Carotid Endarterectomy for a Case with an Extremely Twisted Internal Carotid Artery.

The internal carotid artery (ICA) typically runs posterolaterally to the external carotid artery (ECA) at the level of the common carotid artery (CCA) bifurcation in the neck. The "twisted ICA" is an anatomical variation, wherein the ICA is medial to the ECA. Several studies on the twisted ICA have discussed its anatomical definition, incidence, clinical features, and surgical results in patients with luminal stenosis. Computed tomography angiography (CTA)-based analyses of surgically treated cohorts documented a twist angle, reaching up to 95°. Carotid endarterectomy (CEA) was successfully performed for these patients. This study reports a case of a significantly twisted ICA with severe luminal stenosis that was successfully treated with CEA. An 81-year-old male was incidentally diagnosed with asymptomatic right ICA stenosis based on magnetic resonance (MR) angiography. Three-dimensional (3D)-CTA showed that the ICA revealed 74% stenosis of the ICA, based on the North American Symptomatic Carotid Endarterectomy Trial criteria. The 3D-CTA showed the ICA medial to the ipsilateral ECA at the level of the CCA bifurcation in the neck. It extended proximally to the pharynx, and the twist angle was 102°. Black-blood MR of the carotid plaque exhibited a high intensity on T1-weighted imaging, indicating vulnerability. Intraoperatively, the position of the ICA was corrected using multiple hooks instead of a surgical retractor. He showed no permanent deficits, such as an ipsilateral cerebral infarction, although transient postoperative hoarseness was observed. This case report documented a significantly twisted ICA with luminal stenosis, successfully treated via CEA, by correcting the carotid position using multiple hooks with gentle manipulation.

Early wound healing of the hard-palate mucosal harvest site using artificial dermis fixation by a transparent plate.

BACKGROUND: There are currently no guidelines for the postoperative wound management of the hard-palate donor site in cases involving mucosal harvesting. This study describes our experiences with the use of an artificial dermis for early epithelialization and transparent plate fixation in cases involving hard-palate mucosal harvesting. METHODS: A transparent palatal plate was custom-fabricated using a thermoplastic resin board. After mucosal harvesting, an alginic acid-containing wound dressing (Sorbsan) was applied to the donor site, which was then covered with the plate. After confirming hemostasis, the dressing was changed to artificial dermis a few days later, and the plate was fixed to the artificial dermis. The size of the mucosal defect ranged from 8×25 to 20×40 mm. RESULTS: Plate fixation was adequate, with no postoperative slippage or infection of the artificial dermis. There was no pain at the harvest site, but a slight sense of incongruity during eating was reported. Although the fabrication and application of the palatal plate required extra steps before and after harvesting, the combination of the artificial dermis and palatal plate was found to be very useful for protecting the mucosal harvest site, and resulted in decreased pain and earlier epithelialization. CONCLUSIONS: The combination of artificial dermis and a transparent palatal plate for wound management at the hard-palate mucosal donor site resolved some of the limitations of conventional methods.

[Successful Total Resection with Preceding Arterial Coil Embolization of Intradural Extramedullary Tumor at Craniovertebral Junction Encasing Dominant-side Vertebral Artery].

OBJECTIVE: The surgical resection of craniovertebral junction(CVJ)meningioma is challenging because of the neighboring brainstem, lower cranial nerves, and vertebral artery(VA). Moreover, encasement of the VA by the tumor can raise the risk of complications and require cautious manipulation during surgery. CASE: A 46-year-old woman presented with a one-year history of neck pain. She had temporal hemiplegia and numbness on her left side. Magnetic resonance imaging(MRI)showed a CVJ meningioma pushing the brainstem from the right vertebral side and encasing the right VA. Digital subtraction angiography(DSA)showed two feeding arteries arising from the right VA and a sunburst sign. The right VA was the dominant side but did not have the right posterior inferior cerebellar artery(PICA). The anterior spinal artery(ASA)was dominant in the left VA. We performed a balloon test occlusion(BTO)for 20 min and it did not cause any complications;therefore, we occluded the VA using endovascular coils. After 4 days, we removed the meningioma in the prone position, using a far-lateral approach and C1-laminectomy. The laterally located meningioma pushed the brainstem. After detaching the tumor from the dura, we cut the encased VA and the tumor was resected safely(Simpson grade II). Postoperatively, she developed temporal thermal hypoalgesia on the left side of her body. Magnetic resonance imaging showed a microinfarction in the medulla. CONCLUSION: If the VA test occlusion provides a clear result, pre-operative endovascular sacrifice of the VA encased by CVJ meningioma is a feasible treatment strategy.

