Precise immunological evaluation rationalizes the design of a self-adjuvanting vaccine composed of glycan antigen,TLR1/2 ligand,and T-helper cell epitope

Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam₃CSK₄), and T-helper (Th) cell epitope, and found that this three-component self-adjuvanting vaccine effectively resulted in the production of anti-triSTn IgG antibodies. We herein analyzed immune responses induced by this self-adjuvanting vaccine in detail. We newly synthesized two-component vaccines, i.e., Pam₃CSK₄- or Th epitope-conjugated triSTn, as references to evaluate the immune-stimulating functions of Pam₃CSK₄ and Th epitope. Immunological evaluation of the synthesized vaccine candidates revealed that Pam₃CSK₄ was essential for antibody production, indicating that the uptake of triSTn antigen by antigen-presenting cells (APCs) was promoted by the recognition of Pam₃CSK₄ by TLR1/2. The function of the Th epitope was also confirmed. Th cell activation was important for boosting antibody production and IgG subclass switching. Furthermore, flow cytometric analyses of immune cells, including T cells, B cells, dendritic cells, and other monocytes, were first employed in the evaluation of self-adjuvanting vaccines and revealed that the three-component vaccine was able to induce antigen-specific immune responses for efficient antibody production without excessive inflammatory responses. Importantly, the co-administration of Freund''s adjuvants was suggested to cause excessive myeloid cell accumulation and decreased plasma cell differentiation. These results demonstrate that vaccines can be designed to achieve the desired immune responses via the bottom-up construction of each immune element.

Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responses via bottom-up construction of the necessary immune elements.     

Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines

Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient's general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient's general medical condition.     

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.     

Clinical outcomes and adverse events following transforaminal interbody fusion for lumbar degenerative spondylolisthesis in elderly patients

Transforaminal lumbar interbody fusion (TLIF) procedure is widely used, but the surgical indications for TLIF in elderly patients remain controversial because of potential risks such as inferior bone quality and higher rate of postoperative complications. Clinical efficacy and operative risk of TLIF in elderly patients are unclear. This study investigated the clinical effect and safety of TLIF for lumbar degenerative spondylolisthesis with radiculopathy or neurogenic claudication in patients aged 70 years or older. The clinical records were retrospectively reviewed of 35 consecutive patients aged 70-86 years (mean 74.8 years) who underwent one or two-level TLIF. The preoperative diagnosis included degenerative spondylolisthesis with segmental instability. Clinical outcomes were assessed by the Japanese Orthopaedic Association score, visual analogue scale, Oswestry Disability Index. Radiological fusion rate was also investigated. Clinical and radiological results were compared with those of 43 younger patients. Clinical outcome measures were significantly improved after operation in the elderly patients, but improvement rates were significantly lower than those of younger patients. Fusion rate was similar in both groups. Overall postoperative complications were increased in aged patients, although the prevalence of complications directly related to surgical technique was not significantly increased. Postoperative complications not related to the surgical procedure were factors affecting poor results. TLIF is acceptable for achieving clinical recovery and lumbar fusion with high radiographic fusion success even in elderly patients, although clinical benefits were limited compared with those of younger patients. Postoperative morbidity was mainly related to general or non-operative site complications.     

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.     

Radiographic characteristics of fibrous dysplasia of the clivus: a case report and review of the literature

Whereas fibrous dysplasia is a well-known, developmental skeletal disorder with a benign clinical course, fibrous dysplasia of the clivus is extremely rare and has seldom been reported. Differentiating this benign entity from more aggressive diseases involving the clivus is important for the proper management of lesions in this area. We here report a case of fibrous dysplasia of the clivus and discuss its radiographic features. The patient was 55-year-old male who had suffered from headache for months. Physical and neurological examinations found no abnormalities. The computed tomographic (CT) scan and magnetic resonance imaging (MRI) showed an abnormal mass lesion in the lower of the third clivus. On CT scan, the mass lesion exhibited a ground-glass appearance. The lesion was detected as hypointense and a mixture of hyperintense and isointense areas on T1-weighted and T2-weighted MRI, respectively. Heterogenous enhancement was noted after infusion of GD-DTPA. The patient underwent a transsphenoidal resection of the mass and the histopathologic diagnosis was fibrous dysplasia.     

Renal adenoma treated with partial nephrectomy: a case report

We report a case of renal adenoma which was diagnosed as renal cell carcinoma preoperatively. A 78-year-old man, who had been under observation for bladder cancer for 4 years, was incidentally found to have a small right renal tumor at follow-up computed tomography (CT). Enhanced CT demonstrated a tumor which was hypervascular, 10 x 10 mm size, at the lower pole of the right kidney. There was no evidence of distant metastasis. The preoperative diagnosis was renal cell carcinoma, cT1aN0M0, and we performed right partial nephrectomy. The histopathorogical finding was renal adenoma. Renal adenomas are benign tumors and not uncommon in autopsy cases. However, when they are detected clinically, it is difficult to distinguish them from renal cell carcinoma preoperatively.     

Treatment of spontaneous intracranial hypotension secondary to C-2 meningeal cyst by surgical packing--case report

A 41-year-old man presented with progressive worsening of postural headache. Computed tomography (CT) showed bilateral subdural hematomas without prior history of trauma. The diagnosis was spontaneous intracranial hypotension (SIH). Conservative treatment with oral steroids failed to prevent gradual deterioration of the patient's consciousness. CT myelography revealed massive cerebrospinal fluid (CSF) leakage between the C-1 and C-2 levels. The leak was repaired surgically via a laminectomy. A cyst, thought to be a meningeal cyst, was discovered adjacent to the right C-2 nerve root, and CSF was seen seeping out from around the cyst after a Valsalva maneuver. The presumed dural defect of the cyst was sealed by packing with muscle fragments and fibrin glue. The symptoms disappeared soon after surgery. He was discharged 1 month after surgery without deficits. Most SIH cases are benign and can be managed conservatively, or by the epidural blood patch method. Surgery is more invasive than the epidural blood patch method, but should be performed in patients with a high cervical lesion and massive CSF leakage.