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The role of genetic inheritance in brain development has been well characterized, but little is known about the contributions of natural environmental stimuli, such as the effect of light-dark cycles, to brain development. In this study, we determined the role of light stimuli in neuronal cell migration to elucidate how environmental factors regulate brain development. We show that in early postnatal mouse cerebella, granule cell migration accelerates during light cycles and decelerates during dark cycles. Furthermore, cerebellar levels of insulin-like growth factor 1 (IGF-1) are high during light cycles and low during dark cycles. There are causal relationships between light-dark cycles, speed of granule cell migration, and cerebellar IGF-1 levels. First, changes in light-dark cycles result in corresponding changes in the fluctuations of both speed of granule cell migration and cerebellar IGF-1 levels. Second, in vitro studies indicate that exogenous IGF-1 accelerates the migration of isolated granule cells through the activation of IGF-1 receptors. Third, in vivo studies reveal that inhibiting the IGF-1 receptors decelerates granule cell migration during light cycles (high IGF-1 levels) but does not alter migration during dark cycles (low IGF-1 levels). In contrast, stimulating the IGF-1 receptors accelerates granule cell migration during dark cycles (low IGF-1 levels) but does not alter migration during light cycles (high IGF-1 levels). These results suggest that during early postnatal development light stimuli control granule cell migration by altering the activity of IGF-1 receptors through modification of cerebellar IGF-1 levels.

A 71-year-old male who had been diagnosed with rheumatoid arthritis 3 years previously developed multiple subcutaneous cysts on his buttock, elbow, knee, hand and back. The diameters of the cysts were 10-15 cm. The characteristic fluid and pathology of the cysts led to the diagnosis of multiple rheumatoid bursal cyst (MRBC). The patient was keen to treat the cyst on his buttock as it hampered his sitting position. However, it resisted several kinds of sclerotherapies, including absolute alcohol, OK-432, minocycline and dexamethasone. When the cyst grew further, it was resected surgically; however, the cyst recurred immediately. It was finally brought under control by injecting it with OK-432. The thick cyst wall, which resisted the various sclerotherapies, was removed surgically, and a new capsule developed inside the cavity; adding a sclerotant to newly made thin capsule made us possible to treat this resistant large bursal cyst., (Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Aims: The depth of dermal invasion, lymphatic invasion and tumour formation are thought to be predictors of nodal metastasis in extramammary Paget's disease (EPD). This study investigated the relationship between lymphangiogenesis and nodal metastasis in EPD., Methods and Results: Fifty cases (12 females and 38 males) with primary EPD of the external genitalia whounderwent surgical resection were studied. In 23 cases, inguinal lymph node dissection was performed, and nodal metastasis was found in eight cases. Lymphatic invasion and lymphangiogenesis were evaluated by D2-40 immunostain. Lymphangiogenesis was observed in 25 cases (50%). There were significant differences in the presence or absence of dermal invasion, depth of invasion, lymphatic invasion and nodal metastasis between the lymphangiogenesis group and non-lymphangiogenesis group., Conclusion: Dermal invasion and depth of dermal invasion are predictors for nodal metastasis in EPD. However, in the current study, we demonstrate that lymphangiogenesis is also a predictor of nodal metastasis in EPD., (© 2011 Blackwell Publishing Limited.)

Background: In cases of surgery for syndromic craniosynostosis with posterior flattering, it is not possible to achieve sufficient expansion of the skull through fronto-orbital advancement alone. Although it is necessary to expand the occipital region, the surgery is risky and highly invasive. We applied the distraction osteogenesis technique for skull expansion and performed occipital expansion and fronto-orbital advancement in succession., Methods: Three patients with syndromic craniosynostosis (2 with Crouzon syndrome, 1 with Pfeiffer syndrome) were treated in Juntendo University Hospital between 2002 and 2007. Using the distraction osteogenesis technique, we performed occipital advancement followed immediately by fronto-orbital advancement for 2 cases of Crouzon syndrome and performed fronto-orbital advancement followed by occipital advancement for a case of Pfeiffer syndrome., Results: In all of the cases, we were able to perform bone extension of 25 mm or more and achieve sufficient skull expansion for both of the frontal and occipital regions. Within 1 year after the surgery, in all of the cases, favorable osteogenesis was observed in the distraction gap, and there were no bone defects., Discussion: By using the distraction osteogenesis technique, the difficult procedure of occipital advancement can be performed relatively safely. In addition, as active expansion of the cranium is possible after the surgery, sufficient expansion of the cranium can be successfully performed to a degree that cannot be achieved through conventional methods. New bone is formed in the distraction gap, and there are no bone defects. The present method is extremely useful for skull formation in cases of syndromic craniosynostosis with posterior flattering.

Calcium phosphate bone paste (CPP) has been recently introduced as a reconstructive material in craniofacial surgery. However, we observed that mixing of blood and CPP tended to interfere with CPP hardening. In addition, CPP mixed with blood tended to be absorbed postoperatively. Hence, we used a rabbit model and applied CPP mixed with blood over defects in the skull to investigate the influence of blood on CPP. Calcium phosphate bone paste was mixed with blood for 1 minute and applied to the defects in the calvarial bone of rabbits. At 4 and 24 postoperative weeks, we histologically evaluated morphologic changes in the hydroxyapatite (HA). Our study revealed that HA was not absorbed when a small quantity of blood (15%) was mixed with CPP. However, HA was absorbed almost entirely when a large quantity of blood (30%) was mixed with CPP. In addition, we found that the porosity of HA was increased by the mixture of a small quantity of blood into CPP, and this addition stimulated osteogenesis in HA.