Undiagnosed Peripheral Nerve Disease in Patients with Failed Lumbar Disc Surgery.

STUDY DESIGN: Retrospective study (level of evidence=3). PURPOSE: We examine the relationship between residual symptoms after discectomy for lumbar disc herniation and peripheral nerve (PN) neuropathy. OVERVIEW OF LITERATURE: Patients may report persistent or recurrent symptoms after lumbar disc herniation surgery; others fail to respond to a variety of treatments. Some PN neuropathies elicit symptoms similar to those of lumbar spine disease. METHODS: We retrospectively analyzed data for 13 patients treated for persistent (n=2) or recurrent (n=11) low back pain (LBP) and/or leg pain after primary lumbar discectomy. RESULTS: Lumbar re-operation was required for four patients (three with recurrent lumbar disc herniation and one with lumbar canal stenosis). Superior cluneal nerve (SCN) entrapment neuropathy (EN) was noted in 12 patients; SCN block improved the symptoms for eight of these patients. In total, nine patients underwent PN surgery (SCN-EN, n=4; peroneal nerve EN, n=3; tarsal tunnel syndrome, n=1). Their symptoms improved significantly. CONCLUSIONS: Concomitant PN disease should be considered for patients with failed back surgery syndrome manifesting as persistent or recurrent LBP.

Human Recombinant Peptide Sponge Enables Novel, Less Invasive Cell Therapy for Ischemic Stroke.

Bone marrow stromal cell (BMSC) transplantation has the therapeutic potential for ischemic stroke. However, it is unclear which delivery routes would yield both safety and maximal therapeutic benefits. We assessed whether a novel recombinant peptide (RCP) sponge, that resembles human collagen, could act as a less invasive and beneficial scaffold in cell therapy for ischemic stroke. BMSCs from green fluorescent protein-transgenic rats were cultured and Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAo). A BMSC-RCP sponge construct was transplanted onto the ipsilateral intact neocortex 7 days after MCAo. A BMSC suspension or vehicle was transplanted into the ipsilateral striatum. Rat motor function was serially evaluated and histological analysis was performed 5 weeks after transplantation. The results showed that BMSCs could proliferate well in the RCP sponge and the BMSC-RCP sponge significantly promoted functional recovery, compared with the vehicle group. Histological analysis revealed that the RCP sponge provoked few inflammatory reactions in the host brain. Moreover, some BMSCs migrated to the peri-infarct area and differentiated into neurons in the BMSC-RCP sponge group. These findings suggest that the RCP sponge may be a promising candidate for animal protein-free scaffolds in cell therapy for ischemic stroke in humans.

Preliminary Study of Temporal Change in Free Flap Volume after Tongue Reconstruction.

The purpose of this study was to investigate three-dimensionally temporal change in flap volume after free flap reconstructive surgery in tongue cancer patients. The results revealed an average change in flap volume of 82.3% at 1 year postoperatively. Change in tongue volume at approximately 6 months postoperatively showed a correlation with triglyceride levels. A correlation was also found between albumin levels and tongue volume at 1 year onwards postoperatively. The goal of such surgery in patients with tongue cancer is to reconstruct a functional tongue. Taking postoperative change in tongue volume into consideration is therefore of importance in minimizing postoperative dysphagia.

Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) cell transplantation into infarct brain of mice.

