Bone invasion‐targeted chemotherapy with a novel anionic platinum complex (3Pt) for oral squamous cell carcinoma

Cisplatin (CDDP) is an important drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity and lack of an effect on bone invasion are limitations of CDDP. To increase its antitumor effect on bone invasion and reduce toxicity problems, anionic Pt complex (3Pt) has been developed. The present study aimed to characterize the basis of the cytotoxicity of the novel platinum complex 3Pt in comparison with that of CDDP for oral squamous cell carcinoma. The ionic platinum complex was prepared to increase solubility and avoid platinum nephrotoxicity. Furthermore, 3Pt was designed to target bone hydroxyapatite and has germinal bisphosphonate moieties for drug delivery. In vitro antitumor activity was assayed in two oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of 3Pt, nude mice with OSC‐19 were given 3Pt and CDDP. The in vitro growth‐inhibitory effect of 3Pt was significantly less than that of CDDP. However, both 3Pt and CDDP showed equivalent antitumor effects in vivo. Mice injected with CDDP developed renal cell apoptosis; however, those injected with 3Pt were almost free of renal cell injury. In addition to similar in vivo antitumor effects, 3Pt decreased the volume of bone resorption compared to that with CDDP in a bone invasion model using OSC‐19. In conclusion, considering the potential advantages in terms of noticeable antitumor activity on bone invasion and reduced nephrotoxicity, 3Pt represents a significant improvement in the development of bone‐targeting platinum drugs.     

Effect of local cooling on excitation-contraction coupling in myasthenic muscle: Another mechanism of ice-pack test in myasthenia gravis

Objective

The ice-pack test is a convenient diagnostic testing procedure for myasthenia gravis (MG). We investigated the underlying mechanism of the ice-pack test performed on bilateral masseters.

Comparison of visibility of circumscribed masses on Digital Breast Tomosynthesis (DBT) and 2D mammography: are circumscribed masses better visualized and assured of being benign on DBT?

Objective

To compare the visibility of circumscribed masses on digital breast tomosynthesis (DBT) images and 2D mammograms and determine the usefulness of DBT for differentiation between benign and malignant circumscribed masses.

Methods

Seventy-one (19 malignant and 52 benign) mammographic well-circumscribed masses were included. Visibility of the masses and halo signs on DBT images were retrospectively compared with 2D mammograms. The effects of mammographic breast density on mass visibility were also evaluated.

Results

For DBT, 83% were superior and 17% were equivalent in visibility of the masses to that of 2D, and superiority of DBT was significantly enhanced in the high breast density group compared with the low breast density group (91% vs 68%, respectively, p = 0.016). Three lesions were only detected on DBT. There was no significant difference in the superiority of DBT for lesion visibility between malignant and benign masses. The halo sign was detected in 58% lesions on DBT and in 4% on 2D (p < 0.001).

Conclusion

Circumscribed masses were better visualized on DBT than on 2D mammograms, particularly in high-density breasts. The halo sign often appeared on DBT and gave a clearer mass margin. However, circumscribed masses on DBT are not assured of being benign.

Key Points

? Circumscribed masses were better visualized on breast tomosynthesis than on 2D mammography. ? Tomosynthesis visualized circumscribed masses better than 2D for all breast density categories. ? Halo signs often appeared on tomosynthesis and contributed to detect circumscribed margins. ? Circumscribed masses on tomosynthesis images are not assured of being benign lesions.

     

The physiological accumulation of FDG in the muscles in relation to the side of intravenous administration

Purpose

The purpose of the study was to evaluate the physiological accumulation of ¹⁸F-FDG in the muscles in relation to the side of intravenous administration.

Materials and methods

We retrospectively investigated 3,118 ¹⁸F-FDG-PET/CT examinations. We evaluated the physiological accumulation of FDG in the muscles of the shoulder and arm relative to its dependence on the side of intravenous administration.

Results

Six hundred six of the 3,118 examinations (19.4%) showed physiological accumulation of FDG in the teres minor muscle. Accumulation was seen on the side of administration in 486 examinations (80.2%), contralateral to the side of administration in 56 examinations (9.2%), and bilaterally in 64 examinations (10.6%). Five hundred seventy-seven of the 3,118 examinations (18.5%) showed accumulation of FDG in the muscles between the radioulna near the elbow. Accumulation was observed on the side of administration in 432 examinations (74.9%), contralateral to the side of the administration in 71 examinations (12.3%), and bilaterally in 74 examinations (12.8%).

