SALVAGE THERAPY IN PATIENTS WITH UNRESECTABLE HILAR CHOLANGIOCARCINOMA

We describe our methods and outcomes of multidisciplinary treatments in patients with unresectable hilar cholangiocarcinoma. Fifty‐seven patients with a known outcome were enrolled. Thirty‐four of 57 patients were treated and evaluated by salvage therapy. For salvage therapy, we used internal and external radiotherapy, photodynamic therapy, YAG laser therapy and microwave coagulation therapy. The median survival time was 548 days for the group receiving salvage therapy and 198 days for the group not receiving this treatment. In conclusion, although no randomization of the patients was performed in this retrospective study, our present data provide convincing evidence that salvage therapy is a useful therapeutic approach for unresectable hilar cholangiocarcinomas.     

Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis

The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis.     

The effect of autogenous costochondral grafts on temporomandibular joint fibrous and bony ankylosis: A preliminary experimental study.

PURPOSE: The purpose of this study was to test the functional and histologic fate of costochondral grafts (CG) in temporomandibular joint (TMJ) reconstruction for unilateral ankylosis in the sheep. MATERIALS AND METHODS: Five pure-bred adult Merino sheep were used. Ankylosis was induced by articular damage, disc removal, and placement of a bone graft. At 3 months, a gap arthroplasty was performed with a CG from the thirteenth rib. The sheep were sacrificed 3 months after CG reconstruction. The range of jaw movements were recorded at first operation, at lysis of ankylosis, and at sacrifice. The joints were examined radiologically, macroscopically, and histologically. RESULTS: All sheep showed a decrease in masticatory function, as shown by weight loss and decreased jaw opening, during the ankylosis period. On release, they regained weight and increased the range of jaw movement. Histologically, the joint space was filled with fibrous tissue. However, the partial spaces around the CG head were covered by fibrous tissue and/or fibrous cartilage. CONCLUSIONS: This study shows that, when CGs are used with a gap arthroplasty in a fibrous and bony ankylosed TMJ, masticatory function is restored.     

The evaluation of cystoscopy in the screening of asymptomatic microhematuria

As a prospective study on asymptomatic microhematuria, complete urological examinations including cystoscopy, IVP, ultrasound and urinary cytology were performed on 422 patients over 40 years old between January 1987 and December 1988 (group A). The results of group A was compared with that of retrospective study on 266 patients, who had incomplete urological examination between January 1984 and December 1985 (group B). Cystoscopy was performed on 321 patients (87.2%) in group A and on 108 patients (40.6%) in group B. Bladder tumor was found in 10 cases (2.4%) in group A, including 7 cases of male patients (5.7%), but in only 1 case (0.4%) in group B. Since the negative rate of abnormal urinary cytology was 50% and that of abnormal IVP was 90% in 10 cases of bladder tumor in group A, cystoscopy was considered to be an essential examination for the screening of patients with asymptomatic microhematuria over 40 years old patients.     

Newer antiepileptic drugs]

Ten newer antiepileptic drugs have been developed since 1990s. These drugs have wider therapeutic spectra, fewer side-effects, and lesser drug-to-drug interactions compared with the older typical antiepileptic drugs. Among them, zonisamide was developed in Japan and has been used from 1989. Gabapentin was at length approved in 2006. The other newer antiepileptic drugs are not approved yet in Japan. Felbamate can not be used in Europe because it may induce lethal hepatic toxicity and aplastic anemia. Vigabatrin is not approved in USA because it may induce permanent visual field deficit. The USA guideline for epilepsy treatment recommends that patients with newly diagnosed epilepsy can be treated with gabapentin, lamotrigine, topiramate, and oxcarbazepine. In contrast, based on epilepsy treatment guideline in England, newer antiepileptic drugs are considered only when patients with newly diagnosed epilepsy are unable to use the older antiepileptic drugs for some reasons. All newer antiepileptic drugs are used for intractable partial epilepsies, and lamotrigine and topiramate can also be used for idiopathic generalized epilepsies. The response rate (seizure reduction rate with 50% or more) and drop-out rate are overlapping among all newer antiepileptic drugs. Gabapentin, levetiracetam, and pregabalin are eliminated from kidney, and they had no drug-to-drug interactions and can be titrated rapidly. The serum concentration of lamotrigine is decreased with co-administration of hepatic enzyme inducing drugs and is increased with co-administration of valproic acid. Hypersensitivity reactions are rare with gavapentin, levetiracetam, topiramate, and tiagabin. Psychoses are reported to be induced with zonisamide, however, they can be induced with the other newer drugs (topiramate, levetiracetam, etc.). Drug-induced psychiatric symptoms, especially depression, may be often underdiagnosed. Many of these newer drugs (gabapentine, lamotrigine, levetiracetam, oxycarbazepine, etc.) have effects on chronic neuropathic pain. Some newer drugs show mood stabilizing effects (lamotrigine, oxycarbazepine, etc.), or antianxiety effect (gabapentin, topiramate, levetiracetam, pregavalin, etc.). Wide range of action to central nervous system of these newer antiepileptic drugs may serve not only for clinical seizure suppression, but also for neuroprotection.     

Groove pancreatitis associated with true pancreatic cyst

We report a case of groove pancreatitis (GP) associated with a true pancreatic cyst. An 81-year-old man who had suffered epigastric pain for 4 months was referred to Saisekai Kure Hospital. Computed tomography and endoscopic retrograde pancreatography showed a cystic lesion in the groove area of the pancreas. Serum amylase elevation and imaging findings suggested GP due to the cyst. Six weeks of medical treatment did not improve the clinical symptoms. Therefore, pancreatoduodenectomy was performed. Histologic examination revealed a true cyst with intraluminal necrosis, which produced a protein plug that obstructed the Santorini duct. The parenchyma surrounding the groove area showed marked fibrosis and inflammatory cell infiltration. GP due to true pancreatic cyst was diagnosed. Although GP is usually caused by overconsumption of alcohol, which leads to changes in the pancreatic juice and the ultimate blockage of pancreatic outflow, the histologic features in our patient suggest that true pancreatic cyst stands as a secondary cause of GP.     

Arterial versus total blood volume changes during neural activity-induced cerebral blood flow change: implication for BOLD fMRI.

Quantifying both arterial cerebral blood volume (CBV(a)) changes and total cerebral blood volume (CBV(t)) changes during neural activation can provide critical information about vascular control mechanisms, and help to identify the origins of neurovascular responses in conventional blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). Cerebral blood flow (CBF), CBV(a), and CBV(t) were quantified by MRI at 9.4 T in isoflurane-anesthetized rats during 15-s duration forepaw stimulation. Cerebral blood flow and CBV(a) were simultaneously determined by modulation of tissue and vessel signals using arterial spin labeling, while CBV(t) was measured with a susceptibility-based contrast agent. Baseline versus stimulation values in a region centered over the somatosensory cortex were: CBF=150+/-18 versus 182+/-20 mL/100 g/min, CBV(a)=0.83+/-0.21 versus 1.17+/-0.30 mL/100 g, CBV(t)=3.10+/-0.55 versus 3.41+/-0.61 mL/100 g, and CBV(a)/CBV(t)=0.27+/-0.05 versus 0.34+/-0.06 (n=7, mean+/-s.d.). Neural activity-induced absolute changes in CBV(a) and CBV(t) are statistically equivalent and independent of the spatial extent of regional analysis. Under our conditions, increased CBV(t) during neural activation originates mainly from arterial rather than venous blood volume changes, and therefore a critical implication is that venous blood volume changes may be negligible in BOLD fMRI.