Ectopic neurons are often found in the brains of fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) patients, suggesting that alcohol exposure impairs neuronal cell migration. Although it has been reported that alcohol decreases the speed of neuronal cell migration, little is known about whether alcohol also affects the turning of neurons. Here we show that ethanol exposure inhibits the turning of cerebellar granule cells in vivo and in vitro. First, in vivo studies using P10 mice demonstrated that a single intraperitoneal injection of ethanol not only reduces the number of turning granule cells but also alters the mode of turning at the EGL-ML border of the cerebellum. Second, in vitro analysis using microexplant cultures of P0-P3 mouse cerebella revealed that ethanol directly reduces the frequency of spontaneous granule cell turning in a dose-dependent manner. Third, the action of ethanol on the frequency of granule cell turning was significantly ameliorated by stimulating Ca(2+) and cGMP signaling or by inhibiting cAMP signaling. Taken together, these results indicate that ethanol affects the frequency and mode of cerebellar granule cell turning through alteration of the Ca(2+) and cyclic nucleotide signaling pathways, suggesting that the abnormal allocation of neurons found in the brains of FASD and FSA patients results, at least in part, from impaired turning of immature neurons by alcohol., (Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)

The cephalic index is a method of assessing skull morphology in craniosynostosis. There are known racial differences; however, there are few reports on this index in Japan. In this study, we investigated the cephalic indices of Japanese children with normal brain development using axial slice computed tomography. Children presented to our institution because of head injuries but received no particular diagnosis. One hundred four children with normal brain development (62 males and 42 females) were divided into 7 age categories, namely, 4 categories for those younger than 1 year and 3 categories for those between 1 and 3 years. The cephalic index was calculated according to the following equation: (cephalic width/cephalic length) × 100. The cephalic indices by age groups were as follows: 86.7, 0 to 3 months (n = 21); 87.5, 4 to 6 months (n = 9); 89.2, 7 to 9 months (n = 16); 86.3, 10 to 12 months (n = 9); 85.9, 1 year (n = 25); 86.3, 2 years (n = 15); and 83.7, 3 years (n = 9). In this study, the cephalic indices of Japanese children with normal brain development tended to be more brachycephalic than those of white children, as reported by Haas and Waitzman. Thus, we formulated the classification of current cephalic indices of children with normal brain development in Japan.

The supernumerary nostril is a very rare congenital nasal abnormality, and several cases have been reported in the literature since 1906 when the first case was reported by Lindsay. In the other previously reported cases, the supernumerary nostril typically could present unilaterally or bilaterally, and it was therefore called a double nose, with most reported cases being unilateral. At our institution, we encountered a patient with a supernumerary nostril that was located above the left nostril. We thus performed an operation on this supernumerary nostril and obtained good results and a successful postoperative course. We herein present our findings while also discussing the pertinent literature.

The use of porous concrete columns to decrease the amount of zinc in stormwater runoff is examined. The concentration of zinc in a simulated stormwater fluid (zinc acetate solution), fed through concrete columns (slashed circle10x10cm) decreased by 50-81%, suggesting physical adsorption of zinc by the porous concrete. We propose the use of porous concrete columns (slashed circle50x10cm) as the base of sewage traps. Longer-term, high-zinc concentration monitoring revealed that porous concrete blocks adsorb 38.6mgcm(-3) of zinc. A period of no significant zinc runoff (with an acceptable concentration of zinc in runoff of 0.03mgL(-1), a zinc concentration equal to the Japanese Environmental Standard) is estimated for 41years using a 1-ha catchment area with 20 porous concrete sewage traps. Scanning electron microscopy of the porous concrete used in this study indicates that the needle-like particles formed by hydration action significantly increase zinc adsorption. Evidence suggests that the hydrant is ettringite and has an important role in zinc adsorption, the resulting immobilization of zinc and the subsequent effects on groundwater quality., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Median cleft lip is usually divided into true and false when being discussed. Owing to recent developments of diagnostic imaging methods that have improved the accuracy, the presence of an intermediate type of median cleft lip, which cannot simply be divided into true and false, has been suggested. However, the simple method of classification is still clinically valuable. We have previously reported in this Journal a case of median cleft lip with 2 upper labial frenums. In the present study, based on our experience with false median cleft lip, we set forth a hypothesis that 2 upper labial frenums can be found in true median cleft lip, whereas no upper labial frenum is found in false median cleft lip. A review of the results of previous Japanese cases (7 true and 4 false cases) supported our hypothesis. We also reviewed one of our cases of right cleft lip accompanied by holoprosencephaly and discuss the case from the developmental perspective. The shape of the upper labial frenum may be a factor that can be used for clinically classifying intermediate median cleft lip into either true or false in cases that are otherwise difficult to classify.

Phosphoglycerate mutase (PGAM) is an enzyme of intermediary metabolism that converts 3-phosphoglycerate to 2-phosphoglycerate in glycolysis. Here, we discovered PGAM5 that is anchored in the mitochondrial membrane lacks PGAM activity and instead associates with the MAP kinase kinase kinase ASK1 and acts as a specific protein Ser/Thr phosphatase that activates ASK1 by dephosphorylation of inhibitory sites. Mutation of an active site His-105 in PGAM5 abolished phosphatase activity with ASK1 and phospho-Thr peptides as substrates. The Drosophila and Caenorhabditis elegans orthologs of PGAM5 also exhibit specific Ser/Thr phosphatase activity and activate the corresponding Drosophila and C. elegans ASK1 kinases. PGAM5 is unrelated to the other known Ser/Thr phosphatases of the PPP, MPP, and FCP families, and our results suggest that this member of the PGAM family has crossed over from small molecules to protein substrates and been adapted to serve as a specialized activator of ASK1.

