Benefit of palliative chemotherapy and hospice enrollment in late-stage ovarian cancer patients.

AIM: The ideal timing for transition to best supportive care (BSC) for ovarian cancer patients is not clear. We retrospectively assessed the survival benefit of continuing chemotherapy and hospice enrollment in late-stage ovarian cancer patients. MATERIALS AND METHODS: Eligibility criteria included platinum and taxane treatment, clinical progression within 6 months of the last platinum dose, and progression during chemotherapy. RESULTS: Of the 55 eligible patients (median overall survival after first becoming refractory [1st Ref], 96 days), 22 received chemotherapy (Chemo group), two received radiation therapy, and 13 had medical contraindications for subsequent chemotherapy. The remaining 18 patients (BSC group) were compared with the Chemo group. The Chemo and BSC groups had similar background characteristics, except for the rate of consultation with a regional palliative care physician before or within 1 week of 1st Ref (9% vs 50%, respectively). In multivariate analysis, chemotherapy (hazard ratio 0.251, P = 0.005) and hospice enrollment (hazard ratio, 0.274, P = 0.023) were predictive factors of survival after 1st Ref. CONCLUSIONS: Chemotherapy after 1st Ref can be offered and hospice enrollment during the terminal stages is encouraged for recurrent ovarian cancer patients.

Live births from isolated primary/early secondary follicles following a multistep culture without organ culture in mice.

Although the ovary has a large store of germ cells, most of them do not reach mature stages. If a culture system could be developed from early growing follicles to mature oocytes, it would be useful for biological research as well as for reproductive medicine. This study was conducted to establish a multistep culture system from isolated early growing follicles to mature oocytes using a mouse model. Early growing follicles with diameters of 60-95 µm corresponding to primary and early secondary follicles were isolated from 6-day-old mice and classified into three groups by diameter. These follicles contained oocytes with diameters of ~45 µm and one or a few layered granulosa cells on the basal lamina. Embedding in collagen gel was followed by first-step culture. After 9-day culture, the growing follicles were transferred onto collagen-coated membrane in the second step. At day 17 of the culture series, the oocyte-granulosa cell complexes were subjected to in vitro maturation. Around 90% of the oocytes in follicles surviving at day 17 resumed second meiosis (metaphase II oocytes: 49.0-58.7%), regardless of the size when the follicle culture started. To assess developmental competence to live birth, the eggs were used for IVF and implantation in pseudopregnant mice. We successfully obtained two live offspring that produced next generations after puberty. We thus conclude that the culture system reported here was able to induce the growth of small follicles and the resultant mature oocytes were able to develop into normal mice.

Correction of protein kinase C activity and macrophage migration in peripheral nerve by pioglitazone, peroxisome proliferator activated-gamma-ligand, in insulin-deficient diabetic rats.

Pioglitazone, one of thiazolidinediones, a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, is known to have beneficial effects on macrovascular complications in diabetes, but the effect on diabetic neuropathy is not well addressed. We demonstrated the expression of PPAR-gamma in Schwann cells and vascular walls in peripheral nerve and then evaluated the effect of pioglitazone treatment for 12 weeks (10 mg/kg/day, orally) on neuropathy in streptozotocin-diabetic rats. At end, pioglitazone treatment improved nerve conduction delay in diabetic rats without affecting the expression of PPAR-gamma. Diabetic rats showed suppressed protein kinase C (PKC) activity of endoneurial membrane fraction with decreased expression of PKC-alpha. These alterations were normalized in the treated group. Enhanced expression of phosphorylated extracellular signal-regulated kinase detected in diabetic rats was inhibited by the treatment. Increased numbers of macrophages positive for ED-1 and 8-hydroxydeoxyguanosine-positive Schwann cells in diabetic rats were also corrected by the treatment. Pioglitazone lowered blood lipid levels of diabetic rats, but blood glucose and nerve sorbitol levels were not affected by the treatment. In conclusion, our study showed that pioglitazone was beneficial for experimental diabetic neuropathy via correction of impaired PKC pathway and proinflammatory process, independent of polyol pathway.

