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The no-insulation (NI) technique is a very effective protection method for REBCO pancake coils. However, it is not suitable for a layer-wound coil, which is the optimum configuration for the persistent operation and generation of a homogeneous magnetic field, since an NI layer-wound coil suffers from an extremely long magnetic field delay. Such a delay is caused by large short circuits across the layers inside the winding. To combat this phenomenon, a simple winding method, denoted as ‘intra-layer no-insulation (LNI)’, is proposed in the present work. The method uses insulator sheets to prevent electrical contacts between the layers and copper sheets to increase electrical contacts between the turns in each layer: such a coil has the layer-wound geometry with the NI pancake-like internal circuit. An LNI REBCO coil shows a shorter field delay time constant by three orders of magnitude than an ordinary NI REBCO layer-wound coil, and also exhibits a self-protect behavior with more rapid thermal runaway propagation compared to a NI REBCO double-pancake coil. [ABSTRACT FROM AUTHOR]

The characteristic magnetic field delay time for a no-insulation (NI) REBCO layer-wound coil is three orders of magnitude longer than that for a NI REBCO double-pancake coil. In a NI layer-wound coil, the circumferential current firstly flows along the periphery of the coil winding, and then it diffuses from the top and bottom turns into the middle turns of the winding, resulting in a long characteristic magnetic field delay time due to the current diffusion process. In contrast, the characteristic magnetic field delay time for a NI double-pancake coil is dominated by the circumferential current decay in individual turns. On the basis of a derived scaling law, the characteristic magnetic field delay time for a NI REBCO layer-wound coil for a 400 MHz LTS/REBCO nuclear magnetic resonance (NMR) magnet is 37 h, while that for a NI REBCO double-pancake coil is only <1 min. Thus, it is demonstrated that a double-pancake-winding is greatly preferred to a layer-winding for NMR applications from the view point of the characteristic magnetic field delay time. [ABSTRACT FROM AUTHOR]

Background: Multiple joint arthritis patterns require a comprehensive understanding to optimize patient management. This study aimed to present a patient cohort that deviated from known definitions of coxitis knee (CK), identifying and characterizing this atypical group., Methods: Patients undergoing both total hip arthroplasty and total knee arthroplasty between January 2008 and December 2018 were retrospectively reviewed. The patients were classified into a typical coxitis knee group (classic, long leg arthropathy, and windswept deformity) and an atypical coxitis knee group. Leg-length discrepancy, body mass index (BMI), and radiographic parameters of the groups were compared and analyzed., Results: A total of 31 patients were allocated to the typical coxitis knee group (n = 10), and atypical coxitis knee group (n = 21). In the atypical group, 27 hips were involved, of which 21 had acetabular dysplasia, 5 exhibited subchondral insufficiency fracture-like changes, and only 1 had classic osteoarthritis. Among the 27 knees undergoing total knee arthroplasty, 26 showed varus alignment, 1 was within the normal range, and none was valgus. Acetabular dysplasia involved ipsilateral (n = 1), contralateral (n = 14), and bilateral (n = 6) hips, showing atypical coxitis knee. Patients with acetabular dysplasia were more likely to exhibit atypical CK., Conclusion: Most patients in the cohort displayed acetabular dysplasia and contralateral varus knees, constituting a pattern referred to as acetabular dysplasia-associated gonarthritis. Identifying this novel subtype may have important clinical implications for regions with high risk factors, where acetabular dysplasia and constitutional genu varum are prevalent., (© 2024. The Author(s).)

Background: Primary aim to identify the ideal medial joint gap in extension needed to prevent post-operative flexion contracture following total knee arthroplasty (TKA) in varus osteoarthritic knees by the modified gap balancing technique. A secondary aim was to analyze multiple factors that influence knee extension in TKA by modified gap balancing., Methods: This is a prospective cohort study of 150 patients diagnosed with osteoarthritic varus knee who underwent TKA using the modified gap balancing technique. Operative and clinical records were assessed to determine factors including age, BMI (Body mass index), pre-operative extension angle and the medial extension laxity. Patients were followed for 6-months post-operatively and reviewed for knee extension angle., Results: Six months final follow-up information was available for 148 patients with an average age of 75.5 years. Pre-operative knee extension and BMI were significantly associated with post-operative knee extension. Post-operative flexion contracture of ≧ 10 0 was not seen in any of 34 patients with a medial extension laxity ≧ 0 mm who had no pre-existing flexion contracture, and in 1/9 (11.1%) patients with a medial extension laxity ≧ 1 mm who had pre-existing flexion contracture., Conclusions: Pre-operative extension angle and BMI significantly influence the post-operative knee extension angle in TKA using the modified gap balancing technique. A medial extension laxity of at least 1 mm is ideally needed to prevent post-operative flexion contracture in patients with a pre-existing contracture ≧ 10 0 ., Level of Evidence: Level II; Prospective cohort study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Delhi Orthopedic Association. All rights reserved.)

Aims: This study aimed to investigate the relationship between changes in patellar height and clinical outcomes at a mean follow-up of 7.7 years (5 to 10) after fixed-bearing posterior-stabilized total knee arthroplasty (PS-TKA)., Methods: We retrospectively evaluated knee radiographs of 165 knees, which underwent fixed-bearing PS-TKA with patella resurfacing. The incidence of patella baja and changes in patellar height over a minimum of five years of follow-up were determined using Insall-Salvati ratio (ISR) measurement. We examined whether patella baja (ISR < 0.8) at final follow-up affected clinical outcomes, knee joint range of motion (ROM), and Knee Society Score (KSS). We also assessed inter- and intrarater reliability of ISR measurements and focused on the relationship between patellar height reduction beyond measurement error and clinical outcomes., Results: The ISR gradually decreased over five years after TKA, and finally 33 patients (20.0%) had patella baja. Patella baja at the final follow-up was not related to passive knee ROM or KSS. Interestingly, when we divided into two groups - patella baja and patella normal-alta (ISR ≥ 0.8) - the patella baja group already had a lower patellar height before surgery, compared with the patella normal-alta group. The ISR measurement error in this study was 0.17. Both passive knee flexion and KSS were significantly decreased in the group with a decrease in ISR of ≥ 0.17 at final follow-up., Conclusion: Patellar height gradually decreased over five years of follow-up after TKA. The reduction in patellar height beyond measurement error following TKA was associated with lower clinical outcomes. Cite this article: Bone Jt Open  2021;2(12):1075-1081.