OBJECTIVE: Bone marrow stromal cells (BMSCs) are heterogeneous and their therapeutic effect is pleiotropic. Multilineage-differentiating stress enduring (Muse) cells are recently identified to comprise several percentages of BMSCs, being able to differentiate into triploblastic lineages including neuronal cells and act as tissue repair cells. This study was aimed to clarify how Muse and non-Muse cells in BMSCs contribute to functional recovery after ischemic stroke. METHODS: Human BMSCs were separated into stage specific embryonic antigen-3-positive Muse cells and -negative non-Muse cells. Immunodeficient mice were subjected to permanent middle cerebral artery occlusion and received transplantation of vehicle, Muse, non-Muse or BMSCs (2.5×104 cells) into the ipsilateral striatum 7 days later. RESULTS: Motor function recovery in BMSC and non-Muse groups became apparent at 21 days after transplantation, but reached the plateau thereafter. In Muse group, functional recovery was not observed for up to 28 days post-transplantation, but became apparent at 35 days post-transplantation. On immunohistochemistry, only Muse cells were integrated into peri-infarct cortex and differentiate into Tuj-1- and NeuN-expressing cells, while negligible number of BMSCs and non-Muse cells remained in the peri-infarct area at 42 days post-transplantation. CONCLUSIONS: These findings strongly suggest that Muse cells and non-Muse cells may contribute differently to tissue regeneration and functional recovery. Muse cells may be more responsible for replacement of the lost neurons through their integration into the peri-infarct cortex and spontaneous differentiation into neuronal marker-positive cells. Non-Muse cells do not remain in the host brain and may exhibit trophic effects rather than cell replacement.

Bone marrow stromal cells rescue ischemic brain by trophic effects and phenotypic change toward neural cells.

Background. Transplantation of bone marrow stromal cells (BMSCs) may contribute to functional recovery after stroke. This study was designed to clarify their mechanisms, trophic effects of neurotrophic factors, and neural differentiation. Methods. Mouse neurons exposed to glutamate were cocultured with mouse BMSCs. Either neutralizing antibodies against brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) or Trk inhibitor K252a was added to explore the mechanism of their protective effects. Fluorescence in situ hybridization (FISH) was used to assess BDNF or NGF mRNA expression in BMSCs. The mice were subjected to permanent focal ischemia, and 7 days later, either BMSCs or the vehicle was stereotactically transplanted into the ipsilateral striatum. The mouse brains were processed for FISH and immunostaining 2 or 4 weeks after transplantation. Results. BMSCs significantly ameliorated glutamate-induced neuronal death. Treatment with anti-BDNF antibody significantly reduced their protective effects. FISH analysis showed that the majority of BMSCs expressed BDNF and NGF mRNA in vitro. BMSC transplantation significantly improved the survival of neurons in peri-infarct areas. FISH analysis revealed that approximately half of BMSCs expressed BDNF and NGF mRNA 2 weeks after transplantation; however, the percentage of BDNF and NGF mRNA-positive cells decreased thereafter. Instead, the percentage of microtubule-associated protein 2-positive BMSCs gradually increased during 4 weeks after transplantation. Conclusions. These findings strongly suggest that BDNF may be a key factor underlying the trophic effects of BMSCs. BMSCs might exhibit the trophic effect in the early stage of cell therapy and the phenotypic change toward neural cells thereafter.

Platelet lysate and granulocyte-colony stimulating factor serve safe and accelerated expansion of human bone marrow stromal cells for stroke therapy.

Autologous human bone marrow stromal cells (hBMSCs) should be expanded in the animal serum-free condition within clinically relevant periods in order to secure safe and effective cell therapy for ischemic stroke. This study was aimed to assess whether the hBMSCs enhance their proliferation capacity and provide beneficial effect in the infarct brain when cultured with platelet lysate (PL) and granulocyte-colony stimulating factor (G-CSF). The hBMSCs were cultured in the fetal calf serum (FCS)-, PL-, or PL/G-CSF-containing medium. Cell growth kinetics was analyzed. The hBMSCs-PL, hBMSC-PL/G-CSF, or vehicle was stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion 7 days after the insult. Motor function was assessed for 8 weeks, and the fate of transplanted hBMSCs was examined using immunohistochemistry. As the results, the hBMSCs-PL/G-CSF showed more enhanced proliferation than the hBMSCs-FCS and hBMSCs-PL. Transplantation of hBMSCs expanded with the PL- or PL/G-CSF-containing medium equally promoted functional recovery compared with the vehicle group. Histological analysis revealed that there were no significant differences in their migration, survival, and neural differentiation in the infarct brain between the hBMSCs-PL and hBMSCs-PL/G-CSF. These findings strongly suggest that the combination of PL and G-CSF may accelerate hBMSC expansion and serve safe cell therapy for patients with ischemic stroke at clinically relevant timing.

