A case of metastatic liver tumor from gastric carcinoma curatively undergoing left hemihepatectomy and caudate lobectomy with ivc reconstruction

A 72-year-old male underwent distal gastrectomy with D2 dissection for type 2 advanced gastric carcinoma. Nine months after the surgery, CT scan revealed a solitary liver metastatic legion with IVC invasion. We selected a surgical intervention because of allegic reaction of S-1 and rapid progression of tumor. Left hemihepatectomy and caudate lobectomy with IVC reconstruction was performed. IVC was resected partially and repaired with polytetrafluoroethylene (PTFE) patch graft. The postoperative course was uneventful. The patient was discharged on the 11th postoperative day. He is alive without a recurrence 9 months after surgery and is undergoing weekly paclitaxel. Although the indication of extended hepatectomy is controversial, aggressive surgery with chemotherapy would contribute to improve a prognosis of the patients with metastatic liver tumor from gastric carcinoma.     

Reduced serum vascular endothelial growth factor receptor-2 (sVEGFR-2) and sVEGFR-1 levels in gastric cancer patients

The relationship between gastric cancer and serum vascular endothelial growth factor receptor-1 (sVEGFR-1) and sVEGFR-2, which are soluble form receptor proteins of vascular endothelial growth factor (VEGF), has not been extensively studied. VEGF, sVEGFR-1 and sVEGFR-2 were measured in the sera obtained before surgical operation from 164 gastric cancer patients and from 164 healthy controls matched for age and gender. Compared with controls, the cases showed elevated VEGF (P < 0.01) and reduced sVEGFR-1 (P = 0.07) and sVEGFR-2 (P = 0.02). The difference in VEGF levels was small among men and when the outcome was early cancer. The difference in sVEGFR-1 levels was significant or borderline significant only in men and when the outcome was diffuse type cancer. The difference in sVEGFR-2 levels was significant only in men and when the outcome was advanced or diffuse type cancer. The sensitivities and specificities of VEGF, sVEGFR-1 and sVEGFR-2 were all approximately 60%. For diffuse type cancer, sVEGFR-2 showed a sensitivity of 62.4% and a specificity of 63.4%, which was similar to serum pepsinogen. In conclusion, elevated VEGF and reduced sVEGFR-1 and sVEGFR-2 in serum are characteristic of gastric cancer patients, and the value of serum sVEGFR-2 in the diagnosis of diffuse type gastric cancer should be further evaluated.     

A 4-week versus a 3-week schedule of gemcitabine monotherapy for advanced pancreatic cancer: a randomized phase II study to evaluate toxicity and dose intensity

Background

This randomized phase II study compared the efficacy and toxicity between 4-week and 3-week schedules of gemcitabine monotherapy in advanced pancreatic cancer.

Methods

Patients with advanced pancreatic cancer were randomly assigned to either a 4-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 3 consecutive weeks every 4?weeks) or a 3-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 2 consecutive weeks every 3?weeks). The primary endpoint was the compliance rate during the first 8?weeks between the two groups.

Results

A total of 90 patients were enrolled. The compliance rate during the first 8?weeks was the same (53.3%). For the 4- and 3-week schedules, the tumor response rates were 14.2 and 17.1% (p?=?0.92), median progression free survival was 112 and 114?days (p?=?0.82), and median overall survival was 206 and 250?days (p?=?0.84), respectively. Grade 3?? neutropenia was the major adverse event in both schedules: 37.7 and 35.5% (p?=?0.82). In contrast, thrombocytopenia (platelet count <70000/mm3) was significantly higher for the 4-week schedule: 26.6 and 4.4% (p?=?0.008). The mean received dose intensity was equal: 588 and 550?mg/m2/week (p?=?0.14).

Conclusions

The 3-week schedule of gemcitabine did not improve the compliance rate during 8?weeks compared with the 4-week schedule, but it attained a comparable efficacy with lower toxicity. Further investigation will be needed to introduce it into daily practice. Clinical trial registration number: UMIN ID 974.     

The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity

Adrenomedullin (AM) is a peptide involved both in the pathogenesis of cardiovascular diseases and in circulatory homeostasis. The high-affinity AM receptor is composed of receptor activity-modifying protein 2 or 3 (RAMP2 or -3) and the GPCR calcitonin receptor-like receptor. Testing our hypothesis that RAMP2 is a key determinant of the effects of AM on the vasculature, we generated and analyzed mice lacking RAMP2. Similar to AM-/- embryos, RAMP2-/- embryos died in utero at midgestation due to vascular fragility that led to severe edema and hemorrhage. Vascular ECs in RAMP2-/- embryos were severely deformed and detached from the basement membrane. In addition, the abnormally thin arterial walls of these mice had a severe disruption of their typically multilayer structure. Expression of tight junction, adherence junction, and basement membrane molecules by ECs was diminished in RAMP2-/- embryos, leading to paracellular leakage and likely contributing to the severe edema observed. In adult RAMP2+/- mice, reduced RAMP2 expression led to vascular hyperpermeability and impaired neovascularization. Conversely, ECs overexpressing RAMP2 had enhanced capillary formation, firmer tight junctions, and reduced vascular permeability. Our findings in human cells and in mice demonstrate that RAMP2 is a key determinant of the effects of AM on the vasculature and is essential for angiogenesis and vascular integrity.     