Kisspeptin neurons located in the hypothalamic preoptic area (POA) are suggested to be responsible for the induction of the gonadotropin-releasing hormone (GnRH) surge and the following luteinizing hormone (LH) surge to regulate female mammals' ovulation. Accumulating evidence demonstrates that the preovulatory level of estrogen activates the POA kisspeptin neurons (estrogen positive feedback), which in turn induces a GnRH/LH surge. This study aimed to derive a cell line from goat POA kisspeptin neurons as an in vitro model to analyze the estrogen positive feedback mechanism in ruminants. Neuron-derived cell clones obtained by the immortalization of POA tissue from a female Shiba goat fetus were analyzed for the expression of kisspeptin (KISS1) and estrogen receptor α (ESR1) genes using quantitative real-time reverse transcription-polymerase chain reaction and three cell clones were selected as POA kisspeptin neuron cell line candidates. One cell line (GP64) out of the three clones showed significant increase in the KISS1 level by incubation with estradiol for 24 h, indicating that the GP64 cells mimic endogenous goat POA kisspeptin neurons. The GP64 cells showed immunoreactivities for kisspeptin and estrogen receptor α and retained a stable growth rate throughout three passages. Further, intracellular calcium levels in the GP64 cells were increased by the KCl challenge, indicating their neurosecretory ability. In conclusion, we generated a new KISS1-expressing cell line derived from goat POA. The current GP64 cell line could be a useful model to elucidate the estrogen positive feedback mechanism responsible for the GnRH/LH surge generation in ruminants.

Objective : Only a few cases of insufficiency fractures of the tibial plateau following bisphosphonate use have been reported. The authors report a case with bisphosphonate (BP) -related atypical insufficiency fracture of tibial plateau, which developed delayed union. Patient : A 65-year-old Japanese woman presented with left knee pain without any trauma. She had a 5-year history of risedronate use for primary osteoporosis. Initial X-rays were unremarkable, but magnetic resonance imaging (MRI) confirmed an insufficiency fracture at the left tibial plateau at 3 weeks after the initial visit. Risedronate treatment was stopped because we diagnosed her with a BP-related atypical insufficiency fracture of the tibial plateau. She was treated with rest, a lateral wedge insole and protective weight-bearing with a T-cane for 3 months. Result : At 3-month follow-up, the patient still had a pain and a delayed healing on radiographs. Six months later, X-rays showed that the fracture site had a sclerotic change, but MRI revealed delayed union. At 8-month follow-up, the fracture was healed without any symptoms. Conclusion : All clinicians need to be aware of the delayed healing of atypical insufficiency fracture related with prolonged BP use. J. Med. Invest. 68 : 186-188, February, 2021.

Kisspeptin plays a critical role in governing gonadotrophin-releasing hormone (GnRH)/gonadotrophin secretion and subsequent reproductive function in mammals. The hypothalamic arcuate nucleus (ARC) kisspeptin neurones, which co-express neurokinin B (NKB) and dynorphin A (Dyn) and are referred to as KNDy neurones, are considered to be involved in GnRH generation. The present study aimed to establish cell lines derived from goat KNDy and GnRH neurones. Primary-cultured cells of female Shiba goat foetal hypothalamic ARC and preoptic area (POA) tissues were immortalised with the infection of lentivirus containing the simian virus 40 large T-antigen gene. Clones of the immortalised cells were selected by the gene expression of a neuronal marker, and then the neurone-derived cell clones were further selected by the gene expression of KNDy or GnRH neurone markers. As a result, we obtained a KNDy neurone cell line (GA28) from the ARC, as well as two GnRH neurone cell lines (GP11 and GP31) from the POA. Immunocytochemistry revealed the expression of kisspeptin, NKB and Dyn in GA28 cells, as well as GnRH in GP11 and GP31 cells. GnRH secretion from GP11 and GP31 cells into the media was confirmed by an enzyme immunoassay. Moreover, kisspeptin challenge increased intracellular Ca2+ levels in subsets of both GP11 and GP31 cells. Kisspeptin mRNA expression in GA28 cells, which expressed the oestrogen receptor alpha gene, was significantly reduced by 17β-oestradiol treatment. Furthermore, the transcriptional core promoter and repressive regions of the goat NKB gene were detected using GA28 cells. In conclusion, we have established goat KNDy and GnRH neurone cell lines that could be used to analyse molecular and cellular mechanisms regulating KNDy and GnRH neurones in vitro, facilitating the clarification of reproductive neuroendocrine mechanisms in ruminants., (© 2020 British Society for Neuroendocrinology.)

