Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Effectiveness of prophylactic HPV vaccines against cervical abnormalities and HPV infection in Japan: The J-HERS 2021 multicenter study.

This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine, which was initiated between 2009 and 2013 in Japan. The study involved 1529 eligible women aged 16-39 years who visited 11 outpatient clinics in Japan for various reasons. These patients underwent HPV genotype analysis and a Pap test of cervical cell samples. A total of 299 women (19.6%) had received the prophylactic HPV vaccine (bivalent:quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. In this study (J-HERS 2021), the highest rate of HPV vaccination (53%) was observed in patients aged 22-27 years. Vaccinated individuals exhibited a 49% rate of protection against low-grade intraepithelial lesions (LSILs) and atypical squamous cells, not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and a 100% rate of protection against high-grade squamous intraepithelial lesions (HSILs) or worse (HSIL+). Significant reductions in HPV16 (95%) and HPV18 (100%) infections were noted, but no differences were observed in HPV6 and HPV11 infections. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparing the prevaccination (J-HERS 2011) and postvaccination (J-HERS 2021) periods, 43%, 51%, 88%, and 62% reductions in HPV16, HPV18, HPV16/18, and HPV31/58 infection rates were observed, respectively. Similarly, 62% and 71% reductions in LSIL/ASCH+ and HSIL+ rates were noted, respectively. There were 88% and 87% reductions in LSIL/ASCH+ and HSIL+ rates in 16-21- and 28-33-year-old patients, respectively. Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged <39 years at 9-12 years after initiation of Japan's first nationwide HPV vaccination program. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV-type replacements are inconsistent across vaccination regimens. This demonstrates the effectiveness of the HPV vaccine. However, continuous monitoring of cervical cancer and precancer is necessary in younger generations (born 1997-2007), who were rarely vaccinated due to the prolonged suspension of the vaccine recommendations in Japan.

A novel method of tracheal anastomosis healing using a single submucosal injection of basic fibroblast growth factor: initial report.

OBJECTIVES: For the technical management of tracheal anastomosis, developing new and simple methods is required to relieve anastomotic tension. This study aimed to investigate whether basic fibroblast growth factor (bFGF) only once injected immediately before anastomosis promotes cartilage regeneration at the tracheal anastomosis and whether the regenerated cartilage has the effect of reinforcing the anastomosis in a rabbit model. METHODS: New Zealand white rabbits were anaesthetized, and the cervical trachea was exposed through a cervical midline incision, followed by resection of the 10th tracheal cartilage. The rabbits were categorized into 2 groups: the bFGF group (n = 6) and the control group (n = 6). In the former group, bFGF (25 µg) was administered into the submucosal layer of the cartilage using a 27-G needle immediately before tracheal anastomosis. The animals were sacrificed 4 weeks later. Histological, mechanical and biochemical evaluations were performed on this anastomosed trachea. RESULTS: At 4 weeks of age, the anastomoses were spindle-shaped and displayed maximum diameter at the injection site compared with those in the control group. Histological evaluation showed that cartilage tissue had regenerated between the 9th and 11th tracheal cartilage rings. Tensile test showed that the anastomoses displayed a significantly high strain/stress ratio (P = 0.035). The collagen type II and glycosaminoglycan levels were significantly increased, and the collagen type I level was significantly decreased (P = 0.019, P = 0.013 and P = 0.045, respectively). CONCLUSIONS: A new wound-healing concept of airway anastomosis could be provided by the results that single injection of bFGF regenerated tracheal cartilage in rabbits and strengthened the anastomosis by bridging the regenerated and well-matured cartilage. Further investigation of this method will lead to potential clinical applications for reinforcement of tracheal anastomoses.

A new method of primary engineering of esophagus using orthotopic in-body tissue architecture.

