide in Acinetobacter sp. strain 20B.

Acinetobacter sp. strain 20B was isolated based on the ability to utilize dimethyl sulfide as the sole sulfur source. Since strain 20B oxidized indole as well as dimethyl sulfide, indigo production by recombinant Escherichia coli clones carrying Acinetobacter DNA was used as a selection for cloning genes encoding dimethyl sulfide oxidation genes. The gene encoding an indole-oxidizing enzyme was also found to oxidize dimethyl sulfide. The dimethyl sulfide-oxidizing enzyme genes consisted of six open reading flames designated dsoABCDEF. The deduced amino acid sequences of dsoABCDEF were homologous with those of the multicomponent phenol hydroxylases. DsoABCDEF oxidized dimethyl sulfide to dimethyl sulfoxide, and dimethyl sulfoxide to dimethyl sulfone.