Multiple-suture synostosis is a rare condition among patients with craniosynostosis. Their cranial shapes demonstrate various types depending on the fused sutures, and it tends to be less consistent in comparison to single-suture synostosis. The details regarding surgical intervention for multiple-suture synostosis have rarely been documented. This report presents 4 patients with nonsyndromic multiple-suture synostosis who were incidentally diagnosed as school-aged children. The age at the time of the surgery ranged from 7 to 11 years. All of the patients demonstrated digital printings on radiographs and an increased intracranial pressure. They underwent cranial expansion using the technique of distraction osteogenesis. In 3 patients, a pi osteotomy was performed; however, the osteotomized bone was not detached from the underlying dura. Four distraction devices were applied. In one patient, an occipital osteotomy was performed, and 2 distraction devices were applied. Distraction was completed in all patients, and the results of surgery were satisfactory. Large bony gaps are generally created by the conventional course of skull expansion. In older children, the bone defects are optimally treated by bone grafts. To harvest bone grafts, it is preferable to split the cranial bone. In this series, however, the calvarial bones were so thin that they could not be split. Therefore, the technique of distraction osteogenesis was used. Cranial distraction is a reliable and less invasive modality. In addition, it can allow for skull expansion without bone grafting in school-aged children.

Radial glia are highly polarized cells that serve as neuronal progenitors and as scaffolds for neuronal migration during construction of the cerebral cortex. How radial glial cells establish and maintain their morphological polarity is unknown. Using conditional gene targeting in mice, we demonstrate that adenomatous polyposis coli (APC) serves an essential function in the maintenance of polarized radial glial scaffold during brain development. In the absence of APC, radial glial cells lose their polarity and responsiveness to the extracellular polarity maintenance cues, such as neuregulin-1. Elimination of APC further leads to marked instability of the radial glial microtubule cytoskeleton. The resultant changes in radial glial function and loss of APC in radial glial progeny lead to defective generation and migration of cortical neurons, severely disrupted cortical layer formation, and aberrant axonal tract development. Thus, APC is an essential regulator of radial glial polarity and is critical for the construction of cerebral cortex in mammals.

A nasal bone fracture is usually repositioned using either Walsham or Asch forceps. However, accurate repositioning is often difficult. We therefore performed a repositioning technique using the little finger in 10 patients with a new nasal fracture. The results were satisfactory in all of the patients. Although medical experts may consider our method to be primitive, we believe that our method is both safe and effective, because the operator can recognize both the fractured part and its actual condition using the little finger. With this method, the occurrence of unnecessary new fractures can be prevented, in addition to minimizing the degree of mucosal damage and the occurrence of nasal hemorrhage. Furthermore, we consider that this technique can also reduce the occurrence of postoperative deformities due to the reduced mucosal contracture with this treatment modality. Even if the use of an instrument is deemed necessary, such as in treating saddle-nose-type fractures, initially feeling the fracture with the little finger will still allow for a more precise fracture reduction. We therefore consider our method to be both safe and effective at the initial stage of diagnosis and for the treatment of patients presenting with nasal bone fractures.

In extramammary Paget's disease (EPD), lymph node metastasis occasionally occurs and nodal metastasis influences prognosis. Therefore, in the present study a predictor of nodal metastasis in EPD was examined. Surgical specimens from 54 cases of EPD in the external genitalia were examined on D2-40 immunostain. In 23 cases, dissection of the inguinal lymph nodes was performed. Dermal invasion occurred in 24 patients (44.4%). Nodal metastasis was found in seven patients who had dermal invasion >1 mm. In non-metastatic patients, three had dermal invasion <0.5 mm in depth. Lymphatic invasion was well detected on D2-40 immunostain, and invasion was found in five patients. All four patients with lymphatic invasion, in whom lymph node dissection was performed, had nodal metastasis. However, three patients with dermal invasion, who did not have lymphatic invasion, did have nodal metastasis, and the depth of invasion was >1 mm. Dermal invasion (P < 0.001) and lymphatic invasion according to D2-40 immunostain (P = 0.001) had a positive correlation with nodal metastasis. In conclusion, evaluation using a combination of lymphatic invasion according to D2-40 immunostain and depth of dermal invasion is a strong predictor of nodal metastasis in EPD.

Occasional cases of malignant seeding of cancer cells along the catheter tract, particularly affecting the skin, have been reported after percutaneous biliary drainage. Although radical resection of the abdominal wall may achieve long-term postoperative survival, reconstruction of large abdominal defects that cannot be closed primarily is problematic. We describe the successful surgical repair of a full-thickness defect of the abdominal wall using a free tensor fascia lata musculofasciocutaneous flap anastomosed to the intraabdominal gastroepiploic vessels.

Background: The technique chosen to reconstruct anterior lamellar defects of the upper eyelid requires careful consideration. We modified pre-existing techniques used to reconstruct anterior lamellar defects after tumour resection and have called this procedure a hemi-orbicularis oculi switch flap., Methods: This musculocutaneous flap is elevated with underlying orbicularis and its base abuts the anterior lamellar defect. The flap, which is half the height of the defect, is elevated and inset to cover the defect. Then, taking into consideration the extensibility of upper eyelid skin, the remainder of the defect and the donor site are closed directly., Results: Five patients with basal cell carcinoma, haemangioma, and xanthoma of the upper eyelid were treated by this method. All flaps survived and complications were minimal. Aesthetically and functionally good results were obtained by this method., Conclusions: We have developed a surgical method for the reconstruction of anterior lamellar defects of the upper eyelid. The proposed method is technically simple and safe and provides consistent results for a potentially wide variety of upper eyelid tumours.