PURPOSE: Tissue engineering of esophagus is required for management of long-gap esophageal atresia (LGEA). Collagenous connective tissue membranes fabricated by in-body tissue architecture (iBTA), called biosheets, can repair esophageal defects and generate tissues similar to native esophagus. However, iBTA requires second-stage surgery because of heterotopic preparation of biosheets. Our aim was to develop orthotopic iBTA for primary engineering of the esophagus by interposing a tubular mold to the esophageal defect. METHOD: The cervical esophagus of six rats was transected. An acrylic tube (internal diameter 2.6 mm, length 7.0 mm) was inserted and fixed between the ends of the upper and lower esophagus, and a 3 mm-long esophageal defect was created. Four weeks later, the rats were sacrificed for histological analysis. RESULTS: Postoperatively the rats could intake liquid food. After four weeks, the esophageal defects were filled with regenerated tissues. Histologically the new esophageal walls stained positive for collagen type I. The inner surfaces were covered with stratified squamous epithelium that expressed pan-cytokeratin. In only one of six rats, regeneration of muscular-like tissue was suggested by positive immunohistochemical staining for desmin. CONCLUSION: Orthotopic iBTA can regenerate a substitute esophagus with esophageal epithelium and collagenous wall. This technique may be a novel treatment for esophageal atresia with gaps of various lengths including LGEA.

Subsequent menstrual disorder after spontaneous menarche in Turner syndrome.

OBJECTIVE: Turner syndrome (TS) is a congenital disease characterized by delayed puberty, ovarian dysgenesis and short stature. Although most patients are diagnosed with primary amenorrhea, approximately 15-20% of patients with TS are reported to have spontaneous menarche. However, little is known about their menstruation status after spontaneous menarche. In the current study, we investigated the menstrual abnormalities after spontaneous menarche in TS patients. DESIGN: Retrospective study. PATIENTS: This study included TS patients with spontaneous menarche at Osaka Police Hospital or Komura Women's Clinic between April 2015 and December 2019. MEASUREMENTS: Data regarding the age of menarche, menstruation status and chromosomal karyotype were collected and retrospectively analyzed. RESULTS: Of 172 TS patients, 32 with spontaneous menarche were identified. The median age of menarche was 12 years old. Premature ovarian insufficiency (POI) after menarche was observed in 12 patients (37.5%) and the median age at menopause was 20 years old. The average period from spontaneous menarche to menopause in these patients was 5.1 years. Five patients (15.6%) had irregular menstruation and 15 (46.9%) had regular menstruation. When examined according to the structural abnormality of the X chromosome, all patients with structural abnormality of the X chromosome were diagnosed with POI after spontaneous menarche, and none with mosaic without structural abnormality were diagnosed with POI. CONCLUSION: Approximately one-third of TS patients with spontaneous menarche were diagnosed with POI after menarche for an average of 5.1 years. Counseling is required for TS patients and their parents, including information about menstrual abnormalities or fertility preservation.

Tracheal cartilage growth promotion by intra-tracheal administration of basic FGF.

PURPOSE: This study aimed to investigate whether intra-tracheal administration of basic fibroblast growth factor (b-FGF) promotes the growth of tracheal cartilage. METHODS: Trachea of 4-week old mice were intubated and 2.5 µg b-FGF administered (Group 4) for periods from 1 to 5 days. Cervical tracheal outer diameter and tracheal ring length were compared in Group 1 (no intervention), Group 2 (tracheal intubation), Group 3 (intra-tracheal administration of distilled water) and Group 4, at 8 weeks of age. Outer diameter and tracheal ring length in Group 4 were also compared with that in Group 1 at 12 and 16 weeks of age. RESULTS: At 8 weeks of age, tracheal ring length with b-FGF administration for more than 4 days in Group 4 was significantly increased over that following 1-day administration. At 8 weeks of age, mean outer diameter and the mean tracheal ring length in Group 4 were significantly greater than in the other groups. Mean outer diameter and mean tracheal ring length were significantly greater in Group 4 than in Group 1 at 12 and 16 weeks of age. CONCLUSION: This study has shown that intra-tracheal administration of b-FGF enlarges the tracheal lumen.

Fabrication of an anatomy-mimicking BIO-AIR-TUBE with engineered cartilage.