Totally ossified metaplastic spinal meningioma.

A 61-year-old woman with a very rare case of totally ossified large thoracic spinal metaplastic meningioma, showing progressing myelopathy is presented. Computed tomographic images showed a large totally ossfied intradural round mass occupying the spinal canal on T9-10 level. Magnetic resonance imaging revealed a large T9-10 intradural extramedullary mass that was hypointense to spinal cord on T1- and T2-weighted sequences, partial enhancement was apparent after Gadolinium administration. The spinal cord was severely compressed and displaced toward the right at the level of T9-10. Surgical removal of the tumor was successfully accomplished via the posterior midline approach and the histological diagnosis verified an ossified metaplastic meningioma. The clinical neurological symptoms of patient were improved postoperatively. In this article we discuss the surgical and pathological aspects of rare case of spinal totally ossified metaplastic meningioma.

Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats.

This study was aimed to clarify if the bone marrow stromal cells (BMSCs) significantly improve functional outcome after lacunar stroke when stereotactically transplanted into the brain. Ouabain, a Na/K ATPase pump inhibitor, was stereotactically injected into the right striatum of Wistar rats. One week later, the superparamagnetic iron oxide (SPIO)-labeled rat BMSCs (n=7) or vehicle (n=8) were stereotactically transplanted into the left striatum. Using rotarod test, motor function was serially evaluated through the experiment. A 7.0-T MR apparatus was employed to serially monitor the migration of BMSCs in the host brain. Histological analysis was performed at 7 weeks after ouabain injection, i.e., 6 weeks after BMSC transplantation. Ouabain injection yielded the reproducible, focal lesion in the right striatum, causing continuous motor dysfunction throughout the experiment. BMSC transplantation significantly enhanced the recovery of motor function after ouabain injection. MR imaging demonstrated that the BMSCs aggressively migrated towards the lesion through the corpus callosum. Histological analysis supported the findings on MRI. The BMSCs significantly enhanced the neurogenesis in the subventricular zone (SVZ) on both sides. Some of them also expressed neuronal or astrocytic phenotypes in the neocortex, SVZ, corpus callosum, and peri-lesion area. These findings strongly suggest that the BMSCs may serve therapeutic impacts on lacunar stroke when stereotactically transplanted at clinically relevant timing.

A 5-year activity report from the Oral Cancer Center, Tokyo Dental College.

The Tokyo Dental College Oral Cancer Center was established on April 1st, 2006 at our Ichikawa General Hospital for the purpose of providing multimodal treatment for oral cancer. This report summarizes the Center's activities over the last 5 years. The total number of oral cancer patients treated was 360 (April 2006 to March 2011), with 205 primary cases. We investigated the following treatment-related items: 1) site, 2) age, 3) sex, 4) pathological examination, 5) staging, 6) systemic disorder, 7) double cancer, 8) treatment, and 9) prognosis. Out of 205 patients, 60% were men and 40% were women. Men in their 60s and women in their 80s were seen the most. The most common site was the tongue, at 42%, followed by the mandibular gingiva, maxillary gingiva, oral floor, and buccal mucosa. Squamous cell carcinomas were seen most frequently, at 94% (15% were stage I, 33% stage II, 15% stage III, and 34% stage IV). The most common treatment method was surgical treatment, at 83%. The 5-year survival rate at all stages was 85.4%. At the Oral Cancer Center, oral surgeons take the initiative in establishing treatment in cooperation with other departments and branches. Since the establishment of the Ambulatory Center for Maxillary Prosthetics in October 2011, 26 patients have undergone treatment. Related departments and branches work in teams, enabling comprehensive treatment, from the preoperative state to postoperative functional recovery. We wish to use these strengths to improve oral cancer treatment in Japan and will continue to work toward providing the best possible care for our patients.