Free flap transfer reconstruction in managing tongue carcinoma during pregnancy.

Malignant oral cancers do not commonly occur in pregnant women. But when they do, the presence of a foetus and maternal physiological changes complicate and limit the treatment options. Risk benefit assessment and balancing of them are always important. A 33-year-old woman, who was 25 weeks pregnant, presented with a squamous cell carcinoma on her tongue. She was clinically staged II (T2, N0 and M0). Discussions between the patient, surgical teams and obstetricians agreed to continue her pregnancy while managing the tumour. Hemi-glossectomy and ipsilateral neck dissection was performed. Free antero-lateral thigh flap was transferred to reconstruct the tongue defect, successfully. The patient gave birth to a healthy baby afterward. She is tumour free for 6 years. Free flap reconstruction can be an option, even if the patient is pregnant.

Prenatal diagnosis of Kniest dysplasia with three-dimensional helical computed tomography.

OBJECTIVE: Fetal three-dimensional helical computed tomography (3D-CT) has attracted attention in the diagnosis of fetal skeletal dysplasias because of limited diagnostic capabilities of standard ultrasonography to delineate the skeleton. Here we report the first instance of diagnosing Kniest dysplasia with 3D-CT. METHODS: Fetal 3D-CT was performed for a fetus at 28 weeks' gestation after ultrasonography at 24 weeks had shown moderate shortening of the limbs, mild narrow thorax, and polyhydramnios. The imaging parameters were set so as to reduce estimated fetal irradiation dose to 12.39 mGy of the CT dose index volume and 442 of the dose length product. RESULTS: Fetal 3D-CT revealed dumbbell-shaped femora and platyspondyly with coronal cleft of the lumbar vertebral body. This warranted a diagnosis of Kniest dysplasia and corresponded well with postnatal radiographic findings. In retrospect, however, spinal deformation was somewhat underestimated due to image smoothing associated with image processing in 3D-CT. Genetic testing for COL2A1 confirmed Kniest dysplasia; i.e., a de novo mutation of A-C transversion at the splice acceptor site of the 3' end of intron 16. CONCLUSIONS: The combined use of 3D-CT with ultrasonography is a power tool for the prenatal diagnosis of congenital skeletal dysplasias.

Neuropathy induced by exogenously administered advanced glycation end-products in rats.

UNLABELLED: Aims/Introduction: Advanced glycation end-products (AGE) have been implicated in the development of diabetic neuropathy. It still remains unknown, however, how AGE cause functional and structural changes of the peripheral nerve in diabetes. To explore the role of AGE in diabetic neuropathy, we examined the peripheral nerve by injecting AGE into normal Wistar rats. MATERIALS AND METHODS: Young, normal male Wistar rats were injected intraperitoneally (i.p.) daily for 12 weeks with purified AGE prepared by incubating D-glucose with bovine serum albumin (BSA). A control group received BSA alone. A group of rats given AGE were co-treated with aminoguanidine (50 mg/kg/day, i.p.). Peripheral nerve function and structure, as well as nerve Na(+),K(+)-ATPase activity, were examined in these rats. Immunohistochemical expressions of 8-hydroxy-2'-deoxyguanosine (8OHdG) and nuclear factor-κB (NF-κB)p65 were also examined. RESULTS: Serum AGE levels were increased two to threefold in the AGE-treated group compared with those in the BSA-treated control group. AGE-treated rats showed a marked slowing of motor nerve conduction velocity (MNCV) and decreased nerve Na(+),K(+)-ATPase activity compared with those in the BSA-treated group. These changes were accompanied by intensified expressions of 8OHdG and NF-κBp65 in endothelial cells and Schwann cells. Aminoguanidine treatment corrected MNCV delay, Na(+),K(+)-ATPase activity, and suppressed the expression of 8OHdG and NF-κB, despite there being no influence on serum AGE levels. CONCLUSIONS: The results suggest that an elevated concentration of blood AGE might be one of the contributing factors to the development of neuropathic changes in diabetes.