Generation and Characterization of Intense Ultralow-Emittance Electron Beams for Compact X-Ray Free-Electron Lasers.

The transverse emittance of the electron beam is a fundamental parameter in linac-based x-ray free-electron lasers (FELs). We present results of emittance measurements carried out at SwissFEL, a compact x-ray FEL facility at the Paul Scherrer Institute in Switzerland, including a description of the novel high-resolution measurement techniques and the optimization procedure. We obtained slice emittance values at the undulator entrance down to 200 nm for an electron beam with a charge of 200 pC and an rms duration of 30-40 fs. Furthermore, we achieved slice emittances as low as 100 nm for 10 pC beams with few fs duration. These values set new standards for electron linear accelerators. The quality, verification, and control of our electron beams allowed us to generate high-power FEL radiation for a wavelength as short as 0.1 nm using an electron beam with an energy of only 6 GeV. The emittance values demonstrated at SwissFEL would allow producing hard x-ray FEL pulses with even lower-energy beams, thus paving the way for even more compact and cost-effective FEL facilities.

Enhanced anti-tumour effect of cisplatin with low-voltage electrochemotherapy in hamster oral fibrosarcoma.

The aim of this study was to determine the effects of low-voltage electrochemotherapy with intraperitoneal cisplatin on hamster oral fibrosarcoma. Oral fibrosarcoma was transplanted submucosally into the cheek pouch mucosa of 100 hamsters. After transplantation, the hamsters were randomly divided into four equal groups. These groups received no treatment (D-E-); 2 mg/kg body weight cisplatin treatment without electroporation (D+E-); electroporation without cisplatin treatment (D-E+); or 2 mg/kg body weight cisplatin treatment followed by electroporation (D+E+). Electrical pulse treatment together with cisplatin injection markedly reduced the size of the tumour, whereas cisplatin injection or electrical pulse treatment alone did not. These results clearly indicate that the anti-tumour effect of cisplatin on hamster oral fibrosarcoma was considerably potentiated or enhanced by the administration of local electrical pulses at low voltages.

Expression of a CD44 variant and VEGF-C and the implications for lymphatic metastasis and long-term prognosis of human breast cancer.

The aim of the present study was to determine whether expression of the CD44 variant v7-v8 (CD44v7-v8) or vascular endothelial growth factor-C (VEGF-C) is associated with long-term prognosis in breast cancer patients. A 10-year follow-up of 91 patients with primary breast cancer who were previously assessed for CD44 expression was undertaken. Immunohistochemical evaluation of VEGF-C expression was performed in 87 of these patients and their long-term prognosis was assessed. The disease-free and overall survival rates were significantly poorer for the CD44v7-v8-positive patients than for the patients negative for this marker. VEGF-C expression was detected in 38 out of the 87 patients (43.7%) with primary human breast cancer. There were no significant differences in tumor size, histological type, axillary lymph node status, presence of lymphatic or venous invasion, or presence of estrogen receptors and progesterone receptors between the VEGF-C-positive and -negative patients. There were also no significant differences in the disease-free or overall survival rates in these patient groups. In conclusion after the 10-year follow-up, expression of CD44v7-v8 was associated with poor prognosis for breast cancer patients. However, there was no association between VEGF-C expression and the clinicopathological factors or prognosis of breast cancer patients.

Does eradication of Helicobacter pylori reduce the risk of carcinogenesis in the residual stomach after gastrectomy for early gastric cancer? Comparison of mucosal lesions in the residual stomach before and after Helicobacter pylori eradication.

BACKGROUND AND AIMS: After partial gastrectomy, the mucosa of the residual stomach usually undergoes severe changes, and these lesions are known to be pre-cancerous. Recently, Helicobacter pylori has been highlighted as an agent that induces such mucosal alterations. In the present study, we evaluated whether eradication of H. pylori reduced the risk of carcinogenesis. PATIENTS AND METHODS: The subjects were 12 patients who underwent distal gastrectomy with Billroth I anastomosis for early gastric cancer and were positive for H. pylori. We performed endoscopy and biopsy both before and after H. pylori eradication therapy to assess changes in the gastric mucosa. RESULTS: After eradication therapy, no mucosal edema or erythema was detected. On histological examination, mononuclear cell infiltration had decreased and there was complete absence of neutrophil infiltration. The Ki-67 labeling index and the tissue IL-8 level had also decreased significantly, compared with before eradication. CONCLUSION: Before H. pylori eradication, the mucosa of the residual stomach may be at high risk of carcinogenesis due to induction of mucosal damage and active gastritis by H. pylori. Such changes were almost completely normalized by eradication therapy, so the eradication of H. pylori may reduce the risk of H. pylori-associated carcinogenesis in patients who have undergone gastrectomy for early gastric cancer.

