BACKGROUND AND PURPOSE:Tumor embolization through the meningohypophyseal trunk and inferolateral trunk is known to be effective in skull base tumors; however, microcatheter cannulation into these arteries is difficult, and the number of cases that can be safely embolized is limited. In this study, we present a novel embolization procedure for the meningohypophyseal trunk and inferolateral trunk using the distal balloon protection technique and detail its clinical efficacy and complication risks. We developed this procedure to allow safe embolization in patients who cannot be adequately cannulated with microcatheters into these arteries. MATERIALS AND METHODS:Patients who underwent meningohypophyseal trunk or inferolateral trunk embolization using the distal balloon protection technique for skull base tumors at our institution between 2010 and 2023 were included. In this procedure, the ICA was temporarily occluded with a balloon at the ophthalmic artery bifurcation, the microcatheter was guided to the meningohypophyseal trunk or inferolateral trunk vicinity, and embolic particles were injected into the arteries. The balloon was deflated after the embolic particles that had refluxed into the ICA were aspirated. RESULTS:A total of 25 meningohypophyseal trunks and inferolateral trunks were embolized during 21 operations. Of these 25 arteries, only 9 (36.0%) were successfully cannulated with microcatheters. Nevertheless, effective embolization was achieved in all cases. Permanent complications occurred in only 1 case (4.8%) in which the central retinal artery was occluded during inferolateral trunk embolization, resulting in a visual field defect. No permanent complications resulting from the embolic cerebral infarction were observed. Of 16 cases that underwent MR imaging within a week after embolization, however, 11 (68.8%) demonstrated embolic cerebral infarctions. CONCLUSIONS:In patients with skull base tumors with meningohypophyseal trunk or inferolateral trunk feeders that cannot be catheterized directly, embolization using the distal balloon protection technique for tumor supply can be considered as a salvage technique.

CX3CL1 (fractalkine) is a chemokine that expresses on endothelial cells and supports the migration of its specific receptor CX3CR1-expressing macrophages and some T cells into the targeted tissue. We aimed to study the anti-fibrotic effects of CX3CL1-CX3CR1 pathway blocking in a mouse model for human sclerodermatous chronic GVHD (Scl-cGVHD) with many clinical similarities to human systemic sclerosis (SSc). Scl-cGVHD mice were established on an irradiated BALB/c strain with transplantation of T cell-depleted D10.B2 bone marrow cells and splenocytes, phenotypically displaying skin fibrosis with diffuse alopecia and lung fibrosis. All the clinical symptoms were significantly attenuated by an intraperitoneal injection of anti-CX3CL1 mAb, compared to control IgG-treated mice. Inhibition of skin and lung fibrosis correlated with the extent of infiltrating CX3CR1-positive macrophages and T cells. This trend was more apparent in Scl-cGVHD mice treated with a high mAb dose, with a marked decrease of α-SMA-positive myofibroblasts. In the Scl-cGVHD skin, intraperitoneal anti-CX3CL1 mAb reduced an elevated expression of profibrotic molecules, including IL-4, IL-6, TGF-b, and Spp-1, in parallel with decreased levels of a Nr4a1, a master regulator of CX3CR1 and both M1 and M2 macrophage markers. Gene expression profiles showed Scl-cGVHD skin-specific upregulation of macrophage function genes relevant to tissue fibrosis and inflammation, which was downregulated by mAb treatment. There were no adverse events during the study. The CX3CL1-CX3CR1 pathway may be an attractive pathogenic axis for Scl-cGVHD, and its ligand-specific mAb can be a novel candidate traceable to the treatment of fibrotic disorders such as SSc.

