A surgical case of descending colon cancer with abdominal wall abscess after drainage of abscess

We report a surgical case of descending colon cancer with abdominal wall abscess. A 72-year-old man was admitted to a hospital because of left lower abdominal mass with slight pain. An abdominal CT showed a left lower abdominal wall abscess adjacent to the descending colonic wall thickening. We diagnosed an abdominal wall abscess due to descending colon cancer or colon diverticulitis. The abscess was drained under local anesthesia releasing foul-smelling pus and air. After abscess drainage and general improvement in his condition, we conducted subtotal colectomy with lymph node dissection and excision of abdominal wall abscess cavity. Pathological findings indicated moderately differentiated adenocarcinoma of the descending colon (pT4, pN0, sH0, sP0, sM0, fStage II). The carcinoma had invaded the abdominal wall and transverse colon, but the cancer cells were not shown in the abdominal wall abscess cavity. In abdominal wall abscess treatment, colon cancer should be considered as a potential underlying cause. CT proved useful for assessing the status of the tumor and the abscess. We conducted a radical operation for descending colon cancer after the drainage for abdominal wall abscess.     

Chronopharmacological assessment identified GLUT4 as a factor responsible for the circadian variation of the hypoglycemic effect of tolbutamide in rats

The circadian relationship between the pharmacokinetics and pharmacodynamics of tolbutamide in rats was analyzed using a compartment model. The basal concentration of plasma glucose had a circadian rhythm with the acrophase at 15:19 h. After intravenous administration of tolbutamide at 06:00, 14:00, or 18:00 h, the hypoglycemic effect showed a circadian variation, with the greatest effect at 18:00 h and the lowest effect at 06:00 h. The time courses of unbound tolbutamide concentration in plasma after intravenous administration were predicted using the model-estimated total concentration of tolbutamide and the albumin concentration and resulted in profiles that did not vary with the time of administration. Significant low insulin resistance was observed at 18:00 h to i.v. glucose and insulin loads. There was no obvious time dependency in the expression of glucose transporter 4 (GLUT4) in epididymal adipocytes. The hypoglycemic rate estimated from the plasma glucose concentration was described by the conventional pharmacokinetic-pharmacodynamic model with an effect compartment. The time courses of theoretical signals in the effect compartment described the observed circadian changes in the increased expression profile of GLUT4 normalized by the increased plasma insulin (IRI) concentration (ΔGLUT4/ΔIRI) after dosing. Thus, the time dependency in glucose uptake is responsible for the circadian variation of the hypoglycemic effect of tolbutamide.     

Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is abundantly expressed in most malignancies, but is hardly detectable in normal adult tissues. Previously we have identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8(+) cytotoxic T lymphocytes (CTL). Survivin-2B80-88-specific CTL were induced efficiently from peripheral blood mononuclear cells (PBMC) of oral cancer patients after stimulation with the peptide in vitro. We conducted a phase I clinical study to evaluate the safety and the efficacy of survivin-2B80-88 peptide vaccination in HLA-A24-positive patients with advanced or recurrent oral cancer. The vaccines were given subcutaneously or intratumorally six times at 14-day intervals. Eleven patients were enrolled and 10 patients completed the vaccination protocol. No adverse events were observed in any patients. In two patients, the levels of serum squamous cell carcinoma (SCC) antigen decreased transiently during the period of vaccination. Tumor regression that was compatible with a partial response (PR) was noted in one patient. The remaining nine patients experienced progressive disease (PD). Immunologically, an increase of the peptide-specific CTL frequency was detected in six of the eight patients evaluated by HLA-A24/peptide tetramer analysis. The present clinical trial revealed that survivin-2B peptide vaccination was safe and had therapeutic potential for oral cancer patients. However, subsequent clinical trials in combination with various adjuvant drugs will be required to improve the immunological and therapeutic efficacy. This trial was registered with University Hospital Medical Information Network (UMIN) number UMIN000000976.     

Phase I trial of gemtuzumab ozogamicin in intensive combination chemotherapy for relapsed or refractory adult acute myeloid leukemia (AML): Japan Adult Leukemia Study Group (JALSG)-AML206 study

In order to investigate better molecular-target therapy for acute myeloid leukemia (AML), we conducted a phase I trial of a combination of gemtuzumab ozogamicin (GO) with conventional chemotherapy. Between January 2007 and December 2009, a total of 19 adult Japanese patients with relapsed or refractory CD33-positive AML (excluding acute promyelocytic leukemia) were enrolled. All registered patients received a standard dose of cytarabine (Ara-C) (100 mg/m(2) × 7 days), combined with either idarubicin (IDR) (10-12 mg/m(2) × 3 days) or daunorubicin (DNR) (50 mg/m(2) × 3-5 days), and then GO (3-5 mg/m(2) ), which was administered 1 day after the last infusion of IDR (IAG regimen) or DNR (DAG regimen). While doses of both GO and IDR and the administration period of only DNR were increased, the dose-limiting toxicity (DLT) was assessed. Among 19 patients (nine in the IAG regimen, 10 in the DAG regimen), the median age was 59 years (range 33-64), and the relapsed/refractory ratio was 13/6. In the therapy using 3 mg/m(2) GO in the IAG or DAG regimen, grade 3/4 leukopenia and neutropenia were observed in all patients, but none had grade 3/4 non-hematological toxicities, except febrile neutropenia. Three patients in the IAG regimen who were administered 5 mg/m(2) GO showed DLT. No patients had veno-occlusive disease or sinusoidal obstructive syndrome. In conclusion, 3 mg/m(2) GO combined with Ara-C and IDR or DNR can be safely administered, and phase II trials should be conducted to investigate the clinical efficacy of the combination therapy.     

Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers

Laminins present in the basement membranes (BM) of blood vessels are involved in angiogenesis and other vascular functions that are critical for tumor growth and metastasis. Two major vascular laminins, the α4 (laminin-411/421) and α5 (laminin-511/521) types, have been well characterized. We recently found a third type of vascular laminin, laminin-3B11, consisting of the α3B, β1 and γ1 chains, and revealed its biological activity. Laminin-3B11 potently stimulates vascular endothelial cells to extend lamellipodial protrusions. To understand the roles of laminin-3B11 in blood vessel functions and tumor growth, we examined localization of the laminin α3B chain in normal mammary glands and breast cancers, in comparison with the α4 and α5 laminins. In the immunohistochemical analysis, the α3B laminin was co-localized with the α4 and α5 laminins in the BM of venules and capillaries of normal breast tissues, but α3B was scarcely detected in vessels near invasive breast carcinoma cells. In contrast, the α4 laminin was overexpressed in capillaries of invasive carcinomas, where a large number of macrophages were found. The α5 laminin appeared to be weakly downregulated in cancer tissues, especially in capillary vessels. Furthermore, our in vitro analysis indicated that TNF-α significantly suppressed the laminin α3B expression in vascular endothelial cells, while it, as well as IL-1β and TGF-α, upregulated the α4 expression. These results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis.     

Pulmonary Artery Leiomyosarcoma Diagnosed without Delay

A 63-year-old female presented with abnormal lung shadows but had, apart from this, few symptoms. Computed tomography (CT) revealed multiple nodules and blockage of the pulmonary artery. She was immediately diagnosed with pulmonary artery sarcoma based on a careful differential diagnosis and underwent surgery. Her tumor was pathologically diagnosed as leiomyosarcoma (i.e. intimal sarcoma). Pulmonary artery sarcoma can be easily confounded with thromboembolism in a clinical setting and some cases are diagnosed post mortem only. In our case, clinical prediction scores (Wells score, Geneva score, and revised Geneva score) for the pulmonary embolism showed low probability. Moreover, chest CT showed uncommon findings for pulmonary thromboembolism, as the nodules were too big for thrombi. Because surgical resection can provide the only hope of long-term survival in cases of pulmonary artery sarcoma, clinicians should consider this possibility in the differential diagnosis of pulmonary embolism. Clinical prediction scores and CT findings might help to reach the correct diagnosis of pulmonary artery sarcoma.     

Hardness,elasticity and ultrastructure of primary tooth dentin bonded with a self-reinforcing one-step self-etch adhesive

Objective

This study evaluated the interfacial quality of sound and caries-affected primary tooth dentin bonded with a self-reinforcing one-step self-etch adhesive.

Methods

Non-carious, sound dentin was prepared with water-cooled high-speed diamond burs. Caries-infected dentin was removed with water-cooled low-speed round steel burs and hand instrument. Dentin was bonded with Bond Force (Tokuyama Dental). A nano-indentation tester was employed for determination of hardness (H) and Young's modulus (Y) of resin–dentin interface. Similar resin–dentin interfaces were examined with a SEM/EDX, and with a TEM using ammoniacal silver nitrate tracer for nanoleakage.

Results

In the comparison of the H and Y values between the interfacial dentin and the underlying mineralized dentin, no significant difference was seen in caries-affected dentin, however, the values of the interfacial dentin were significantly lower in sound dentin. The H value of the interfacial dentin of sound dentin was significantly lower than that of caries-affected dentin with significantly higher Ca content. No significant difference was observed in the Y values of the interfacial dentin of the two substrates. For both sound and caries-affected dentin, TEM revealed silver deposits in the interfacial dentin and adhesive layer, and smear layer remained within the resin–dentin interface. However, Ca and P contents of the adhesive layer at 10 μm above the dentin surface were the same as those present in the interfacial dentin.

Conclusions

Both for sound teeth and caries teeth, Bond Force does not prevent the nanoleakage along the resin–dentin interface.     

Application of cone beam CT 3D images to cephalometric analysis

Orthodontic diagnosis is currently based primarily on two-dimensional (2D) measurements. The development of maxillofacial cone beam X-ray computed tomography (CBCT) has promoted the use of three-dimensional (3D) measurements for orthodontic diagnosis. This technology is also expected to generate new analytic methods aiming at establishing optimal occlusion according to the individual's maxillary shape and function. However, during the transitional stage from 2D to 3D measurements, it is necessary to relate 3D data to existing data analysis methods (e.g., lateral cephalogram) for the assessment of skeletal and dental relationship. Our objectives were to develop a new cephalometric analysis method based on 3D data obtained by CBCT from four aspects: (1) measurement of magnification of cephalogram, (2) assessment of the dimensional accuracy of CBCT images, (3) development of a method of cephalometric analysis using CBCT images and (4) comparison of cephalometric analytical values obtained from CBCT images with those obtained from existing cephalograms. The results demonstrated that our analytical method facilitated cephalometric analysis of CBCT images and therefore allowed direct comparison of CBCT images with existing cephalograms. Cephalometric analysis using CBCT images resulted in a smaller range of inter-operator measurement variability than that using conventional cephalograms.