Ten-year follow-up results of a randomized clinical trial comparing left thoracoabdominal and abdominal transhiatal approaches to total gastrectomy for adenocarcinoma of the oesophagogastric junction or gastric cardia.

BACKGROUND: The optimal surgical approach for treatment of oesophagogastric junction (OGJ) cancer is controversial. A randomized clinical trial (JCOG9502) comparing transhiatal (TH) and left thoracoabdominal (LTA) approaches was stopped after the first interim analysis owing to limited efficacy for LTA resections. Complete 10-year follow-up data are now available. METHODS: Patients with histologically proven adenocarcinoma of the OGJ or gastric cardia with oesophageal invasion of 3 cm or less were randomized to a TH or LTA approach. Both groups underwent total gastrectomy and splenectomy with D2 nodal dissection plus para-aortic lymphadenectomy above the left renal vein. For LTA, a thorough mediastinal lymphadenectomy below the left inferior pulmonary vein was also mandatory. The primary endpoint was overall survival. RESULTS: A total of 167 patients (82 TH, 85 LTA) were enrolled. The 10-year overall survival rate was 37 (95 per cent c.i. 26 to 47) per cent for the TH approach and 24 (15 to 34) per cent for the LTA technique (P = 0·060). The hazard ratio for death was 1·42 (0·98 to 2·05) for the LTA technique. Subgroup analysis based on the Siewert classification indicated non-significant survival advantages in favour of the TH approach. CONCLUSION: LTA resections should be avoided in the treatment of adenocarcinoma of the OGJ or gastric cardia. REGISTRATION NUMBER: NCT00149266 (https://www.clinicaltrials.gov).

Thrombus-targeted perfluorocarbon-containing liposomal bubbles for enhancement of ultrasonic thrombolysis: in vitro and in vivo study.

BACKGROUND: External low-frequency ultrasound (USD) in combination with microbubbles has been reported to recanalize thrombotically occluded arteries in animal models. OBJECTIVE: The purpose of this study was to examine the enhancing effect of thrombus-targeted bubble liposomes (BLs) developed for fresh thrombus imaging during ultrasonic thrombolysis. METHODS: In vitro: after the administration of thrombus-targeted BLs or non-targeted BLs, the clot was exposed to low-frequency (27 kHz) USD for 5 min. In vivo: Rabbit iliofemoral arteries were thrombotically occluded, and an intravenous injection of either targeted BLs (n = 22) or non-targeted BLs (n = 22) was delivered. External low-frequency USD (low intensity, 1.4 W cm(-2) , to 12 arteries, and high intensity, 4.0 W cm(-2) , to 10 arteries, for both the targeted BL group and the non-targeted BL group) was applied to the thrombotically occluded arteries for 60 min. In another 10 rabbits, recombinant tissue-type plasminogen activator (rt-PA) was intravenously administered. RESULTS: In vitro: the weight reduction rate of the clot with targeted BLs was significantly higher than that of the clot with non-targeted BLs. In vivo: TIMI grade 3 flow was present in a significantly higher number of rabbits with USD and targeted BLs than rabbits with USD and non-targeted BLs, or with rt-PA monotherapy. High-intensity USD exposure with targeted BLs achieved arterial recanalization in 90% of arteries, and the time to reperfusion was shorter than with rt-PA treatment (targeted BLs, 16.7 ± 5.0 min; rt-PA, 41.3 ± 14.4 min). CONCLUSIONS: Thrombus-targeted BLs developed for USD thrombus imaging enhance ultrasonic disruption of thrombus both in vitro and in vivo.

Efficacy of endotoxin adsorption therapy (polymyxin B hemoperfusion) for methicillin-resistant Staphylococcus aureus toxic shock syndrome: a case report about five patients.

