Sphincter of Oddi Motor Activity in Patients with Anomalous Pancreaticobiliary Junction

Sphincter of Oddi motor activity was investigated in seven patients with an anomalous pancreaticobiliary junction and in six controls by endoscopic manometry under fluoroscopy. Characteristic phasic wave activity was observed in the sphincter segment in both groups. Amplitude of the phasic contractions was significantly higher in the disease group than in controls (100.8 +/- 14.1 mm Hg vs. 55.2 +/- 4.3 mm Hg, p less than 0.02). Although those with the anomalous pancreaticobiliary junction had a longer common channel (15-30 mm), the length of the sphincter segment with the phasic wave activity was not different. The phasic activity was not seen at the junction of the pancreatic and bile ducts in disease groups. Bile obtained from within the bile duct showed a very high concentration of amylase. Morphine given to cause spasm of the sphincter increased basal pressure and frequency of the phasic waves in all controls. The response to morphine was similar in two patients in whom the anomalous junction was studied, but the procedure was complicated by acute pancreatitis in one of them. These findings suggest that contractions of the sphincter of Oddi in patients with the anomalous junction may contribute to reflux between the pancreatic and bile ducts, leading to various pathologic conditions associated with this anomaly.     

Anomalous Junction of Pancreaticobiliary Duct without Congenital Choledochal Cyst: A Possible Risk Factor for Gallbladder Cancer

Among 1586 patients subjected to endoscopic retrograde cholangiopancreatography, an anomalous junction of the pancreaticobiliary duct (AJPB) was found in 24 patients (1.5%). Eighteen of the 24 had an associated congenital choledochal cyst, and six did not. Four of these six patients (66.7%) had gallbladder cancer. A clinicopathological study was performed on these four and 43 such cases reported in the literature. The diagnosis of AJPB was made by direct cholangiography. Median age of these 47 (53.5 yr) was younger than those without AJPB. The length of the common channel ranged from 15 to 53 mm. The pancreatic-biliary type junction was present in 36 of 39 cases (92.3%). Gallstones were present in 7 of 40 (17.5%). Levels of amylase in bile were high in 10 of 11. Presence of AJPB without congenital choledochal cyst may be a high risk factor in gallbladder cancer; hence prophylactic cholecystectomy should be considered for patients with AJPB, without congenital choledochal cyst.     

Can negative cardiac effect of proton pump inhibitor and high-dose H2-blocker have clinical influence on patients with stable angina?

BACKGROUND: Aspirin and anti-platelet drugs are used commonly for patients with coronary heart disease. Proton pump inhibitor (PPI) and high-dose H2-blocker were recommended for preventing NSAIDs-related ulcer. Previously H2-blocker reported to have some negative cardiovascular effects. Additionally, a recent in vitro study showed that PPI reduced cardiac contractility. In this study, we evaluated whether chronic administration of PPI and high-dose H2-blocker affects left ventricular function. METHOD: Fifty-two stable angina patients were enrolled and classified into PPI group ([P]; lansoprazole: 15mg/day, n=28), H2-blocker group ([H]; famotidine: 40mg/day, n=8), and control ([C]; none or mucosal-defense drug, n=16). Eligible patients showed normal cardiac function in initial catheterization without administrated PPI or H2-blocker. They received percutaneous coronary intervention and follow-up catheterization. We compared changes in ejection fraction (EF: %), end diastolic/systolic volume index (EDVI/ESVI: ml/m(2)), and peak positive/negative dp/dt (+/-dp/dt: mmHg/s) in left ventricular angiography series. RESULT: There were no significant differences among three groups regarding patient characteristics, backgrounds of angiographic and intervention, except for fewer smokers in [C]. Other drugs such as beta- and Ca-blocker did not have effects on cardiac function except for aspirin during 255+/-115 days follow-up. Rate of EF changes significantly decreased in [P], and tended to decrease in [H] (C: 3.8+/-9.8%, H: -1.6+/-7.6%, P: -2.1+/-5.9%; p<0.05 for [C] vs. [P]). Those of ESVI changes were significantly greater in [P], and tended to be greater in [H] (C: -4.5+/-16.2%, H: 4.9+/-15.5%, P: 7.3+/-16.2%; p<0.05 for [C] vs. [P]), though, EDVI changes' were similar (C: 2.5+/-8.9%, H: 2.6+/-3.6%, P: 1.6+/-6.1%; p=ns). Rate of +/-dp/dt-changes tended to decrease in [H] (+dp/dt: C: 3.9+/-15.5%, H: -10.0+/-25.2%, P: 0.3+/-19.6%; p=ns, -dp/dt: C: -0.1+/-19.5%, H: -8.5+/-20.4%, P: 5.7+/-27.7%; p=ns). CONCLUSION: In this study, PPI and high-dose H2-blocker have EF-reducing tendency. However, these changes were small and these drugs seemed to exhibit little influence clinically.     

