Risk of cancer in patients with autoimmune pancreatitis.

OBJECTIVES: Although simultaneous occurrences of autoimmune pancreatitis (AIP) and cancer are occasionally observed, it remains largely unknown whether cancer and AIP occur independently or these disorders are interrelated. The aim of this study was to examine the relationship between AIP and cancer. METHODS: We conducted a multicenter, retrospective cohort study. One hundred and eight patients who met the Asian diagnostic criteria for AIP were included in the study. We calculated the proportion, standardized incidence ratio (SIR), relative risk, and time course of cancer development in patients with AIP. We also analyzed the clinicopathological characteristics of AIP patients with cancer in comparison with those without cancer. RESULTS: Of the 108 AIP patients, 18 cancers were found in 15 patients (13.9%) during the median follow-up period of 3.3 years. The SIR of cancer was 2.7 (95% confidence interval (CI) 1.4-3.9), which was stratified into the first year (6.1 (95% CI 2.3-9.9)) and subsequent years (1.5 (95% CI 0.3-2.8)) after AIP diagnosis. Relative risk of cancer among AIP patients at the time of AIP diagnosis was 4.9 (95% CI 1.7-14.9). In six of eight patients whose cancer lesions could be assessed before corticosteroid therapy for AIP, abundant IgG4-positive plasma cell infiltration was observed in the cancer stroma. These six patients experienced no AIP relapse after successful cancer treatment. CONCLUSIONS: Patients with AIP are at high risk of having various cancers. The highest risk for cancer in the first year after AIP diagnosis and absence of AIP relapse after successful treatment of the coexisting cancers suggest that AIP may develop as a paraneoplastic syndrome in some patients.

Intraductal papillary-mucinous neoplasm of the pancreas penetrating to the stomach and the common bile duct.

CONTEXT: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas occasionally penetrates to others organs. We present a case of IPMN penetrating to the stomach and the common bile duct. CASE REPORT: A 75-year-old man was admitted to the hospital because of epigastric pain. Computed tomography (CT) showed a papillary tumor protruding into the markedly dilated main pancreatic duct and splenic vein obstruction. The tumor was diagnosed as IPMN arising in the main duct, but he rejected surgery and he was followed without treatment. One year later, gastroduodenoscopy revealed gastropancreatic fistula and we were able to pass an endoscope through the fistula and directly examine the lumen of the main pancreatic duct and the papillary tumor adjacent to the fistula. Absence of malignant cells on histopathology suggested mechanical penetration rather than invasive penetration. CT showed splenic vein reperfusion due to decreased inner pressure of the main pancreatic duct. Two and a half years later, CT revealed biliopancreatic fistula formation. Endoscope biliary drainage was performed but failed. Despite jaundice, he is still ambulatory and seen in the clinic three years after the first admission. CONCLUSIONS: We have experienced a case of IPMN penetrating to the stomach and the common bile duct that has taken a slow course. It represents the importance of distinguishing mechanical penetration from invasive penetration as well as mechanical splenic vein obstruction from splenic vein invasion.

[A case report of primary small cell esophageal carcinoma responding successfully to radiochemotherapy].

Primary small cell esophageal carcinoma is a rare cancer with a poor prognosis, for which to date there is no recommended standard treatment. We present a 60-year-old male with this disease who was successfully managed by the combination of radiation and chemotherapy. The patient was referred to our hospital for liver dysfunction of unknown cause. On admission, he was diagnosed as having a primary small cell esophageal carcinoma and multifocal metastasis in the liver. He received cisplatin and 5-fluorouracil(CDDP 40mg/m2-days 1, 8, 5-FU 400 mg/m2-days 1-5, 8-12)and local radiation of 50 Gy for the esophagus, followed by 4 courses of chemotherapy the same as listed above. At the end of therapy, radiological findings showed that both primary and metastatic lesions completely disappeared. Unfortunately, he died of liver failure due to the recurrence of metastatic small cell carcinoma in the liver 13 months after the end of initial therapy. However, the primary cancer lesion had not recurred by that time. These findings suggest the beneficial effect of the combination of radiotherapy and chemotherapy for advanced-stage small cell esophageal carcinoma.

