Aberrant Gene Methylation in the Lymph Nodes Provides a Possible Marker for Diagnosing Micrometastasis in Gastric Cancer

Background  

This study was designed to determine whether gene methylation is a novel diagnostic marker for micrometastasis to the lymph nodes (LNs) in gastric cancer.     

Idiopathic Granulomatous Appendicitis Treated Surgically with Long-Term Follow-Up: Report of a Case

Isolated granulomatous inflammation of the appendix is extremely rare, and its etiology is still unknown. Thus, differentiating between idiopathic granulomatous appendicitis and isolated appendiceal Crohn's disease is difficult. We report a case of idiopathic granulomatous appendicitis with long-term follow-up after surgery. A 26-year-old woman was referred to our hospital for investigation of persistent right lower abdominal pain. Abdominal computed tomography showed a mass, suggesting an inflammatory tumor around the appendix; thus, we suspected subacute appendicitis and performed laparoscopically assisted ileocecal resection. Histological examination of the resected specimen revealed several noncaseous epithelioid granulomas in the wall of the appendix, but no foreign bodies, obstructing lesions, or parasites. Stains for acid-fast bacillus and fungi, and serology for yersinia were all negative. The patient has been followed up for 9 years and remains asymptomatic. This clinical course suggests that her isolated granulomatous appendicitis was idiopathic granulomatous appendicitis unrelated to Crohn's disease.     

Multiple Inflammatory Pseudotumor of the Liver,Mimicking Cholangiocarcinoma with Tumor Embolus in the Hepatic Vein: Report of a Case

A 68-year-old Japanese woman complaining of general fatigue and intermittent high fever was admitted to our hospital. Abdominal ultrasonography showed two tumors in the lateral segment of the liver, with soft tissue in the left hepatic vein that was considered to be a tumor embolus. A diagnosis of cholangiocarcinoma was made based on various radiological and laboratory examinations and therefore a surgical resection was performed. Microscopically, the tumor consisted of inflammatory cells, which had aggressively invaded the hepatic vein and Arantius' duct. The pathological diagnosis was inflammatory pseudotumor (IPT) that had invaded the hepatic vein. Although many cases of hepatic IPT have been previously reported, cases of hepatic IPT massively invading the hepatic vein are very rare as far as we could determine, based on a literature search. We herein report this case and discuss the diagnosis and treatment regarding hepatic IPT with massive venous invasion.     

Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model

Bone repair involves a complex set of regulated signaling pathways that control the formation of new bone matrix and the resorption of damaged bone matrix at the fracture site. It has been reported that the optimal time point for single-dose zoledronic acid (ZA) administration systemically increased the strength of bone morphogenetic protein (BMP)-7-mediated callus. However, its repair mechanism during bone fracture healing remains unknown. We aimed to investigate the synergic effect of recombinant human (rh) BMP-2 and ZA in a rat femoral fracture model. Fifty-eight rats were divided into 4 groups. Group I (n = 14) animals were implanted with a carrier alone. Group II (n = 15) animals were implanted with a carrier containing 1-μg rhBMP-2. Group III (n = 14) animals were implanted with a carrier and a subcutaneous systemic ZA injection 2 weeks after surgery. Group IV (n = 15) animals were implanted with a carrier containing 1-μg rhBMP-2 and ZA subcutaneous injection 2 weeks after surgery. The rats were euthanized after 6 weeks and their fractured femurs were explanted and assessed by manual palpation, radiographs, and high-resolution micro-computerized tomography (micro-CT) and were subjected to biomechanical and histological analysis. The fusion rates in Group IV (93.3%) were considerably higher than those in Groups I (28.6%), II (53.3%), and III (57.1%). Additionally, the radiographic scores of Group IV were higher than those in Groups I, II, and III. In micro-CT analysis, the tissue volume (TV) of the callus was higher in Group IV than in Groups I and II (p < 0.05). New bone volume (BV) and trabecular spacing (Tb.Sp) also showed essentially the same trend as that of TV. The ratio of BV to TV (BV/TV), the trabecular number (Tb.N), and the trabecular thickness (Tb.Th) was higher in Groups III and IV than in Groups I and II (p < 0.05). In biomechanical analysis, the ultimate loads at failure and stiffness in Groups III and IV were on average higher than those in Groups I and II (p < 0.05), while the energy absorption of Group IV was higher than those of Groups I and II (p < 0.05). The synergic effect of rhBMP-2 and ZA given systemically as a single dose at the optimal time was efficacious for fracture repair and significantly enhanced bone fusion. Our results suggest that this combination facilitates bone healing and has potential clinical application.     

