Established, emerging and future applications of FDG-PET/CT in the uterine cancer.

Integrated positron emission tomography/computed tomography (PET/CT) with 2-[¹8F]fluoro-2-deoxy-D-glucose (FDG) is a useful technique to acquire both glucose metabolic and anatomic imaging data using a single device in a single diagnostic session and has opened a new field in clinical oncologic imaging. FDG-PET/CT has been used successfully for the staging, optimization of treatment, re-staging, therapy monitoring, and prognostic prediction of uterine cervical cancer and endometrial cancer as well as various malignant tumours. The present review discusses the current role of FDG-PET/CT in the management of uterine cancer, discussing its usefulness and limitations in the imaging of these patients.

Changes in corneal topography after 25-gauge transconjunctival sutureless vitrectomy versus after 20-gauge standard vitrectomy.

PURPOSE: To evaluate the changes in regular and irregular corneal astigmatism after 25-gauge transconjunctival sutureless vitrectomy and 20-gauge standard vitrectomy. DESIGN: Prospective observational comparative case series. PARTICIPANTS: Thirty-two eyes of 32 patients undergoing 25-gauge transconjunctival sutureless vitrectomy and 25 eyes of 24 patients undergoing 20-gauge standard vitrectomy. METHODS: Corneal topography was obtained preoperatively and at 2 weeks and 1 month postoperatively. MAIN OUTCOME MEASURES: The dioptric data of the central 3-mm zone of the cornea were decomposed using Fourier harmonic analysis into spherical power, regular astigmatism, asymmetry, and higher-order irregularity. RESULTS: None of the 4 Fourier indices changed throughout the observation period in the 25-gauge group. In the 20-gauge group, regular astigmatism, asymmetry, and higher-order irregularity were increased significantly at 2 weeks after vitrectomy (P<0.05, Wilcoxon signed-ranks test) and returned to preoperative levels by 1 month. The spherical power in the 20-gauge group did not change after surgery. For regular astigmatism, asymmetry, and higher-order irregularity, the 20-gauge group showed significantly greater surgically induced changes than the 25-gauge group (P<0.05, Mann-Whitney U test). CONCLUSIONS: Twenty-five-gauge transconjunctival sutureless vitrectomy does not induce significant changes in corneal topography and exerts little influence on the optical quality of the cornea.

Multimodality treatments for nodal relapse after endoscopic mucosal resection of a superficial esophageal squamous cell carcinoma.

Patients with esophageal intraepithelial carcinoma (m1) and carcinoma invading the lamina propria (m2) are generally considered good candidates for endoscopic mucosal resection (EMR) in Japan, as hardly any of them show lymph node metastasis. Although a few cases of esophageal carcinoma invading the lamina propria have been reported to show nodal involvement, lymph node metastasis and subsequent death due to carcinoma after EMR of m1 or m2 esophageal carcinoma has never been reported in the English literature. Here we describe a patient who suffered relapse of lymph node metastasis after EMR of an esophageal carcinoma invading the lamina propria without any of the reported risk factors associated with lymph node metastasis, including vascular invasion. Unfortunately, the patient died due to disease recurrence, despite receiving multimodality treatments including chemoradiotherapy and salvage surgery.

Advanced glycation end product deposits in climatic droplet keratopathy.

BACKGROUND: Climatic droplet keratopathy (CDK), known as spheroid degeneration of the cornea, is one of the most frequent degenerative corneal disorders affecting visual function. However, the histochemical nature of the deposits seen in CDK is still unclear. AIM: To investigate the pathogenesis of CDK, we investigated the immunohistochemical localisation of advanced glycation end products (AGEs) in surgical specimens of CDK. METHODS: Immunohistochemical localisation of N(epsilon)-(carboxymethyl)-l-lysine (CML), N(epsilon)-(carboxyethyl)-l-lysine (CEL), pyrraline, pentosidine and imidazolone was examined in three corneas with CDK, six corneas with bullous keratopathy and three corneas without any corneal diseases. RESULTS: In all the specimens with CDK, immunoreactivity was strong in CML, moderate in pyrraline and pentosidine, and weak in imidazolone. Immunoreactivity was absent in CEL. In contrast, no immunoreactivity to CML, pyrraline, pentosidine, imidazolone or CEL was detected in corneas with bullous keratopathy, or in corneas without any corneal diseases. CONCLUSIONS: CDK is caused by an aggregation of AGE-modified proteins. The result is consistent with etiological findings that ultraviolet irradiation and ageing, both of which are accelerators of AGE formation, are closely related to the development of CDK.

