Extra copy number of BCL2 is correlated with increased BCL-2 protein expression and poor survival in diffuse large B-cell lymphoma treated with chemoimmunotherapy.

The clinical significance of extra copy (EC) genotypes of BCL2, MYC, and BCL6 have not been fully elucidated. We evaluated the EC and translocation statuses of BCL2, MYC, and BCL6 in 190 diffuse large B-cell lymphoma (DLBCL) cases using fluorescence in situ hybridization. EC genotype was sub-classified according to copy number-gained tumor cell ratio (EC1, >20% but ≤50%; EC2, >50%). Only the BCL2-EC groups, not MYC-EC or BCL6-EC groups, displayed significantly increased immunoreactivity of the corresponding protein. Moreover, the BCL2-EC2 group was significantly associated with poor overall survival (OS) and progression-free survival (PFS) in a 147 R-CHOP-treated patient subset, which was also statistically significant as per the multivariate survival analysis for PFS. No significant differences in the survival of MYC, BCL6, concurrent BCL2/MYC, BCL6/MYC, BCL2/BCL6, or triple EC groups were observed. BCL2-EC may contribute to increased BCL-2 protein expression and serve as a predictor of treatment outcomes in DLBCL.

Extratendinous migration of calcific tendinitis of the rotator cuff: imaging findings and clinical characteristics with temporal changes.

PURPOSE: The aim of this study was to analyze the imaging findings and clinical characteristics of extratendinous migration of calcific tendinitis of the shoulder with temporal changes. METHODS: Seventy-six patients with extratendinous calcific tendinitis of the shoulder diagnosed by ultrasonography (US) or magnetic resonance imaging (MRI) were enrolled in this retrospective study. Clinical symptoms and imaging findings (on radiography, US, and MRI) of extratendinous calcific tendinitis during an acute painful attack were analyzed. Temporal changes were analyzed in 28 patients before an acute attack and 40 patients after an acute attack. For comparison, 65 patients with intratendinous calcific tendinitis were included. RESULTS: Patients with extratendinous calcific tendinitis had a significantly higher average visual analogue scale (VAS) score (8.8±1.6) than the intratendinous group (6.4±2.2) (P<0.001). The fragmented type (80.5%) was the most common shape on US; sonographic black hole appearance (14.6%) and echogenic fluid (9.8%) were characteristic findings of intrabursal calcifications. In 28 patients with previous radiographs, radiographic type III (78.6%) was dominant and the location of calcific deposits changed (82.1%) during the acute painful attack, which was also perceivable in 12 patients with previous US or MRI. In follow-up radiographs of 40 patients, calcifications shrunk by more than 50% or became invisible in 82.5% of patients, with symptom improvement (VAS score, 8.9±1.5 to 1.9±1.2). Follow-up US and MRI of 16 patients also showed decreased size (56.3%) or disappearance (43.7%) of calcific deposits. CONCLUSION: Extratendinous calcific tendinitis has distinctive imaging features, the temporal changes of which correlate well with clinical symptoms.

Smooth Muscle Distribution Patterns of Choledochal Cysts and Their Implications for Pathogenesis and Postoperative Complications.

OBJECTIVES: Histopathologic characteristics of choledochal cysts and their clinical implications have not been previously comprehensively studied. METHODS: Smooth muscle distribution patterns and other histologic findings (inflammation, metaplasia, dysplasia, and heterotopia) in 233 surgically resected choledochal cysts were evaluated. RESULTS: Mean patient age was 23.3 ±â€…19.8 years, with male:female ratio of 0.3. Most cases were Todani type I (175 cases, 75.1%) or IVa (56 cases, 24.1%). Choledochal cysts with thin scattered/no muscle fiber (175 cases, 75.1%) were the predominant pattern and were associated with more frequent postoperative biliary stricture (P = .031), less frequent pyloric metaplasia (P = .016), and mucosal smooth muscle aggregates (P < .001) compared to cysts with thick muscle bundles. Severe chronic cholangitis (P = .049), pyloric metaplasia (P = .019), mucosal smooth muscle aggregates (P < .001), biliary intraepithelial neoplasia (P = .021), and associated bile duct (P = .021) and gallbladder carcinomas (P = .03) were more common in adults (age >20 years vs ≤20 years), suggesting that chronic irritation in association with developmental anomalies involves tumorigenesis from choledochal cysts. CONCLUSION: Smooth muscle distribution pattern of choledochal cyst may predict postoperative complication, raising clinical implications of smooth muscle patterns in postoperative management of choledochal cysts.

Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune Pancreatitis.

Type 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous cystic neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surrounding stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The pericystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1.

Suppressive Effect of 4-Hydroxy-2-(4-Hydroxyphenethyl) Isoindoline-1,3-Dione on Ovalbumin-Induced Allergic Asthma.

4-Hydroxy-2-(4-hydroxyphenethyl)isoindoline-1,3-dione (PD1) is a synthetic phthalimide derivative of a marine compound. PD1 has peroxisome proliferator-activated receptor (PPAR) γ agonistic and anti-inflammatory effects. This study aimed to investigate the effect of PD1 on allergic asthma using rat basophilic leukemia (RBL)-2H3 mast cells and an ovalbumin (OVA)-induced asthma mouse model. In vitro, PD1 suppressed ß-hexosaminidase activity in RBL-2H3 cells. In the OVA-induced allergic asthma mouse model, increased inflammatory cells and elevated Th2 and Th1 cytokine levels were observed in bronchoalveolar lavage fluid (BALF) and lung tissue. PD1 administration decreased the numbers of inflammatory cells, especially eosinophils, and reduced the mRNA and protein levels of the Th2 cytokines including interleukin (IL)-4 and IL-13, in BALF and lung tissue. The severity of inflammation and mucin secretion in the lungs of PD1-treated mice was also less. These findings indicate that PD1 could be a potential compound for anti-allergic therapy.

Establishment of secondary iron overloaded mouse model: evaluation of cardiac function and analysis according to iron concentration.

Periodic blood transfusion can lead to secondary iron overload in patients with hematologic and oncologic diseases. Iron overload can result in iron deposition in heart tissue, which decreases cardiac function and can ultimately lead to death due to dilated cardiomyopathy and cardiac failure. In this study, we established murine model of secondary iron overload, studied the changes in cardiac function with echocardiography, and examined the histopathologic changes. Three experimental groups of the six week-old C57/BL mice (H-2(b)) were injected intraperitoneally with 10 mg of iron dextran daily 5 days a week for 2, 4, and 6 weeks. Cumulative doses of iron for the three experimental groups were 100, 200, and 300 mg, while the control groups were injected with the same amounts of phosphate-buffered saline. We studied the cardiac function under anesthesia with echocardiography using a GE Vivid7 Dimension system. Plasma iron levels and liver iron contents were measured. The hearts and livers were harvested and stained with H&E and Perls Prussian blue for iron, and the levels of iron deposit were examined. We assessed the cardiac measurements after adjustment for weight. On echocardiography, thicknesses of the interventricular septum and posterior ventricular wall (PS) during diastole showed correlation with the amount of iron deposit (P < 0.01). End-diastolic volume showed dilatation of the left ventricle in the 300 mg group (P < 0.01). Changes in the fractional shortening were not statistically significant (P = 0.07). Plasma iron levels and liver iron contents were increased proportionally according to the amount of iron loaded. The histopathologic findings of PS and liver showed higher grade of iron deposit proportional to the cumulated iron dose. In this study, we present an animal model which helps understand the cardiac function changes in patients with secondary iron overload due to repeated blood transfusions. Our results may help characterize the pathophysiologic features of cardiomyopathy in patients with secondary iron overload, and our model may be applied to in vivo iron-chelating therapy studies.