Exposure to a ram during spring stimulates luteinizing hormone (LH) secretion and can induce ovulation in sexually quiescent ewes ("ram effect"). Kisspeptin (Kiss) present in the arcuate nucleus (ARC) and the preoptic area (POA) is a potent stimulators of LH secretion. Our aim was to investigate whether Kiss neurons mediate the increase in LH secretion during the ram effect. With double immunofluorescent detection, we identified Kiss neurons (Kiss IR) activated (Fos IR) by exposure to a ram for 2 hours (M2) or 12 hours (M12) or to ewes for 2 hours (C). The density of cells Kiss + Fos IR and the proportion of Kiss IR cells that were also Fos IR cells were higher in M2 and M12 than in C in ARC (P < 0.002) and POA (P < 0.02). In ARC, these parameters were also higher in M12 than in M2 (P < 0.02 and P < 0.05). Kiss antagonist (P234 10-6M) administered by retrodialysis in POA for 3 hours at the time of introduction of the ram reduced the amplitude of the male-induced increase in LH concentration compared with solvent (P < 0.02). In ARC, P234 had a more limited effect (P < 0.038 1 hour after P234) but pulse frequency increased less than after solvent (P = 0.07). In contrast, Kiss antagonist (P271 10-4M) infused in ARC but not POA 6 to 18 hours after introduction of the ram prevented the LH surge in the ewe (0/6 vs 4/5 and 4/6 in C). These results suggest that both populations of Kiss neurons are involved in the ram-induced pulsatile LH secretion and in the LH surge., (Copyright © 2017 Endocrine Society.)

Elucidating the physiological mechanisms that control reproduction is an obvious strategy for improving the fertility of cattle and developing new agents to control reproductive functions. The present study aimed to identify kisspeptin neurons in the bovine hypothalamus, clarifying that a central mechanism is also present in the cattle brain, as kisspeptin is known to play an important role in the stimulation of gonadotropin-releasing hormone (GnRH)/gonadotropin secretion in other mammals. To characterize kisspeptin neurons in the bovine hypothalamus, the co-localizations of kisspeptin and neurokinin B (NKB) or kisspeptin and dynorphin A (Dyn) were examined. Hypothalamic tissue was collected from Japanese Black or Japanese Black × Holstein crossbred cows during the follicular and luteal phases. Brain sections, including the arcuate nucleus (ARC) and the preoptic area (POA), were dual immunostained with kisspeptin and either NKB or Dyn. In the ARC, both NKB and Dyn were co-localized in kisspeptin neurons during both the follicular and luteal phases, demonstrating the presence of kisspeptin/NKB/Dyn-containing neurons, referred to as KNDy neurons, in cows. In the POA, no co-localization of kisspeptin with either NKB or Dyn was detected. Kisspeptin expression in the follicular phase was higher than that in the luteal phase, suggesting that kisspeptin expression in the POA is positively controlled by estrogen in cows. The kisspeptin neuronal populations in the ARC and POA likely play important roles in regulating the GnRH pulse and surge, respectively, in cows.

Study Design: A retrospective study., Objectives: Diffusion tensor imaging (DTI) reflects pathological change in the spinal cord more sensitively than conventional magnetic resonance imaging (MRI). Electrophysiological examination enables quantitative assessment of spinal cord function. Few studies have addressed the correlation between intraoperative spinal cord-evoked potentials (SCEPs) and DTI. The purpose of this study was to examine whether DTI is an objective index for the diagnosis of the segmental level of dysfunction in cervical spondylotic myelopathy (CSM)., Setting: Yamaguchi University Graduate School of Medicine, Japan., Methods: Using 3.0-Tesla MRI, DTI values for the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured at the disc level C2/C3 through C6/C7 in 11 normal subjects and 10 subjects with CSM. Subjects with CSM were divided into two groups based on the extent of compression according to conventional MRI: single level (n=3) and multilevel (n=7). Intraoperative SCEPs were measured in subjects with CSM. For each group, the ADC and FA values were compared with SCEPs with respect to the segmental levels of dysfunction., Results: For all three subjects with single-level compression and six of seven with multilevel compression, the maximal ADC value was observed at the segmental level of dysfunction as per the SCEP. Minimum FA values were observed at those sites in two of three patients with single-level compression and in only two of seven with multi-level compression., Conclusion: Our results suggest that ADC might serve as a supplementary diagnostic indicator of the segmental levels of dysfunction in CSM.

Background: Rehabilitation facilitates the reorganization of residual/regenerated neural pathways and is key in improving motor function following spinal cord injury. Neuromuscular electrical stimulation (NMES) has been reported as being clinically effective. Although it can be used after the acute phase post-injury, the optimal stimulation conditions to improve motor function remain unclear. In this paper, we examined the effectiveness of NMES with alternating currents in the kilohertz (kHz) frequency in gait rhythm stimulation therapy., Methods: Tests were performed using 20 mature female Fischer rats. Incomplete spinal cord injuries (T9 level) were made with an IH impactor using a force of 150 kdyn, and NMES was administered for 3 days from the 7th day post-injury. The needle electrodes were inserted percutaneously near the motor point of each muscle in conscious rats, and each muscle on the left and right leg was stimulated for 15 min at two frequencies, 75 Hz and 8 kHz, to induce a gait rhythm. Motor function was evaluated using Basso, Beattie, Bresnahan (BBB) scores and three-dimensional (3D) gait analysis. Rats were divided into four groups (5 rats/group), including the NMES treatment 75-Hz group (iSCI-NMES 75 Hz), 8-kHz group (iSCI-NMES 8 kHz), injury control group (iSCI-NT), and normal group (Normal-CT), and were compared., Results: There was no significant difference in BBB scores among the three groups. In 3D gait analysis, compared with the injury control group, the 8-kHz group showed a significant improvement in synergistic movement of both hindlimbs., Conclusion: We suggest that kHz stimulation is effective in gait rhythm stimulation using NMES.