INTRODUCTION: We devised a strategy for the fabrication of an 'anatomy-mimicking' cylinder-type engineered trachea combined with cartilage engineering. The engineered BIOTUBEs are used to support the architecture of the body tissue, for long-segment trachea (>5 cm) with carinal reconstruction. The aim of the present study was to fabricate an anatomy-mimicking cylinder-type regenerative airway, and investigate its applicability in a rabbit model. METHODS: Collagen sponge rings (diameter: 6 mm) were arranged on a silicon tube (diameter: 6 mm) at 2-mm intervals. Chondrocytes from the auricular cartilage were seeded onto collagen sponges immediately prior to implantation in an autologous manner. These constructs were embedded in dorsal subcutaneous pouches of rabbits. One month after implantation, the constructs were retrieved for histological examination. In addition, cervical tracheal sleeve resection was performed, and these engineered constructs were implanted into defective airways through end-to-end anastomosis. RESULTS: One month after implantation, the engineered constructs exhibited similar rigidity and flexibility to those observed with the native trachea. Through histological examination, the constructs showed an anatomy-mimicking tracheal architecture. In addition, the engineered constructs could be anastomosed to the native trachea without air leakage. CONCLUSION: The present study provides the possibility of generating anatomy-mimicking cylinder-type airways, termed BIO-AIR-TUBEs, that engineer cartilage in an in-vivo culture system. This approach involves the use of BIOTUBEs formed via in-body tissue architecture technology. Therefore, the BIO-AIR-TUBE may be useful as the basic architecture of artificial airways.

Long-term follow-up of tracheal cartilage growth promotion by intratracheal injection of basic fibroblast growth factor.

BACKGROUND: Intratracheal injection of basic fibroblast growth factor (b-FGF) has been shown to enlarge the tracheal lumen 4 weeks after treatment. The objective of this study was to investigate the long-term effect of tracheal cartilage growth promotion by intratracheal injection of b-FGF. MATERIALS AND METHODS: New Zealand white rabbits were classified into four groups to receive either distilled water alone (Group 1; n = 16; control), 40 µg (Group 2; n = 10), 100 µg (Group 3; n = 13), or 200 µg (Group 4; n = 16) of b-FGF dissolved in water. The treatment was injected into the posterior wall of the cervical trachea using a tracheoscope. The animals were sacrificed 4 or 12 weeks later. RESULTS: Four weeks after treatment, the mean luminal areas of tracheas for Groups 1, 2, 3, and 4 were 27.2, 25.6, 32.2, and 36.2 mm2, respectively. At 12 weeks, these were 29.3, 37.9, 42.5, and 56.0 mm2, respectively. The levels of glycosaminoglycan at 12 weeks were 93.9, 152.5, 123.2, and 210.6 µg/mg, respectively. At 12 weeks, the levels of type II collagen were 77.2, 133.1, 99.2, and 148.9 µg/mg, respectively. CONCLUSION: Twelve weeks after a single injection of b-FGF, the mean luminal area of the trachea continued to increase.

Unexpected diagnosis of stage IIA dysgerminoma in streak gonad in a patient with Swyer syndrome: a case report.

Patients with Swyer syndrome, which is also known as 46,XY pure gonadal dysgenesis, are at an increased risk of gonadoblastoma and germ cell tumor. Prophylactic gonadectomy is recommended for these patients. We report a case of stage IIA dysgerminoma arising in a streak gonad in a patient with Swyer syndrome, which was not diagnosable preoperatively and intraoperatively. The patient was primarily amenorrheic and identified as female phenotypically. She underwent gonadectomy at 27 years of age. Preoperative image analysis showed a relatively small uterus without adnexal masses. Laparoscopic findings showed bilateral streak gonads. Postoperatively, histopathological examination revealed that the patient had dysgerminoma in her left streak gonad. Preoperative and intraoperative diagnosis of dysgerminoma in normal size ovaries is thought to be difficult. Although it is rare, considering the occurrence of dysgerminoma in streak gonad with extension to the mesosalpinx, prompt prophylactic gonadectomy is strongly recommended for these patients regardless of the size of the ovaries.

Engineering and repair of diaphragm using biosheet (a collagenous connective tissue membrane) in rabbits.