Novel nitric oxide donor (FK409) ameliorates liver damage during extended liver resection with warm ischemia in dogs.

BACKGROUND: Nitric oxide attenuates ischemia-reperfusion injury by maintaining organ circulation through its actions as a vasoregulator, an inhibitor of platelet aggregation, and an attenuator of leukocyte adhesion. Otherwise, the harmful effects of enhanced nitric oxide production induced by inducible nitric oxide synthase mediate ischemia-reperfusion injury. FK409 has been characterized as a spontaneous nitric oxide donor. The aim of this study was to evaluate the effects of FK409 on extended liver resection with ischemia using a canine model. STUDY DESIGN: Adult mongrel dogs were subjected to 60 minutes of warm ischemia by partial inflow occlusion. After reperfusion the nonischemic lobes were resected and the remnant liver function was evaluated. The dogs were divided into two groups: the control group (n = 7) and the FK409 group (n = 6), which was given FK409 through the portal vein. RESULTS: The hepatic tissue blood flow, serum liver enzymes levels, and serum endothelin-1 level after reperfusion were significantly better in the FK409 group than in the control group. Electron microscopy demonstrated that endothelial cells and Ito cells were well-preserved in the FK409 group. The 3-day survival rate was statistically better in the FK409 group (67%) than in the control group (14%). CONCLUSIONS: FK409 appears to have protective effects during extended liver resection with ischemia.

A spontaneous nitric oxide donor ameliorates small bowel ischemia-reperfusion injury in dogs.

Nitric oxide (NO) appears to play an important role in tissue injury during reperfusion. FK409 is the first spontaneous NO donor that increases plasma guanosine 3',5'-cyclic monophosphate. We investigated the effects of the NO donor FK409 (FK) on ischemia-reperfusion injury in a canine warm ischemia model. Fourteen adult mongrel dogs were divided into two groups: the control group and the FK group, which received FK. The superior mesenteric artery and vein were both clamped for 2 h and then reperfused for 12 h. Arterial and intramucosal pH were well maintained in the FK group in comparison with the control group. Histologically, ischemia-reperfusion injury was significantly more severe in the control group than in the FK group. The serum NO levels were significantly higher in the FK group than in the control group during FK administration. FK409 has protective effects on ischemia-reperfusion injury of the small intestine due to NO release.

Study on endoscopic esophageal mucosal resection with ligating device. I--Clinical study.

BACKGROUND/AIMS: EEMRL (endoscopic esophageal mucosal resection with a ligating device) has become increasingly popular. In this article, we review 13 clinical cases of EEMRL. METHODOLOGY: Since 1993, we have performed EEMRL to treat 15 lesions in 13 patients. Twelve squamous cell carcinomas (mucosal cancer in 10 and submucosal cancer in 2) were included among the 15 lesions. RESULTS: EEMRL failed to achieve complete resection of the 2 submucosal lesions (3.0 and 2.8 cm in maximum diameter). However, esophageal lesions could be removed successfully when 2.5 cm or less in maximum diameter. The procedure was not associated with any complication. CONCLUSIONS: Our clinical study showed that this technique may be indicated for esophageal cancer with a maximum diameter < or = 2.5 cm and confined to the mucosa. EEMRL is a technically easy and minimally invasive therapy which could be useful for the treatment of early esophageal cancer.

Study on endoscopic esophageal mucosal resection with ligating device. II--Experimental study.

BACKGROUND/AIMS: This study reports on animal experiments regarding the safety of endoscopic esophageal mucosal resection with a ligating device (EEMRL), as well as the amount of mucosa which can be removed by this technique, the depth of resection and the feasibility of piecemeal resection. METHODOLOGY: Three experiments were performed in six mongrel dogs under general anesthesia. RESULTS: When EEMRL was done without submucosal injection of saline, resection reached the muscular layer and caused esophageal perforation. The average dimensions of the mucosal pieces resected using 8-, 10-, and 12-mm devices was 13 x 10 mm, 18 x 15 mm, and 22 x 18 mm, respectively. Resection reached the mid-plane of the submucosa and the depth was almost uniform. After piecemeal resection, there was no macroscopically visible mucosa at the resection site and each mucosal piece was resected along the mid-plane of the submucosa. CONCLUSIONS: The experimental study indicated that submucosal injection of saline is essential to prevent esophageal perforation. It also showed that EEMRL allows resection up to the mid-plane of the submucosa, that the 12-mm device allows en bloc resection of lesions < or = 15 mm in diameter and that EEMRL is suitable for piecemeal resection.