BACKGROUND: Toxic shock syndrome (TSS), which can be life-threatening, is clinically and pathologically characterized by the presence of high fever, skin rash, desquamation, hypotension, and multiple organ failure caused by an enterotoxin produced by Staphylococcus aureus. In this study, we evaluated the effects of endotoxin adsorption therapy (polymyxin B [PMX] hemoperfusion) in critical patients with methicillin-resistant Staphylococcus aureus TSS (MRSA-TSS) who showed no improvement with the conventional therapy. METHODS: Five MRSA-TSS patients (men/women: 3/2; median age: 39 years) who showed no improvement with the conventional therapy underwent PMX hemoperfusion in addition to the conventional therapy. The primary outcomes were change in the systolic arterial pressure (SAP) and requirement of a vasopressor after PMX hemoperfusion, and the secondary outcomes were change in laboratory data and sequential organ failure assessment (SOFA) scores 24 h after the therapy. RESULTS: The median duration of PMX hemoperfusion was 9 h (range, 4-20 h). SAP significantly increased (from 89 to 125 mmHg, P<0.05) and the requirement of a vasopressor significantly decreased (from 10 to 2, P<0.05) after PMX hemoperfusion. Furthermore, the patients' white blood cell count decreased (from 17640 to 10090 /uL, P<0.05), and SOFA scores decreased (from 13 to 9, P<0.05) after PMX hemoperfusion. All patients recovered and were discharged from the ICU. CONCLUSION: Our results showed that PMX hemoperfusion significantly improved the hemodynamics and severity in patients with life-threatening MRSA-TSS.

Non-contact heart rate monitoring method for elderly people In bed with random body motions using 24 GHz dual radars located beneath the mattress in clinical settings.

We have developed a non-contact heart rate monitoring system for elderly people In bed using two radars placed on the bed base. The system is designed to increase accuracy despite body motion noise and change of body position and sleeping posture In bed. In order to achieve this, we combined an automatic gaIn control (AGC) method with a real-time radar-output channel selection method which is based on a spectrum shape analysis (SSA). Field tests were carried out with elderly subjects at a nursing home. The accuracy was maintained because the system successfully avoided the null detection point (NDP) problem, respiratory harmonic interference and intermodulation problems. The heart rate accuracy (r = 0.703) was higher than that of the conventional method. The system was proved to be effective In monitoring vital signs without the need for any physical contact with the subjects.

Functional outcomes after extended surgery for gastric cancer.

BACKGROUND: Extended gastrectomy with para-aortic nodal dissection (PAND) or thorough dissection of mediastinal nodes using a left thoracoabdominal (LTA) approach is an alternative to D2 lymphadenectomy, with variable postoperative results. METHODS: Two randomized controlled trials have been conducted to compare D2 lymphadenectomy alone (263 patients) versus D2 lymphadenectomy plus PAND (260), and the abdominal-transhiatal (TH) approach (82) versus the LTA approach (85), in patients with gastric cancer. Prospectively registered secondary endpoints bodyweight, symptom scores and respiratory function were evaluated in the present study. RESULTS: Bodyweight was comparable after D2 and D2 plus PAND, but higher after TH than after LTA procedures at 1 and 3 years. At 1- and 3-year follow-up symptom scores were comparable between D2 and D2 plus PAND. A LTA approach resulted in significantly worse scores than a TH approach in terms of meal volume, return to work, incisional pain and dyspnoea up to 1 year. The decrease in vital capacity was significantly greater after LTA than TH procedures up to 6 months. CONCLUSION: Bodyweight and postoperative symptoms were not affected by adding PAND to a D2 procedure. A LTA approach aggravated weight loss, symptoms and respiratory functions compared with a TH approach.

Multipole electron-density modelling of synchrotron powder diffraction data: the case of diamond.