[Cerebrospinal fluid shunts for hydrocephalus and related disorders].

Cerebrospinal fluid (CSF) shunts are commonly employed to treat patients with hydrocephalus. A large number of papers have been published focusing on complications and failures of CSF shunts. However, there appears to be a paucity of knowledge comprehensively covering both common complications and rare ones. In this systematic review, we surveyed articles about surgical complications of CSF shunts as comprehensively as possible. Quantitative analysis was performed to determine the frequency of well-known complications, mortality and revision rates of CSF shunts. Furthermore, rare complications of CSF shunts have also been reviewed.

Risk factors for postoperative dysphagia in oral cancer.

With the founding of its Oral Cancer Center at the Ichikawa General Hospital, Tokyo Dental College established a support system for patients and family members that not only provides surgery and other conventional cancer-oriented treatments, but also palliative care, nutritional support, rehabilitation, and discharge support. With this in mind, the present study sought to examine the nature of support for oral cancer patients with postoperative eating and swallowing disorders by investigating these disorders and identifying their risk factors. The study population comprised 75 surviving oral cancer patients (46 men and 29 women) discharged from the Tokyo Dental College Oral Cancer Center following treatment over a 2-year period from April 2009 to March 2011. Risk factors affecting eating and swallowing function were identified by statistical analysis. Mean age of the patients was 67.3±13.7 years. Fifteen patients had stage I cancer, while 25 had stage II, 13 had stage III, and 22 had stage IV. The feeding route at the time of discharge was oral feeding in 74 patients and a combination of oral and gastrostomy tube feeding in 1 patient. The Tokyo Dental College Ichikawa General Hospital has standardized the expert evaluation and rehabilitation of oral cancer patients with eating and swallowing disorders by establishing a multidisciplinary support system from the preoperative stage onwards. In this context, the results of our analysis of factors influencing the ability of oral cancer patients to orally ingest food after treatment suggest that preoperative cancer stage classification, neck dissection, and tracheotomy are all influential factors. Patients affected by these factors require further multidisciplinary treatment, which in turn necessitates more extensive coordination with other medical professionals and community health care providers.

Sepantronium bromide (YM155) induces disruption of the ILF3/p54(nrb) complex, which is required for survivin expression.

YM155, a small-molecule survivin suppressant, specifically binds to the transcription factor ILF3, which regulates the expression of survivin[1]. In this experiment we have demonstrated that p54(nrb) binds to the survivin promoter and regulates survivin expression. p54(nrb) forms a complex with ILF3, which directly binds to YM155. YM155 induces disruption of the ILF3/p54(nrb) complex, which results in a different subcellular localization between ILF3 and p54(nrb). Thus, identification of molecular targets of YM155 in suppression of the survivin pathway, might lead to development of its use as a novel potential target in cancers.

Interleukin enhancer-binding factor 3/NF110 is a target of YM155, a suppressant of survivin.

Survivin is responsible for cancer progression and drug resistance in many types of cancer. YM155 selectively suppresses the expression of survivin and induces apoptosis in cancer cells in vitro and in vivo. However, the mechanism underlying these effects of YM155 is unknown. Here, we show that a transcription factor, interleukin enhancer-binding factor 3 (ILF3)/NF110, is a direct binding target of YM155. The enhanced survivin promoter activity by overexpression of ILF3/NF110 was attenuated by YM155 in a concentration-dependent manner, suggesting that ILF3/NF110 is the physiological target through which YM155 mediates survivin suppression. The results also show that the unique C-terminal region of ILF3/NF110 is important for promoting survivin expression and for high affinity binding to YM155.

Upper gastrointestinal tract cancers as double-cancers in elderly patients with oral squamous cell carcinoma.