Resting muscle sympathetic nerve activity, cardiac metaiodobenzylguanidine uptake, and exercise tolerance in patients with left ventricular dysfunction.

BACKGROUND: Sympathetic nerve overactivity and reduced exercise tolerance are characteristic features of patients with heart failure. However, to what extent sympathetic nerve overactivity contributes to limiting exercise tolerance has not been clearly defined. METHODS: Myocardial iodine 123-metaiodobenzylguanidine (MIBG) scintigraphy, muscle sympathetic nerve activity (MSNA), and cardiopulmonary exercise testing were performed within 3 days in 30 patients with left ventricular dysfunction (LVD). Cardiac sympathetic nerve activity was estimated using H/M ratio and washout rate (WR) of 123I-MIBG imaging. MSNA was recorded by microneurography. RESULTS: The patients with peak VO(2) < 20 mL/minute/kg (group II, n = 15) had significantly higher MSNA and WR, and lower H/M ratio than those with peak VO(2) > or = 20 mL/minute/kg (group I, n = 15) (P < .05). Peak VO(2) had negative correlations with MSNA and WR (r = 0.58, 0.56), and positive correlations with early H/M ratio and delayed H/M ratio (r = 0.71, 0.75) in group II. Moreover, MSNA had negative correlations with early H/M ratio and delayed H/M ratio (r = 0.78, 0.66), and a positive correlation with WR (r = 0.79) in group II. However, similar relations were not found in group I. CONCLUSIONS: A link between cardiac and peripheral sympathetic nerve activities contributed to limiting exercise tolerance in patients with LVD patients and reduced exercise tolerance.

Listeria Monocytogenes Septicemia and Meningitis Caused by Listeria Enteritis Complicating Ulcerative Colitis.

An 80-year-old man, who had been diagnosed with ulcerative colitis, was admitted due to a fever and bloody diarrhea and was treated with a glucocorticoid and azathioprine. After 5 days, he developed an impaired consciousness, headache, and neck stiffness. A sample of the colonic mucosa, blood cultures, and cerebrospinal fluid revealed Listeria monocytogenes infection. Intravenous ampicillin improved the symptoms of fever, bloody diarrhea, and headache without any neurological sequelae. Physicians should consider that Listeria enteritis complicating ulcerative colitis can cause septicemia and meningitis in immunosuppressed patients. A patient's central nervous system can avoid the effects of Listeria meningitis by an early diagnosis and appropriate treatment.

The effect of residential exercise training on baroreflex control of heart rate and sympathetic nerve activity in patients with acute myocardial infarction.

STUDY OBJECTIVES: Exercise training has been shown to favorably affect the prognosis after acute myocardial infarction (AMI), but the mechanisms of such favorable effects remain speculative. The aim of this study was to determine whether exercise training improves baroreflex control of heart rate and muscle sympathetic nerve activity (MSNA) in patients with AMI. DESIGN: Prospective randomized clinical study. PARTICIPANTS: Thirty patients with an uncomplicated AMI were randomized into trained or untrained groups. Arterial BP, heart rate, and MSNA were measured at rest, and during baroreceptor stimulation (phenylephrine infusion) and baroreceptor deactivation (nitroprusside infusion). These measurements were performed at baseline and after 4 weeks of exercise training. MEASUREMENTS AND RESULTS: Peak oxygen uptake increased significantly (12.3 +/- 10.7% [mean +/- SD]) with exercise training. Resting MSNA reduced from 34 +/- 12 to 27 +/- 8 bursts/min in the trained group but not in the untrained group. Arterial baroreflex sensitivity (BRS) [from 8.9 +/- 3.0 to 10.3 +/- 3.0 ms/mm Hg, p < 0.05] and MSNA response to baroreceptor stimulation (change of integrated MSNA from - 47 +/- 23 to - 70 +/- 21%, p < 0.01) improved significantly in the trained group, but not in the untrained group. Despite baroreceptor deactivation improving MSNA response in both groups, there was no significant difference between the two groups. CONCLUSIONS: Exercise training increased arterial BRS and decreased sympathetic nerve traffic after AMI, which indicate that the sympathoinhibitory effect of exercise training may, at least in part, contribute to the beneficial effect of exercise training in patients with AMI.