A luteinising hormone (LH) surge is fundamental to the induction of ovulation in mammalian females. The administration of a preovulatory level of oestrogen evokes an LH surge in ovariectomised females, whereas the response to oestrogen in castrated males differs among species; namely, the LH surge-generating system is sexually differentiated in some species (e.g. rodents and sheep) but not in others (e.g. primates). In the present study, we aimed to determine whether there is a functional LH surge-generating system in male goats, and whether hypothalamic kisspeptin neurones in male goats are involved in the regulation of surge-like LH secretion. By i.v. infusion of oestradiol (E2; 6 μg/h) for 16 h, a surge-like LH increase occurred in both castrated male and ovariectomised female goats, although the mean peak LH concentration was lower and the mean peak of the LH surge was later in males compared to females. Dual staining with KISS1 in situ hybridisation and c-Fos immunohistochemistry revealed that E2 treatment significantly increased c-Fos expression in the medial preoptic area (mPOA) KISS1 cells in castrated males, as well as ovariectomised females. By contrast, dual-labelled cells were scarcely detected in the arcuate nucleus (ARC) after E2 treatment in both sexes. These data suggest that kisspeptin neurones in the mPOA, but not those in the ARC, are involved in the induction of surge-like LH secretion in both male and female goats. In summary, our data show that the mechanism that initiates the LH surge in response to oestrogen, the mPOA kisspeptin neurones, is functional in male goats. Thus, sexual differentiation of the LH surge-generating system would not be applicable to goats., (© 2014 British Society for Neuroendocrinology.)

The oestrogen-induced luteinising hormone (LH) surge is evident in male primates, including humans, whereas male rodents never show the LH surge, even when treated with a preovulatory level of oestrogen. This suggests that the central mechanism governing reproductive hormones in primates is different from that in rodents. The present study aimed to investigate whether male Japanese monkeys conserve a brain mechanism mediating the oestrogen-induced LH surge via activation of kisspeptin neurones. Adult male and female Japanese monkeys were gonadectomised and then were treated with oestradiol-17β for 2 weeks followed by a bolus injection of oestradiol benzoate. Both male and female monkeys showed an oestrogen-induced LH surge. In gonadectomised monkeys sacrificed just before the anticipated time of the LH surge, oestrogen treatment significantly increased the number of KISS1-expressing cells in the preoptic area (POA) and enhanced the expression of c-fos in POA KISS1-positive cells of males and females. The oestrogen treatment failed to induce c-fos expression in the arcuate nucleus (ARC) kisspeptin neurones in both sexes just prior to LH surge onset. Thus, kisspeptin neurones in the POA but not in the ARC might be involved in the positive-feedback action of oestrogen that induces LH surge in male Japanese monkeys, as well as female monkeys. The present results indicate that oestrogen-induced activation of POA kisspeptin neurones may contribute to the LH surge generation in both sexes. The conservation of the LH surge generating system found in adult male primates, unlike rodents, could be a result of the capability of oestrogen to induce POA kisspeptin expression and activation., (© 2014 British Society for Neuroendocrinology.)

Neurokinin B (NKB), encoded by TAC3, is thought to be an important accelerator of pulsatile gonadotropin-releasing hormone release. This study aimed to clarify the transcriptional regulatory mechanism of goat TAC3. First, we determined the full-length mRNA sequence of goat TAC3 from the hypothalamus to be 820 b, including a 381 b coding region, with the putative transcription start site located 143-b upstream of the start codon. The deduced amino acid sequence of NKB, which is produced from preproNKB, was completely conserved among goat, cattle, and human. Next, we cloned 5'-upstream region of goat TAC3 up to 3400 b from the translation initiation site, and this region was highly homologous with cattle TAC3 (89%). We used this goat TAC3 5'-upstream region to perform luciferase assays. We created a luciferase reporter vector containing DNA constructs from -2706, -1837, -834, -335, or -197 to +166 bp (the putative transcription start site was designated as +1) of goat TAC3 and these were transiently transfected into mouse hypothalamus-derived N7 cells and human neuroblastoma-derived SK-N-AS cells. The luciferase activity gradually increased with the deletion of the 5'-upstream region, suggesting that the transcriptional suppressive region is located between -2706 and -336 bp and that the core promoter exists downstream of -197 bp. Estradiol treatment did not lead to significant suppression of luciferase activity of any constructs, suggesting the existence of other factor(s) that regulate goat TAC3 transcription.

With the advances in echoendoscopes, the frontier of therapeutic endoscopic ultrasonography (EUS) is expanding. A 50-year-old male presented to us with unrelenting pain following an episode of alcoholic pancreatitis. Imaging studies revealed evidence of pancreatic ductal hypertension with a pseudocyst in the head of the pancreas. Following unsuccessful attempts at drainage of the pancreatic duct (PD) via the minor or major papilla at endoscopic retrograde cholangiopancreatography, he underwent endoscopic ductal drainage with the EUS-assisted rendezvous technique. The PD was punctured under the guidance of EUS. A guidewire was then introduced into the PD and was guided into the duodenal lumen through the minor papilla. The tip of the guidewire was grasped with forceps coming out of a duodenoscope introduced instead of the echoendoscope. A pancreatic stent was inserted over the guidewire across the minor papilla. After the endoscopic pancreatic stenting, the patient achieved symptomatic relief.

The nanostructure and its transition of in a poly(acrylic acid) (PAA) brush in the water surface monolayers of poly(hydrogenated isoprene)-b-poly(acrylic acid) with different block lengths and block ratios were investigated by X-ray reflectivity as a function of surface pressure (brush density) and salt concentration in the subphase. The PAA brush showed the same behavior after salt addition as did the poly(methacrylic acid) (PMAA) brush, which was investigated previously. The brush chains expanded and then shrunk after passing the maximum with increasing added salt concentration. This behavior could be explained by the change in electric charges on the PAA brush chains as was observed on the PMAA brush. The PAA brush chains showed a critical brush density, where there was a transition between the carpet layer only and carpet + brush layer structures, as did the PMAA and poly(styrene sulfonic acid) (PSS) brushes. The critical brush density was about 0.4 chains nm(-2), which was higher than that of the PSS brush, a strong acid brush, and was close to that of the PMAA brush, a weak acid brush. However, the critical brush density of the PAA brush was independent of the hydrophilic chain length whereas that of the PMAA brush decreased with increasing PMAA chain length. In addition, the PAA brush had a thicker carpet layer than the PSS and PMAA brushes. Hence, the mechanism of PAA brush formation was predicted to be different from that of not only the PSS brush (strong acid brush) but also the PMAA brush.