Papillary fibroelastoma in the left ventricular outflow tract

Summary We report a case of a papillary fibroelastoma originating from the left ventricular endocardium in the outflow tract which was discovered by echocardiography in an asymptomatic patient. Two echocardiographic features were observed: (1) the tumor surface was smooth, and characteristic papillary formation was not detected; and (2) the outline of the mass was clearly defined as a dense echo, with the central, radiolucent, portion surrounded by a highly refractive linear echo at the level of the maximum diameter of the mass. The excised tumor was covered with a gelatinous substance that masked multiple papillae on the surface, but its echolucent center could not be explained by the pathology of the tumor which was solid centrally. Our case indicates that a papillary fibroelastoma may sometimes show echocardiographic findings similar to those of a myxoma, although other investigators have not noted the smooth surface and the echolucent center makes it indistinguishable from a myxoma. Thus, in some cases, it is difficult to distinguish papillary fibroelastoma from myxoma by echocardiography.     

Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone

Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy.     

Endobronchial lipoma: review of 64 cases reported in Japan

BACKGROUND: Several recent studies discuss bronchoscopic techniques for treating endobronchial lipoma, an extremely rare benign tumor. OBJECTIVES: To describe the epidemiology of endobronchial lipoma and to propose appropriate therapeutic policies for treating this tumor. METHODS: We reviewed 64 cases of endobronchial lipoma: 33 cases previously reported in 30 different articles, and 31 case reports presented at thoracic meetings in Japan. RESULTS: Of the 64 patients included in this study (50 male and 14 female; mean age, 60 years), 40 patients had endobronchial lipoma in the right lung and 23 patients had it in the left lung. The overwhelming majority of the tumors (n = 61) were found in the first three subdivisions of the tracheobronchial tree. Forty-eight patients (75%) were symptomatic, and their symptoms included cough, sputum, hemoptysis, elevated temperature, and dyspnea. Additionally, abnormal radiographic findings were reported for 51 patients (80%): 18 patients had atelectasis, 14 patients had infiltration or consolidation, 6 patients showed volume loss of the lung, and mass shadow was identified in 9 patients, and another abnormality including pleural effusion was found in 4 patients. Forty patients underwent surgical resection: 4 pneumonectomies, 24 lobectomies, 8 bilobectomies, and 4 resections by bronchotomy. Bronchoscopic resection was carried out in 17 cases: 7 cases by Nd-YAG laser, 5 cases by electrosurgical snaring forceps, and another 5 cases with a combined therapy using both procedures. CONCLUSIONS: Bronchoscopic resection should be considered as the first choice of treatment for endobronchial lipoma; however, surgical therapy is indicated for patients who show the possibility of a complicated malignant tumor, who have destructive peripheral lung disease, who have extrabronchial growth, or who may have technical difficulties during the bronchoscopic procedure.     

Decreased plasma adiponectin concentrations in women with low-grade C-reactive protein elevation

OBJECTIVE: Inflammation has been suggested as a risk factor for the development of atherosclerosis, while some components of metabolic syndrome X have been related to inflammatory markers. We hypothesized that adipocyte secreting protein, adiponectin and leptin, for which have been demonstrated an association with metabolic syndrome X and coronary artery disease, may be associated with inflammatory markers in nondiabetic humans. DESIGN AND METHODS: We measured high-sensitivity C-reactive protein (hs-CRP), as an inflammatory marker, and adiponectin and leptin concentrations in 384 nondiabetic Japanese women (mean+/-s.e.m. age 53.6+/-0.8 Years, body mass index (BMI) 23.0+/-0.2 kg/m(2)) undergoing measurement of markers of metabolic syndrome X. RESULTS: The women who had a low-grade hs-CRP elevation (>2.0 mg/l) were significantly older and had higher BMI, body fat mass (BFM), total cholesterol (TC), triglyceride (TG), atherogenic index (AI=(TC-HDLC)/HDLC), where HDLC is high-density lipoproten-cholesterol), fasting blood glucose and leptin concentrations before and after adjustment for BMI or BFM, while lower HDLC and adiponectin concentrations before and after adjustment compared with women with normal CRP levels (<0.5 mg/l). BMI, BFM, TG, AI and leptin before and after adjustment were found to be correlated with hs-CRP levels, while HDLC and adiponectin before and after adjustment were inversely correlated (all P<0.0001). hs-CRP was independently associated with white blood cell count, blood urea nitrogen and AI and inversely with adiponectin/BFM in the stepwise regression analysis model. CONCLUSIONS: These data demonstrate a significant decrease in plasma adiponectin in low-grade chronic inflammation, and suggest that there is an important linkage between inflammation/adipose tIssue/atherosclerosis.