Iodine 123-metaiodobenzylguanidine imaging reflect generalized sympathetic activation in patients with left ventricular dysfunction.

BACKGROUND: Iodine 123-metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. To determine the role of MIBG imaging as a measure of generalized sympathetic nerve activity, MIBG imaging was evaluated with muscle sympathetic nerve activity (MSNA) and plasma norepinephrine (noradrenaline) level in patients with old myocardial infarction. METHODS: Myocardial MIBG scintigraphy, MSNA and plasma norepinephrine measurement were performed within 3 days in 35 patients with old myocardial infarction. Patients were divided into three groups according to their ejection fraction (EF); preserved (EF > or = 50%, 12 patients), intermediate (35% < EF < 50%, 13 patients), or depressed (EF < or = 35%, 10 patients). The heart to mediastinum (H/M) ratio was obtained 4 h after tracer injection from the chest anterior view image. MIBG washout rate was calculated from the early and delayed images. MSNA was recorded by microneurography. RESULTS: Plasma norepinephrine level had weak negative correlations with early H/M ratio (r = 0.37, P<0.05) and delayed H/M ratio (r = 0.33, P<0.05), and a positive correlation with MIBG washout rate (r = 0.54, P<0.01). MSNA had weak negative correlations with early H/M ratio (r = 0.51, P<0.05) and delayed H/M ratio (r = 0.52, P<0.05). However, a strong correlation was found between MSNA and MIBG washout rate (r = 0.88, P<0.001). Despite no significant differences in plasma norepinephrine level and H/M ratio, patients with intermediate and depressed EF had higher MIBG washout rate and MSNA compared with those with preserved EF. CONCLUSIONS: Increased in cardiac sympathetic nerve activity was associated with augmented sympathetic outflow of the skeletal muscle and hence, MIBG washout rate allow the assessment of general sympathetic nerve activity.

Autoimmune pancreatitis complicated by gastric varices: a report of 3 cases.

We present three cases of autoimmune pancreatitis (AIP) complicated by gastric varices. Case 1: A 57-year-old man was diagnosed with AIP complicated by gastric varices and splenic vein obstruction. Splenomegaly was not detected at the time of the diagnosis. The AIP improved using steroid therapy, the splenic vein was reperfused, and the gastric varices disappeared; case 2: A 55-year-old man was diagnosed with AIP complicated by gastric varices, splenic vein obstruction, and splenomegaly. Although the AIP improved using steroid therapy, the gastric varices and splenic vein obstruction did not resolve; case 3: A 68-year-old man was diagnosed with AIP complicated by gastric varices, splenic vein obstruction, and splenomegaly. The gastric varices, splenic vein obstruction, and AIP did not improve using steroid therapy. These three cases suggest that gastric varices or splenic vein obstruction without splenomegaly may be an indication for steroid therapy in patients with AIP because the complications will likely become irreversible over time.

Different time course of changes in tricuspid regurgitant pressure gradient and pulmonary artery flow acceleration after pulmonary thromboendarterectomy: implications for discordant recovery of pulmonary artery pressure and compliance.

