Phase II study of intraperitoneal submicron particle paclitaxel (SPP) plus IV carboplatin and paclitaxel in patients with epithelial ovarian cancersurgery.

Submicron particles (~800 nm) of paclitaxel (SPP) contain 1-2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. This study compared two dose-levels of SPP instilled into the peritoneal cavity (IP) in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment emergent adverse events. Clinical response was determined by symptoms, physical exams, CT scans, and serum CA-125 measurements. Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m2 and three received 200 mg/m2. Seven subjects completed the 12-month follow-up period. Six patients were evaluable due to one subject who had unevaluable scans throughout the follow-up period and was thus excluded from PFS determination. Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas.

Overtreatment in a see-and-treat approach to cervical intraepithelial lesions.

OBJECTIVE: To determine the overtreatment rate at colposcopy in women who underwent a see-and-treat protocol. METHODS: We identified 3,192 patients (mean age 36 years, standard deviation 8.7) who underwent a see-and-treat protocol in Radboud University Nijmegen Medical Center between January 1981 and December 2010. Overtreatment, defined as cervical intraepithelial neoplasia 1 or less at final histopathology analysis, was investigated in relation to the age of the women, time of referral, cervical smear result, colposcopic impression, and histopathology result. RESULTS: A total of 579 women (18.1%, 95% confidence interval [CI] 16.7-19.5) were overtreated. The lowest overtreatment rate (4.5%, 95% CI 3.5-5.5) was seen in women with both a high-grade cervical smear result and a high-grade colposcopic impression. Women aged younger than 40 years were less likely to be overtreated (13.1%, 95% CI 11.7-14.5) than women aged 40-49 years (24.2% 95% CI 21.2-27.4, number needed to harm nine) and aged 50 years and older (42.2%, 95% CI 36.5-47.7, number needed to harm three). CONCLUSIONS: The overtreatment rate is low for patients with both a high-grade smear result and a high-grade colposcopic impression, justifying a see-and-treat approach for these patients. In women with either a high-grade smear result or a high-grade impression on colposcopy, a see-and-treat approach may still be preferable but has higher overtreatment rates. Given the side effects of cervical surgery on pregnancy outcome, young women, in particular those who have either a low-grade smear result or low-grade impression on colposcopy, are better served by a two-step approach. In older women, a see-and-treat policy may be preferable.

Soft dentin results in unique flexible teeth in scraping catfishes.

Teeth are generally used for actions in which they experience mainly compressive forces acting toward the base. The ordered tooth enamel(oid) and dentin structures contribute to the high compressive strength but also to the minor shear and tensile strengths. Some vertebrates, however, use their teeth for scraping, with teeth experiencing forces directed mostly normal to their long axis. Some scraping suckermouth catfishes (Loricariidae) even appear to have flexible teeth, which have not been found in any other vertebrate taxon. Considering the mineralized nature of tooth tissues, the notion of flexible teeth seems paradoxical. We studied teeth of five species, testing and measuring tooth flexibility, and investigating tooth (micro)structure using transmission electron microscopy, staining, computed tomography scanning, and scanning electron microscopy-energy-dispersive spectrometry. We quantified the extreme bending capacity of single teeth (up to 180°) and show that reorganizations of the tooth (micro)structure and extreme hypomineralization of the dentin are adaptations preventing breaking by allowing flexibility. Tooth shape and internal structure appear to be optimized for bending in one direction, which is expected to occur frequently when feeding (scraping) under natural conditions. Not all loricariid catfishes possess flexible teeth, with the trait potentially having evolved more than once. Flexible teeth surely rank among the most extreme evolutionary novelties in known mineralized biological materials and might yield a better understanding of the processes of dentin formation and (hypo)mineralization in vertebrates, including humans.

99mTc-HMPAO-labeled autologous versus heterologous leukocytes for imaging infection.

UNLABELLED: Radiolabeled autologous leukocytes are the gold standard for imaging infectious foci in patients. Good results have also been reported for radiolabeled heterologous leukocytes from noninfected donors. Until now, the 2 methods have not been directly compared. In this study, we compared the infection-imaging potential of 99mTc-hexamethylpropyleneamine oxime (HMPAO)-labeled autologous granulocytes with that of 99mTc-HMPAO-labeled granulocytes from either infected or noninfected donors in rabbits with Escherichia coli infection. METHODS: The radiolabeled granulocyte preparations were studied in rabbits with an E. coli infection in the left calf muscle. The soft-tissue infections were scintigraphically visualized after injection of 18 MBq of either 99mTc-HMPAO purified autologous granulocytes or radiolabeled purified heterologous granulocytes from infected or noninfected donor rabbits. Gamma camera images were acquired at 2 min and at 1, 2, and 4 h after injection. After the last image, the rabbits were killed and uptake of the radiolabel in the dissected tissues was determined. RESULTS: The 99mTc-HMPAO autologous granulocytes and heterologous granulocytes from infected donors accurately revealed the infectious focus in the calf muscle at 2 h after injection. At 4 h after injection, a significantly better (P < 0.05) delineation of the infection was established with the 99mTc-HMPAO autologous granulocytes and 99mTc-HMPAO heterologous granulocytes from the infected rabbits than with the heterologous granulocytes from noninfected donors. With both cell preparations, the intensity of uptake in the infected calf muscle continuously increased until 4 h after injection. The 99mTc-HMPAO heterologous granulocytes from noninfected donors showed no significant increase in contrast after 2 h after injection. Absolute uptake in the infected calf muscle was much higher for 99mTc-HMPAO autologous granulocytes (7.81 +/- 1.21 percentage injected dose [%ID]) and 99mTc-HMPAO heterologous infected granulocytes (8.91 +/- 1.92 %ID) than for the radiolabeled heterologous noninfected granulocytes (2.32 +/- 0.75 %ID) (P < 0.04) at 4 h after injection. The ratio of infected muscle to noninfected contralateral muscle was significantly higher for 99mTc-HMPAO autologous granulocytes and 99mTc-HMPAO heterologous granulocytes from infected donors than for 99mTc-HMPAO heterologous granulocytes from noninfected donors (5.53 +/- 1.09, 3.86 +/- 0.75, and 1.86 +/- 0.31, respectively; P < 0.05). CONCLUSION: For nuclear medicine imaging of infection, purified granulocytes derived from infected rabbits are superior to purified granulocytes derived from noninfected donor rabbits. In addition, autologous granulocytes gave similar results to heterologous granulocytes from infected donor rabbits, suggesting the need for intrinsic cell activation for specific granulocyte migration.