Induction chemotherapy and hepatic artery embolization followed by extended resection for locally advanced gallbladder cancer: a case report.

BACKGROUND: Surgical resection plays a critical role in the curative therapy of patients with gallbladder cancer. However, extended resection for locally advanced gallbladder cancer is a controversial procedure because of the high operative morbidity, mortality, and poor prognosis after surgery, without consensus of its suitability. Several reports have described preoperative treatment modalities to reduce the risk of mortality and morbidity and improve the curability of surgery for locally advanced GBCA. However, only a few well-designed studies have verified the benefits of these preoperative strategies. CASE PRESENTATION: A 62-year-old male patient presented to our department with a gallbladder tumor detected on abdominal ultrasound during an annual medical checkup. Multi-phase enhanced CT revealed a gallbladder tumor with a maximum diameter of 34 mm, invading the right hepatic artery, pancreatic head, hepatic flexure of the colon, and first portion of the duodenum. We diagnosed gallbladder carcinoma as cT4 cN0 cM0 cStage IVA in the Union for International Cancer Control (UICC) classification 8th edition. After administration of 12 cycles of gemcitabine and cisplatin plus S-1 regimen, tumor shrinkage was observed on computed tomography, and elevated serum CA19-9 levels were reduced to normal limits. After preoperative hepatic artery embolization, we performed gallbladder bed resection with pancreaticoduodenectomy (minor hepatopancreatoduodenectomy) and combined resection of the right hepatic artery and hepatic flexure of the colon. Histological examination revealed no evidence of lymph node metastasis (ypT4 ypN0 ycM0 yp Stage IVA in the 8th edition of the UICC). The proximal bile duct and dissected margins were negative. CONCLUSIONS: The combination of induction chemotherapy and preoperative hepatic artery embolization, followed by minor hepatopancreatoduodenectomy and combined resection of the involved arteries and partial colon, could be a feasible treatment strategy for patients with locally advanced gallbladder cancer invading neighboring organs.

Augmentation of surface plasmon-enhanced second harmonic generation from Au nanoprisms on SiO2/Si: interference contribution.

We present an augmentation of Surface Plasmon (SP)-enhanced second harmonic generation (SHG) due to interference field enhancement in Au nanoprisms (AuNPs) on SiO2-coated Si substrates. The SiO2 spacer contributed for the optical interference and increased the coupling efficiency of the pump light with the SP polarization as well as a decoupling efficiency of the SHG waves from nonlinear polarization. The intensity of the SP-enhanced SHG signals increased 4.5-fold with respect to the AuNPs on the bare SiO2 substrate by setting the SiO2 spacer layer to the appropriate thickness. The numerical analysis revealed that the optimal SHG conversion was determined by the balance between the degree of the optical interference at the fundamental and SHG wavelengths.

Second Harmonic Generation from Phase-Engineered Metasurfaces of Nanoprisms.

Metasurfaces of gold (Au) nanoparticles on a SiO2-Si substrate were fabricated for the enhancement of second harmonic generation (SHG) using electron beam lithography and lift-off. Triangular Au nanoprisms which are non-centro-symmetric and support second-order nonlinearity were examined for SHG. The thickness of the SiO2 spacer is shown to be an effective parameter to tune for maximising SHG. Electrical field enhancement at the fundamental wavelength was shown to define the SHG intensity. Numerical modeling of light enhancement was verified by experimental measurements of SHG and reflectivity spectra at the normal incidence. At the plasmonic resonance, SHG is enhanced up to ∼3.5 × 103 times for the optimised conditions.

Spatial resolution and cathodoluminescence intensity dependence on acceleration voltage in electron beam excitation assisted optical microscopy using Y2O3:Eu3+ film.

This study presents relationship between acceleration voltage and spatial resolution of electron-beam assisted (EXA) optical microscope. The nanometric illumination light sources of the present EXA microscope was red-emitting cathodoluminescence (CL) in the Y2O3:Eu3+ thin film excited by focused electron beam. Our experimental results demonstrated that the spatial resolutions of the EXA microscope were higher as the acceleration voltage was higher. We managed to make images of the scattered gold particles with approximately 90 nm-resolutions at the voltages higher than 20 kV. The dependence of the spatial resolution on the acceleration voltage was explained by the distribution of simulated electron scattering trajectories in the luminescent thin film.

Focal fibrocartilaginous dysplasia in the ulna with the radial head dislocation: a case report and literature review.

Focal fibrocartilaginous dysplasia (FFCD) is a rare benign bone lesion, which mainly occurs in the proximal tibia. In the upper extremity, only 21 cases have been reported so far and 14 of these involved the ulna. We present an additional case of FFCD in the distal ulna that showed progressive bowing of the right forearm and the radial head dislocation. Resection of the abnormal tissue, osteotomy of the radius and ulna, and gradual lengthening of the ulna were performed. On the basis of the previously published data of 14 cases and our data, we have summarized the etiology, clinical features, natural history, and treatment of FFCD in the ulna.