Conclusion

The present study finds that not only accumulation in the teres minor muscles but also accumulation in the muscles between the radioulna near the elbow occurs significantly more frequently on the side of intravenous administration compared to the contralateral side.

     

Positive gallium-67 and thallium-201 scans in thymic rebound after chemotherapy for lymphoma

It is a diagnostic problem to distinguish thymic rebound or rebound thymic hyperplasia from thymic malignancy, but it is frequently made more difficult because most patients have had previous malignancies. Recently we evaluated a six-year-old girl with thymic rebound after chemotherapy for lymphoma, by both gallium-67 and thallium-201 scans. On gallium-67 scan, intensive uptake was seen in the anterior mediastinum. CT revealed a triangular-shaped, homogeneous mass in the anterior mediastinum. On early scan of thallium-201 study, slight accumulation was seen in the anterior mediastinum and was enhanced in delayed scans. Considering the clinical state and imaging results, thymic rebound after chemotherapy was the most likely diagnosis, and follow-up observation was done without therapy. During the course, there were no signs of relapse. Some reports have described both positive and negative thallium-201 accumulation in thymic rebound. Although more experience with similar cases is necessary, it is likely that thallium-201 also tends to accumulate in thymic rebound as well as gallium-67.     

A study of the accessory hepatic vein to segments VI and VII with a morphological reconsideration of the human liver

Introduction The liver is supplied by the common hepatic artery from the celiac trunk and by the portal vein from the gastrointestine. This double blood supply to the liver by the hepatic artery and the portal vein produced a complicated structure in the liver. For the blood outflow, we can see right, intermediate and left hepatic veins, and irregular veins: the accessory hepatic veins. These veins drain the blood in the liver into the inferior vena cava. In this study, we studied the layout of the accessory hepatic vein draining segments 6 and 7 in the human livers and attempted to reconsider the structure of the liver by the layout of the accessory hepatic vein. Methods Sixty livers were subjected in this study. They were prepared by using forceps to trace the layout of the blood vessels inside the livers. We carefully examined the relation between the layouts of the accessory vein to the segments 6 and 7 and of the portal vein. The confluence patterns of the accessory hepatic vein into the inferior vena cava were also examined to find the character of the vein. The relation between the accessory hepatic vein and standard hepatic veins was also studied. Results We found 2.2 accessory hepatic veins in one liver on average in our study. The vein was always within the area of segments 6 and 7, and did not surpass the boundary. We found at most five accessory hepatic veins in a liver in two cases. The accessory hepatic vein to the segments 6 and 7 always had its stem on the dorsal side to the portal vein. Different from the stem, the periphery of the accessory hepatic vein freely distributed with the peripheral branches of the portal vein. The area distributed by the accessory vein was also always dorsal part within the segments 6 and 7. The vein was small usually, but was big in few cases. When the vein was big, the area became solely drained by the accessory vein, because the standard hepatic veins (right and intermediate hepatic veins) did not reach the area, and we did not find any communication between the accessory vein and the standard veins. As the remaining region in the segments 6 and 7 became smaller, the draining right standard hepatic vein became shorter and smaller. Discussion The region drained by the accessory hepatic vein excluded the standard hepatic veins. Therefore, there are two different draining venous networks in the area of segments 6 and 7 classified by Couinaud. Conclusion The accessory hepatic vein draining segments 6 and 7 distributed somewhere dorsal side in the segments 6 and 7. The area where the accessory vein distributed was the region where standard hepatic veins did not reach. This would suggest that the region drained by the accessory hepatic vein makes an isolated segment in the liver in the segments 6 and 7 by the Couinaud’s Classification. The area might have a unique blood circulation system.     