BACKGROUND: Prosthetic patches can be used to repair large congenital diaphragmatic hernia defects but may be associated with infection, recurrence, and thoracic deformity. Biosheets (collagenous connective tissue membranes) have been used in regenerative medicine. We evaluated the efficacy of Biosheets in a rabbit model. METHODS: Biosheets were prepared by embedding silicone plates in dorsal subcutaneous pouches of rabbits for 4weeks. In group 1 (n=11), Gore-Tex® sheets (1.8×1.8cm) were implanted into a diaphragmatic defect. In group 2 (n=11), Seamdura®, a bioabsorbable artificial dural substitute, was implanted in the same manner. In group 3 (n=14), biosheets were autologously transplanted into the diaphragmatic defects. All rabbits were euthanized 3months after transplantation to evaluate their graft status. RESULTS: Herniation of liver was observed in 5 rabbits (45%) in group 1, 8 (73%) in group 2, and 3 (21%) in group 3. A significant difference was noted between groups 2 and 3 (P=0.017). Biosheets had equivalent burst strength and modulus of elasticity as native diaphragm. Muscular tissue regeneration in transplanted biosheets in group 3 was confirmed histologically. CONCLUSION: Biosheets may be applied to diaphragmatic repair and replacement of diaphragmatic muscular tissue. LEVEL OF EVIDENCE: Level III.

Ovarian insufficiency following allogeneic hematopoietic stem cell transplantation.

Ovarian insufficiency is a serious complication for young women who undergo hematopoietic stem cell transplantation (HSCT). Reduced-intensity conditioning (RIC) has been utilized more widely due to its reduced toxicity; however, there is a lack of data concerning ovarian function after HSCT with RIC. We investigated the ovarian function in patients who received HSCT with RIC, compared to those who received myeloablative conditioning (MAC). The records of 69 female patients who received allogeneic HSCT at the institution under 40 years of age at transplantation from 1991 to 2012 were retrospectively analyzed. Prevalence of ovarian insufficiency was significantly lower in patients conditioned with RIC than in those conditioned with MAC (4/27 = 14.8% for RIC and 36/42 = 85.7% for MAC, p < 0.0001). A younger age at HSCT was associated with a lower risk of ovarian insufficiency. Among the 40 patients with ovarian insufficiency, four patients recovered ovarian function, and two conceived following hormone-replacement therapy (HRT). A higher serum E2 level prior to HRT was a significant predictor for the restoration of ovarian function (p = 0.0028). In conclusion, RIC was significantly less toxic to ovarian function compared with MAC. HSCT-associated ovarian insufficiency is not irreversible, and a higher E2 level may predict the restoration of ovarian function.

Tracheal cartilage growth by intratracheal injection of basic fibroblast growth factor.

BACKGROUND/PURPOSE: We have previously shown that intratracheal injection of slowly released (in gelatin) basic fibroblast growth factor (bFGF) significantly enlarged the tracheal lumen by a slight margin. This study aimed to investigate differences in tracheal cartilage growth by the intratracheal injection of bFGF doses in a rabbit model. METHODS: Water (group 1; n=7; control) or 100µg (group 2; n=8) or 200µg (group 3; n=8) of bFGF dissolved in water was injected into the posterior wall of the cervical trachea of New Zealand white rabbits using a tracheoscope. All animals were sacrificed four weeks later. RESULTS: The mean circumferences of cervical tracheas for groups 1, 2, and 3 were 18.8±0.83, 21.1±2.0, and 22.1±1.3mm, respectively. A significant difference was found between groups 1 and 2 (P=0.034) and groups 1 and 3 (P=0.004). The mean luminal areas of cervical tracheas for groups 1, 2, and 3 were 27.0±2.1, 32.2±4.8, and 36.3±4.6mm2, respectively. A significant difference was found between groups 1 and 3 (P=0.001). CONCLUSION: Intratracheal injection of bFGF in the dose range used significantly promoted the growth of tracheal cartilage in a rabbit model. LEVELS OF EVIDENCE: Level II at treatment study (animal experiment).

Patch tracheoplasty in body tissue engineering using collagenous connective tissue membranes (biosheets).