Dermokine (DMKN) is a secreted glycoprotein expressed predominantly in the upper epidermis, particularly granular layers, whose expression pattern resembles the terminal differentiation molecules. It comprises three splice variants in mice and five in humans. Our recent investigation generating all three isoforms of DMKN deficiency in C57BL/6 mice [DMKN-KO(B6)] demonstrated ichthyosiform skin with transepidermal water imbalance, Th17-prone immune response, and average molecular permeability in the early neonatal stage, resulting in lethal under low humidity. In adult DMKN-KO(B6), the imiquimod- and IL-23-induced psoriasis models were exacerbated, while the atopic model induced by ovalbumin transdermal sensitization was comparable to the wild-type. However, the influence of DMKN deficiency may also depend on the genetic background of the mice. Therefore, we newly established DMKN-KO mice on a BALB/c background [DMKN-KO(BALB/c)]. The DMKN-KO(BALB/c) reproduced ichthyosiform skin in the neonatal period but was somewhat milder and with a better prognosis than DMKN-KO(B6). Unlike the experimental findings on the B6 background, the transcutaneous sensitization and elicitation with ovalbumin exhibited a significantly higher serum titer of antigen-specific IgE in DMKN-KO(BALB/c) than in DMKN-KO(B6) and wild-type(BALB/c). Consistent with this, skin thickness and inflammatory cell infiltration were also exacerbated in DMKN(BALB/c). The phenotype and inflammatory cell infiltration of imiquimod- and recombinant IL-23-induced psoriasis models were as aggravated in DMKN-KO(BALB/c) as in DMKN-KO(B6). The expression of disease-related cytokines in lesional skin correlated with the severity of each model. Exacerbation by the recombinant IL-23 subcutaneous injection suggests that secreted DMKN acts on skin immunity independently of its role in maintaining homeostasis of the keratinization and barrier function. DMKN may have unique regulatory roles in the pathogenesis of ichthyosis, atopic dermatitis, and psoriasis, depending on the immunogenetic background.

Cyst formation in the third ventricle and the histopathological findings were rarely reported. We report a similar case of late-onset aqueductal membranous occlusion (LAMO) caused by a thin gliotic cyst and a review of related literature. A 28-year-old woman with enlarged lateral ventricles was referred to our hospital with complaints of headache and dizziness. In our hospital, the obvious cause of the hydrocephalus was unknown on any examination and we decided performing endoscopic third ventriculostomy for hydrocephalus. A thin cyst covering the entrance of the aqueduct was identified and we perforated it. Histopathological finding of the cyst wall was gliosis and our case was similar to LAMO, although not typical. The postoperative symptoms and ventricle size improved for 4 years. When suspecting cases similar to definition of LAMO, neuroendoscopic surgery would be the first-choice treatment and might detect causes undetectable on preoperative imaging such as our thin membrane.

Systemic sclerosis (SSc) is a connective tissue disorder representing fibrosis and vascular damage in the skin and internal organs. An activated differentiation of local progenitor cells to myofibroblasts is likely a key mechanism underlying overproduction of extracellular matrix and resultant tissue fibrosis in SSc. Calpains are family members of Ca2+-dependent cysteine proteases for which the biological action may contribute to fibrosis in various organs. However, the precise mechanism of calpain-dependent fibrosis and the potential utility of their inhibitors in SSc remain unclear. This study aimed to investigate if one of calpain inhibitors ALLN could possess the antifibrotic effects on a bleomycin-induced SSc model mice and cultured human dermal fibroblasts, offering an innovative therapeutic approach for skin sclerosis in SSc. Intraperitoneal administration of ALLN was well tolerated throughout the in vivo experiments. Intraperitoneal ALLN (3mg/kg/day, three times a week) remarkably suppressed the excess dermal fibrosis by 72% in the bleomycin-injected mouse skin. Infiltrating F4/80+ macrophages and CD3+ T cells tended to decrease in number in the ALLN-treated mouse skin compared to the control. On the other hand, in vitro ALLN treatment significantly inhibited over-phosphorylation and nuclear transport of Smad3 in TGF-β1-stimulated fibroblasts. TGF-β1-dependent increase of collage type 1, fibronectin 1, α-smooth muscle actin, and epithelial-mesenchymal transition markers including SLUG and ZEB1, was attenuated in mRNA and protein expression by ALLN. Our data provide evidence that calpain may be a primary contributor and novel therapeutic target for skin fibrosis in SSc, with a treatment perspective of its inhibitor ALLN.