Fabrication of bright and thin Zn2SiO4 luminescent film for electron beam excitation-assisted optical microscope.

We fabricated a bright and thin Zn2SiO4 luminescent film to serve as a nanometric light source for high-spatial-resolution optical microscopy based on electron beam excitation. The Zn2SiO4 luminescent thin film was fabricated by annealing a ZnO film on a Si3N4 substrate at 1000 °C in N2. The annealed film emitted bright cathodoluminescence compared with the as-deposited film. The film is promising for nano-imaging with electron beam excitation-assisted optical microscopy. We evaluated the spatial resolution of a microscope developed using this Zn2SiO4 luminescent thin film. This is the first report of the investigation and application of ZnO/Si3N4 annealed at a high temperature (1000 °C). The fabricated Zn2SiO4 film is expected to enable high-frame-rate dynamic observation with ultra-high resolution using our electron beam excitation-assisted optical microscopy.

Multidisciplinary treatment including systemic chemotherapy for a malignant phyllodes tumour of the prostate.

A 22-year-old man was referred to our hospital with macroscopic hematuria and consistent anal pain. Magnetic resonance imaging revealed an enlarged prostate tumour invading the bladder and rectum. A biopsy revealed an unclassified spindle cell sarcoma. Subsequently, radical cystoprostatectomy and resection of the rectum were performed. A histopathological examination revealed a prostatic malignant phyllodes tumour with a negative surgical margin. However, a local recurrence was identified 2 months after surgery. Induction therapy included 4 cycles of systemic chemotherapy comprising etoposide with ifosfamide and cisplatin. Although a partial response was observed at the local site, lung metastasis developed. Second-line chemotherapy with ifosfamide and doxorubicin with radiotherapy to the pelvis was administered and led to complete regression; however, its efficacy was transient. Although additional chemotherapy was administered, the patient eventually died due to the rapidly growing, recurrent tumour.

Second-order nonlinear optical susceptibilities of nonelectrically poled DR1-PMMA guest-host polymers.

Guest-host nonlinear optical polymers have attracted considerable interest due to their applications in fast electro-optical modulators and wavelength converters. In general, the electrical poling procedures, for which high DC external fields are applied, are necessary for aligning guest chromophores in polar order and activating the second-order nonlinearity. We present the nonelectrical poling behaviors for guest-host polymers: DR1 (4-[ethyl (2-hydroxyethyl) amino]-4'-nitroazobenzene) is the guest, and PMMA (poly (methyl methacrylate)) is the host. Second-order nonlinear optical susceptibility was induced in the conventional guest-host polymers after annealing at temperatures above the glass transition points of the host polymer even without applying the external fields. This phenomenon did not occur in the side-chain polymers, where the guests were directly bonded to the host chains. The guest polar alignments were most likely generated from the guest hydroxyl groups chemisorbing on the substrates. The polar alignments of the guest formed not only near the surface of the substrate, but also inside the host polymers. The optimized conditions for the SHG conversion were examined in the context of the polymer film thickness and guest concentration. The nonelectrical poling techniques described in this study are useful for enhancing the surface nonlinearity in the several materials, and they will be useful for further developments in nanophotonics and plasmonics.

[A case of colonic adenocarcinoma incidentally occurring in an Indiana pouch].

We present a rare case of colonic adenocarcinoma occurring in an Indiana pouch. A 68-year-old man underwent radical cystectomy with Indiana pouch urinary diversion for the treatment of bladder cancer 16 years ago. He was referred to our hospital for the treatment of a right staghorn stone, left renal stone, and pouch stones. Cystoscopic findings showed a 10×10 mm tumor distal to ureter anastomosis. Under the diagnosis of colonic adenocarcinoma in an Indiana pouch, tumor and stones were successfully removed. Adenocarcinoma occurrence after ureterosigmoidostomy is well-known. However, diagnosis of adenocarcinoma in an Indiana pouch is extremely rare.

[A case of inverted urothelial carcinoma of bladder].

We present a case of inverted urothelial carcinoma of the bladder. A 60-year-old male was referred to our hospital for bilateral ureteral stones. When transurethral ureterolithotripsy was performed to treat these stones, a tumor at the trigone of bladder was incidentally diagnosed. This tumor was pedunculated and its surface was not uniformly round. After the operation, this tumor was diagnosed as inverted urothelial carcinoma through the histopathologic examination. The patient was subsequently followed up for 6 months and there was no evidence of recurrence. Although this is a rare case, it is worth considering there is an urothelial carcinoma with inverted proliferation.

[A case of mesothelial cyst at the inguinal region].