Background: Full-thickness skin defects with exposed bone are often hard to heal. The lack or delayed re-vascularization is considered one of the major causes, and the periosteum is also suggested to have an important role in tissue regeneration., Materials and Methods: Full-thickness skin defect wounds with exposed bone were made in the parietal region of Wister rats. The periosteum of the exposed parietal bone was removed in the periosteum-lacking group, but maintained in the control group (periosteum-intact group). The wound was covered by an artificial dermis made of collagen. The wound healing process was histologically compared. Double immunostaining of alpha-smooth muscle actin (SMA) and von Willebrand factor (vWF) was used for re-vascularization examination, and the blood vessel density in the artificial dermis was quantified., Results: The density of the blood vessels in the uninjured parietal tissue was approximately 80 vessels/mm(2). To reach this density, 7 and 21 days were required for the control (periosteum-intact) and the periosteum-lacking groups, respectively. This coincided with complete revascularization, fibroblast migration and the reentry of blood vessels to the upper layer of the wound were observed., Conclusion: The described results support the importance of the periosteum in the full-thickness skin defect healing process.

Various reports describe surgical techniques for closing a meningomyelocele defect. We have used a combination flap consisting of a vertical bipedicled flap and V-Y advancement flap and used this technique in the successful repair of 11 meningomyelocele defects. The vertical bipedicled flap enhances the blood supply to the V-Y advancement flap with no sacrifice of muscle tissue. This flap can easily be moved to the midline, and the donor area can be primarily sutured with no complications. Our method has several advantages compared with previously reported methods: 1) no skin grafts are needed; 2) no muscle tissue is killed; 3) it is simple and easy, leading to less blood loss and minimal operative time; and 4) it is safe and produces reliable results while eliminating wound dehiscence and skin necrosis.

The purpose of the treatment of mandibular fractures is to restore proper dental occlusion and stable temporomandibular joint movement, as well as the reduction of the displaced fracture. Consideration must be given to the selection of the most appropriate surgical and rehabilitation methods in such patients. Typical surgical methods for the treatment of mandibular fractures include the arch bar method or plating at the location of the fracture combined with fixing the mandible to the maxilla using the arch bar method. However arch bars and circumdental wires, which require teeth for fixation, damage teeth and periodontal tissue, and tend to be uncomfortable for patients during the fixation period. Moreover, daily maintenance of oral hygiene is difficult for patients with an arch bar. Surgeons are also exposed to the risk of blood-transmitted diseases through skin punctures by wires when affixing these devices. For these reasons, we chose to study the potential of the MMFS method, which is thought to lessen all of the following problems: tissue damage, operating time, patient discomfort, and possible exposure to percutaneous infectious disease due to puncture of gloves and skin by the wires. We demonstrated the utility of the MMFS method in the present study.

Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, the response to radiotherapy differs among individual tumors. Our objective here was to identify a set of discriminating genes that can be used for characterization and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal cancer patients who underwent preoperative radiotherapy were studied. Biopsy specimens were obtained from rectal cancer before preoperative radiotherapy. Response to radiotherapy was determined by histopathologic examination of surgically resected specimens and classified as responders or nonresponders. By determining gene expression profiles using human U95Av2 Gene Chip, we identified 33 novel discriminating genes of which the expression differed significantly between responders and nonresponders. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with an accuracy of 82.4%. The list of discriminating genes included growth factor, apoptosis, cell proliferation, signal transduction, or cell adhesion-related genes. Among 33 discriminating genes, apoptosis inducers (lumican, thrombospondin 2, and galectin-1) showed higher expression in responders whereas apoptosis inhibitors (cyclophilin 40 and glutathione peroxidase) showed higher expression in nonresponders. The present study suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy to establish an individualized tailored therapy for rectal cancer. Global expression profiles of responders and nonresponders may provide insights into the development of novel therapeutic targets.

Background: Maintaining sufficient blood flow to the gastric tube after a subtotal esophagectomy for esophageal cancer is crucial for decreasing esophagogastric anastomotic leakage., Methods: After subtotal esophagectomy for esophageal cancer, the supercharge technique was performed in 21 esophageal reconstruction patients to additionally revascularize the gastric tube using the splenic artery and vein, external carotid artery, and internal jugular vein. Operative results of the supercharge group were retrospectively compared with those of the control group (patients not receiving the technique)., Results: Both operation time and operative blood loss in the supercharge group were significantly longer and larger than those of the control group. However, the incidence of anastomotic leakage was significantly lower in the supercharge group than in the control group., Conclusion: This practical supercharge technique reduces leakage during esophageal anastomosis.

Background/aims: Predictive indicators of radiosensitivity in rectal cancer are required in order to avoid unnecessary preoperative radiotherapy. Telomeres are specialized structures at the ends of chromosomes that protect against that such as irradiation. Lower telomerase activity has been reported to be related to radiosensitivity in vitro or vivo. The aim of this study was to examine the possible role of telomerase reverse transcriptase expression, which is correlated to telomerase activity, in determining tumor radiosensitivity, local recurrence, and disease-free survival in patients with rectal carcinomas., Methodology: We studied 96 cases with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, the number of cells stained positive for telomerase reverse transcriptase protein was evaluated by immunohistochemistry., Results: The expression pattern of telomerase reverse transcriptase protein correlated with tumor radiosensitivity (P=0.0007). All tumors that had a high percentage of telomerase reverse transcriptase positive cells were radioresistant. High telomerase reverse transcriptase expression pattern is a predictive marker for high local recurrence or poor survival in patients with rectal cancer (P=0.011, P=0.0005). Telomerase reverse transcriptase expression and histopathological grade were significant prognostic variables for disease-free survival in the multivariate analysis (P=0.0003, P=0.0091)., Conclusions: Telomerase reverse transcriptase raises the predictive possibility of tumor radiosensitivity in rectal cancer. Telomerase reverse transcriptase might be a useful parameter for patient selection for preoperative radiotherapy in rectal carcinoma.

