Reproductive and obstetric outcomes after radical abdominal trachelectomy for early-stage cervical cancer in a series of 31 pregnancies.

STUDY QUESTION: What are the reproductive and obstetric outcomes in patients undergoing radical abdominal trachelectomy (RAT) for early-stage cervical cancer? SUMMARY ANSWER: When RAT was performed before a pregnancy achieved with fertility treatments, pregnancy rate of 36.2% was obtained and 71.4% of these women gave birth at ≥ 32 weeks of gestation. WHAT IS KNOWN ALREADY: Reproductive and obstetric outcomes after radical vaginal trachelectomy (RVT) are well documented; however, these outcomes after RAT have not been well studied. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of patients at a single institution who underwent RAT and became pregnant. Reproductive and obstetric outcomes of 114 patients who had undergone RAT from September 2002 to December 2010 were investigated. PARTICIPANTS/MATERIAL, SETTING, METHODS: Women of reproductive age with early-stage cervical cancer who wished to preserve their fertility were documented. MAIN RESULTS AND THE ROLE OF CHANCE: Patients' median age was 33 years (25-40 years). A total of 31 pregnancies were achieved in 25 patients and 6 patients had 2 pregnancies. Eighteen of 25 patients (72.0%) had infertility problems; 17 patients conceived with IVF-embryo transfer and 1 patient with intrauterine insemination. The pregnancy rate among patients who wished to conceive was 36.2% (25/69). Among 31 pregnancies in 25 patients, 4 patients had first trimester miscarriage and 1 patient had second trimester miscarriage. Excluding the five patients who miscarried and the five ongoing pregnancies, all the 21 patients had deliveries by Cesarean section. Four patients had a preterm birth in the second trimester and 17 patients delivered in the third trimester. Of the 17 pregnancies that reached the third trimester, 2 (11.8%) were preterm births between 29 and 32 weeks, 11 (64.7%) were delivered between 32 and 37 weeks and 4 (23.5%) at ≥ 37 weeks of gestation. LIMITATIONS, REASONS FOR CAUTION: Because of the retrospective data collection, not all pregnancies may have been recorded. WIDER IMPLICATIONS OF THE FINDINGS: Prospective multicenter studies are needed to determine if the results shown in this retrospective cohort can be generalized to all patients with early-stage cervical cancer who wish to undergo the fertility-sparing RAT procedure.

Bone augmentation by bone marrow mesenchymal stem cells cultured in three-dimensional biodegradable polymer scaffolds.

Poly-lactic-glycolic acid (PLGA) is a biocompatible as well as biodegradable polymer and used in various medical applications. In this study, we evaluated efficiency of the specially designed three-dimensional porous PLGA as a scaffold for bone augmentation. First, cell attachment/proliferation, differentiation, and mineralization of Fisher 344 rat marrow mesenchymal stem cells (MSCs) cultured on the PLGA scaffold were analyzed. Viable MSCs were impregnated into pore areas of the scaffold and a moderate increase of DNA contents was seen. High alkaline phosphatase, osteocalcin content, and calcium content of MSCs in PLGA scaffolds under osteogenic differentiation conditions were seen after 14 or 21 days of culture. Subsequently, we implanted the PLGA/MSCs composites on rat calvaria bone for 30 days. Newly formed bone was seen in only the composite PLGA/MSCs implantation group, which had been precultured under osteogenic condition. We also demonstrated that the newly formed bone originated from the donor composites. These results demonstrate that the three-dimensional PLGA scaffold can support osteogenic differentiation of MSCs, and the scaffold combined with osteogenic MSCs can be used for in vivo bone tissue augmentation.

Real-time orthognathic surgical simulation using a mandibular motion tracking system.

We developed a new orthognathic surgical simulation system able to predict both occlusal correction and mandibular repositioning in three dimensions. This system uniquely integrates the real motion of the dental cast model with the virtual motion of the reconstructed cranio-facial model. The skeletal change of the mandibular osteotomy is simulated on the PC monitor while the occlusal change is confirmed by checking the cast model on the simulator. The simulation process is easily repeated and the operator can make several attempts to determine the final mandibular position. The occlusal relationship at the simulated mandibular posture is registered and the occlusal wafer splint, which ensures intermaxillary fixation, is fabricated on the simulator. This surgical simulation system appears to satisfy clinical demands well and is an important facilitator of communication between orthodontists and surgeons. Here, we outline the system and apply it to a demonstration case of orthognathic surgery.