Retention and removal of a new viscous dispersive ophthalmic viscosurgical device during cataract surgery in animal eyes.

AIMS: To assess the retention and removal properties of a new viscous dispersive ophthalmic viscosurgical device (OVD), DisCoVisc, in comparison with those of cohesive (Provisc), dispersive (Viscoat), and viscoadaptive (Healon5) OVDs. METHODS: In 20 porcine eyes, cataract surgery was simulated using one of the four OVDs which were stained with fluorescein for better visualisation. Three parameters were measured. Firstly, the presence/absence of OVDs in the chamber at the completion of phacoemulsification was recorded. Secondly, the time until the OVDs were completely removed from the anterior chamber using the phaco needle was measured. Thirdly, after intraocular lens (IOL) implantation, the time needed to completely remove the OVDs from the chamber with irrigation/aspiration tip was recorded. RESULTS: At the completion of phacoemulsification, the OVDs retained in 0% (0/5) for Provisc, 80% (4/5) for Healon5, 100% (5/5) for DisCoVisc, and 100% (5/5) for Viscoat. The retention of OVDs during phacoemulsification was greatest with Viscoat followed by, in descending order, DisCoVisc, Healon5, and Provisc. The removal of OVDs after IOL implantation took longest with Viscoat followed by Healon5, DisCoVisc, and Provisc. CONCLUSION: The viscous dispersive DisCoVisc showed excellent retention during phacoemulsification, while its removal after IOL implantation was very easy. When compared with the viscoadaptive Healon5, DisCoVisc was retained better in the chamber and was easier to remove. These features of DisCoVisc should be highly advantageous when considering covering the entire cataract surgery procedure with a single OVD.

Cystic adenomyosis with florid glandular differentiation mimicking ovarian malignancy.

We report a case of cystic adenomyosis, presenting as a huge exophytic cystic mass with florid glandular differentiation. MR findings of the mass mimicked ovarian carcinoma associated with endometriosis. The presence of signal voids bridging the uterus and tumour should suggest a mass of uterine origin. Hyperintense protuberance in a hypointense loculus on T(2) weighted images may suggest benign disease. However, surgical exploration and resection is still required to exclude an ovarian malignancy.

Treatment with mild brain hypothermia for cardiopulmonary resuscitation after myoclonic seizures in infant with robertsonian type of trisomy 13.

Congenital chromosomal abnormality with trisomy 13 is known to be associated with poor life prognosis and lethal. Therefore, physician advice the patients be kept in intensive treatment with resuscitation and state of the art intensive care when sudden change in the general condition with this trisomy is observed. We report herein, the treatment with mild brain hypothermia therapy for cardiopulmonary resuscitation after myoclonic seizures in infant with Robertsonian type of trisomy 13 in intensive care unit. Our study indicated that brain hypothermia therapy and steroid pulse therapy on an infant who was believed to have post-resuscitation hypoxic encephalopathy was highly effective as the patient's general condition recovered to the original state after four months.

Concentration of bisphosphonate (incadronate) in callus area and its effects on fracture healing in rats.

The aim of the present study was to investigate effects of incadronate on early stages of fracture healing and to detect its concentration in callus area (Ca.Ar). Rats were injected three times per week with either two doses of incadronate (10 microg/kg and 100 microg/kg) or vehicle for 2 weeks. Femora were then fractured and fixed and animals were divided into pretreatment (P-10 and P-100) and continuous treatment (C-10 and C-100) groups. Incadronate treatment was stopped in P-10 and P-100 groups but continued in C-10 and C-100 groups. Animals were killed at 2 weeks and 4 weeks after fracture. Results showed significantly large callus, compared with the control, only in C-100 group at 4 weeks but not at 2 weeks. Both linear labeled surface (LS) and eroded surface (ES) decreased significantly in C-10 and C-100 groups at 2 weeks and 4 weeks. Osteoclast number (N.Oc) decreased significantly in C-10 and C-100 groups at 2 weeks but increased slightly at 4 weeks. However, there was no significant difference in the above parameters in P-10 and P-100 groups at 4 weeks. Apoptotic osteoclasts were observed only in the C-100 group at 4 weeks. A time-course decrease in incadronate concentration was detected in P-10 and P-100 groups whereas an increase was observed in C-10 and C-100 groups. These findings suggest that larger callus under incadronate treatment may result from the inhibition of bone resorption, histological characteristics of callus may be correlated with incadronate concentration, and metabolism of incadronate in bone may be related to the rate of bone turnover.