Background/aims: Ku protein stimulates DNA repair and signals the damage/stress responses, which may affect apoptosis and cell proliferation. The expression of Ku70 has been reported to be related to cell proliferation in a human gastric cancer cell line. However, in colorectal carcinoma, the clinical significance of Ku70 expression remains unclear. We examined the expression pattern of Ku70 in sporadic colorectal cancer and its relation to clinicopathological parameters and survival., Methodology: We studied 101 consecutive cases of advanced colorectal carcinoma. In resected specimens, the number of cells stained positive for Ku70 protein was evaluated by immunohistochemistry., Results: The percentage of cells expressing Ku70 in different tumors ranged from 4.2-99.7%. The elevated Ku70 expression group comprised 52 of 101 cases (52%). No significant correlation was seen between Ku expression pattern and the clinical parameters except depth of invasion. pTNM stage, histopathological grade and Ku70 were significant variables for prognosis of survival in the multivariate analysis., Conclusions: This is the first report correlating reduced survival with elevated expression of Ku protein in colorectal adenocarcinoma. Ku may be a new prognostic marker useful for selecting adjuvant treatment strategies.

Background/aims: The local recurrence ratio following surgery alone is higher in patients with rectal cancer than in those with colon cancer. Preoperative radiotherapy reduces the rate of local recurrence and improves the chances of survival in patients with resectable advanced rectal carcinoma. Identification of predictive indicators of radiosensitivity is useful in selecting patients best suited for preoperative radiotherapy and thus helps to avoid unnecessary preoperative treatment. We investigated whether the combination of Ku, p53, p21, and p16 predicted tumor radiosensitivity., Methodology: We studied 96 cases with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, all immunoreactive nuclei of cells stained positive for Ku, p53, p21, and p16 were evaluated by immunohistochemistry. The expression of p53, p21 and p16 in more than 5% of tumor cells were defined as positive, whereas both Ku70 and Ku86 protein in more than 70% of such cells were defined as Ku positive. The expression patterns of Ku, p53, p21, and p16 were examined for association with tumor radiosensitivity, which was determined according to the criteria of histopathologic assessment of radiotherapy effects., Results: Univariate analysis showed a correlation between the expression patterns of Ku, p53, p21, and p16 and tumor radiosensitivity, while multivariate analysis showed that the expression pattern of Ku and p16 significantly correlated with tumor radiosensitivity. The combination of Ku and p16, or Ku, p53, p21 and p16 was therefore a good predictive marker for tumor radiosensitivity., Conclusions: These findings tend to support the hypothesis that the combination of Ku, p53, p21, and p16 expression after radiotherapy can act as a marker for radiosensitivity. Further investigation is needed, as the number of cases in this study was limited.

We treated four patients with scaphocephaly using a combination of distraction and contraction techniques and achieved satisfactory results. Radial osteotomies in the frontal and occipital bones flattened these abnormal bossing bones and accelerated the disappearance of bony bumps created by distraction. This technique facilitates the achievement of the desired shape of the skull through fine adjustments of the distraction and contraction devices.

Background/aims: Tumor-specific antigens such as Melanoma-associated antigens could be attractive targets for immunotherapy. It will be a great help for cancer immunotherapy to distinguish what types of tumor expresses tumor-specific antigen., Methodology: We investigated the expression pattern of MAGE-A1 by immunohistochemical typing methods in human colorectal cancers obtained from consecutive patients undergoing surgical treatment at the hospital of the University of Tokyo., Results: In 35 of 89 cases (39%), MAGE-A1 positive immunoreactivity was detected in the malignant glands. MAGE-A1 positive immunoreactivity was significantly higher among the patients under the age of 70 than among those 70 years of age and older (p=0.04). Among the patients under the age of 70, the tumors located in the distal colon (descending colon, sigmoid colon and rectum) showed significantly more positive MAGE-A1 immunoreactivity than those in the proximal colon (cecum, ascending colon and transverse colon) (p=0.04). The expression pattern of MAGE-A1 was not associated with gender, size, depth, histological type, vessel invasion, lymphatic invasion, lymph nodal invasion or stage of disease., Conclusions: Relatively better results can be expected with MAGE-A1 immunotherapy among patients with distal colon cancer under the age of 70.

Reconstruction for polysyndactyly of the toes aims at cosmetic improvement. A previous method that uses a skin graft has inherent disadvantages of mismatched pigmentation between the graft and the surrounding skin and scar formation at the donor site. The authors' new improved surgical technique for the treatment of polysyndactyly of the toes does not require a skin graft and therefore avoids these problems. The authors designed a subcutaneous flap from the distal portion of a rectangular flap of skin from the dorsal side of the interdigital webbing and moved the former flap to the sidewall of the base of a toe. Both flaps are the same size; therefore, an interdigital space had to be of sufficient size to accommodate both of them. To ensure an adequate blood supply to the flap, careful handling of the subcutaneous flap is essential for success. This procedure can apply to polysyndactyly of the fourth, fifth, and sixth toes when the fourth and fifth toes adhere over the distal side of the distal interphalangeal joint and when the skin on the dorsal side of the fifth toe, regarded as the excessive one, is at lease twice the size of the dorsal rectangular flap. Ten patients with polysyndactyly of the toe were treated with this method. Aesthetically good results were obtained.