Is laser conization adequate for therapeutic excision of adenocarcinoma in situ of the uterine cervix?

AIMS: To determine the safety of uterine-preserving operations for adenocarcinoma in situ of the cervix. METHODS: Fifteen cases of adenocarcinoma in situ (AIS) were diagnosed using neodymium:yttrium aluminum garnet (Nd:YAG) laser conization. The accuracy of preconization histology or cytology was evaluated in 15 AIS cases. In these AIS cases, we investigated how far the tumor was located from the squamocolumnar junction (SCJ) and the endocervix. Fourteen cases of the 15 AIS-affected patients were treated using laser conization alone. These patients were closely followed up. RESULTS: Precise agreement between preconization diagnosis and conization histology was seen in 46.7% (7/15) of the AIS cases. In 14 of the 15 cases of AIS (93.3%), the tumor was adjacent to the transitional zone, within 3 mm of the SCJ, and in the other case (6.7%), the tumor was between 0 and 5 mm away from the SCJ. In all subjects, cone height was 8-18 mm (mean 13.1 mm). None of the 15 patients showed any recurrence of AIS during follow up ranging from 15 to 75 months (43.1 months on average). CONCLUSIONS: Women with AIS who want to preserve their fecundity might be treated with laser conization alone.

Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold.

Cartilage engineered from mesenchymal stem cells (MSCs) requires a scaffold to keep the cells in the cartilage defect and to act as a support for inducing hyaline cartilage formation. We developed a novel three-dimensional special poly-lactic-glycolic acid (PLGA) scaffold that provided structural support and stimulated repair. Three-dimensional PLGA scaffolds seeded with cultured MSCs were transplanted into large defects in rabbit knees and analyzed histologically at 4 and 12 weeks after the operation. Our findings showed that in the engineered cartilage with the PLGA scaffold, the defects were filled with smooth, shiny white tissue macroscopically and hyaline-like cartilage histologically at 12 weeks after the transplantation. The structure of the novel PLGA scaffolds provided architectural support for the differentiation of progenitor cells and demonstrated successful induction of in vivo chondrogenesis.

HMOCC-1, a human monoclonal antibody that inhibits adhesion of ovarian cancer cells to human mesothelial cells.

OBJECTIVES: Ovarian carcinoma is one of the most common gynecologic cancers and shows the worst prognosis since current therapies are not sufficiently effective at achieving and maintaining remission. To develop new treatment, a monoclonal antibody recognizing human ovarian cancer cells was raised in KM mice. METHODS: A human monoclonal antibody targeting RMG-I (an ovarian carcinoma cell line) was established with hybridomas of myeloma cells and spleen cells from KM mice. The immunohistochemical reactivity of various types of ovarian carcinoma and other tumors was investigated. RMG-I cells were treated with N-glycosidase F, NaOH, H(2)SO(4), and Gal NAC-alpha-benzyl to investigate the target antigens by Western blotting. The effect of HMOCC-1 on adhesion of RMG-I cells to cultured human mesothelial cells was also investigated. RESULTS: The new human monoclonal antibody, HMOCC-1, was an immunoglobulin M that recognized ovarian epithelial carcinoma. Immunohistochemical staining revealed HMOCC-1 positivity in 83.2% of ovarian carcinomas. The antigen recognized by HMOCC-1 was apparently a glycoprotein since Western blotting yielded a broad band (34.8-49.1 kDa). HMOCC-1 inhibited the attachment of RMG-I cells to monolayers of cultured peritoneal mesothelial cells in a concentration-dependent manner. CONCLUSIONS: This new human monoclonal antibody reacted with most ovarian cancers tested. The antigen recognized by HMOCC-1 is a glycoprotein located on the cell membrane. Inhibition of the attachment of RMG-1 cells to mesothelial cells by HMOCC-1 suggests a potential role for this antibody in the treatment of ovarian cancer.

P16 overexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix.