BACKGROUND: Collagenous connective tissue membranes (biosheets) are useful for engineering cardiovascular tissue in tissue engineering. The aim was to evaluate the use of biosheets as a potential tracheal substitute material in vivo in a rabbit model. METHODS: Group 1: Rectangular-shaped Gore-Tex (4×7mm) was implanted into a 3×6mm defect created in the midventral portion of the cervical trachea. Group 2: Rectangular-shaped dermis was implanted into a tracheotomy of similar size. Group 3: Biosheets were prepared by embedding silicone moulds in dorsal subcutaneous pouches in rabbits for 1month. Rectangular-shaped biosheets were implanted into a tracheotomy of similar size in an autologous fashion. All groups (each containing 10 animals) were sacrificed 4weeks after implantation. MAIN RESULTS: All materials maintained airway structure for up to 4weeks after implantation. Regenerative cartilage in implanted Biosheets in group 3 was confirmed by histological analysis. Tracheal epithelial regeneration occurred in the internal lumen of group 3. There were significant differences in the amounts of collagen type II and glycosaminoglycan between group 3 and group 1 or 2. CONCLUSION: We confirm that cartilage can self-regenerate onto an airway patch using Biosheets.

Tracheoplasty with cartilage-engineered esophagus environments.

PURPOSE: Our objective was to investigate the feasibility of engineering cartilage on the esophagus layer and outside the esophagus. Moreover, we investigated the feasibility of tracheoplasty with cartilage engineered on the esophagus in rabbits. METHODS: Chondrocytes were isolated from auricular cartilages. 1. Engineered cartilage formation by histological findings on/into the esophageal layer was compared with that of injectable scaffold and preformed scaffold with chondrocytes. 2. Chondrocytes adhered to gelatin+vicryl mesh™ and b-FGF, were implanted on the outer esophageal surface. Four weeks after seeding, we found that cartilage was implanted in the midposterior portion of the cervical trachea (n=5), and it was retrieved 8weeks after seeding. RESULTS: 1. A gelatin sponge incorporating ß-TCP with vicryl mesh™ showed the best performance for fabricating engineered cartilage on the outer side of the esophagus. 2. Two of 5 rabbits died due to obstructed esophagus. Cartilage engineered outside the esophagus by a composite scaffold as the main material in the gelatin sponge, maintained the airway structure for up to 1month after implantation. Tracheal epithelial regeneration occurred in the internal lumen of this engineered cartilage. CONCLUSION: Tracheoplasty with cartilage engineered outside the esophagus may be useful for reconstructing airways.

Slow release of basic fibroblast growth factor (b-FGF) enhances mechanical properties of rat trachea.

AIM: Severe tracheomalacia is a life-threatening disease, but symptoms usually improve with growth. The aims of this study were to investigate how slow release basic-Fibroblast Growth Factor (b-FGF) acts on tracheal cartilage, and whether growth-promoted trachea is more resistant against an increase in externally-applied pressure. METHODS: Biodegradable gelatin hydrogel sheets soaked in 10 µl of distilled water (sham) or 0.5 or 5 µg/10 µl of b-FGF solution were inserted behind the cervical trachea of three-week-old male Wistar rats. The cervical trachea was harvested 4 weeks later. Extratracheal pressure was increased from 0 to 40 cmH2O in a chamber, while video-recording the internal lumen. The luminal area at each pressure was expressed as a proportion to that at 0 cmH2O. The amounts of collagen type II and glycosaminoglycan were measured by ELISA. RESULTS: The luminal areas at 40 cmH2O in the control (no intervention), sham, and each of the b-FGF groups were 0.65, 0.62, 0.72, and 0.73, respectively. The amounts of collagen type II and glycosaminoglycan in each group were 127, 136, 193, 249 µg/mg, respectively, and 15, 16, 19, 33 µg/mg, respectively. There were significant differences between the control group and the FGF 5 group (P=0.02, 0.01, 0.01, for luminal area, collagen, and glycosaminoglycan, respectively). CONCLUSION: 5 µg of slow-release b-FGF promotes matrix production (collagen type II and glycosaminoglycan). The growth-enhanced trachea was more resistant to collapse, suggesting that slowly released b-FGF might be useful in patients with severe tracheomalacia.