The accurate diagnosis and treatment of posterior plagiocephaly have been a source of controversy. The unilateral lambdoid synostosis that is characterized by flattening of ipsilateral occipital bone is a rare type of craniosynostosis. An 8-month-old infant with unilateral lambdoid synostosis is reported. The patient exhibited right occipital flattening, mastoid bulge, and right frontal bone prominence, with the right auricle displaced anteroinferiorly on gross examination. A Towne projection radiograph of the skull and three-dimensional computed tomography scans revealed that the right lambdoid suture was prematurely fused. Correction of the cranial shape was performed using distraction osteogenesis combined with a barrel stave osteotomy. Significant improvement in the skull was observed 1 year after surgery.

Recent evidence supports the use of end-to-side neurorrhaphy for the treatment of certain peripheral nerve disorders. However, the mechanism by which nerves regenerate following this procedure is still unclear. To address this question, the authors designed a new end-to-side coaptation model in rats in which the donor nerves were uninjured. The regenerated axons at the coaptation site were observed directly using fluorescent dye as the neural tracer. The sciatic nerve from adult Wistar rats was transplanted between the left and right median nerves. Fifteen rats were divided into three groups. In group I, the donor (right median) nerve was sutured end to side to the divided grafted nerve using a noninjury technique. In group II, the aponeurosis of the spinal muscles was harvested and the sciatic and right median nerves were coapted end to side noninjuriously by wrapping them in the excised aponeurosis. In group III, a perineurial window was created and a partial neurectomy was carried out at the suture site, after which the sciatic and right median nerves were sutured end to side. Sixty days after the operation, nerve regeneration was evaluated by recording action potentials in the grafted nerve, by performing electromyography in the flexor muscles in the forearm, and by histological examination. The grafted nerves were fixed and sectioned, the number of regenerated nerve fibers was counted, and axonal diameters were measured. Fluorescent dye crystal was used, in conjunction with confocal microscopy, to observe the regenerated axons at the co-aptation site. The results showed that nerve regeneration had occurred in the animals, as determined electrophysiologically and histologically. Both the right and left flexor muscles of the forearm contracted simultaneously as a result of indirect electric stimulation of the grafted nerve, which suggests that the regenerated nerve was physiologically connected with the donor nerve. Nerve fiber counts did not show any differences among groups (p > 0.05), but axonal diameters were significantly greater in group III than in the other two groups. Fluorescent dye staining revealed the presence of regenerated nerve fibers beyond the coaptation site. In group III, the regenerating nerves were observed within the whole section of the coaptation site and collateral sprouting was found to occur even at a site distal to the suture. From these results, the authors conclude that in end-to-side neurorrhaphy, nerve regeneration occurs by collateral sprouting from the donor nerve.

Background/aims: The EDG-2 (endothelial cell differentiation gene-2) has been characterized as one of the high-affinity receptors of lysophosphatidic acid: an extracellular lipid mediator which can induce tumor progression. Recent studies have revealed that EDG-2 plays an important role in various pathological events including cell proliferation and tumor development. The investigation of EDG-2 is thus considered important for eliciting the mechanism of tumorigenesis. However, in colorectal tissue, the clinical significance of EDG-2 expression remains unclear. In the current study, we examined the immunohistochemical expression of EDG-2 in colorectal mucosa and adenoma, and clarified its relation with the clinicopathological features., Methodology: One hundred and sixty-one colorectal polyps were resected endoscopically or surgically at our institute from 2000 to 2001. According to the degree of dysplasia, adenomas were grouped into two categories: low-grade (mild or moderate dysplasia) and high-grade (severe dysplasia or carcinoma in situ). We investigated EDG-2 expression by immunohistochemistry., Results: EDG-2 was expressed almost exclusively in the cytoplasm in colorectal normal mucosa and adenoma. EDG-2 expression in normal mucosa and adenoma was 8% and 76%, respectively. EDG-2 expression was increased in low-grade adenoma compared with that in normal mucosa (P < 0.001). EDG-2 expression was significantly greater in adenomas with larger diameters (P < 0.001)., Conclusions: We demonstrated that EDG-2 expression was increased in the early stage of adenoma. A significant correlation between EDG-2 expression and the size of the adenomas suggests that EDG-2 may play an important role in the growth of these adenomas.

Background/aims: P16, the tumor suppressor gene, plays a crucial role in the most important regulatory pathway involved in the G1/S transition, but its role in gastrointestinal neoplasia remains unclear., Methodology: To evaluate the possible p16 role in the development of colonic neoplasms, the authors studied p16 immunohistochemical expression of 84 lesions of colorectal cancers, 6 lesions of hyperplastic polyps, 59 lesions of adenomas and 8 lesions of carcinoma in adenoma. Immunohistochemical staining was processed by streptavidin biotin technique. The degree of expression pattern was classified into four types: absent, scattered, or nested, diffuse. Also, the correlation between immunohistochemical expression pattern and clinicopathological features was evaluated., Results: Compared with normal colonic mucosa, in which virtually no p16 expression was observed, p16 was overexpressed in hyperplastic polyps (33%:2/6) adenomas (46%:27/59), carcinoma in adenoma (88%:7/8) and in adenocarcinomas (98%:82/84). In colorectal cancers, when divided into positive (diffuse or nested) and negative (absent or scattered) subgroups, the negative group showed a higher ratio of lymphatic infiltration (p = 0.04), a higher ratio of deeper invasion (p < 0.01) and a higher ratio showing histology of mucinous carcinoma or poorly differentiated adenocarcinoma (p < 0.01)., Conclusions: In colorectal cancers, a significant correlation of reduced p16 expression and lymphatic invasion was observed, which suggested and colorectal cancers with reduced p16 expression have more aggressive potential of lymphatic infiltration. Also a significant correlation between the overexpression of p16 and tumor progression was demonstrated.

