Assessment of intratumor heterogeneity in mesenchymal uterine tumor by an <Superscript>18</Superscript>F-FDG PET/CT texture analysis

Objective

The aim of this study was to retrospectively evaluate the clinical significance of ¹⁸F-FDG PET/CT textural features for discriminating uterine sarcoma from leiomyoma.

Methods

Fifty-five patients with suspected uterine sarcoma based on ultrasound and MRI findings who underwent pretreatment ¹⁸F-FDG PET/CT were included. Fifteen patients were histopathologically proven to have uterine sarcoma, 14 patients by surgical operation and one by biopsy, and 40 patients were diagnosed with leiomyoma by surgical operation or in a follow-up for at least 2 years. A texture analysis was performed on PET/CT images from which second- and higher order textural features were extracted in addition to standardized uptake values (SUVs) and other first-order features. The accuracy of PET features for differentiating between uterine sarcoma and leiomyoma was evaluated using a receiver-operating-characteristic (ROC) analysis.

Results

The intratumor distribution of ¹⁸F-FDG was more heterogeneous in uterine sarcoma than in leiomyoma. Entropy, correlation, and uniformity calculated from normalized gray-level co-occurrence matrices and SUV standard deviation derived from histogram statistics showed greater area under the ROC curves (AUCs) than did maximum SUV for differentiating between sarcoma and leiomyoma. Entropy, as a single feature, yielded the greatest AUC of 0.974 and the optimal cut-off value of 2.85 for entropy provided 93% sensitivity, 90% specificity, and 92% accuracy. When combining conventional features with textural ones, maximum SUV (cutoff: 6.0) combined with entropy (2.85) and correlation (0.73) provided the best diagnostic performance (100% sensitivity, 94% specificity, and 95% accuracy).

Conclusions

In combination with the conventional histogram statistics and/or volumetric parameters, ¹⁸F-FDG PET/CT textural features reflecting intratumor metabolic heterogeneity are useful for differentiating between uterine sarcoma and leiomyoma.

     

Lung cancer in a child with a substantial family history of cancer.

The occurrence of primary lung cancer is rare in childhood. The case of an 11-year-old boy with primary lung cancer is presented in this report. He had a substantial family history of cancer. His chief complaint was coughing with right chest pain. A chest radiograph showed a coin lesion in the right lower lung. A right lower lobectomy revealed a squamous cell carcinoma (stage IIIA at Japanese TNM classification). Systemic chemotherapy using cisplatin, vindesine, THP-adriamycin and cyclophosphamide was performed. Six months after surgery, a recurrent tumor occurred. An analysis of the familial cancer related genes (p53 gene and mismatch repair gene) showed no abnormality.     

Solid and cystic tumor of the pancreas Clinicopathologic and genetic studies of four cases

Background. Solid and cystic tumor (SCT) of the pancreas can be distinguished from other pancreatic neoplasms by its nearly exclusive occurrence in young women, and its favorable prognosis after complete resection. Methods. We experienced four cases with SCT of the pancreas, and analyzed these tumors by immuno-histochemical and electron microscopic studies, as well as genetic analysis of ras oncogene mutation.     

Epstein‐Barr virus‐positive diffuse large B‐cell primary central nervous system lymphoma associated with organized chronic subdural hematoma: A case report and review of the literature

We here report on a rare case of Epstein‐Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) detected in both brain parenchyma and in an organized chronic subdural hematoma (OCSH). A 96‐year‐old man diagnosed with asymptomatic OCSH in the left frontal convexity was referred to our hospital because of a de novo mass lesion just beneath the OCSH on contrast‐enhanced magnetic resonance imaging. The size of the OCSH remained stable. We diagnosed the lesion as a malignant tumor. At surgery, the organized hematoma and the soft fragile tumor were removed. Histological examinations revealed pleomorphic lymphoid cells not only in the brain tissue but also in the OCSH component with tumor necrosis, and these were immunopositive for B‐cell markers. In situ hybridization revealed positive signals for EBV‐encoded small RNAs, consistent with EBV‐positive DLBCL. Since the membranes of the subdural hematoma were fibrous and the tumor progression resulted in necrosis of the tumor, the DLBCL may have originally developed in the OCSH and infiltrated into the brain parenchyma. We believe that this rare case provides crucial information for the understanding of DLBCLs associated with OCSH.     

Usefulness and safety of the early rehabilitation program for patients with acute aortic dissection]

The usefulness and safety of the early rehabilitation program (2- and 3-week courses) were validated for patients with acute aortic dissection. This program undergone by 42 consecutive patients between 1996 and 1997 was compared to the conventional program undergone by 66 patients between 1993 and 1995, using the prognosis and complications for elderly patients. Mortality rate and morbidity rate were not significantly different between the early and conventional programs. The incidence of intensive care unit (ICU) syndrome in elderly patients was 16% (3 of 19 cases) vs 50% (15 of 30 cases), respectively (p < 0.05). The duration of hospital stays was 26 +/- 7 vs 37 +/- 13 days, respectively (p < 0.05). The early rehabilitation program for patients with acute aortic dissection was safe and useful to prevent complications in elderly patients, and was cost effective.     