Axillary mass suspected to be occult breast carcinoma: a case study of skipped axillary lymph node metastasis from endometrial carcinoma in which core-needle biopsy was useful for diagnosis

A 55-year-old Japanese woman presented with metrorrhagia and was diagnosed with endometrial carcinoma. Chest computed tomography (CT), ultrasonography (US) and magnetic resonance imaging (MRI) showed a left axillary mass. Regarding the diagnosis of the axillary mass, lymph node metastasis from the uterus was first suspected. Metastasis from the breast, lung, thyroid or stomach was considered next. On a general search including positron emission tomography (PET)-CT, there was no abnormality except endometrial carcinoma and the left axillary mass. Skipped axillary lymph node metastasis of endometrial carcinoma is extremely rare, with a reported incidence of 0.03% of endometrial carcinoma cases. The differential diagnosis was double carcinoma of the uterus and breast. We carried out US-guided core needle biopsy (CNB) of the axillary mass, and the histopathological findings suggested axillary lymph node metastasis from endometrioid carcinoma. US-guided CNB is a valid method for accurate diagnosis of an axillary mass.     

Differentiation of bacterial and non-bacterial community-acquired pneumonia by thin-section computed tomography

Background and objective

The management of community-acquired pneumonia (CAP) depends, in part, on the identification of the causative agents. The objective of this study was to determine the potential of thin-section computed tomography (CT) in differentiating bacterial and non-bacterial pneumonia.

Patients and methods

Thin-section CT studies were prospectively examined in hospitalized CAP patients within 2 days of admission, followed by retrospective assessment by two pulmonary radiologists. Thin-section CT findings on the pneumonias caused by each pathogen were examined, and two types of pneumonias were compared. Using multivariate logistic regression analyses, receiver operating characteristic (ROC) curves were produced.

Results

Among 183 CAP episodes (181 patients, 125 men and 56 women, mean age ± S.D.: 61.1 ± 19.7) examined by thin-section CT, the etiologies of 125 were confirmed (94 bacterial pneumonia and 31 non-bacterial pneumonia). Centrilobular nodules were specific for non-bacterial pneumonia and airspace nodules were specific for bacterial pneumonia (specificities of 89% and 94%, respectively) when located in the outer lung areas. When centrilobular nodules were the principal finding, they were specific but lacked sensitivity for non-bacterial pneumonia (specificity 98% and sensitivity 23%). To distinguish the two types of pneumonias, centrilobular nodules, airspace nodules and lobular shadows were found to be important by multivariate analyses. ROC curve analysis discriminated bacterial pneumonia from non-bacterial pneumonia among patients without underlying lung diseases, yielding an optimal point with sensitivity and specificity of 86% and 79%, respectively, but was less effective when all patients were analyzed together (70% and 84%, respectively).

Conclusion

Thin-section CT examination was applied for the differentiation of bacterial and non-bacterial pneumonias. Though showing some potential, this examination at the present time would not be applicable for patients with underlying lung diseases, severe conditions of pneumonia, or immunocompromised conditions.     

Effect of gefitinib on N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mice

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). N-Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen found in tobacco smoke, induces lung tumors in A/J mice. NNK induces cellular transformation resulting in the over-expression of EGFR. Accordingly, EGFR may be a target for cancer prevention. In this study, we investigated the effect of gefitinib on NNK-induced tumorigenesis and the carcinogenicity of gefitinib in A/J mice.A total of 180 four-week-old female A/J mice were randomly divided into six groups: group 1 (controls), treated with deionized water; group 2, treated with 5 mg/kg p.o. gefitinib; group 3, treated with 50 mg/kg p.o. gefitinib (to test the carcinogenicity of gefitinib); group 4 (controls for NNK treatment), treated with deionized water; group 5, treated with 5 mg/kg p.o. gefitinib; and group 6, treated with 50 mg/kg p.o. gefitinib and injected with NNK once at 8 weeks of age to test the chemopreventive activity of gefitinib. Gefitinib was given once a day, 5 days a week by gavage, beginning at 4 weeks of age and continuing for 26 weeks. All mice were sacrificed at 30 weeks of age. The multiplicities of the NNK-induced lung tumors were significantly suppressed in a dose-dependent manner. Gefitinib had no effect on body weight at a low dose. The administration of gefitinib alone for 26 weeks did not induce tumorigenesis; instead, it significantly suppressed the incidence of spontaneous tumors in the mice, in contrast with other anti-cancer agents. Gefitinib did not induce lung fibrosis when compared with control mice by Azan–Mallory staining. Our results suggest that gefitinib has a weak but significant chemopreventive effect with no carcinogenicity or pulmonary toxicity in A/J mice.