Lymphangioma of the tongue is relatively rare and may cause facial structural deformity. Using a combination of a V-shaped and central resection, we successfully treated a 6-year-old girl who had massive lymphangioma of the tongue. Postoperatively, her tongue was located completely within her mouth with good cosmetic results. Sensory and motor nerves to the tongue appeared to be intact. Her speech was also improved.

Background/aims: DPD (dihydropyrimidine dehydrogenase) activity shows a correlation with 5-fluorouracil chemosensitivity. To quantify DPD activity is important for selection of chemosensitive cases of not only sporadic colorectal cancer but also rectal cancer with preoperative radiotherapy. However, it is not cost-effective. We investigated the relation between the immunohistochemical expression pattern of DPD and its activity in rectal cancer treated with radiotherapy, and compared the immunohistochemical DPD expression pattern of preradiation biopsy specimens with that of resected tissues., Methodology: DPD expression pattern of preradiation biopsy specimens were compared with that of resected tissues. Eighteen colorectal cancer tissue samples were obtained after surgery from October 2000 to January 2001. DPD activity was quantified by sandwich enzyme-linked immunosorbent assay. The streptoavidin-biotin peroxidase complex technique was used for the immunohistochemical expression pattern., Results: DPD was stained in the cytoplasm of cancer cells. There was a significant correlation between the immunohistochemical expression pattern of DPD and its activity in tumor tissue treated with or without radiotherapy. The immunohistochemical expression pattern of preradiation biopsy specimens was almost the same as that of resected tissues., Conclusions: The immunohistochemical expression pattern of DPD correlated with its activity in tumor tissue treated with preoperative radiotherapy. Immunohistochemical evaluation is considered to be an effective method of predicting the sensitivity to 5-fluorouracil of rectal cancer treated with preoperative radiotherapy.

The identification of predictive indicators of radiosensitivity is extremely useful in selecting patients suited for preoperative radiotherapy and avoiding unnecessary preoperative treatment. In this study, we evaluated the possible role of the immunohistochemical expression pattern of p53 and Ku70 protein in determining tumor radiosensitivity in rectal cancer before preoperative irradiation. We examined pretreatment biopsy materials from 111 patients by immunohistochemistry. The expression pattern of p53 and Ku70 was evaluated for association with tumor radiosensitivity, which was defined according to the criteria of the Japanese Research Society for Cancer of the Colon and Rectum. There was a significant correlation between the expression pattern of p53 and tumor radiosensitivity (P = 0.045); Ku70 and tumor radiosensitivity (P < 0.001); and the combination of p53 and Ku70, and tumor radiosensitivity (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in both p53 and Ku70-positive cases for radioresistance were all superior to those of the group positive for p53 alone. In conclusion the examination of the combination of p53 and Ku70 may predict the radiosensitivity of rectal cancer before preoperative irradiation.

Background: Preoperative radiotherapy reduces the rate of local recurrence and improves the chance of survival in patients with resectable, advanced rectal carcinoma. However, because not all tumors respond similarly to radiation, sorting out suitable patients is required to irradiate tumors rationally. The authors examined the possible role of Ku protein in determining tumor radiosensitivity and disease free survival in patients with rectal carcinoma., Methods: The authors studied 96 patients with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, the number of cells that were stained positive for Ku protein was evaluated by immunohistochemistry. The expression pattern of Ku protein was examined for an association between tumor radiosensitivity (which was determined according to T classification downstaging, complete pathologic response, or Response Evaluation Criteria in Solid Tumors) and disease free survival., Results: There was a high degree of correlation between the percentage of cells that expressed the 70-kDa Ku protein (Ku70) and the 86-kDa Ku protein (Ku86) in the tumor sections (correlation coefficient = 0.85; P < 0.001). The expression pattern of Ku protein was correlated not only with tumor radiosensitivity but also with disease free survival. Pathologic TMN classification, histopathologic grade, and Ku70 expression were significant prognostic variables for disease free survival in a multivariate analysis (P = 0.0031, P = 0.030, and P = 0.023, respectively)., Conclusions: Ku70 and Ku86 raise the predictive possibility of tumor radiosensitivity. Ku may be a useful parameter for selecting patients with rectal carcinoma for preoperative radiotherapy., (Copyright 2002 American Cancer Society.)

Aplasia cutis congenita is a rare condition characterized by the congenital absence of skin. The authors report a case of aplasia cutis congenita of the scalp associated with bilateral coronal synostosis. Simultaneous fronto-orbital advancement and skull reconstruction for large defect at the fontanelle were performed in the initial operation. A tissue expander made it possible to resect most of the hairless scar and totally cover the reconstructed defect and skull. During the second stage, the residual hairless scar was completely covered with hair-bearing scalp by tissue expansion and the residual skull defects were successfully reconstructed with split calvarial bone grafting.