Accurate structure factors are extracted from synchrotron powder diffraction data measured on crystalline diamond based on a novel multipole model division of overlapping reflection intensities. The approach limits the spherical-atom bias in structure factors extracted from overlapping powder data using conventional spherical-atom Rietveld refinement. The structure factors are subsequently used for multipole electron-density modelling, and both the structure factors and the derived density are compared with results from ab initio theoretical calculations. Overall, excellent agreement is obtained between experiment and theory, and the study therefore demonstrates that synchrotron powder diffraction can indeed provide accurate structure-factor values based on data measured in minutes with limited sample preparation. Thus, potential systematic errors such as extinction and twinning commonly encountered in single-crystal studies of small-unit-cell inorganic structures can be overcome with synchrotron powder diffraction. It is shown that the standard Hansen-Coppens multipole model is not flexible enough to fit the static theoretical structure factors, whereas fitting of thermally smeared structure factors has much lower residuals. If thermally smeared structure factors (experimental or theoretical) are fitted with a slightly wrong radial model (s(2)p(2) instead of sp(3)) the radial scaling parameters (kappa' parameters) are found to be inadequate and the ;error' is absorbed into the atomic displacement parameter. This directly exposes a correlation between electron density and thermal parameters even for a light atom such as carbon, and it also underlines that in organic systems proper deconvolution of thermal motion is important for obtaining correct static electron densities.

[Large cell neuroendocrine carcinoma of the lung].

Large cell neuroendocrine carcinoma (LCNEC) is a neuroendocrine tumor comprising a subgroup of large cell carcinoma and is a type of lung cancer showing a neuroendocrine characteristic similar to that of small cell lung carcinoma In our institution, we started to diagnose LCNEC by immunostaining in 2002, and we herein report 9 patients diagnosed with LCNEC from January 2002 to May 2008. The average patient age was 74.9, male/female ratio was 8/1, and all 9 patients had a smoking history. Pathological stages IA/IB/IIB/IIIA comprised 4/1/2/2, respectively. Peripherally located and lobulated tumors were noted on preoperative computed tomography (CT), and moderate uptake of fluoro-2-deoxy-D-glucose (FDG), which balanced with the size, was recognized on positron emission tomography (PET). All 9 patients underwent surgery and 7 underwent radical surgery. Postoperative adjuvant chemotherapy was performed for 4 patients. Three showed recurrence, and 2 of these 3 died of the primary disease. The remaining 7 patients have survived to date. The possibility of LCNEC must be considered when peripherally located lung cancer with lobulation is noted on CT and shows moderate uptake of FDG for its size on PET, and multimodal treatment is needed if the diagnosis is determined postoperatively.

Effect of carbohydrates on the ability of bull sperm to bind to bovine oviduct epithelial cells.

In the present study, we investigated the effect of various carbohydrates on the ability of bovine spermatozoa to bind to the bovine oviduct epithelial cells (OECs). We also examined the fertilization competence and motility of spermatozoa that bind to OECs in the presence of carbohydrates. Frozen-thawed spermatozoa were incubated with OECs, with and without various carbohydrates. The sperms were then divided into two fractions: OEC-binding sperms (B-sperm) and non-OEC binding sperms (NB-sperm). The fertilization rate, ability to bind the zona pellucida, and membrane integrity of the spermatozoa as determined using a hypo-osmotic-swelling test (HOST) were lower in NB-sperm than in the unseparated spermatozoa (control). The motility of the B-sperm was maintained for a longer time than that of the control spermatozoa. The addition of N-acetyl-d-glucosamine (GlcNAc, 5 mm) to the sperm-OEC mixture increased the number of B-sperm. D-mannose (5 mm) and D-fucose (5 mm) had no effect on the number of B-sperm. The motility of B-sperm, which bound to OECs in the presence of GlcNAc, however, was not maintained. When either OECs or the spermatozoa were treated with GlcNAc prior to sperm-OEC co-incubation, only sperm-side treatment enhanced sperm-OEC binding, but B-sperm motility was not maintained. The motility of spermatozoa incubated with GlcNAc was lower than that of controls. These results indicate that GlcNAc enhances sperm binding to OECs, probably via sperm surface modification, but does not promote increased sperm survival.

Stage migration caused by D2 dissection with para-aortic lymphadenectomy for gastric cancer from the results of a prospective randomized controlled trial.