PURPOSE:To determine the incidence of and risk factors for symptomatic adjacent segment disease(SASD)requiring additional surgery in patients previously treated with minimally invasive surgery-transforaminal lumbar interbody fusion(MIS-TLIF)for degenerative lumbar disease.MATERIALS AND METHODS:A series of 467 consecutive patients who had undergone MIS-TLIF of one or two segments to treat degenerative lumbar disease was identified. The mean age of the patients at the time of the index operation was 67.7 years and the mean follow-up period was 33.2 months(range, 6.0-110.1 months). The incidence rate of SASD surgeries was calculated using the Kaplan-Meier method. The log-rank test and Cox regression analysis were used for risk factor analysis based on age, sex, number of fused segments, presence of laminectomy adjacent to index fusion, and L1 plumb line.RESULTS:The overall incidence rate of SASD requiring additional surgery was 2.8%. Kaplan-Meier analysis predicted a disease-free rate of adjacent segments in 94.3% of the patients at 4 years and in 90.8% of the patients at 8 years after the index operation. In the analysis of risk factors, a negative L1 plumb line was associated with a 5.6 times higher incidence of SASD requiring additional surgery than that associated with a positive L1 plumb line(p=0.0096). There was no significant difference in the survival rates based on age, sex, number of fused segments, and concomitant laminectomy to adjacent segment.CONCLUSION:Approximately 9.2% of the patients were predicted to undergo additional surgery for treating SASD within 8 years of MIS-TLIF. In this study, presence of a negative L1 plumb line indicated higher incidence of additional SASD associated surgeries than that shown by a positive L1 plumb line. Therefore, surgeons should carefully consider this factor while performing MIS-TLIF.

Title Clinical significance of serum HMGB-1 and sRAGE levels in systemic sclerosis: association with disease severity. Author(s) Yoshizaki, Ayumi; Komura, Kazuhiro; Iwata, Yohei; Ogawa, Fumihide; Hara, Toshihide; Muroi, Eiji; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Sato, Shinichi Citation Journal of clinical immunology, 29(2), pp.180-189; 2009 Issue Date 2009-03 URL http://hdl.handle.net/10069/22498 Right © Springer Science+Business Media, LLC 2008; The original publication is available at www.springerlink.com NAOSITE: Nagasaki University's Academic Output SITE

Objective To improve bleeding management during brain tumor surgery, feeder arteries supplying the tumor are often embolized presurgically. However, access to feeder arteries can be limited, and embolization of feeders from internal carotid artery (ICA) branches often causes complications. We evaluated the PercuSurge GuardWire (Medtronic, Minneapolis, Minnesota, United States) system (PGWS) with aspiration catheter as amodification of the embolization technique used to block tumor-supplying branches of the ICA.Methods Two skull-base tumors were treated with preoperative embolization. One was a meningioma; the other was a hemangiopericytoma. In each case, the microcatheter could not be threaded into the ICA feeder arteries. Therefore, particulate embolic material was injected near the ICA branch while maintaining ICA balloon protection by the PGWS at the orifice of the ophthalmic artery. After embolization, we removed the remaining embolic material in the ICA using an aspiration catheter. In both cases, there were no postembolization complications and no high-intensity areas in the diffusion-weighted magnetic resonance image, and the tumorectomy proceeded as scheduled.Conclusion This modified technique may be a promising alternative for reducing embolic complications and improving the success rate, although case accumulation is needed to confirm this result.

The functional prognosis for deep-seated meningiomas is mostly dictated by the approach chosen and the dissection technique employed to remove tumor tissue from deep veins, cranial nerves and the brainstem. Accordingly, in this study among a consecutive 293 meningioma operations, the incidence, location, preservation rate of cranial nerve function, and the most appropriate approach selection for deep-seated meningiomas were retrospectively analyzed. The rate of vision improvement was 89% in 36 cases with visual dysfunction, the olfaction preservation was 93% in 30 cases operated via a basal interhemispheric approach, and hearing rate improvement was 44% in 9 cases with hearing disturbances. In order to determine the most appropriate approach to gain direct observation and secure dissection, detailed neuro-imagings including 320-row area detector CT, preoperative embolization of feeders from the internal carotid artery, and a thorough understandings of the biological behavior and pathology of the tumor-brain interface are important. Finally, after due delligence, it may become apparent that a multi-staged operation and/or Simpson Grade IV surgery might be a good alternative choice. (Received August 27, 2013;accepted September 25, 2013)