Hypoglycemia associated with the production of insulin-like growth factor II in adrenocortical carcinoma.

A 78-year-old woman was hospitalized for congestive heart failure and repeated hypoglycemic attacks. The laboratory data showed a serum insulin level within the normal range and an increased level of serum insulin-like growth factor (IGF) II. Abdominal ultrasonogram and computed tomography scan revealed a huge mass lying above the left kidney. She was diagnosed as having an adrenocortical carcinoma. After the removal of the tumor, the plasma glucose level and the serum level of IGF-II were normalized. The tumor cells stained positively for IGF-II immunohistochemically. These findings suggested that the hypoglycemia was due to IGF-II produced by the adrenocortical carcinoma.

The effect of a selective cyclooxygenase-2 inhibitor in extended liver resection with ischemia in dogs.

BACKGROUND: Pringle's procedure is commonly used during liver surgery, and it sometimes causes liver failure. Metabolites of arachidonic acid, which are converted by cyclooxygenase (Cox), are involved in ischemia-reperfusion injury. This study evaluated the effects of FK 3311, which selectively inhibits Cox-2, on ischemia-reperfusion injury during liver resection in dogs. MATERIALS AND METHODS: The animals were divided into four groups and subjected to 60 min of warm ischemia by partial inflow occlusion. The FK-treated groups (FK0.2: 0.2 mg/kg, FK1: 1 mg/kg, FK3: 3mg/kg) received FK3311, and the control group received vehicle. Following reperfusion, the nonischemic lobes were resected and remnant liver function was evaluated. RESULTS: Tissue blood flow and serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase were significantly better in the FK1 and FK3 groups, especially FK1, than in the control group. Thromboxane B(2) was significantly lower in the FK1 and FK3 groups than in the control group. The level of 6-keto-prostaglandin F(1alpha) was significantly lower in the FK3 group and relatively unchanged in the FK1 group. Histological damage was milder in the FK1 group. There were significantly fewer polymorphonuclear neutrophils in the FK1 group than in the control group. CONCLUSIONS: FK3311 ameliorates the ischemia-reperfusion injury caused by Pringle's procedure during extensive liver resection. This agent may be clinically useful in extended liver surgery involving vascular isolation.

Changing predictors of postoperative mortality in acute type A aortic dissection. Is only coronary artery compromise significant?

OBJECTIVES: Rapid emergency transport and early diagnosis and surgical treatment for acute type A aortic dissection have improved postoperative survival, which has, however, plateaued at about 80%. End-organ malperfusion is regarded as a strong predictor of postoperative mortality, replacing factors such as cardiac tamponade complications, aortic rupture, and left ventricular dysfunction due to aortic insufficiency. It is thus important to reevaluate risk factors for surgical death to assess current therapeutic strategies. METHODS: We statistically analyzed potential risk factors for perioperative death in 88 patients undergoing surgical repair for type A aortic dissection between January 1990 and December 1999. RESULTS: Univariate analysis showed that cardiopulmonary arrest (adjusted odds ratio: 13.78; p < 0.01) and malperfusion of more than 1 vital organ (adjusted odds ratio 4.97, p < 0.01), especially myocardial ischemia due to coronary artery dissection (adjusted odds ratio 3.21, p < 0.05), significantly increased the likelihood of operative death. Multivariate logistic regression analysis showed only cardiopulmonary arrest (p < 0.01) and concomitant coronary artery bypass grafting necessitated in cases complicated by evolving myocardial infarction (p < 0.05) to be independent predictors of postoperative mortality. CONCLUSION: Preoperative complication from coronary dissection was the most important predictor of early postoperative mortality in this series. In such cases, rapid surgical intervention before myocardial infarction develops is vital to saving lives.

Lifting of lesions during endoscopic mucosal resection (EMR) of early colorectal cancer: implications for the assessment of resectability.