Optimal amount of basic fibroblast growth factor in gelatin sponges incorporating ß-tricalcium phosphate with chondrocytes.

BACKGROUND: A gelatin sponge with slowly releasing basic fibroblast growth factor (b-FGF) enhances chondrogenesis. This study investigated the optimal amount of b-FGF in gelatin sponges to fabricate engineered cartilage. MATERIALS AND METHODS: b-FGF (0, 10, 100, 500, 1000, and 2000 µg/cm(3))-impregnated gelatin sponges incorporating ß-tricalcium phosphate (ß-TCP) were produced. Chondrocytes were isolated from the auricular cartilage of C57B6J mice and expanded. The expanded auricular chondrocytes (10×10(6) cells/cm(3)) were seeded onto the gelatin sponges, which served as scaffolds. The construct assembly was implanted in the subcutaneous space of mice through a syngeneic fashion. Thereafter, constructs were retrieved at 2, 4, or 6 weeks. RESULTS: (1) Morphology: The size of implanted constructs was larger than the size of the scaffold with 500, 1000, and 2000 µg/cm(3) b-FGF-impregnated gelatin sponges incorporating ß-TCP at 4 and 6 weeks after implantation. (2) The weight of the constructs increased roughly proportional to the increase in volume of the b-FGF-impregnated scaffold at 2, 4, and 6 weeks after implantation, except in the 2000 µg/cm(3) b-FGF-impregnated constructs group. (3) Histological examination: Extracellular matrix in the center of the constructs was observed in gelatin sponges impregnated with more than 100 µg/cm(3) b-FGF at 4 weeks after implantation. The areas of cells with an abundant extracellular matrix were positive for cartilage-specific marker type 2 collagen in the constructs. (4) Protein assay: Glycosaminoglycan and collagen type 2 expression were significantly increased at 4 and 6 weeks on implantation of gelatin sponges impregnated with more than 100 µg/cm(3) b-FGF. At 6 weeks after implantation, the ratio of type 2 collagen to type 1 collagen in constructs impregnated with 100 µg/cm(3) or more b-FGF was higher than that in mice auricular cartilage. CONCLUSION: Gelatin sponges impregnated with more than 100 µg/cm(3) b-FGF incorporating ß-TCP with chondrocytes (10×10(6) cells/cm(3)) can fabricate engineered cartilage at 4 weeks after implantation.

Promotion of tracheal cartilage growth by intra-tracheal injection of basic fibroblast growth factor (b-FGF).

PURPOSE: Basic fibroblast growth factor (b-FGF) is a very effective growth factor that induces the proliferation of chondrocytes. This study aimed to investigate whether intra-tracheally-injected b-FGF solution promotes the growth of tracheal cartilage. METHODS: Group 1: 500 µl of distilled water was injected at the posterior wall of the cervical trachea of New Zealand white rabbits by using a tracheoscope (n=5). Group 2: 100 µg/500 µl of b-FGF solution was injected at the posterior wall of the cervical trachea (n=5). Group 3: Biodegradable gelatin hydrogel microspheres incorporating 100 µg/500 µl of b-FGF solution were injected at the posterior wall of the cervical trachea (n=5). All animals were sacrificed 4 weeks later, and the outer diameter and luminal area of the cervical trachea at the site of b-FGF injection were measured. RESULTS: The cervical tracheas in the two b-FGF injection groups were spindle-shaped and had a maximum diameter at the injection site. The median outer diameter of the cervical trachea in Groups 1, 2, and 3 was 7.3, 8.0, and 8.0mm, respectively, showing a significant difference among Groups 1, 2, and 3 (P=0.04). The median luminal area in Groups 1, 2, and 3 was 27.4, 29.4, and 32.1mm(2), respectively. The ad hoc test showed a marginally significant difference only between groups 1 and 3 (p=0.056). CONCLUSION: Intra-tracheal injection of slowly released b-FGF enlarged the tracheal lumen.

The junction between hyaline cartilage and engineered cartilage in rabbits.