BACKGROUND:Little is known about the pathogenesis and clinical course of fusiform compared with saccular aneurysms. The case of a ruptured fusiform aneurysm accompanied by dissection at the M2 portion of the middle cerebral artery (MCA) is reported, along with pathological findings.CASE DESCRIPTION:A 41-year-old female presenting with subarachnoid hemorrhage was revealed to have a ruptured fusiform aneurysm at the M2 portion of the right MCA on angiography. She was treated with superficial temporal artery-MCA anastomosis and trapping of the aneurysm. The aneurysm consisted of a whitish fusiform dilatation with a thickened wall of the MCA and two red protrusions on it. Pathological examinations revealed disruption and fragmentation of the internal elastic lamina and intimal thickening in the fusiform lesion. There were two aneurysmal protrusions on the main fusiform dilatation. In one protruded lesion, a dissection of the intima was observed.CONCLUSION:We propose that a dissection and saccular aneurysm additionally developed on the wall of a preexisting segmental ectasia of the MCA in our case. In this report, we discuss the etiology of fusiform aneurysms of the MCA.

Management of gliomas depends on histological diagnosis; there are, however, limitations to the systems presently used. Tumors in the same entity can have different clinical courses, especially when they are diagnosed as WHO grade II–III. Previous studies revealed that genetic subgrouping of gliomas provides useful information that could help establishment of treatment procedures on the basis of the genetic background of the tumors. Recently, the authors analyzed the chromosomal copy number aberrations (CNAs) of adult supratentorial gliomas by comparative genomic hybridization using microdissected tissue sections. The tumors were classified into subgroups according to chromosomal CNAs. WHO grade II–III gliomas contained a variety of genetic subgroups that correlated well with the clinical course. Of these, long progression-free survival was observed for tumors with +7q and those with −1p/19q, low-grade tumors of 2 major lineages, and, in our preliminary data, both were closely correlated with mutation of IDH1. Furthermore, in contrast with +7q tumors, the great majority of +7 or +7/−10q groups had wildtype IDH1. Genetic studies suggest that cytogenetic characterization may provide an additional classification system for gliomas, and new criteria could help to establish rational and objective means for analysis of treatment procedures.

Cancers metastatic to the skull or dura may cause subdural hematoma (SDH). However, the frequency is low, and the presence of underlying cancers has almost always been known in such situations. We report a case of skull angiosarcoma manifesting as SDH, posing a diagnostic challenge to physicians. A 75-year-old man visited our clinic with sensorimotor disturbance of gradual onset approximately 1 month after a minor head trauma. He was diagnosed with SDH after imaging studies, and underwent surgery to evacuate the hematoma. Because the hematoma was organized, surgery was switched from burr-hole drainage to craniotomy. The bone flap as well as the dura over the hematoma had grossly normal appearance, and only the hematoma itself was submitted for histological examination. Although postoperative recovery was uneventful, the patient experienced recurrence of the SDH 2 months after surgery. At the second surgery, the bone flap and dura were intermingled with tumor tissue, and histological examination revealed that an epithelioid angiosarcoma originating from the skull was responsible for the SDH. Timely diagnosis of angiosarcoma manifesting as SDH is difficult because of its rarity. In retrospect, however, the diagnosis might have been established earlier if the bone flap and/or the dura had been biopsied at the time of the first surgery. The present case gives us a lesson that SDH may be an unusual manifestation of malignant tumors of skull or dural origin, and histological examination of not only hematoma capsule but also of the surrounding tissues may provide important diagnostic clues.

