Vascular endothelial growth factor (VEGF) was identified in 1980s as a protein that increases vascular permeability and induces endothelial cell-specific mitosis. VEGF plays an important role in angiogenesis during the embryonic stage and in angiogenesis and in increasing vascular permeability during postnatal life, both physiologically and pathologically. Great progress has been made in studies of VEGF, mainly in the field of oncology, and VEGF-targeted therapy has been successfully used to treat patients with cancer. In research related to chronic inflammation, several reports concerning rheumatoid arthritis or retinopathy and VEGF have been published. In the lower respiratory tract, increased levels of VEGF have been detected in biological samples from patients with asthma. However, VEGF has not been studied in detail in upper-airway diseases, such as rhinosinusitis. This review article focuses on VEGF and allergic rhinitis to advance studies of VEGF in chronic inflammation of the upper respiratory tract. VEGF levels in nasal secretions and nasal lavage fluid were higher in perennial allergic rhinitis than in nonallergic rhinosinusitis, after, rather than before, the antigen provocation test. The major VEGF isoforms were confirmed to be VEGF₁₂₁ and VEGF₁₆₅ in allergic rhinitis. Expression of VEGF mRNA was higher in serous versus mucous acini. In allergic rhinitis, serous acini produced significant quantities of VEGF, which was hypersecreted after antigen provocation. VEGF seems to play an important role in the pathophysiology of allergic rhinitis. Modulation of VEGF function seems to contribute to the successful treatment of conditions with airway inflammation such as allergic rhinitis.

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The fundamental principles of survival analysis are reviewed. In particular, the Kaplan-Meier method and a proportional hazard model are discussed. This work is the last part of a series in which medical statistics are surveyed.

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Background: Recent studies have examined the effects of intranasal corticosteroids (INSs) in relieving the ocular symptoms of seasonal allergic rhinoconjunctivitis (SAR) and perennial allergic rhinitis. However, because most of these studies were based on subjective assessments by patients, the associated factors and mechanism of action are unknown.
Methods: A single-center, randomized, double-blind, parallel-group study was carried out in which patients with SAR were randomly assigned to an INS mometasone furoate nasal spray (MFNS) group or to a placebo group and treated once daily for 4 weeks. Substance P concentrations in tears were measured, ocular and nasal symptoms were recorded by patients in an allergy diary, and findings were recorded by an ophthalmologist.
Results: There was no significant difference between treatment groups in the mean change from baseline of substance P concentration in tears after 4 weeks of treatment, but the mean change tended to increase in the placebo group and tended to decrease in the MFNS group (P = 0.089). All ocular and nasal symptom scores, except eye tearing, were significantly lower in the MFNS group than in the placebo group. Furthermore, substance P concentrations were strongly correlated with ocular and nasal symptom scores.
Conclusions: In patients with SAR, INSs tend to decrease the substance P concentration in tears, which is correlated with the severity of ocular and nasal symptoms.

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Objective: The aim of this study was to evaluate changes in bone mineral density (BMD) in patients using a levonorgestrel-releasing intrauterine system (LNG-IUS) or a TCu380A intrauterine device (IUD) after 2 years.
Patients and Methods: The medical records of all patients who underwent LNG-IUS (n=38) or TCu380A IUD (n=26) insertion from May 2006 through December 2010 were reviewed. The patients were 40 to 45 years old at the time of insertion, had undergone a BMD examination of the femur and lumbar spine before the loop insertion, and had also received a follow-up BMD examination 2 years later. Patients were excluded if risk factors known to affect BMD were noted in their medical records. The 2 groups of patients were compared with regard to age, parity, body-mass index (BMI), and levels of osteocalcin and pyridinoline. Changes in BMI, osteocalcin, and pyridinoline after 2 years were also compared.
Results: The LNG-IUS and TCu380A IUD groups showed no differences in mean age, mean parity, mean BMI, preinsertion or postinsertion BMD values of the femur or lumbar spine, changes after 2 years in the BMD of the femur or lumbar spine, or changes after 2 years in osteocalcin or pyridinoline level (P>0.05).
Conclusions: Women using the LNG-IUS for 2 years have changes in BMD and osteocalcin and pyridinoline levels similar to those of TCu380A IUD users. The use of the LNG-IUS for 2 years may have no adverse effect on BMD.

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Purpose: To evaluate usefulness of a new semicircular capsulotomy marker in continuous curvilinear capsulorrhexis (CCC).
Methods: In 20 eyes of 20 patients who underwent cataract surgery, a newly designed semicircular marker with an internal diameter of 5.5 mm was used to place a circular mark directly on the lens capsule. The mark was then used as a guide to complete CCC of the set diameter. The resultant size of CCC in each case was confirmed by analysis of the video image.
Results: The average CCC diameter size was 5.2 ± 0.3 mm. In all cases, the edge of the intraocular lens was completely covered by the anterior capsule.
Conclusion: The semicircular capsulotomy diameter marker was useful in making a complete CCC of a set diameter.