This article presents 2 uncommon cases of Langerhans cell histiocytosis of the acetabulum in adults. Langerhans cell histiocytosis is a benign lesion of bone with a diversity of radiographic appearances depending on location. Radiographs of our cases showed a clearly defined radiolucent area at the acetabulum. Magnetic resonance imaging revealed specific findings for Langerhans cell histiocytosis of the acetabulum. Gadolinium-enhanced images showed that abnormal signal was spread to the whole acetabulum surrounding the lesion. Orthopedic surgeons should be aware of the existence of this lesion and attentive to patients who report spontaneous hip pain, although Langerhans cell histiocytosis is a rare condition in adults. It is generally agreed that prognosis is more dependent on age at the time of diagnosis rather than on therapy. We recommend simple curettage for Langerhans cell histiocytosis of the acetabulum in adults to obtain a definite diagnosis and relieve pain.

Background/aims: Due to the development of contrast-enhanced harmonic imaging, ultrasound can reveal more precise hemodynamic information than conventional angiography. In this study, the value of contrast-enhanced harmonic imaging was studied in the evaluation of response in treatment of pancreatic cancer., Methodology: Thirteen pancreatic cancer patients treated with gemcitabine were enrolled in this study. Contrast-enhanced harmonic ultrasonography was performed to evaluate the treatment response during every period of treatment. After intravenously injecting the contrast agent, pancreatic tumors were observed in a real-time and subsequently in an intermittent fashion. Findings obtained by contrast-enhanced harmonic imaging were compared with dynamic CT findings and serum tumor marker levels., Results: Tumor markers were reduced by at least 50% in 6 patients. We could not evaluate tumor size reduction rates on the B-mode US because the tumor margin was unclear. On the other hand, the hypovascular area was clearly depicted on the perfusion image of contrast-enhanced harmonic imaging in all patients throughout the observation period, and changes in tumor size could be easily evaluated. The tumor size reduction rates in these 6 cases were 13.1 +/- 5.5% by dynamic CT and 21.1 +/- 14.1% by contrast-enhanced harmonic imaging., Conclusions: Contrast-enhanced harmonic imaging is useful for evaluating treatment response for pancreatic cancer.

The aim of our study was to assess the utility of endoscopic ultrasonography (EUS) and contrast-enhanced EUS (CE-EUS) for the depiction and differential diagnosis of pancreatic tumors focusing in particularly those 2 cm or smaller. We compared different diagnostic procedures, contrast-enhanced multidetector computed tomography (CE-CT) and EUS with the use of power Doppler (PD-EUS) and CE-EUS for detection and differential diagnosis of pancreatic tumors. The study included 156 consecutive patients with suspected pancreatic tumors, who underwent CE-CT, and EUS followed by PD-EUS and CE-EUS. CE-EUS was performed by power Doppler mode using sonographic contrast agent Levovist. Thirty-six of 156 patients examined had tumors of < or =2 cm. EUS had significantly higher sensitivity (94.4%) for detection of pancreatic carcinomas of 2 cm or less in comparison to CE-CT (50%). For small pancreatic tumor of 2 cm or less, sensitivities for differentiating ductal carcinomas from other tumors were 50.0%, 11.0% and 83.3% for CE-CT, PD-EUS and CE-EUS. CE-EUS was significantly more sensitive than PD-EUS and CE-CT. EUS and subsequent CE-EUS are more sensitive than CE-CT in the detection and the differentiation of small pancreatic tumors.

Background: A prospective, randomized study was performed to determine whether gemcitabine infusion at a low dose (250 mg/m2) is comparable or superior to the standard-dose infusion (1000 mg/m2) in terms of the survival period, clinical benefit, and frequency of adverse effects in patients with advanced pancreatic adenocarcinoma., Methods: Twenty-five patients who were histologically proven to have locally advanced pancreatic cancer or pancreatic cancer with distant metastases were initially enrolled in the present study. They were treated with gemcitabine infusion at either a dose of 1000 mg/m2 over 30 min (the standard regimen) on days 1, 8, and 15 of every 4-week cycle or at a dose of 250 mg/m2 over 30 min every week. Survival time, response rate, time to treatment failure, clinical benefit response, and adverse effects were compared between the two groups., Results: Twenty-one patients received gemcitabine for more than 1 month. The median survival period was 7.2 months for patients who received the low-dose infusion regimen, in contrast to 5.2 months for patients administered the standard-dose infusion regimen. The time to treatment failure was 5.6 months for patients in the low-dose infusion regimen, in contrast to 3.4 months for patients in the standard-dose infusion regimen. There were no significant differences in either survival time to time to treatment failure or clinical benefits between the two groups, but the incidence of adverse reactions in patients administered the low-dose therapy was significantly lower than that in patients receiving the standard-dose therapy (P<0.05). In particular, patients in the standard infusion regimen group experienced more hematologic toxicity than those in the low-dose regimen., Conclusions: These findings suggest that the low-dose gemcitabine infusion regimen can be continuously administered to patients with locally advanced and systemically spreading pancreatic cancer because of its reduced toxicity, resulting in better quality of life and an improved safety profile as compared to the standard infusion treatment regimen.