BACKGROUND AND STUDY AIMS: This study assessed the indications for and limitations of endoscopic mucosal resection (EMR) for early colorectal cancer, focusing on the way in which the lesion lifts after submucosal injection. PATIENTS AND METHODS: The study included 94 patients with early colorectal cancer who received EMR treatment. The lifting of the lesion after submucosal injection was analyzed (classified as completely lifted/soft; completely lifted/hard; incompletely lifted; and non-lifted) along with the endoscopic findings, pathological findings, and clinical course. RESULTS: Almost all completely lifted/soft lesions were mucosal cancers. Some of the completely lifted/hard lesions were staged as sm2. The incompletely lifted lesions included stages sm1 to sm3. Non-lifting lesions were almost always deeper than sm3. The lifting condition was significantly associated with the depth of invasion, and the lesion type was related to the extent of lifting but not to tumor size or recurrent disease. Recurrent disease was noted in three patients who underwent piecemeal EMR. CONCLUSIONS: The indication for EMR is easily assessed on the basis of the lifting characteristics of the tumor after submucosal injection, which was found to be significantly related to the depth of invasion. The factor limiting the indication for EMR is not the size of a tumor, but its lifting condition.

Effect of intratumoral OK-432 administration of thymidine phosphorylase expression in human gastric carcinoma.

It is known that thymidine phosphorylase (dThdPase) is increased in various types of malignant tumors and is induced by cytokines. In this study, we have investigated the effects of OK-432, which induces multiple cytokines, on dTHdPase expression and angiogenesis in human gastric carcinomas. We examined 25 patients who underwent gastrectomy for gastric carcinoma. OK-432 was directly injected in tumors in 16 (OK group) of 25 patients via endoscopy before operation and the other 9 patients were not treated (control group). The dThdPase activity in carcinoma tissues of the OK group was significantly higher than that of the control group (P < 0.05). The amounts of IL-1 alpha, IFN-alpha, and IFN-gamma in carcinomas in the OK group were significantly higher than in the controls (P < 0.05), and these were significantly correlated with the dThdPase activity. Intratumoral OK-432 administration enhances the expression of dThdPase in gastric carcinoma cells by inducing various cytokines.

Extended surgery with en bloc resection of the right common iliac vessels for lymph node metastasis of mucinous colon carcinoma: report of a case.

We report herein the case of a 63-year-old woman who underwent surgery for recurrent mucinous carcinoma of the cecum. Recurrent metastatic lymph nodes had invaded the right common iliac vessels and right ureter, but she had no distant metastases and no peritoneal dissemination. Extended surgery with en bloc resection of the right iliac vessels and right ureter, and femorofemoral bypass were performed. Postoperatively, several complications developed which were successfully treated by further operations. By 1 year after surgery, she had no recurrent tumors on radiological examination, suggesting that our aggressive surgery with resection of the invaded regional vessels had effectively removed the recurrent tumors. This procedure may therefore significantly prolong the survival time and improve the quality of life of such patients.

The effect of Celsior solution on 12-hour cardiac preservation in comparison with University of Wisconsin solution.

BACKGROUND: Celsior is a new extracellular-type preservation solution which has been developed to act not only as a storage medium but also as a perfusion fluid during initial donor heart arrest, poststorage graft reimplantation and early reperfusion. We designed this experimental study to evaluate the effect of the Celsior solution in comparison with the University of Wisconsin solution from the viewpoint of energy depletion. METHODS: Adult mongrel dogs weighing 9 to 13 kg were divided into two groups. In the UW group (n=7), a 4 degrees C University of Wisconsin solution was used for coronary vascular washout and storage following cardiac arrest using a glucose-insulin-potassium solution. In the Celsior group (n=7), the Celsior solution was used to obtain cardiac arrest, coronary vascular washout and storage. High energy phosphate levels and myocardial pH were measured using (31)P-nuclear magnetic resonance spectroscopy immediately after preservation and at 3, 6 and 12 hours after preservation. After 12-hour cold storage, left ventricular free wall tissues were harvested for histological examination. RESULTS: High energy phosphate levels and myocardial pH were significantly better preserved in the Celsior group than in the UW group. In the histological findings, glycogen granules were preserved well in the Celsior group. CONCLUSIONS: We conclude from our study that the Celsior solution is comparable to the University of Wisconsin solution for use in 12-hour heart preservation in canine models.