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Objectives: Several authors have recently reported the benefits of endoscopic gastrocnemius recession (EGR) for the treatment of nontraumatic equinus contracture. However, little is known about its potential for correcting severe posttraumatic equinus contracture. This study aimed to evaluate the effectiveness of dual-portal EGR in patients with severe, intractable equinus following severe trauma to the leg and foot. The recent technique of EGR with supplemental modified procedures was reviewed to improve its capability for correcting deformities and to provide information to avoid complications.
Methods: The subjects were 4 patients with intractable, progressive, severe posttraumatic soft-tissue equinus contractures after at least 3 months of unsuccessful conservative treatment. The exclusion criteria were spastic contracture, including osseous equinus. One patient with gastrocnemius equinus underwent EGR alone as a straightforward correction. Three patients with gastrocnemius-soleus equinus underwent EGR to correct the gastrocnemius component followed by a modified percutaneous tendo-Achilles lengthening (TAL) procedure to correct any residual deformities. All data of the preoperative period and each successive postoperative period (1, 3, and 6-12 months) were prospectively collected and included the degree of ankle dorsiflexion, American Orthopaedic Foot and Ankle Society (AOFAS) clinical rating scale score, the Visual Analogue Scale-Foot and Ankle (VAS-FA) score, and any related complications. Intraoperatively, the degree of ankle-dorsiflexion was recorded immediately following each procedure.
Results: The mean increase in intraoperative dorsiflexion was 35° ± 9.1° (range: 25°-45°) in all 4 patients and 21.7° ± 10.4° (range, 10°-30°) in the 3 patients undergoing EGR and modified TAL, respectively. There were significant differences in the improvements (p<0.05) in the preoperative period and each successive postoperative period in the increased values of ankle dorsiflexion, AOFAS scores, and VAS-FA scores. There were no significant iatrogenic complications.
Conclusion: Intractable, severe posttraumatic equinus is not commonly encountered by orthopaedic surgeons. Despite the rarity of this condition, which is responsible for the limited number of patients in this series, our results indicates that dual-portal EGR, with or without modified TAL, is a promising treatment, with satisfactory effectiveness and lower risks of complications, for correcting this problematic deformity.

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Objective: The aim of this study was to analyze the efficacy and feasibility of gemcitabine monotherapy in patients with unresectable advanced or recurrent biliary tract cancer (BTC).
Methods: Six patients with unresectable advanced BTC and 12 patients with recurrent BTC received gemcitabine monotherapy. Gemcitabine (800-1,000 mg/m²) was administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Disease and toxicity were assessed once a week in all patients until the completion of gemcitabine treatment. Computed tomographic/magnetic resonance imaging studies were done every 8 weeks during chemotherapy, and every 4 weeks if progressive disease was suspected. Tumor response was determined according to the Response Evaluation Criteria in Solid Tumors. Toxicity was assessed using the National Cancer Institute Common Toxicity Criteria version 2.0. The time to progression and survival time were also calculated.
Results: In patients with unresectable BTC, the overall response rate and the median time to progression for patients with partial response or stable disease was 66.7% and 5.68 months, respectively. Clinical benefit was observed in 3 patients with stable disease (50%). The median survival time was 5.2 months. In patients with recurrent BTC, 4 patients (33%) obtained partial responses and 2 patients (17%) had stable disease. The median time to progression was 8.2 months. Six of 12 patients (50%) obtained clinical benefit. The median survival time for cancer of the intrahepatic bile duct, the extrahepatic bile duct, and the ampulla of Vater were 2.8 months, 8.5 months, and 10.7 months, respectively. No significant correlation between the survival time and the resectability of the initial procedure (R number) was detected. The survival time for patients with a performance status of 0 or 1 was significantly longer than that for patients with a performance status of 2 (P=0.0051). Neither grade 3/4 hematologic toxicity nor grade 3/4 nonhematologic toxicity was observed. No treatment-related deaths were observed.
Conclusion: Gemcitabine monotherapy may provide a more favorable prognosis in patients with advanced BTC than does best supportive care alone. Moreover, this regimen may represent a therapeutic option for the adjuvant setting in patients with BTC.