Background: Coded phase inversion harmonic ultrasonography, a newly available sonographic technique, enables visualisation of slow flow in minute vessels in a real time fashion with the use of a sonographic contrast agent containing monosaccharide. Our purpose was to employ this novel technique to observe microvessels in pancreatic tumours., Subjects and Methods: Sixty five patients with suspicious pancreatic tumours received contrast enhanced coded phase inversion harmonic ultrasonography, contrast enhanced computed tomography, and endosonography. Final diagnoses based on histological findings were pancreatic ductal carcinomas in 49 patients, inflammatory pseudotumours with chronic pancreatitis in seven, and endocrine tumours in nine. For contrast enhanced coded harmonic ultrasonography, Levovist, a contrast agent, was injected intravenously as a bolus. When the first microbubble signal appeared in the pancreas, images of the ideal scanning plane were displayed in a real time continuous fashion (vessel images). Subsequently, interval delay scanning (perfusion images) was taken to demonstrate parenchymal flow. Tumour vascularity was evaluated by using the two types of imaging. Sensitivities for depicting pancreatic tumours were compared between three examinations., Results: Contrast enhanced ultrasonography demonstrated tumour vessels in 67% of pancreatic ductal carcinomas, although most were relatively hypovascular compared with the surrounding pancreatic tissue. The vascular patterns of tumours obtained by contrast enhanced ultrasonography were closely correlated with those obtained by contrast enhanced computed tomography. Values for sensitivity in depicting pancreatic tumours of 2 cm or less in size were 68% for contrast enhanced computed tomography, 95% for endosonography, and 95% for contrast enhanced ultrasonography., Conclusion: Contrast enhanced coded phase inversion harmonic ultrasonography successfully visualised fine vessels in pancreatic tumours and may play a pivotal role in the depiction and differential diagnosis of pancreatic tumours.

Objective: To compare the effectiveness of contrast-enhanced Dynamic Flow imaging and contrast-enhanced power Doppler imaging using Levovist(®) as a microbubble contrast agent in evaluating intratumoral vascularity in hepatocellular carcinoma (HCC)., Materials and Methods: Twenty-nine patients with 54 hepatocellular carcinoma nodules (before treatment, 31; after treatment, 23) were studied with both Dynamic Flow and power Doppler imaging with intravenous injection of Levovist(®). Tumor vascularity was categorized as 0, no blood flow signals within the tumor; 1, dotlike blood flow signals within the tumor; 2, moderate blood flow signals within the tumor; and 3, abundant blood flow signals within the tumor. Detectability of intratumoral vascularity of hepatocellular carcinoma in three groups based on tumor depth, blooming and noise artifacts on contrast-enhanced Dynamic Flow and contrast-enhanced power Doppler imaging were also compared with results obtained using dynamic CT as a the gold standard. The effectiveness of contrast-enhanced Dynamic Flow and contrast-enhanced power Doppler imaging in assessing therapeutic effect were compared at the same time., Results: The ability of contrast-enhanced Dynamic Flow Doppler imaging to detect tumor vascularity in the superficial and intermediate hepatocellular carcinoma groups was close to that of contrast-enhanced power Doppler imaging (p>0.05). However, contrast-enhanced Dynamic Flow imaging demonstrated tumor parenchymal stain in 28 hepatocellular carcinoma nodules (61%), which was not detected by contrast-enhanced power Doppler imaging. Further, significantly fewer artifacts appeared in contrast-enhanced Dynamic Flow imaging than in contrast-enhanced power Doppler imaging (p<0.001). In assessing therapeutic response, the sensitivity of contrast-enhanced Dynamic Flow imaging was similar to that of dynamic CT. In deep areas, however, those more than 6 cm below the surface of the body, contrast-enhanced Dynamic Flow imaging was less sensitivity than contrast-enhanced power Doppler imaging (p=0.005)., Conclusion: Contrast-enhanced Dynamic Flow imaging provides an effective approach to assessing intratumoral vascularity and therapeutic response in HCC lesions situated less than 6 cm from the surface of the body. It is superior to contrast-enhanced power Doppler imaging in its ability to detect tumor parenchymal stain and production of fewer artifacts.

Objective: This study was performed to evaluate the usefulness of contrast-enhanced coded phase-inversion harmonic sonography in assessing the therapeutic response of percutaneous radiofrequency ablation in patients with hepatocellular carcinoma., Subjects and Methods: Sixty-seven patients with a total of 107 examinations on 91 hepatocellular carcinoma nodules underwent coded harmonic angio, a technique of coded phase-inversion harmonic sonography, using the IV microbubble contrast agent Levovist before and after percutaneous radiofrequency ablation. The intratumoral blood vessels and tumor parenchymal stain were detected in the early arterial phase and the late vascular phase, respectively. The results of contrast-enhanced imaging with coded harmonic angio were compared with those of three-phase dynamic CT., Results: Before treatment, all examined 107 hepatocellular carcinoma nodules were found to be hypervascular on contrast-enhanced imaging with coded harmonic angio. After radiofrequency ablation, contrast-enhanced coded harmonic angio detected persistent signal enhancement in 41 examined nodules (38.3%), whereas this technique showed no intratumoral enhancement in the remaining 66 (61.7%) examined nodules. Compared with dynamic CT, the sensitivity, specificity, and diagnostic accuracy of contrast-enhanced coded harmonic angio were 95.3%, 100%, and 98.1%, respectively. With contrast-enhanced coded harmonic angio, we found that it was difficult to identify the safety margin that can be detected on dynamic CT., Conclusion: Contrast-enhanced imaging with coded harmonic angio may provide an alternative approach that has high diagnostic agreement with dynamic CT in assessing the therapeutic effect of radiofrequency ablation in hypervascular hepatocellular carcinomas, in spite of having limitations in identifying the safety margin.

