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.     

Three-dimensional assessment of urinary stone on non-contrast helical computed tomography as the predictor of stonestreet formation after extracorporeal shock wave lithotripsy for stones smaller than 20 mm

The incidence of stonestreet formation after extracorporeal shock wave lithotripsy (ESWL) rises with increasing stone burden. However, stonestreet after ESWL is often experienced even in stones smaller than 20 mm. To examine whether the non-contrast helical computed tomography (CT) data could predict stonestreet formation in these stones, 53 radiopaque stones of 5-20 mm treated with ESWL were evaluated. Maximal dimension was measured on plain radiograph. From an attenuation value histogram graphed from the CT data, total stone volume and mean attenuation value were calculated. Seven stonestreets longer than 25 mm developed. There was no significant difference in maximal dimension and total stone volume between stones that did and stones that did not develop stonestreet. Mean attenuation value was the sole significant predictive factor. Application of mean attenuation value with cut-off level of 650 HU would anticipate stonestreet formation with a sensitivity of 85.7% and a specificity of 71.7%. The estimated risk of stonestreet formation is high in the treatment of stones with higher mean attenuation value.     

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.     

Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.

Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. Introduction: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa.     

Kimura's disease associated with minimal change nephrotic syndrome: A case report

Kimura's disease is a rare disorder that involves regional lymph nodes and the major salivary glands, which become infiltrated by eosinophils and lymphocytes. Renal lesions associated with Kimura's disease are rare. We describe the case of a 60-year-old Japanese woman who first noted a nodular mass in a salivary gland. As the nodule grew, nephrotic syndrome and heart failure developed. A biopsy of the nodule revealed Kimura's disease, and surgical excision was performed. After the operation, the heart failure and nephrotic syndrome, which were diagnosed as minimal change disease on renal biopsy, improved rapidly without steroid therapy. Four months later, the nephrotic syndrome recurred without recurrence of Kimura's disease. The patient showed marked improvement during prednisolone therapy (40 mg/d) and was in complete remission 4 weeks after the initiation of steroid therapy. This case shows that surgical excision and prednisolone therapy are useful for nephrotic syndrome associated with Kimura's disease.     

Intrapulmonary Schwannoma

A 58-year-old woman was admitted due to an abnormal shadow on chest X-ray, without any symptoms. Chest computed tomography showed a round mass in the anterior segment of the right upper lobe. Segmentectomy was performed and histopathological examination revealed a primary neurogenic tumor of Schwann cell origin. Immunohistochemical staining demonstrated the presence of S-100 protein in the tumor cells. We present a case of intrapulmonary schwannoma and review 62 cases of primary schwannoma of the lung.     

The structure of the avian fast skeletal muscle troponin T gene: seven novel tandem-arranged exons in the exon x region

To elucidate the mechanism that produces enormous molecular diversity in troponin T (TnT) of fast skeletal muscle, we determined the 5-half genomic sequence of the chicken fast muscle TnT gene. The sequence of ca. 16 kb included seven exons (exons 1, 2, 3, 4, w, 5, and 6), which have been reported previously and presumed by sequencing TnT cDNAs. Additionally we found six 15 nt and one 18 nt sequences in the region between exons 5 and 6 (i.e. the exon x region). They were encompassed by consensus splice donor and acceptor sites and preceded by putative branch sites, and designated herein as exons xa to xg. Our result shows that the sequence derived from exons x1, x2, and x3, the exons presumed previously by cDNA sequencing, is actually encoded by the seven exons xa to xg, establishing the precise gene structure in the exon x region. Based on our data, together with that on the 3-half genomic sequence of the quail fast muscle TnT gene, we conclude that the avian fast skeletal muscle TnT gene includes 27 exons, 16 of which are alternatively spliced.