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We present a rare case of hepatocellular carcinoma (HCC) in which spontaneous complete necrosis was confirmed with surgical resection. An 80-year-old man with HCC was referred to Nippon Medical School Tama Nagayama Hospital. The medical history included hypertension, managed with medication, and partial lobectomy of the lung owing to a lung schwannoma. A previously untreated abdominal aortic aneurysm, 51 mm in maximum diameter, was detected. The serum concentration of proteins induced by vitamin k antagonism or absence (PIVKA-2) was 14,300 mAU/mL, and that of alpha-fetoprotein was 184.2 ng/mL. Antibodies against hepatitis B surface antigens and hepatitis C virus were not detected in the serum. Computed tomography (CT) demonstrated a hypervascular tumor, 68 mm in diameter, in the left paramedian sector of the liver with washout of contrast medium in the delayed phase. An HCC in the left paramedian sector was diagnosed. Laparotomy was performed 40 days after CT scanning. Intraoperative ultrasonography showed that the HCC had shrunk to 30 mm in diameter. A left paramedian sectionectomy was performed. On macroscopic examination the surgical specimen was a firm mass, 30 mm in diameter, with a fibrous capsule. Histologic examination showed that the tumor in the cirrhotic liver had been completely replaced by central coagulative necrosis, circumferential fibrosis, and dense infiltrates of inflammatory cells. No viable HCC cells were observed in the coagulative necrosis. Organized thrombi in the hepatic artery were detected in the tumor. The tumor also contained multiple foci of old hemorrhage, ductular proliferation, and granulation tissue. The patient was discharged 10 days after the operation. After 1 month, the serum concentrations of PIVKA-2 (25 mAU/mL) and alpha-fetoprotein (5.9 ng/mL) had decreased to within their normal ranges.

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Like other forms of laparoscopic surgery, laparoscopic pancreaticoduodenectomy (Lap-PD) is a minimally invasive procedure that can greatly reduce bleeding during surgery. We performed Lap-PD for a case of intraductal papillary mucinous neoplasm. To remove the resected tissue from the body, we made a small incision directly above the line of transection of the distal pancreas (the cut stump). This procedure requires complex reconstructive procedures, which we performed through the same small incision. All reconstructive procedures, except for hepaticojejunostomy, were performed under direct visualization; hepaticojejunostomy was performed laparoscopically. The reconstructive surgery was effective and was as safe as open abdominal surgery. We also discuss the value of using an endoscopic linear stapler for Lap-PD pancreatic transection, to reduce extravasation of pancreatic fluid into the abdominal cavity during the resection of tumors involving the pancreatic ducts, such as intraductal papillary mucinous neoplasm.

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We present a case of breast reconstruction using bilaterally divided transverse rectus abdominis musculocutaneous flaps after the removal of severe siliconoma. In Japan, we have examined many patients who have had foreign substance injected into the breasts for augmentation. Most of these patients have had delayed complications. We believe that autologous tissue transfer is an ideal procedure for breast reaugmentation in patients who want to have artificial materials removed from the breasts but to maintain breast contour.

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The etiology of autism remains unclear, but relationships to cerebellar factors have been reported. We report 2 cases of infantile cerebellar pilocytic astrocytoma in children with autism spectrum disorder. Cerebellar tumors may be related to the pathogenesis of autism.

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Screening for anemia has been performed in schools in Japan for over 30 years. The long-term effect of the nuclear power plant disaster on the prevalence of anemia in school age children is unknown. This research was performed to evaluate the prevalence of anemia in school age children and to determine grade-level and gender-related reference hemoglobin (Hb) levels prior to the nuclear disaster. Data for this research were obtained from results of screening for anemia obtained by venous blood sampling in schools in 2002. Mean Hb levels were calculated for each grade level (elementary school grades 1-6 and junior high school years 1-3) and according to gender, and the prevalence of anemia was determined. In our research, Tokyo Health Service Association guidelines were used to determine reference Hb levels for anemia. We demonstrated that Hb levels in boys increased with age during childhood and adolescence (from 13.1 ± 0.7 g/dL in 7 year olds to 14.9 ± 1.1 g/dL in 15 year olds); in girls, Hb levels peaked at menarche (13.7 ± 0.8 g/dL in 12 year olds), decreasing slightly thereafter (13.4 ± 1.1 g/dL in 15 year olds). The prevalence of anemia was 0.26% in elementary school boys, 0.27% in elementary school girls, and 1.21% in junior high school boys. The prevalence of anemia in second- and third-year junior high school girls was lower than that in first-year junior high school girls. Among all junior high school girls, 5.73% had mild anemia. Iron-deficiency anemia is the commonest type of anemia in high school girls, secondary to the relative lack of iron due to menstruation, the growth spurt and exercise. Appropriate dietary therapy and treatment of anemia, together with education about the dietary prevention of anemia, are important to reduce the prevalence of anemia in high school students. When complete blood counts are performed in regions thought to be affected by the Fukushima nuclear power plant disaster, our report can serve as a reference during evaluation of Hb levels.

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