Carcinogenesis of cervical cancer has been investigated, and p16(INK4a) overexpression in squamous cell carcinoma of the cervix has been reported as a result of infection by human papillomavirus (HPV) (eg, HPV 16), and the consequence of the retinoblastoma (Rb) protein inactivation by HPV E7 protein. However, to our knowledge, there have been no studies on the relation between p16(INK4a) overexpression associated with HPV and small cell carcinoma of the cervix, which behaves more aggressively clinically than squamous cell carcinoma. The purpose of this study was to determine whether p16(INK4a) is overexpressed in small cell carcinoma, and if p16(INK4a) is overexpressed, the types of HPV that are related to this cancer. We reviewed 10 cases of small cell carcinoma and examined them for p16(INK4a) overexpression by immunohistochemistry. We also performed HPV typing with polymerase chain reaction (PCR)-sequencing analysis and in situ hybridization and found that p16(INK4a) was overexpressed in every case. PCR-sequencing analyses revealed that all cases were HPV-positive and that 9 cases were positive for HPV 18. Five of the 9 cases positive for HPV 18 were also positive by in situ hybridization and yielded a punctate signal, considered to represent the integrated form. In conclusion, p16(INK4a) was overexpressed and HPV 18 was frequently detected in an integrated form in small cell carcinoma. Therefore, inactivation of Rb protein by HPV 18 E7 protein may be associated with carcinogenesis of small cell carcinoma the same as inactivation of Rb protein by HPV 16 E7 protein is associated with carcinogenesis of squamous cell carcinoma.

Correlation of p16INK4A overexpression with human papillomavirus infection in cervical adenocarcinomas.

SUMMARY: As human papillomavirus (HPV) infection is the main risk factor for squamous cell carcinoma of the cervix and overexpression of p16INK4a occurs when retinoblastoma protein is inactivated by high-risk HPV, the authors studied the association of HPV infection and expression of p16INK4a in cervical adenocarcinomas. Specimens of cervical glandular neoplasias were immunostained with a p16INK4a-specific monoclonal antibody (clone E6H4). Approximately 80% of glandular neoplasms showed overexpression of p16INK4a. Exfoliated cells from 14 adenocarcinomas were further examined by p16INK4a-specific immunocytochemistry, and 12 cases showed overexpression of p16INK4a, suggesting that immunostaining for p16INK4a may be a useful diagnostic tool for cervical adenocarcinomas. The authors further examined HPV DNA in cervical adenocarcinomas with the polymerase chain reaction method. Overexpression of p16INK4a was positive in 94% of cases in which HPV16 or 18DNA was positive, a finding suggesting that HPV16 or 18 may play an important role in cervical adenocarcinomas. Overexpression of p16INK4a may be an indicator of pathogenic activity of high-risk HPVs.

Tumor imprint cytology of sclerosing stromal tumor of the ovary.

Over 90 cases of sclerosing stromal tumor of the ovary (SST) have been reported in the English-language literature, but these authors did not mention the cytologic examination of SST. In 2 patients with SST, we were able to collect specimens for tumor imprint cytology. The number of cells in the specimens was extremely small. Two types of benign cells were observed against a clean background, comprising cells with round nuclei surrounded by abundant cytoplasm and cells with spindle-shaped or oval nuclei that had scanty cytoplasm. Our present findings suggest that intraoperative imprint cytology was able to rule out cancer. Considering that SST most commonly occurs in young women requiring conservative treatment, imprint cytology seems to have a potential diagnostic significance.

Studies on comonomer compositional distribution of bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)s and thermal characteristics of their factions.

The comonomer-unit compositional distributions have been investigated for bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HH)] samples with 3HH unit content of 13.8, 18.0, 22.0, and 54.0 mol %. They were comonomer compositionally fractionated using chloroform/n-heptane mixed solvent at ambient temperature. The fractionation of P(3HB-co-18.0 mol %3HH) and P(3HB-co-22.0 mol % 3HH), which could not be carried out effectively at room temperature, were refractionated at 70 degrees C in the mixed solvent. Fractions with different 3HH unit content in a wide range (from 4.4 to 80.7 mol %) were obtained. By use of these fractions with narrow compositional distribution, the comonomer composition dependence of thermal properties was investigated by differential scanning calorimetry. The melting point (T(m)) and heat of fusion (DeltaH) decreased as the 3HH unit content increased in the range of low 3HH content (<40 mol %), while they increased as the 3HH unit content increased in the high 3HH content range (>70 mol %). The minimum T(m) and DeltaH values were found to exist at 3HH unit content of about 60 mol %. The glass transition temperature (T(g)) decreased linearly with the increase of 3HH unit content. The values of T(m), DeltaH, and T(g) of P(3HB-co-3HH)s were compared with those of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxypropionate), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), and the effects of comonomer types on the thermal properties were revealed.