We describe one case of hepatocellular carcinoma (HCC) arising in secondary haemochromatosis in a non-cirrhotic liver. The patient was a 40-year-old male. He had severe pancytopenia due to myelodysplastic syndrome (MDS) and developed secondary haemochromatosis as a result of a large amount of erythrocyte transfusion. Multiple nodules of the liver appeared about 6 years after the diagnosis of MDS. Needle biopsy of the nodules histologically confirmed them to be moderately differentiated HCCs. The liver parenchyma was shown to be non-cirrhotic and a deposit of hemosiderin was also identified, consistent with a finding of haemochromatosis of the liver. Transarterial chemoembolization was performed to treat multiple HCCs. There are a number of reports describing HCC occurrence in non-cirrhotic patients with hereditary haemochromatosis. However, HCC in secondary haemochromatosis without cirrhosis is extremely rare.

Purpose: To investigate the value of a new wide-band contrast harmonic imaging method in depicting intratumoral vascularity in hepatocellular carcinoma., Materials and Methods: Twenty-two patients with 28 hepatocellular carcinoma nodules evaluated with Contrast Harmonic Echo, a new wide-band harmonic imaging method, using Levovist(®) as a contrast-enhancing agent. Intermittent imaging was carried out in the early arterial phase for 10 to 40 seconds, in the late vascular phase for 1 to 2 minutes, and in the postvascular phase for 5 to 7 minutes. Subtraction images were obtained using the multishot method during the late vascular phase. The ability of Contrast Harmonic Echo imaging to detect vascularity in hepatocellular carcinoma was compared to that of unenhanced color Doppler imaging by analzing results obtained using dynamic CT as a gold standard., Results: Contrast harmonic Echo imaging detected intratumoral vessels, tumor parenchymal stain, and perfusion defect in the early arterial phase, the late vascular phase, and the postvascular phase, respectively. In the late vascular phase, the subtraction image clearly delineated the tumor parenchymal strain. Intratumoral vascularity was detected in 25 (89%) of the hepatocellular carcinoma nodules by Contrast Harmonic Echo, compared with 15 (54%) when color Doppler imaging was used (p<0.05). The diagnostic sensitivity, specificity, and accuracy of Contrast Harmonic Echo were 96.1%, 100% and 96.4%, respectively, corresponding to results obtained using dynamic CT., Conclusion: Contrast Harmonic Echo imaging is superior to unenhanced color Doppler imaging in depicting intratumoral vessels and parenchymal stain, and agrees closely with results obtained with three-phase dynamic CT.

Purpose: To investigate the usefulness of contrast-enhanced Agent Detection Imaging in assessing intratumoral vasculature in hepatocellular carcinoma., Materials and Methods: Fourteen hepatocellular carcinoma nodules in 11 patients were studied with contrast-enhanced Agent Detection Imaging, a wide-band color Doppler imaging method, employing, Levovist(®), a microbubble contrast agent. High acoustic power was used with contrast-enhanced Agent Detection Imaging. Intermittent transmission of Agent Detection Imaging was performed at intervals of 200, 500, and 350 milliseconds in the early arterial phase (10 to 40 seconds), late vascular phase (1 to 3 minutes) and postvascular phase (5 to 7 minutes), respectively. The results were compared with those of three-phase dynamic CT., Results: Intratumoral blood vessels in the early arterial phase and tumor parenchymal stain in the late vascular phase were depicted in 12 (88%) of the 14 hepatocellular carcinoma nodules, while all nodules were demonstrated as perfusion defect in the postvascular phase on contrast-enhanced Agent Detection Imaging. The results of Agent Detection Imaging, that were compared with those of dynamic CT, were all 100% : diagnostic sensitivity (12/12), specificity (2/2), and accurary (14/14)., Conclusion: Contrast-enhanced Agent Detection Imaging is a promising method for depicting intratumoral vascularity in hepatocellular carcinoma.

Objective: To evaluate the usefulness of contrast-enhanced power Doppler imaging with the personal ultrasound imager in depicting intratumoral vascularity in hepatocellular carcinoma., Materials and Methods: Contrast-enhanced power Doppler imaging was used to examine 52 hepatocellular carcinoma nodules in 29 patients, using both the personal ultrasound imager and the conventional ultrasound machine in combination with intravenous injection of Levovist(®). Results obtained using dynamic CT were used as the gold standard. The ability of the personal ultrasound imager to detect intratumoral vascularity was compared with that of the conventional ultrasound machine, and the usefulness of the personal ultrasound imager in assessing therapeutic effect after nonsurgical treatment was compared with that of dynamic CT at the same time., Results: The personal ultrasound imager and the conventional ultrasound machine, using the fundamental power Doppler imaging mode (p=0.13) and contrast-enhanced power Doppler imaging mode (p=0.41), did not differ significantly in depicting the vascularity of the 52 hepatocellular carcinomas. The sensitivity, specificity, and accuracy of contrast-enhanced power Doppler imaging on the personal ultrasound imager were 95.5%, 87.5%, and 94.2%, respectively, in close agreement with results obtained using dynamic CT. After the 22 hepatocellular carcinomas were treated, the personal ultrasound imager provided diagnostic accuracy of 90.9% on residual tumors when compared with results obtained by dynamic CT, and results obtained using the conventional ultrasound machine were similar., Conclusion: The highly portable personal ultrasound imager using Levovist(®)-enhanced power Doppler imaging can clearly depict the intratumoral vascularity of hepatocellular carcinoma nodules before and after treatment, achieving results very close to those obtained using the conventional diagnostic ultrasound machine. The personal ultrasound imager is an alternative to the conventional ultrasound machine for depicting tumor vascularity.