BACKGROUND: Pulmonary artery pressure (PAP) is reduced dramatically after pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, it is unclear whether pulmonary artery compliance increases in conjunction with the reduction in PAP. Pulmonary artery compliance may affect right ventricular afterload and prognosis. METHODS AND RESULTS: In 33 patients with CTEPH (9 men, 22-76 years), changes in the tricuspid regurgitation pressure gradient (TRPG) and the acceleration time (ACT) of pulmonary artery flow (a surrogate parameter of pulmonary artery compliance) were examined before and after pulmonary thromboendarterectomy using echocardiography to clarify factors affecting the changes. At 6 months, both TRPG and ACT normalized (or=100 ms, respectively) in 25 patients (group A) but not in 8 (group B). In group B, there were 5 with normal TRPG and shortened ACT at 6 months that normalized at 17+/-3 months. Group A patients showed shorter disease period and shorter period without anticoagulation than group B patients (p=0.04, 0.02 respectively). All patients in group A had the proximal type, and 2 patients of group B had the distal type (p=0.05). Clinical improvement was more remarkable in group A. CONCLUSIONS: The recovery of PAP and the ACT of pulmonary artery flow was not always concordant after pulmonary thromboendarterectomy, suggesting a presence of a time lag in the recovery between pressure and compliance in some patients. A long period of CTEPH, a long period without anticoagulation and the distal embolism type may be predictive factors of an unfavorable operative result with reduced pulmonary artery compliance, and hence poor recovery of clinical performance.

Correlation of heart rate turbulence with sympathovagal balance in patients with acute myocardial infarction.

To examine the relationship among heart rate turbulence parameters, arterial baroreflex sensitivity, and cardiac sympathetic nerve activity, 15 patients with acute myocardial infarction, presenting with sinus rhythm and > or = 3 ventricular premature beats/24 hr were studied at least 2 weeks after acute myocardial infarction. Turbulence onset (TO) and turbulence slope (TS) were averaged from 3 respective ventricular premature beats. Early heart-to-mediastinum ratio (H/M), delayed H/M, and washout rate were calculated from iodine-123-metaiodobenzylguanidine (123I MIBG) scintigraphy. Arterial baroreflex sensitivity was calculated by phenyrephrine method. Arterial baroreflex sensitivity correlated significantly with TO (r = - 0.75, p < .01) and TS (r = 0.53, p < .05). TO had no correlations with early H/M, delayed H/M, and washout rate. There were no significant correlations between TS and early H/M. However, TS had significant correlation with delayed H/M (r = 0.74, p < .01) and washout rate (r = -0.71, p < .01). Thus, heart rate turbulence of TO and TS parameters depend on sympathovagal balance.

Candesartan and arterial baroreflex sensitivity and sympathetic nerve activity in patients with mild heart failure.

The purpose of this study was to investigate the effects of candesartan on arterial baroreflex sensitivity (BRS) and sympathetic activity in patients with mild heart failure (HF). Arterial pressure, heart rate, plasma renin activity, plasma angiotensin II and noradrenaline, and muscle sympathetic nerve activity (MSNA) were measured before therapy and after 4 weeks in 20 patients with mild HF. Patients were assigned to a candesartan group (n = 10) or a placebo group (n = 10). Baroreflex sensitivity was assessed by using phenylephrine. Candesartan induced an increase in plasma renin activity and plasma angiotensin II associated with a reduction in arterial pressure without affecting heart rate. Although plasma noradrenaline was unchanged (320 +/- 322 pg/ml to 339 +/- 104 pg/ml), MSNA decreased significantly (52 +/- 11 bursts/min to 42 +/- 9 bursts/min; p < 0.01)) and BRS increased significantly (6.9 +/- 3.6 msec/mm Hg to 10.2 +/- 3.3 msec/mm Hg; p < 0.01) after candesartan. However, there were no significant changes in the measured variables in the placebo group. These data indicate that candesartan treatment enhanced BRS and reduced sympathetic activity in patients with mild HF. Thus, the inhibitory effect of candesartan on sympathetic activity may, at least in part, contribute to the beneficial effect of angiotensin II receptor blockade in patients with mild HF.

Influence of angiotensin II type 1-receptor antagonist CV11974 on infarct size and adjacent regional function after ischemia-reperfusion in dogs.