Effect of bisphosphonate (incadronate) on fracture healing of long bones in rats.

This study was designed to test whether bisphosphonates disturb the process of fracture healing. Female Sprague-Dawley rats were injected with either two doses of bisphosphonate (incadronate) (10 microg/kg and 100 microg/kg) or vehicle three times a week for 2 weeks. Right femora were then fractured and fixed with intramedullary wires. Incadronate treatment was stopped in pretreatment groups (P-10 and P-100 groups), while the treatment was continued in continuous treatment groups (C-10 and C-100 groups). Animals were sacrificed at 6 and 16 weeks after surgery. Soft X-ray of all fractured femora was taken. After mechanical testing, fractured femora were stained in Villanueva bone stain and embedded in methyl methacrylate. Cross-sections near fracture line were analyzed by microradiography and histomorphometry. Radiographic study showed that bony callus was present in all the fractures and incadronate treatment led to a larger callus, especially in C-100 group at both 6 and 16 weeks. Histologic study showed that the process of fracture healing in pretreatment groups was delayed at 6 weeks, but reached control level thereafter and showed same characteristics as in control at 16 weeks. Woven bony callus could still be seen in continuous treatment groups at 16 weeks. Mechanical study indicated that the ultimate load of C-100 group was slightly higher than the other treatment groups and control. The results suggest that pretreatment with incadronate did not affect fracture healing at 16 weeks after fracture. However, continuous incadronate treatment could lead to larger callus, but it delayed remodeling process during fracture healing, especially with high-dose treatment.

Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats.

The aim of this study was to investigate the long-term effect of incadronate on fracture healing of the femoral shaft in rats. Female Sprague-Dawley 8-week-old rats were injected subcutaneously (sc) with either vehicle (V group) or two doses of incadronate (10 microg/kg and 100 microg/kg) three times a week for 2 weeks. Right femoral diaphysis was then fractured and fixed with intramedullary stainless wire. Just after fracture, incadronate treatment was stopped in pretreatment groups (P groups: P-10 and P-100) or continued in continuous treatment groups (C groups: C-10 and C-100). All rats were killed at 25 weeks or 49 weeks after surgery. Fractured femur was evaluated radiologically and mechanically and then stained in Villanueva bone stain and embedded in methyl methacrylate. Undecalcified cross-sections from the fracture area were evaluated microradiologically and histomorphometrically. Radiographic observation showed that the fracture line disappeared in all groups. Cross-sectional area in the C-100 group was the biggest among all groups and in the C-10 group was larger than that in the V group at 25 weeks. Histological and histomorphometric observations showed that the process of fracture healing was delayed under continuous treatment with incadronate as evidenced by the delay of both lamellar cortical shell formation and resolution of original cortex in C groups. Percent linear labeling perimeter, mineral apposition rate (MAR), and bone formation rate (BFR) in C groups significantly decreased compared with the other groups, indicating that the callus remodeling was suppressed under continuous treatment, especially with a high dose. Mechanical study showed that the stiffness and ultimate load of the fractured femur in the C 100 group were the highest among all groups at both 25 weeks and 49 weeks. In conclusion, this study showed that long-term continuous treatment with incadronate delayed the process of fracture healing of femur in rats, especially under high dose but it did not impair the recovery of mechanical integrity of the fracture.

Osteoclasts are present in gp130-deficient mice.

Interleukin (IL)-6, IL-11, leukemia inhibitory factor, and oncostatin M similarly induce osteoclast formation in cocultures of osteoblastic cells and bone marrow cells. These cytokines share a common signal transducer, gp130, which forms a receptor complex with the specific receptor for each cytokine. To investigate the role of gp130 in osteoclast development, we examined bone tissues in gp130-deficient and wild-type newborn mice of the ICR background. Soft x-ray radiographs and microfocus x-ray computed tomographs revealed that bone marrow cavities were present in tibiae and radii of both wild-type and gp130-deficient mice. Microfocus x-ray computed tomography and histological examination demonstrated a decrease in the amount of trabeculae at the metaphysial region in tibiae and radii of the gp130-deficient mice compared with the wild-type mice. The number ofosteoclasts in gp130-deficient mice was about double that in the wild-type mice. There were no apparent differences in the distributions of alkaline phosphatase-positive osteoblasts and the osteoid surface on the trabecular bone at the metaphysial region between the wild-type and gp130-deficient mice. The volume of mineralized trabecular bones was also decreased at mandibulae, accompanied by the increased number of osteoclasts in gp130-deficient mice compared with the wild-type and heterozygous mice. These results suggest that the formation of osteoclasts is not solely dependent on gp130 signaling, at least during fetal development. The osteoclastic bone resorption in gp130-deficient mice may be caused by the functional redundancy of bone-resorbing hormones and cytokines other than those of the IL-6 family.