BACKGROUND: Extended lymphadenectomy (D2) provides accurate nodal staging of gastric cancer. The aim of this study was to clarify the degree of stage migration seen with D2 combined with para-aortic lymph node dissection for gastric cancer invading the subserosa, the serosa and adjacent structures (T2ss-4) in patients considered not to have distant metastases (M0). METHODS: Between July 1995 and April 2001, 523 patients were recruited and randomized in a prospective phase III trial comparing D2 with D2 and para-aortic nodal dissection for T2ss-4 gastric cancer without macroscopic para-aortic nodal metastases. Stage migration was evaluated by Japanese Gastric Cancer Association staging in 260 patients who underwent D2 with para-aortic dissection by analysing pathological information from the dissected lymph nodes. RESULTS: Node (N)-stage migration was observed in 1 per cent (1 of 82) of patients with N1 disease, 20 per cent (12 of 59) with N2, 43 per cent (10 of 23) with N3 and 8.8 per cent (23 of 260) of all patients. Final stage migration occurred in 9 per cent (5 of 58) of patients with stage IIIa, 19 per cent (8 of 42) with stage IIIb, 56 per cent (9 of 16) with stage IVa and 8.5 per cent (22 of 260) of all patients. Metastasis to N4 nodes was found in 4 per cent (four of 95) of tumours invading the subserosa and 17.4 per cent (19 of 109) of tumours penetrating the serosa. The overall incidence of N4 involvement was 8.8 per cent (23 of 260). CONCLUSION: Extended para-aortic lymphadenectomy for gastric cancer provides accurate nodal staging and results in stage migration, which may improve stage-specific survival regardless of overall survival benefit.

Evaluation of sentinel node identification with isosulfan blue in gastric cancer.

AIMS: The aim of this study was to clarify whether the metastasis of gastric cancer can be detected by identifying the sentinel lymph nodes (SNs) using only lymphatic dye. METHOD: The study was based on 101 patients clinically diagnosed with T1 and T2 gastric cancer. Isosulfan blue was intraoperatively injected within the submucosal layer around the lesion through an endoscope and blue stained nodes (BNs) were identified as SNs and harvested. Standard radical gastrectomy with D2 lymphadenectomy was performed on all patients and SNs and other nodes were evaluated. RESULTS: Out of 101 patients, 21 had lymph-node metastases. The accuracy of SN identification was 97.0% (98/101) and the metastasis detection rate was 85.7% (18/21). With improvement of the manoeuvre in the latter 84 cases, the detection rate was elevated up to 100.0% (18/18), as was the accuracy (84/84). CONCLUSION: The sentinel concept using lymphatic dye is applicable to gastric cancer, but the identification of SNs with lymphatic dye requires some practice. Furthermore, the issue of intraoperative metastasis detection remains to be resolved.

Effect of betaxolol hydrochloride on heart rate variability indices during exercise stress testing in patients with hypertension.

Betaxolol hydrochloride is a beta1-selective antagonist that produces vasodilation in patients with hypertension and ischemic heart disease. The goal of the present study was to characterize the effect of betaxolol on heart rate variability indices (HRV), a well-established prognostic marker. Symptom limited-treadmill exercise testing was performed in 17 hypertensive patients (60.9 +/- 14.8 years-old) before and immediately a 3 weeks course of betaxolol hydrochloride (5 mg daily). Frequency domain HRV (high frequency spectra, HF; 0.15-0.40 Hz: low frequency spectra, LF; 0.04-0.15 Hz) was measured during exercise treadmill testing using MemCalc software. Betaxolol hydrochloride significantly decreased the maximal systolic blood pressure and heart rate (184 +/- 29 vs. 156 +/- 26 mmHg, P < 0.01; 132 +/- 21 vs. 113 +/- 15 bpm, P < 0.01) and significantly increased HF and LF during exercise treadmill testing (HF, 32 +/- 36 vs. 56 +/- 55 men/Hz, P < 0.01; LF, 64 +/- 58 vs. 95 +/- 86 men/Hz, P < 0.01). Thus, treatment with betaxolol hydrochloride resulted in a decrease in blood pressure during exercise treadmill testing and in an increase in HRV. This suggests that this agent could have beneficial effects on long-term prognosis in patients with hypertension.