BACKGROUND:The purpose of this study was to evaluate and analyze overall postoperative results from microvascular decompression (MVD) by combining the cure rate of symptoms with the complication rate. A new scoring system for obtaining objective surgical results from MVD for trigeminal neuralgia (TN) and hemifacial spasm (HFS) is proposed to document treatment results using consistent criteria in a standardized manner.METHOD:Surgical results combining complications , if any, were obtained from a questionnaire sent to patients who had undergone surgery for TN or HFS in recent years and had been followed-up for more than 1 year after surgery (TN patients, n = 54; HFS patients, n = 81) When surgical outcome is complete resolution of symptoms, the efficacy of surgery (E) is designated E-0, but when moderate symptoms are still persist postoperatively, the score is designated E-2. When no complications are seen after surgery, the complication score (C) is C-0, while the score is C-2 if troublesome complications remain. In addition, total evaluation of the results (T) is judged by combining the E and C scores. For example, when E is 0, and C is C-2, the total evaluation is scored as T-2, which is diagnosed as fair.FINDINGS:The response rate of the questionnaire was 80.7% (109/135). Overall surgical data were evaluated and analyzed using our new scoring system. Analysis of the collected data revealed an outcome of T-0 was 70% (35/50 patients) and T-1 was 24% (12/50) and T-2 was 6% (3/50) in TN, whereas in HFS, T-0 was 61% (36/59) and T-1 was 27.1% (16/59) and T-2 was 6.8% (4/59) and T-3 was 5.1% (3/59).CONCLUSION:The total results of MVD should be evaluated and analyzed by combining the cure rate of symptoms together with the complication rate. This new scoring system could allow much more objective analysis of the results of following MVD. Adopting this scoring system to objectively judge treatment results for TN and HFS, individual surgeons can compare their own overall surgical results with those of other institutes. Comparative results of MVD can also be provided to patients considering therapy to allow informed decision-making on the basis of good quality evidence.

Background Although dermokine-, a glycoprotein expressed in epithelial cells, does not have significant homology to other proteins, its carboxyl-terminal domain shares a high pI value with many cytokines, suggesting similar functions. Objective To better understand the biology of dermokine, we here determined its localization under pathological conditions and examined factors that regulate its expression. Methods We generated an anti-human dermokine-/ monoclonal antibody cross-reacting with the mouse protein. Using this antibody, immunohistological staining and Western blotting of dermokine-/ were performed with various tissue samples. Results Although human dermokine-/ was expressed in almost all granular layers, upper spinous layers of the skin were also stained with anti-dermokine-/ antibody in inflammatory skin disorders. Dermokine-/ was expressed in keratoacanthoma and a part of well-differentiated squamous cell carcinoma (SCC). However, dermokine-/ was not detected in poorly differentiated SCC or tumours derived from non-keratinocytes. In mice, dermokine-/-expressed keratinocytes were increased in models of contact hypersensitivity, ultraviolet-irradiated skin injury and wound healing. Consistent with expanded distribution in inflammatory skin diseases, proinflammatory cytokines such as interleukin-1, interleukin-12, and tumour necrosis factor- augmented dermokine-/ expression in cultured human keratinocytes. In contrast, growth factors including epidermal growth factor, insulin-like growth factor-I, keratinocyte growth factor and transforming growth factor- significantly reduced dermokine expression. Conclusion These results provide novel insights into the physiological and pathological significance of dermokine in the epidermis.

Funding sources: None. Conflicts of interest: None declared. Madam, A 3‐year‐old girl visited Kanazawa University Hospital with a history of skin lesions on her face lasting several months. At the time of her first visit in March 2007, she had umbilicated vesiculopapules with small necrotic centres and erythematous oedema on her face (Fig. 1a) and upper limbs, as well as aphthous stomatitis. The skin lesions were exacerbated by sun exposure. She also had a low‐grade fever and general malaise. Blood cell and platelet counts were normal. No atypical lymphocytes were found in peripheral blood smears. Computed tomography did not detect any abnormity. Anti‐Epstein–Barr virus (EBV) antibody titres indicated a previous infection pattern of EBV, but a high amount of EBV DNA (4·4 × 105 copies per 106 white blood cells) was detected in peripheral blood mononuclear cells (PBMC). Informed consent was obtained according to the Declaration of Helsinki, and approval for the study was obtained from the Human Research Committee of Kanazawa University.