Recombinant sendai virus-mediated gene transfer to adipose tissue-derived stem cells (ASCs)

Adipose tissue-derived stem cells (ASCs) are expected to have clinical applications as well as other stem cells, because ASCs can be obtained safely from adult donors and used in autologous therapies without concern about rejection and the need for immunosuppression. However, the use of gene transfer with Sendai virus (SeV) vectors, which can efficiently introduce foreign genes without toxicity into several cells, with ASCs has not yet been investigated. This study documents on the use of SeV vectors for gene transfer to ASCs. The dose-dependent GFP expression of ASCs transfected with SeV vectors after 48 h of culture at 37 degrees C was first evaluated. Next, the cellular toxicity of ASCs transfected with SeV vectors was verified. In addition, SeV vectors were compared with adenovirus (AdV) vectors. Finally, the time-dependent GFP expression of ASCs transfected with SeV vectors was evaluated. The results showed that transfection of ASCs with SeV vectors results in more efficient expression of transgene (GFP expression) in the ASCs than with AdV vectors after 48 h of culture at 37 degrees C. Moreover, while the transfection of ASCs with AdV vectors at high MOIs was cytotoxic (a lot of transfected cells died) that of ASCs with SeV vectors at high MOIs was not necessarily cytotoxic. In addition, the preservation of multilineage ASCs transfected with SeV was observed. In conclusion, this is the first report describing the successful use of SeV-mediated gene transfer in ASCs, and the results indicate that SeV may thus provide advantages with respect to safety issues in gene therapy.     

Three cases of acute pulmonary thromboembolism diagnosed by transesophageal echocardiography

We report 3 cases of acute pulmonary thromboembolism (PTE) diagnosed by transesophageal echocardiography (TEE). In all these cases, cardiovascular state of the patient was unstable and therefore computerized tomography and catheterization of the pulmonary artery for diagnosis of PTE could not be performed. TEE was useful for diagnosis of acute PTE. All three patients passed away eventually and we had a difficult experience for treatment of acute PTE. We should take various measures against deep vein thrombosis for prevention of acute PTE.     

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected.     

Renal cell carcinoma with unusual metastasis to the gallbladder

Gallbladder involvement in patients with renal cell carcinoma (RCC) is extremely rare. We present a report of a 61-year-old man with a synchronous RCC metastasis to the gallbladder presenting as an intraluminal polypoid mass simulating primary gallbladder carcinoma. Enhanced abdominal computed tomography demonstrated a well-enhanced polypoid lesion in the gallbladder. Intraoperative rapid pathological examination of the gallbladder tumor showed clear cell-type cancerous cells. Microscopically, tumor cells of both the resected kidney and gallbladder had round uniform nuclei, clear cytoplasm, and well-defined cytoplasmic borders, forming alveolar patterns. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA), which is usually positive in primary clear cell carcinoma of the gallbladder. Therefore, the final diagnosis was RCC with a synchronous gallbladder metastasis.     

Intracisternal infusion of magnesium sulfate solution improved reduced cerebral blood flow induced by experimental subarachnoid hemorrhage in the rat

Magnesium has neuroprotective and antivasospastic properties in the presence of subarachnoid hemorrhage (SAH). The present study investigated the effect of intracisternal administration of magnesium on cerebral vasospasm in the experimental SAH rat model. The rat double-SAH model (0.2 mL autologous blood injected twice into the cisterna magna) was used. Normal saline (SAH group, N = 8) or 10 mmol/L magnesium sulfate in normal saline (SAH + MG group, N = 8) was infused into the cisterna magna at 1.5 μL/min for 30 min on day 5. Control rats without SAH also received intracisternal infusion of normal saline (control group, N = 6). Local cerebral blood flow (CBF) at 24 locations and the weighted average were quantitatively measured by the autoradiographic technique using [¹⁴C]iodoantipyrine during infusion. The weighted average CBF was significantly reduced (P < 0.01, Student’s t-test) in the SAH group (0.78 ± 0.16 mL g⁻¹ min⁻¹) compared to the control group (1.0 ± 0.15 mL g⁻¹ min⁻¹) and was significantly improved (P < 0.01, Student’s t-test) in the SAH + MG group (0.98 ± 0.18 mL g⁻¹ min⁻¹). Local CBF was significantly reduced (P < 0.05, unpaired t test) in 16 locations in the SAH group and significantly improved (P < 0.05, unpaired t test) in 12 locations in the SAH + MG group. Intracisternal infusion of magnesium sulfate significantly improved reduced CBF induced by experimental SAH in the rat.     

Computer-assisted neurosurgical navigational system for transsphenoidal surgery--technical note.

Transsphenoidal surgery carries the risk of carotid artery injury even for very experienced neurosurgeons. The computer-assisted neurosurgical (CANS) navigational system was used to obtain more precise guidance, based on the axial and coronal images during the transsphenoidal approach for nine pituitary adenomas. The CANS navigator consists of a three-dimensional digitizer, a computer, and a graphic unit, which utilizes electromagnetic coupling technology to detect the spatial position of a suction tube attached to a magnetic sensor. Preoperatively, the magnetic resonance images are transferred and stored in the computer and the tip of the suction tube is shown on a real-time basis superimposed on the preoperative images. The CANS navigation system correctly displayed the surgical orientation and provided localization in all nine patients. No intraoperative complications were associated with the use of this system. However, outflow of cerebrospinal fluid during tumor removal may affect the accuracy, so the position of the probe when the tumor is removed must be accurately determined. The CANS navigator enables precise localization of the suction tube during the transsphenoidal approach and allows safer and less-invasive surgery.