Background: Extended lymphadenectomy including lateral node dissection (EXT-L) contributes to a low incidence of local recurrence of lower rectal cancer. However, EXT-L is frequently associated with impairment of sexual and urinary function. We therefore compared the effectiveness of preoperative radiotherapy with that of EXT-L., Methods: One hundred fifteen patients were studied. Seventy-eight patients underwent preoperative radiotherapy with a total dose of 50 Gy (Rad[+] group), and 37 did not (Rad[-] group). Seventy-five patients received EXT-L (EXT-L[+] group), and 40 did not (EXT-L[-] group). Patients were further divided into 4 subgroups (Rad[+]&EXT-L[-], Rad(+)&EXT-L[+], Rad[-]&EXT-L(+), and Rad[-]&EXT-L[-]), and clinicopathologic features were examined. In the Rad(+) group, the relation between the p53 gene and survival was also examined., Results: There was a significant difference in disease-free survival between the Rad(+) and Rad(-) groups (5-year disease-free survival rate, 74.6% vs 45.9%; P =.006). However, there was no significant difference between the Rad(+)&EXT-L[-] and Rad[-]&EXT-L(+) groups. The p53 gene status did not affect survival in the Rad(+) group., Conclusions: This study suggests that in terms of curative effect, preoperative radiotherapy can be one alternative therapy in place of EXT-L for patients with lower rectal cancer.

Several perforator-based flaps have been developed recently and, although preoperative evaluation of perforator vessels is important, the conventional method using the Doppler flowmeter is still being used. The authors tried to identify perforator vessels in the abdominal region using scanning laser Doppler imaging and then compared the results with those obtained using an ultrasonic Doppler flowmeter in 10 healthy volunteers. The scanning laser Doppler detected several perforator vessels (range, 2-5 vessels; mean, 3.1 vessels) within a 7.5 x 7.5-cm area in the abdominal region. These results suggest that scanning laser Doppler imaging is a useful tool in the identification of perforator vessels.

[reaction: see text] The Sc(OTf)3/FERRODIOL (2) complex was prepared at -78 degrees C in CH2Cl2 in the presence of 2,6-lutidine and MS 4A. The chiral scandium Lewis acid-catalyzed asymmetric Diels-Alder reaction of cyclopentadiene (3) with 3-acyloxazolidin-2-ones (4) effectively produced the adduct (5) in a high yield with good selectivity, i.e., endo/exo = 90:10 up to 91% ee (endo).

Background: Ependymoma is a tumor that usually develops in the central nervous system and is extremely rare in the ovary. The first case of ovarian ependymoma was reported by Kleinman et al. (Kleinman GM, Young RH, Scully RE. Ependymoma of the ovary: report of three cases. Hum Pathol 1984;15:632-8.) in 1984, and only eight cases have been reported since then. Criteria for the histopathologic diagnosis of ependymoma are already established, but there has been no investigation of the cytologic diagnosis of ovarian ependymoma., Methods: An imprint cytologic specimen was obtained from a recurrent ovarian ependymoma. The imprint cytologic features were compared with the findings of histologic examination, immunostaining, and electron microscopy., Results: Imprint cytology revealed clusters of small cells with tapering cytoplasmic processes and a round nucleus. On the basis of these features, a neurogenic tumor could be included in the differential diagnosis. Furthermore, many rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes, characteristic of ependymoma, were found. The presence of ependymal rosettes and perivascular pseudorosettes also were confirmed by the histopathologic examination. Together with positive immunostaining for glial fibrillary acidic protein, this led to the diagnosis of ependymoma, which also was supported by the electron microscopic findings., Conclusions: Careful observation of the imprint cytologic specimen of an ovarian ependymoma should reveal numerous rosette-like collections of cells that were suggestive of ependymal rosettes or perivascular pseudorosettes. In addition, if we remember that ependymoma can develop in the ovary and find cells with tapering processes that suggest a neurogenic tumor, it may be possible to detect histologic features characteristic of ependymoma by the imprint cytology. To our knowledge, this is the first report on the imprint cytologic diagnosis of ependymoma originating in the ovary., (Copyright 2001 American Cancer Society.)

Cisplatin (DDP) is one of the key drugs used to treat patients with ovarian cancer, although resistance to DDP can occur. Paclitaxel and SN-38 (an active metabolite of irinotecan (CPT-11)) are two drugs that are effective in patients with DDP-resistant ovarian cancer. To study how these drugs may overcome the intrinsic and / or acquired resistance of cancer cells to DDP, we investigated the effect of a combination of DDP with paclitaxel and a combination of DDP with SN-38 on three ovarian cancer cell lines, RTSG (intrinsically resistant cell line), KF (DDP-sensitive cell line), and KFra (acquired resistant cell line obtained from KF). We found that these combinations showed additive to synergistic antitumor activity. A time-dependent platinum (Pt) accumulation was observed in the DDP-sensitive KF cell line, while a decrease occurred in the KFra cell line. Little accumulation was observed in RTSG. Intracellular Pt accumulation was increased in all three cell lines by exposure to paclitaxel or SN-38. Ouabain, a Na(+),K(+)-ATPase inhibitor, decreased Pt accumulation in KF and KFra cell lines and inhibited the paclitaxel- and SN-38-induced increases in Pt accumulation in these cell lines. When we assessed the mRNA levels of the multidrug resistance-associated protein (MRP), which may be an efflux pump for DDP, the combination of paclitaxel or SN-38 with DDP down-regulated these levels, which are up-regulated by DDP alone. These results suggest that paclitaxel and SN-38 overcome DDP resistance of ovarian cell lines by controlling intracellular accumulation of DDP via both the influx and efflux systems.