A 54-year-old man presented with the left inguinal swelling. The operation was performed with diagnosis of the hydrocele of spermatic cord. A tumor was 3.0 cm x 2.5 cm in size, cystic with yellowish serous fluid. After the operation, this tumor is diagnosed as mesothelial cyst through the histopathologic examination. This is a rare case, however it is worth to consider that there is a possibility to be a mesothelial cyst when the tumor has been found at the inguinal region.

Generation of Hermite-Gaussian modes and vortex arrays based on two-dimensional gain distribution controlled microchip laser.

We have demonstrated high-order Hermite-Gaussian (HG) mode generation based on 2D gain distribution control edge-pumped, composite all-ceramic Yb:YAG/YAG microchip lasers using a V-type cavity. Several hundred milliwatts to several watts HG(mn) modes are achieved. We also generated different kinds of vortex arrays directly from the oscillator with the same power level. In addition, a more than 7 W doughnut-shape mode can be generated in the same cavity.

Pump-seed synchronization for MHz repetition rate, high-power optical parametric chirped pulse amplification.

We report on an active synchronization between two independent mode-locked lasers using a combined electronic-optical feedback. With this scheme, seed pulses at MHz repetition rate were amplified in a non-collinear optical parametric chirped pulse amplifier (OPCPA). The amplifier was seeded with stretched 1.5 nJ pulses from a femtosecond Ti:Sapphire oscillator, while pumped with the 1 ps, 2.9 µJ frequency-doubled output of an Yb:YAG thin-disk oscillator. The residual timing jitter between the two oscillators was suppressed to 120 fs (RMS), allowing for an efficient and broadband amplification at 11.5 MHz to a pulse energy of 700 nJ and an average power of 8 W. First compression experiment with 240 nJ amplified pulse energy resulted in a pulse duration of ~10 fs.

[Myocardial metastasis from renal cell carcinoma treated with sorafenib].

We present a case of myocardial metastasis from renal cell carcinoma (RCC) during the treatment with sorafenib. A 63-year-old male, who had undergone right radical nephrectomy, received interferon-alpha (IFN), interleukin (IL-2) and 5-flurouracil (5-FU) for the treatment of lung and pleural metastases. However, since this metastasis showed progressive disease, we administered sorafenib. Nine months after the introduction of sorafenib, he complained of dyspnea. Chest computed tomography and cardiac ultrasonography revealed a low density mass at the cardiac muscle of the left cardiac ventricle, suggesting myocardial metastasis of RCC. Molecular targeted therapy achieved a longer survival in advanced RCC patients in comparison with the immunotherapy using cytokines. Therefore, in metastasis evaluation, some organs which have been regarded as rare sites should be carefully evaluated.

Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis.

Disturbed endochondral ossification in X-linked hypophosphatemia indicates an involvement of P(i) in chondrogenesis. We studied the role of the sodium-dependent P(i) cotransporters (NPT), which are a widely recognized regulator of cellular P(i) homeostasis, and the downstream events in chondrogenesis using Hyp mice, the murine homolog of human X-linked hypophosphatemia. Hyp mice showed reduced apoptosis and mineralization in hypertrophic cartilage. Hyp chondrocytes in culture displayed decreased apoptosis and mineralization compared with WT chondrocytes, whereas glycosaminoglycan synthesis, an early event in chondrogenesis, was not altered. Expression of the type III NPT Pit-1 and P(i) uptake were diminished, and intracellular ATP levels were also reduced in parallel with decreased caspase-9 and caspase-3 activity in Hyp chondrocytes. The competitive NPT inhibitor phosphonoformic acid and ATP synthesis inhibitor 3-bromopyruvate disturbed endochondral ossification with reduced apoptosis in vivo and suppressed apoptosis and mineralization in conjunction with reduced P(i) uptake and ATP synthesis in WT chondrocytes. Overexpression of Pit-1 in Hyp chondrocytes reversed P(i) uptake and ATP synthesis and restored apoptosis and mineralization. Our results suggest that cellular ATP synthesis consequent to P(i) uptake via Pit-1 plays an important role in chondrocyte apoptosis and mineralization, and that chondrogenesis is ATP-dependent.

[Genetic basis for skeletal disease. Orthopaedic intervention for bone dysplasias].

The aims of orthopaedic intervention for bone dysplasias are to maintain joint function, to prevent neurological complications, and then to improve the patient's quality of life. Bone lengthening technique can not only increase the body height, but also correct malalignment of the limb at the same treatment session, which is important to prevent early occurrence of the degenerative osteoarthritis. Intramedullary nailing for osteogenesis imperfecta protects long bones from fractures and prevents malunion when fracture takes place. Spinal instrumentation surgery is effective for prevention of the neurological complications and deterioration of the spinal deformities.

Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of parathyroid hormone-related protein.

Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone-related protein (PTHrP) expression in primary chondrocytes and the mesenchymal cell line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.

MSX2 stimulates chondrocyte maturation by controlling Ihh expression.

Several studies indicated that a homeobox gene, Msx2, is implicated in regulation of skeletal development by controlling enchondral ossification as well as membranous ossification. However, the molecular basis by which Msx2 conducts chondrogenesis is currently unclear. In this study, we examined the role of Msx2 in chondrocyte differentiation using mouse primary chondrocytes and embryonic metatarsal explants. Treatment with BMP2 up-regulated the expression of Msx2 mRNA along with chondrocyte differentiation in murine primary chondrocytes. Overexpression of wild-type Msx2 stimulated calcification of primary chondrocytes in the presence of BMP2. We also found that constitutively active Msx2 (caMsx2) enhanced BMP2-dependent calcification more efficiently than wild-type Msx2. Consistently, caMsx2 overexpression up-regulated the expression of alkaline phosphatase and collagen type X induced by BMP2. Furthermore, organ culture experiments using mouse embryonic metatarsals indicated that caMsx2 clearly stimulated the maturation of chondrocytes into the prehypertrophic and hypertrophic stages in the presence of BMP2. In contrast, knockdown of Msx2 inhibited maturation of primary chondrocytes. The stimulatory effect of Msx2 on chondrocyte maturation was enhanced by overexpression of Smad1 and Smad4 but inhibited by Smad6, an inhibitory Smad for BMP2 signaling. These data suggest that Msx2 requires BMP2/Smad signaling for its chondrogenic action. In addition, caMsx2 overexpression induced Ihh (Indian hedgehog) expression in mouse primary chondrocytes. Importantly, treatment with cyclopamine, a specific inhibitor for hedgehogs, blocked Msx2-induced chondrogenesis. Collectively, our results indicated that Msx2 promotes the maturation of chondrocytes, at least in part, through up-regulating Ihh expression.

Regulation of osteoclast differentiation and function by phosphate: potential role of osteoclasts in the skeletal abnormalities in hypophosphatemic conditions.

UNLABELLED: Mice fed with a low Pi diet exhibited decreased osteoclast number. Hyp mice also showed decreased osteoclasts, and high Pi reversed it. Low Pi reduced osteoclast formation and bone resorption in vitro. Hypophosphatemia may suppress osteoclast differentiation/function, leading to skeletal abnormalities. INTRODUCTION: Skeletal abnormalities seen in hypophosphatemic disorders indicate a critical role of phosphate (Pi) in skeletogenesis. However, the role of osteoclasts in the pathogenesis of the disturbed skeletogenesis is unclear. MATERIALS AND METHODS: Mice fed with a low-Pi diet and Hyp mice that are characterized by hypophosphatemia and impaired osteogenesis were studied. Effects of Pi on osteoclast formation and bone resorption were also examined in vitro. RESULTS: Histomorphometric examination showed that mice on a low-Pi diet exhibited decreased osteoclast number. Furthermore, osteoclast number in Hyp mice was also decreased compared with wildtype (WT) mice. Of note, feeding of Hyp mice with high-Pi diet significantly reversed hypophosphatemia, improved disturbed osteogenesis, and increased osteoclast number. Osteoclast-like cell (OLC) formation and bone resorption in Hyp bone marrow cells was not different from WT bone marrow cells. On the other hand, OLC formation and bone resorption were decreased in conjunction with reduced mRNA expression of RANKL in WT bone marrow cells cultured in the medium containing low Pi (0.5 mM). Recombinant human matrix extracellular phosphoglycoprotein (MEPE), a candidate for phosphatonin, also decreased osteoclast formation, whereas fibroblast growth factor 23 (FGF23), another phosphatonin candidate, showed no effects. CONCLUSIONS: Our results suggest that Pi controls the differentiation and function of osteoclasts. These actions of Pi on osteoclasts may be associated with the pathogenesis of the skeletal abnormalities in hypophosphatemic disorders.

[Role of the type 3 sodium-dependent phosphate transporter in the calcification of growth plate chondrocytes].

Phosphate is a second most abundant mineral next to calcium. The facts that hypophosphatemia is associated with the retardation of skeletal development and phosphate levels increase during endochondral ossification suggest that phosphate plays a role in cartilage differentiation. The type 3 sodium-dependent phosphate transporter (NPT3) expressed in growth plate chondrocytes transports extracellular phosphates into the cells. These phosphates are utilized for ATP synthesis, which in turn promotes apoptosis of growth plate chondrocytes through activation of the caspase signal pathways. Subsequently, matrix vesicles released from apoptotic chondrocytes accelerate calcification of chondrocytes. Our results suggest that phosphate plays a critical role in terminal differentiation of chondrocytes.