Depressed serum selenoprotein P: possible new predicator of increased risk for cerebrovascular events

Selenium protection against cellular damage by oxygen radicals is accomplished through selenoproteins. Thus, selenium protection during the development of stroke, an oxidative stress–related disease, may not be appropriately reflected in the total serum selenium concentration. Therefore, we hypothesized that serum selenoproteins should also be measured to understand the relationship between selenium status and oxidative stress. To establish whether stroke is associated with changes in serum selenoprotein levels, a population-based, nested case-control study was performed. The subjects were recruited from 1632 residents older than 40 years who had completed health examinations in 1992. Blood samples collected from 30 controls and 30 initial stroke victims between 1992 and 1994 were analyzed for total serum selenium and selenium-containing protein distribution. Selenium-containing proteins were separated using 2 high-performance liquid chromatography columns in tandem and detected by inductively coupled plasma–mass spectrometry. The mean serum selenium concentration was lower in the patients who had a stroke than in the controls (105.2 vs 116.5 μg/L). Selenium contents in glutathione peroxidase and albumin did not show any significant difference; however, selenoprotein P was significantly lower in the stroke cases than in the controls (54.5 vs 63.0 μg/L, P = .006). Results from multivariate logistic regression analysis showed that reduced serum level of selenoprotein P was associated with a higher risk of stroke (odds ratio = 0.28; 95% confidence interval, 0.10-0.85).     

Baroreceptors mask sympathetic responses to high intraocular pressure in dogs

These experiments were designed to investigate whether increasing intraocular pressure (IOP) in anesthetized dogs produces differential control of sympathetic nerve activities to various organs (heart, kidney, liver, and spleen) and if these sympathetic responses are modified by baroreceptors. We performed simultaneous multi-recordings of cardiac, renal, hepatic and splenic sympathetic nerve activities (CNA, RNA, HNA and SpNA, respectively) during 2 min of increasing IOP to a mean pressure of 30 mmHg. After increasing IOP in dogs with the intact baroreceptors, all of measured nerve activities did not change significantly throughout the experiment. In dogs with denervation of baroreceptors (cervical vagotomy with denervation of the carotid sinus and aortic nerves), only RNA and CNA showed significant increases in response to the increased IOP. However, time course changes in HNA and SpNA did not show any significant differences as compared with the baseline or that of the control group. These results indicate that systemic sympathetic nerve responses to increasing IOP are masked by systemic baroreceptors. As animals were denervated of their systemic baroreceptors, the unidirectional sympathoexcitatory responses to increased IOP were observed on CNA and RNA, but not on HNA and SpNA. These sympathetic outflow, when systemic baroreceptors are impaired as observed in old age, may play an important role in management of glaucoma attack with the use of adrenolytic drugs.     

Adult wilms tumor in the renal pelvis: case report with review of the literature

An 84-year-old man was referred to our hospital with gross hematuria. Abdominal computed tomography demonstrated a well-circumscribed enhanced mass in the right pelviureteral junction. Retroperitoneoscopic nephroureterectomy was performed because of a clinical diagnosis of renal pelvic carcinoma. Pathologic examination led to a final diagnosis of an adult Wilms tumor arising from the renal pelvis. This is the first report of a Wilms tumor in the renal pelvis of an adult patient.     

Development of watertight and bioabsorbable synthetic dural substitutes

Abstract:  We have developed novel watertight and bioabsorbable synthetic dural substitutes. The substitutes were designed such that they had a three-layered structure, and each layer comprised a bioabsorbable copolymer prepared from l -lactide, glycolide, and ε-caprolactone. Various copolymers were synthesized, and appropriate compositions were selected for preparing the substitutes based on the results of leakage tests. Experimental substitutes that prevented the leakage of saline through the suture lines between the substitutes and dura mater were prepared. An in vitro study was performed in which the substitutes were sutured to porcine dura mater, and the amount of saline leakage was measured. It was demonstrated that leakage through the suture line could be completely suppressed by using the substitutes we developed along with favorable suturing techniques.