OBJECTIVES/HYPOTHESIS: Tracheoplasty using costal cartilage grafts to enlarge the tracheal lumen was performed to treat congenital tracheal stenosis. Fibrotic granulomatous tissue was observed at the edge of grafted costal cartilage. We investigated the junction between the native hyaline cartilage and the engineered cartilage plates that were generated by auricular chondrocytes for fabricating the airway. STUDY DESIGN: Controlled, prospecive study. METHODS: In group 1, costal cartilage from New Zealand white rabbits was collected and implanted into a space created in the cervical trachea. In group 2, chondrocytes from auricular cartilages were seeded on absorbable scaffolds. These constructs were implanted in the subcutaneous space. Engineered cartilage plates were then implanted into the trachea after 3 weeks of implantation of the constructs. The grafts in group 1 and 2 were retrieved after 4 weeks. RESULTS: In group 1, histological studies of the junction between the native hyaline cartilage and the implanted costal cartilage demonstrated chondrogenic tissue in four anastomoses sides out of the 10 examined. In group 2, the junction between the native trachea and the engineered cartilage showed neocartilage tissue in nine anastomoses sides out of 10. CONCLUSIONS: Engineered cartilage may be beneficial for engineered airways, based on the findings of the junction between the native and engineered grafts.

Slow release of basic fibroblast growth factor (b-FGF) promotes growth of tracheal cartilage.

PURPOSE: Tracheomalacia is a major cause of morbidity in conditions such as oesophageal atresia. However, symptoms usually improve with age. A more rapid growth of tracheal cartilage can be induced by basic-Fibroblast Growth Factor (b-FGF). This study aimed to investigate whether slow-release b-FGF could act as a novel treatment for tracheomalacia. METHODS: Biodegradable gelatin hydrogel sheets incorporating 0.5, 5, or 50 µg/20 µl of b-FGF solution were inserted between the cervical trachea and esophagus of rats. No intervention was performed in rats in a control group. All animals were sacrificed 4 weeks later, and the luminal area of the cervical trachea and the thickness of the cartilage were measured. RESULTS: The mean luminal areas in the control group and in the b-FGF groups were 3.1, 3.2, 3.8, and 2.6mm(2), respectively, and showed a peak area at 5 µg of b-FGF. A significant difference was seen only between the control group and the b-FGF 5 µg group (p<0.05). The mean thickness of the tracheal cartilage was 0.12, 0.13, 0.19, and 0.32 mm in the control and the b-FGF groups, respectively, and showed a dose-dependent increase, which was statistically significant between the b-FGF 5 µg or 50 µg groups and the control group (p<0.01). CONCLUSION: This study showed that slow-release b-FGF enlarges the tracheal lumen and thickens the cartilage in a dose-dependent fashion.

Estrogen therapy initiated at an early age increases bone mineral density in Turner syndrome patients.

Patients with Turner syndrome (TS) almost develop osteoporosis, resulting from chromosomal deficiency and estrogen deficiency by gonadal dysgenesis. The aim of this study was to assess bone mineral density (BMD) during continuous estrogen therapy in young TS patients by measuring lumbar spine BMD of 67 TS patients using dual-energy X-ray absorptiometry. Twenty-seven patients who were treated with adult-doses of estrogen prior to the first evaluation, exhibited a significantly higher initial BMD than 30 patients treated with low-dose estrogen therapy and 10 patients without estrogen therapy (0.808 g/cm², 0.714 g/cm², and 0.664 g/cm², respectively). During continuous adult-dose estrogen therapy, BMD significantly increased in each group (maximum BMD during the study, 0.842 g/cm², 0.790 g/cm², and 0.724 g/cm², respectively). Initial and maximum BMD showed significant negative correlation with the age at which adult-dose estrogen therapy was initiated (r = -0.57 and -0.45, respectively). Among the patients not treated with adult-dose estrogen therapy prior to the first evaluation, the annual increase in the rate and amount of BMD was significantly higher when adult-dose estrogen therapy was initiated before age 18 (rate, 4.4 % before age 18 vs. 3.1 % after age 18; amount, 0.03 g/cm² before age 18 vs. 0.02 g/cm² after age 18). In summary, estrogen therapy increased BMD in young TS patients and might be more effective if initiated by age 18.