The presence of nonischemic regional dysfunction at the adjacent region of the ischemic myocardium was demonstrated in clinical studies. Recent studies demonstrated an angiotensin II type 1 (AT1)-receptor antagonist reduced myocardial ischemia-reperfusion injury. We investigated the role of the adjacent region after reperfusion by studying the effects of AT1-receptor antagonist on myocardial function and infarct size. We investigated 12 open-chest anesthetized dogs undergoing 90 min of left anterior descending coronary artery occlusion followed by 4 h of reperfusion. Six dogs injected with an AT1-receptor antagonist (CV11974) immediately after reperfusion were compared with 6 control dogs. Percent systolic shortening (%SS) was measured by two sets of the pair sonomicrometer crystals implanted to adjacent and remote nonischemic myocardium. After 4 h of reperfusion, infarct size was measured. There were no significant differences of the %SS at baseline between two regions. In both groups, %SS at adjacent region after reperfusion was significantly decreased as compared with remote region. There were no significant differences between the two groups. Infarct size, as a percentage of the area at risk, was smaller in the AT, group than in control group (25.49+/-7.53% vs 68.58+/-26.88% P<0.01). AT1-receptor antagonist reduces infarct size. This effect is not related to the change of regional myocardial function at adjacent region after reperfusion.

Early prediction of regional functional recovery in reperfused myocardium using single-injection resting quantitative electrocardiographic gated SPET.

By evaluating concordant or discordant perfusion and systolic wall thickening patterns, resting quantitative electrocardiographic (ECG) gated single-photon emission tomography (SPET) can identify various myocardial pathological conditions with different functional recovery after revascularisation therapy. However, no data are available on the ability of this methodology to predict regional functional recovery after primary percutaneous transluminal coronary angioplasty (PTCA). This study evaluated whether single-injection ECG gated SPET imaging performed at rest with 99mTc-tetrofosmin early after successful PTCA can predict recovery of regional wall motion. ECG gated SPET was performed 3 days and 3 weeks after successful PTCA in 26 patients. Regional functional parameters were automatically calculated with a 20-segment model on the day 3 image, and segments with perfusion/thickening mismatch were defined as showing preserved perfusion (>55% uptake on the end-diastolic image: mean-standard deviation of the normal value) without systolic wall thickening (mean-standard deviation of the normal value). On the third day, the regional wall motion score of 37 mismatched segments (3.8+/-2.1) was significantly lower than that of 41 matched normal segments (6.0+/-2.9), but was significantly higher than that of 108 matched abnormal segments (1.4+/-1.9, both P<0.01). At 3 weeks after acute MI, the regional wall motion score of mismatched segments (6.4+/-3.9) improved to the level of matched normal segments (7.1+/-3.0) and was significantly higher than that of matched abnormal segments (2.5+/-3.0, P<0.01). Absolute change in the regional wall motion score (3 days to 3 weeks) of mismatched segments (2.6+/-3.5) was significantly greater than that in the regional wall motion score of matched normal segments and matched abnormal segments (1.1+/-1.3 and 1.2+/-2.6, respectively, both P<0.05). Twenty-seven of 37 segments (73%) with perfusion/thickening mismatch showed significant improvement in regional wall motion, whereas improvement in regional wall motion was observed in 22 of 108 segments (20%) with matched abnormal segments and 6 of 41 segments (15%) with matched normal segments. Segments with perfusion/thickening mismatch had a significantly higher incidence of regional functional improvement than did matched abnormal or matched normal segments (chi2=42.3, P<0.01). Thus, by estimating both perfusion and wall thickening, single-injection resting ECG gated SPET imaging with 99mTc-tetrofosmin early after primary PTCA can predict recovery of regional wall motion after successful reperfusion.

Quantitative estimation of myocardial salvage after primary percutaneous transluminal coronary angioplasty in patients with angiographic no reflow.

Angiographic Thrombolysis in Myocardial Infarction (TIMI) flow grade