Preadministration of incadronate disodium can prevent bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage.

The purpose of this study is to determine whether short-term preadministration of bisphosphonates prevents bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage. Six-month-old female Sprague Dawley rats were injected with incadronate disodium (YM-175, 10 micrograms/kg) or vehicle, three times per week for 2 weeks (YM or V groups). Then, the left hindlimb was fixed to the abdomen with a bandage (V-B, YM-B groups), or only the abdomen was bandaged as control (V-SHM, YM-SHM groups), for 4 weeks. The animals were subsequently killed and left proximal tibiae were processed undecalcified for quantitative histomorphometric evaluation. Immobilization-induced cancellous bone loss resulted not only from increased percent eroded surface area but also from decreased percent labeling surface and bone formation rate in V-B compared with V-SHM animals. In contrast, preadministration of YM-175 decreased percent eroded surface significantly and prevented the loss of cancellous bone mass in YM-B compared with V-B animals. Cancellous bone mass was neither increased nor decreased by preadministration of YM-175 in YM-SHM animals. Our results suggest that preadministration of bisphosphonates is effective in prevention of bone loss at the tibial metaphysis when induced by hindlimb immobilization in rats.

Hyaluronan synthase expression in bovine eyes.

PURPOSE: Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan, is a component of the extracellular matrix (ECM). It is expressed in eyes and plays important roles in many biologic processes, including cell migration, proliferation, and differentiation. Hyaluronan is produced by HA synthase (HAS), which has three isoforms: HAS1, HAS2, and HAS3. In this study, the HAS expression in the anterior segment of bovine eyes was investigated to determine the significance of HA in eyes. METHODS: To obtain bovine HAS probes, degenerate oligonucleotide primers, based on well-conserved amino acid sequences including the catalytic region of each HAS isoform, were used for reverse transcription-polymerase chain reaction to amplify mRNA from bovine corneal endothelial cells (BCECs). Hyaluronan synthase-1 expression in the anterior segment of bovine eyes at the protein level was investigated by immunohistochemistry. RESULTS: All three HAS isoforms were expressed in BCECs at the mRNA level. Amplified cDNA fragments of HAS1, HAS2, and HAS3 from BCECs can be aligned to human counterparts, showing similarities of 100%, 97.3%, and 100%, respectively, at the amino acid level. Hyaluronan synthase 1 was expressed at the protein level in corneal epithelium, keratocyte, corneal endothelium, conjunctival epithelium, ciliary epithelium, capillary endothelium, and trabecular meshwork. CONCLUSIONS: Hyaluronan synthase isoforms were expressed in the ocular anterior segment and are speculated to be involved in HA production in situ.

Advanced glycation end products in diabetic corneas.

PURPOSE: Corneal complications are often associated with diabetes mellitus and can be vision threatening. Corneas in diabetic patients are exposed to increased glucose concentration despite cornea's avascular property, and this condition may contribute to the accumulation of advanced glycation end products (AGEs). The focus of this study was to examine the role of AGEs in the pathogenesis of diabetic keratopathy. METHODS: An anti-AGE monoclonal antibody (6D12), which recognizes a N(epsilon)-carboxymethyl lysine (CML)-protein adduct as an epitope, was prepared. Immunohistochemical localization of CML was examined in human age-matched diabetic and nondiabetic corneas (8 of each). In vitro, type I collagen-, type IV collagen-, or laminin-coated 96-well plates were glycated by glucose-phosphate. In some experiments, aminoguanidine was present in the incubation mixture. The amounts of CML-protein adducts in the extracellular matrix (ECM) were determined by enzyme-linked immunosorbent assay using 6D12. SV40-immortalized human corneal epithelial cells were seeded onto modified or unmodified ECM in 96-well plates and allowed to attach for 3 hours. Attached cells were fixed, and the areas of attached cells in each condition were measured. Attached cells without fixation were removed, and cell number was counted. RESULTS: In all of the 8 diabetic corneas, CML immunoreactivity was observed in the epithelial basement membrane, whereas CML immunoreactivity was not found in the corresponding area in 7 of 8 nondiabetic corneas. In vitro, nonenzymatic glycation of laminin on the culture dish attenuated adhesion and spreading of corneal epithelial cells. The presence of amninoguanidine in the incubation mixture during glycation inhibited CML formation and promoted the adhesion and spreading of corneal epithelial cells in a dose-dependent manner. CONCLUSIONS: The accumulation of AGEs on the basement membrane, particularly on laminin, may play a causative role in the corneal epithelial disorders of diabetic patients.