Chimerism and T-cell receptor repertoire analysis after unrelated cord blood transplantation with a reduced-intensity conditioning regimen following autologous stem cell transplantation for multiple myeloma

A 65-year-old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high-dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U-CBT). U-CBT with a reduced-intensity conditioning regimen (RI-CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45 x 10(7)/kg body weight was infused on day 0. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Neutrophil engraftment (>0.5 x 10(9)/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella-zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U-CBT. We retrospectively analyzed T-cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U-CBT. Therefore, low-TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.     

Remaining issues of recommended management in current guidelines for asymptomatic common bile duct stones

Current guidelines for treating asymptomatic common bile duct stones (CBDS) recommend stone removal, with endoscopic retrograde cholangiopancreatography (ERCP) being the first treatment choice. When deciding on ERCP treatment for asymptomatic CBDS, the risk of ERCP-related complications and outcome of natural history of asymptomatic CBDS should be compared. The incidence rate of ERCP-related complications, particularly of post-ERCP pancreatitis for asymptomatic CBDS, was reportedly higher than that of symptomatic CBDS, increasing the risk of ERCP-related complications for asymptomatic CBDS compared with that previously reported for biliopancreatic diseases. Although studies have reported short- to middle-term outcomes of natural history of asymptomatic CBDS, its long-term natural history is not well known. Till date, there are no prospective studies that determined whether ERCP has a better outcome than no treatment in patients with asymptomatic CBDS or not. No randomized controlled trial has evaluated the risk of early and late ERCP-related complications vs the risk of biliary complications in the wait-and-see approach, suggesting that a change is needed in our perspective on endoscopic treatment for asymptomatic CBDS. Further studies examining long-term complication risks of ERCP and wait-and-see groups for asymptomatic CBDS are warranted to discuss whether routine endoscopic treatment for asymptomatic CBDS is justified or not.     

Development of enzyme-linked immunosorbent assay for 8-iso-prostaglandin F2α, a biomarker of oxidative stress in vivo, and its application to the quantification in aged rats

8-iso-Prostaglandin F_2α (8-iso-PGF_2α) is one of the isoprostanes that are mainly generated nonenzymatically in vivo from arachidonic acid through free radical-induced lipid peroxidation. To assess oxidative stress in vivo, we developed a quantitative enzyme-linked immunosorbent assay (ELISA) for 8-iso-PGF_2α. A sensitive calibration curve allowed the quantification of the amounts from 0.23 pg to 98.4 pg with 4.7 pg of 50% displacement in one assay. The ELISA method was applied to the measurement of the plasma levels of 8-iso-PGF_2α in young rats (4–8 weeks of age) and aged rats (106–123 weeks). The average level of esterified form in the plasma from aged rats was 30.6-fold higher than that in the plasma from young rats, reflecting the enhanced status of oxidative stress in aged animals. In addition, the aged rats exhibited higher levels of this F₂-isoprostane esterified to lipids from liver and kidney, suggesting local oxidative injury in specific organs. These results indicate the utility and accuracy of our ELISA for 8-iso-PGF_2α as a biomarker in vivo to assess systemic oxidative stress in animals or humans as well as oxidative injury at local sites.     

Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling

Since the rate-determining step to the intestinal absorption of poorly soluble drugs is the dissolution in the gastrointestinal (GI) tract, postprandial changes in GI physiology, in addition to any specific interactions between drug and food, are expected to affect the pharmacokinetics and bioavailability of such drugs. In this study, in vitro dissolution testing using biorelevant media coupled with in silico physiologically based pharmacokinetic (PBPK) modeling was applied to the prediction of food effects on the absorption of a poorly soluble drug, celecoxib, from 200 mg capsules. A PBPK model was developed based on STELLA^® software using dissolution kinetics, solubility, standard GI parameters and post-absorptive disposition parameters. Solubility, dissolution profiles and initial dissolution rate from celecoxib 200 mg capsules were measured in biorelevant and compendial media. Standard GI parameters (gastric emptying rate and fluid volume) were varied according to the dosing conditions. Disposition parameters were estimated by fitting compartmental models to the oral PK data, since intravenous data are not available for celecoxib. Predictions of food effects and average plasma profiles were evaluated using the AUC and C_max and the difference factor (f₁). An approximately 7-fold difference in the maximum percentage dissolved was observed in in vitro dissolution tests designed to represent the fed and fasted states. By contrast, the food effect estimated by simulating the plasma profiles with the PBPK model predicted only a slight delay in the peak plasma level (1 h), and modest increases in the C_max and AUC of 1.9-fold and 1.3-fold in the fed state, respectively. The PBPK approach, combining in silico simulation coupled with biorelevant dissolution test results, thus corresponds much better to the food effect observed for celecoxib in vivo. Additionally, point estimates of AUC and C_max as well as f₁ calculations demonstrated clear advantages of using results in biorelevant rather than compendial media in the PBPK model.