Against a background of a rapidly aging society, the number of patients with oral cancers in Japan is increasing yearly. The number of double-cancers with oral cancer as the first malignancy is also reportedly on the rise. Esophageal and gastric cancers are the most common second malignancies. At our institution, our policy is to proactively perform upper gastrointestinal (GI) fiberscopy (GIF) in patients with oral cancer. In anticipation of a probable further increase in the number of patients with double-cancers consisting of oral and GI tract malignancies, we retrospectively analyzed the occurrence of upper GI tract cancers in patients with oral squamous cell carcinoma (OSCC). The cohort consisted of 171 patients in whom OSCC had been diagnosed and who had undergone upper GIF between March 1996 and August 2008. Multivariate analysis was performed. Upper GIF identified 8 patients (7 men, 1 woman, totaling 4.7% of 171 patients) with double-cancer in the upper GI tract. One patient had a triple malignancy consisting of oral, esophageal and gastric cancers. Seven patients had esophageal cancer, while two had gastric cancer. An age of over 65 years was significantly higher in patients with double-cancers including esophageal cancer than in patients without esophageal cancer (OR=10.454, 95% CI=1.143-95.621). None of the other analyzed patient factors (sex, smoking habit, drinking habit, site of OSCC, TNM classification, staging results) showed a significant difference. These results indicate that, when treating elderly patients with oral cancers, physicians need to devise suitable treatment plans which take into account the possibility of upper GI tract cancer, particularly esophageal cancer, as a double-cancer.

Antitumor activity of YM155, a selective small-molecule survivin suppressant, alone and in combination with docetaxel in human malignant melanoma models.

PURPOSE: Aggressive cell growth and chemoresistance are notorious obstacles in melanoma therapy. Accumulating evidence suggests that survivin is preferentially expressed in cancer cells and plays a crucial role in cell division and apoptosis dysfunction. Here, we evaluated the therapeutic potential of YM155, a selective survivin suppressant, alone and in combination with docetaxel using human melanoma models. EXPERIMENTAL DESIGN: A375 and SK-MEL-5 human malignant melanoma cells were treated with siRNA, YM155, and/or docetaxel, and cell viability, mRNA and protein expression levels, cell-cycle distribution, and immunohistochemical staining were then evaluated. Furthermore, the efficacy of YM155 combined with docetaxel was further examined in established xenograft models. RESULTS: Survivin suppression was sufficient to induce spontaneous apoptosis of melanoma cells. YM155 showed nanomolar antiproliferative effects and induced tumor regression in established melanoma xenograft models. Docetaxel showed antitumor activity against melanoma cells, although it also induced survivin upregulation and G(2)/M mitotic arrest; however, cotreatment with YM155 decreased survivin expression below basal levels. Combination treatment of YM155 and docetaxel induced a greater rate of apoptosis than the sum of the single-treatment rates and promoted tumor regression without enhanced body weight loss in the melanoma xenograft models. CONCLUSIONS: Survivin is responsible for the inherent low levels of spontaneous apoptosis in melanoma cells. The concomitant combination of YM155 with docetaxel diminished the accumulation of survivin in G(2)/M mitotic arrest, and induced more intense apoptosis compared with each single treatment. YM155 in combination with docetaxel is well tolerated and shows greater efficacy than either agent alone in mouse xenograft models.

[Sacral dural arteriovenous fistula: report of 4 cases].

Spinal dural arteriovenous fistula (SDAVF) in the sacral region is relatively rare and remains difficult to diagnose because of the uncommon origin of its feeder. It also has higher incidence of recurrence than usual thoraco-lumbar lesion and needs subsequent treatment. We reviewed 51 cases of SDAVF over the past 10 years. Especially in patients with sacral lesion, clinical features and the findings on spinal angiography were analyzed. Four patients (7.8%) had SDAVF in the sacral region. In all cases, SDAVF were supplied by the lateral sacral artery. Multiple feeders were observed in 3 (75%) out of 4 patients and 2 patients (50%) had multiple fistulas. Endovascular embolizations were performed in all patients, and neurological symptoms were improved in two patients (50%) and the other two were stabilized (50%). There was no recurrence during a follow-up period of 3 months to 8 years. We should keep in mind that SDAVF in the sacral region can have multiple shunts and feeders derived from the lateral sacral artery.