Risk factors for myocardial injury during off-pump coronary artery bypass grafting.

BACKGROUND: Although off-pump coronary artery bypass grafting (CABG) is now used worldwide for coronary revascularization, the pre- and intraoperative risk factors for myocardial injury associated with the surgical procedure remain to be elucidated. We performed a multivariate analysis to investigate factors that contribute to myocardial injury during off-pump CABG. METHODS: The study population consisted of 22 patients who underwent off-pump CABG without apparent intraoperative complications. Blood samples were obtained before surgery and at 3 and 12 hours after the last anastomosis and serum Troponin T (cTnT) levels were measured to assess myocardial injury. Patient characteristics and factors related to preoperative cardiac function and the intraoperative process were analyzed to determine their correlation with serum cTnT levels, and the Spearman's correlation coefficient (r(s)) was computed. RESULTS: Neither age, preoperative cardiac function, time required for anastomosis, the number of grafts, nor the total amount of bleeding were associated with serum cTnT levels. Serum cTnT at 3 and 12 hours after completed anastomosis correlated with the product of mean systolic blood pressure and mean heart rate (double product) during anastomosis. The r(s) values at 3 and 12 hours were 0.62 (P = .002) and 0.58 (P = .004), respectively. With respect to the serum cTnT level at 12 hours, creatinine clearance (Ccr) had a slight effect on the serum cTnT values. CONCLUSIONS: High blood pressure and an increased heart rate during anastomosis are unfavorable factors for off-pump CABG. However, strict control of the blood pressure and heart rate makes it possible to subject even patients at high-risk to off-pump CABG from the viewpoints of myocardial injury.

Identification of risk factors for the development of complications following extended and superextended lymphadenectomies for gastric cancer.

BACKGROUND: Extended lymphadenectomy for gastric carcinoma has been associated with high mortality and morbidity rates in several multicentre randomized trials. METHODS: Using data from 523 patients registered for a prospective randomized trial comparing extended (D2) and superextended (D3) lymphadenectomies, risk factors for overall complications and major surgical complications (anastomotic leakage, intra-abdominal abscess and pancreatic fistula) were identified by multivariate logistic regression analysis. RESULTS: Mortality and morbidity rates were 0.8 per cent (four of 523) and 24.5 per cent (128 of 523) respectively. Pancreatectomy (relative risk 5.62 (95 per cent confidence interval (c.i.) 1.94 to 16.27)) and prolonged operating time (relative risk 2.65 (95 per cent confidence interval 1.34 to 5.23)) were the most important risk factors for overall complications. A body mass index of 25 kg/m2 or above, pancreatectomy and age greater than 65 years were significant predictors of major surgical complications. CONCLUSION: Pancreatectomy should be reserved for patients with stage T4 disease. Age and obesity should be considered when planning surgery.

A new method to detect systemic inflammatory response syndrome by continuous monitoring system: an experimental study in rats.

A continuous monitoring system was designed for detection of systemic inflammatory response syndrome (SIRS) using spectrum analyser and local temperature mapping system with deep body thermometer. This method demonstrated significant increases of heart and respiratory rates and deep body temperature from normal levels within 120 minutes after lipopolysaccharide administration in rats. Our monitoring system appears promising for clinical detection of SIRS in the early stages to prevent multiple organ failure.

A phase I study of S-1 combined with weekly cisplatin for metastatic gastric cancer in an outpatient setting.