Extracellular matrix production regulation by TGF-beta in corneal endothelial cells.

PURPOSE: Production of extracellular matrix (ECM) by corneal endothelial cells is related to physiologic functions and pathologic conditions and is regulated by many cytokines, including transforming growth factor-beta (TGF-beta). In this study, the molecular mechanism of ECM production regulation by TGF-beta was investigated in cultured corneal endothelial cells. METHODS: The production of ECM components (laminin and fibronectin) was detected in cultured corneal endothelial cells by western blot analysis. To determine the signal transduction pathways, mutant TGF-beta type I receptor (TbetaR-I) and/or Smad protein family members (intracellular signal transducers in TGF-beta signaling) were overexpressed by transfecting their cDNA into the cultured cells, and the effects on ECM production were observed. RESULTS: The production of laminin and fibronectin was stimulated by treatment with TGF-beta1 or TGF-beta2. After transient transfection of cDNA of the constitutively active (CA) mutant of TbetaR-I, the production of laminin and fibronectin was stimulated even in the absence of TGF-beta. The transfection of the dominant negative mutant of TbetaR-I counteracted the effects of TGF-beta. These results confirm that TGF-beta directly stimulates ECM production from corneal endothelial cells through TbetaR-I. The ECM production stimulation by TGF-beta or CA TbetaR-I was accelerated by the overexpression of Smad2, Smad3, and/or Smad4 and inhibited by that of Smad7. These results show that TGF-beta signals connected to ECM production are regulated by Smad family members, located downstream of TbetaR-I. CONCLUSIONS: The results of this study show that TGF-beta stimulates ECM production from corneal endothelial cells through TbetaR-I and Smad family transducers.

In vivo and in vitro study of radio-frequency application with a new long linear probe: implication for the maze operation.

BACKGROUND: The maze operation for atrial fibrillation is effective but highly invasive. We tested, both in vitro and in vivo, a new technique for creating long linear atrial lesions with a custom-made, 25-mm long, stainless-steel, linear probe and a corresponding 500-kHz generator for assistance in the maze operation. METHODS: In the in vitro study with the isolated canine atria, the power of the delivered radio-frequency energy and the saline irrigating flow rate were changed independently, and the sizes of the lesions were measured. In the in vivo study radio-frequency energy was delivered to 4 portions (ie, the smooth and trabeculated portions of the right and left atria). The sizes of the lesions were measured, and the histologic features of the lesions were examined. Electrical isolation of the right atrial appendage from the remaining right atrium was attempted by using this linear probe. RESULTS: In the in vitro study the size of the lesion became larger as the delivered power was increased, although the lesion was limited when the flow rate was high. In the in vivo study the size of the lesion was equal at the 4 different sites. Histologic examinations demonstrated linear and transmural lesions, and electrophysiologic examinations revealed conduction block between the right atrial appendage and the remaining right atrium. CONCLUSIONS: The new original long linear probe was effective for creating transmural linear atrial lesions with the irrigation method, presenting the possibility of an intraoperative technique that mimics the maze procedure.

Lamivudine therapy for a hepatitis B surface antigen (HBsAg)-positive leukemia patient receiving myeloablative chemotherapy and autologous stem cell transplantation.

Hepatitis B virus (HBV) can be a cause of fatal liver failure after chemotherapy for viral carrier patients and limits the indication of myeloablative therapy for them. We describe an HBsAg-positive leukemia patient who successfully underwent autologous PBSC transplant. After chemotherapeutic treatment his serum HBV DNA level rose in association with hepatitis. To prevent progression to fulminant hepatitis, we administered lamivudine, a viral reverse transcriptase inhibitor, during the transplantation procedure. The patient did not show any increase of HBV DNA or a worsening of his hepatitis. Thus, lamivudine may be a promising treatment for HBsAg-positive patients receiving myeloablative chemotherapy and autologous stem cell transplantation.