A dose-escalation study was conducted for patients with metastatic gastric cancer to determine the recommended dose of weekly intravenous (i.v.) cisplatin combined with a fixed dose of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1, on an outpatient basis. Secondary endpoints were to define the toxicity profile and to determine tumour responses. S-1 was fixed at a dose of 70 mg/m(2)/day and was administered for 2 weeks followed by a 1-week rest. Three dose levels of cisplatin (10, 15 and 20 mg/m(2)) were studied. Cisplatin was infused over 30 min on days 1 and 8. 20 patients were enrolled. No dose-limiting toxicities (DLTs) were recorded during the administration of cisplatin up to 20 mg/m(2), except for grade 3 diarrhoea and stomatitis in one patient at dose level 3. No grade 4 adverse events occurred. However, grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were seen in 7 of 13 patients at dose level 3 within the first two treatment cycles. This was determined to be the maximum acceptable level that would not negate the advantages observed with use of an oral drug such as S-1. An objective tumour response was seen at all dose levels, and the overall response rate in the 18 patients evaluated was 61%. A higher response rate of 78% was observed in 9 patients who had received no prior chemotherapy. Oral S-1 with weekly cisplatin is a feasible and promising combination regimen that is appropriate for an outpatient setting. A randomised phase II study comparing this combination with S-1 alone in chemo-nai;ve patients is warranted.

Flow-mediated dilation in brachial artery in the second half of pregnancy and prediction of pre-eclampsia.

Endothelial injury and increased vascular reactivity are involved in the pathogenesis of pre-eclampsia (pregnancy-induced hypertension). To investigate whether flow-mediated dilation (endothelium-dependent dilation) and the reactive hyperemic response can predict pre-eclampsia, we prospectively measured flow-mediated dilation and the Doppler flow velocity pattern (V, cm/s) in the brachial artery using high-resolution ultrasound in 43 pregnant women (32+/-5 years old) in the second half of their pregnancy, and compared the findings with traditional risk factors. Regarding the Doppler flow velocity pattern, the pulsatility index (PI)=(systolic V-diastolic V)/mean V and resistance index (RI)=(systolic V-diastolic V)/systolic V were calculated. For the flow-mediated dilation, the per cent diameter changes were determined based on those from baseline to hyperemic conditions. Nine women suffered from pre-eclampsia and 34 women remained normotensive. Only flow-mediated dilation was found to be significantly lower in the subsequently developed pre-eclampsia patients (1.6+/-1.0% in subsequently developed pre-eclampsia patients vs 11.0+/-4.5% in normotensive patients, P<0.05). Neither the other traditional factors nor the Doppler flow velocity pattern were significantly different between the subsequently developed pre-eclampsia and normotensive patients. If a normal cutoff value of 3.0% obtained from age-matched 14 nonpregnant women (32+/-7 years old) in our laboratory was used, the positive predictive value of flow-mediated dilation (<3.0%) for subsequent pre-eclampsia is 90% and the negative predictive value is 100%. In conclusion, flow-mediated dilation in brachial artery can be a simple and noninvasive modality to predict pre-eclampsia.

The non-contact monitoring of heart and respiratory rates using laser irradiation: an experimental simultaneous monitoring with and without clothes during biochemical hazards.

The purpose of this study is to develop a non-contact method to evaluate the heart and respiratory rates simultaneously using a single optical sensor which can be used without the removal of clothes before a decontamination procedure in biochemical hazards. We measured the heart and respiratory rates with and without clothes to assess the vital sign monitoring before decontamination. In order to monitor the heart and respiratory rates of rabbits simultaneously, the respiratory and cardiac peaks were separated using fast Fourier transform from a 5 mW helium-neon laser (wavelength 632.8 nm) reflected off the chest walls of rabbits. A cloth (50 mm x 50 mm, 2 mm thick) was placed on the chest of the rabbits to simulate the vital sign monitoring with clothes. The heart rate measured using this method agreed with the rate derived from an electrocardiogram (r = 0.82, p<0.05). The respiratory rate correlated with the manually measured respirator rate (r = 0.93, p<0.05). This method appears promising as a non-contact method for monitoring the heart and respiratory rates of patients under biochemically hazardous conditions.