Purpose: To investigate the usefulness of contrast advanced dynamic flow imaging and contrast pulse subtraction imaging in the intranodular hemodynamics of hepatic tumors., Materials and Methods: Ten patients underwent contrast advanced dynamic flow imaging and contrast pulse subtraction imaging using Levovist(®), a microbubble contrast agent. Fourteen hepatic tumor nodules were studied: 9 were hepatocellular carcinoma, 1 metastasis, 1 hemangioma, 1 adenomatous hyperplasia, and 2 metastatic lymph nodes of hepatocellular carcinoma. Real-time scanning of contrast advanced dynamic flow imaging and intermittent interval-delay scanning of contrast pulse subtraction imaging were carried out in the early arterial phase, the late vascular phase, and the postvascular phase. The results obtained from contrast advanced dynamic flow imaging and contrast pulse subtraction imaging were compared with those obtained by precontrast power Doppler imaging and three-phase dynamic CT, respectively., Results: The rate of detection of intranodular vascularity by contrast advanced dynamic flow imaging (93%) or contrast pulse subtraction imaging (93%) was significantly higher than that of precontrast power Doppler imaging (29%) and was as high as that of dynamic CT. Characteristic intranodular hemodynamics were detected in hepatocellular carcinoma, metastasis, hemangioma, and adenomatous hyperplasia with typical appearance of an intranodular blood vessel image in the early arterial phase, a parenchymal stain image in the late vascular phase, and a perfusion defect image in the post-vascular phase., Conclusion: Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging clearly show the intranodular hemodynamics in hepatic tumors.

Hepatocellular adenoma sometimes causes intraperitoneal hemorrhage. It is, however, rare for small hepatocellular adenoma to cause intrahepatic huge hemorrhage without intraperitoneal bleeding. Here we describe such a rare case of hepatocellular adenoma with huge intrahepatic hemorrhage in a 25-year-old female, who had taken oral contraceptives for the last 2 weeks. She was admitted to our hospital with a sudden onset of right-upper-quadrant abdominal pain and temporally fell in shock state. Plain CT depicted low density area measuring more than 13 cm in diameter in the right lobe of the liver. Huge tumor was also suggested by abdominal ultrasound, contrast enhanced CT, magnetic resonance imaging (MRI) and angiography. The patient was diagnosed as intrahepatic rupture of hepatic tumor. Because of the risk of re-hemorrhage and malignancy, she underwent right hepatic lobectomy. Histopathologial examination of the resected specimen showed a typical small hepatocellular adenoma with the surrounding huge hematoma in the liver. The case presented here is very rare but seems to be suggestive to the natural course and management of hepatocellular adenoma.

Objective: To determine if the image quality of a personal ultrasound imager (PUI) is as good as that of a conventional machine (CM)., Materials and Methods: Ninety patients were studied by the same operator using both the PUI and CM. The quality of the B-mode images obtained from these patients was scored 0, 1 or 2, defined as poor, fair, or good, respectively. Liver-tumor vascularity depicted by power Doppler imaging (PDI) and directional PDI (DPDI) was classified as 0, no blood signal; 1, dot-like blood signal within the tumor; 2, mild blood-flow signal within the tumor; and 3, abundant blood-flow signal within the tumor., Results: The mean score of PUI and CM B-mode image quality was 7.47±0.92 and 7.54±0.99 (mean±SD), respectively (p=0.531). On PDI, grade of vascularity of the liver tumors determined with the PUI was 4.44 and 4.68 in those determined with the CM (p=0.78). On DPDI, tumor vascularity was 3.12 when scored by the PUI and 4.29 when scored with the CM (p=0.03). The qualities of images acquired by the PUI and CM were significantly correlated., Conclusion: The quality of B-mode images acquired using the PUI and CM are statistically the same, and they share a similar ability to detect intratumoral blood-flow signals on PDI. Because of its extreme portability, the PUI is expected to become a valuable diagnostic tool in the clinic.

Purpose: To assess the reliability of contrast material-enhanced real-time gray-scale ultrasonography (US) in evaluating posttreatment response of hepatocellular carcinoma (HCC)., Materials and Methods: Fifty HCC nodules were examined with contrast-enhanced coded phase-inversion harmonic US before and after treatment. Intratumoral vascularity was assessed with continuous imaging in the early arterial phase and with interval-delay scanning to depict tumor parenchymal flow during the blood pool phase. Vascular findings at US were compared with those at dynamic computed tomography (CT)., Results: In 50 HCC nodules before treatment, positive enhancement of tumor vessels and tumor parenchymal flow (stain) were observed in 47 (94%) and 46 (92%), respectively. Either tumor vessel or stain was visualized with coded harmonic US in 49 of 50 nodules. Eighty-one coded harmonic US studies were performed in 49 posttreatment HCC nodules. Compared with dynamic CT, the sensitivity, specificity, and accuracy of coded harmonic US in helping to detect positive enhancement in pretreatment HCC were 98% (49 of 50), 100% (50 of 50), and 98% (49 of 50), respectively. After treatment, positive enhancement of tumor vascularity was observed in 39 (48%) of 81 posttreatment studies, and no enhancement was observed in others (52%). Coded harmonic US demonstrated partial and no enhancement of tumor vascularity in four and one nodule, respectively; after transcatheter arterial embolization with iodized oil, evaluation of tumor vascularity with dynamic CT was difficult because of the presence of oil., Conclusion: With enhancement, coded harmonic US depicted tumor vascularity by showing tumor vessels in a real-time fashion at continuous imaging and tumor parenchymal flow at interval-delay scanning.

Purpose. To evaluate the detectability of tumor vascularity in hepatic tumors by second harmonic imaging with the administration of a microbubble contrast agent, Levovist. Materials and methods: Twenty-four patients with hepatic tumors (21 hepatocellular carcinoma, one focal nodular hyperplasia and two liver metastasis) were studied using Aloka SSD 5500 with the administration of Levovist. Intermittent harmonic gray-scale imaging (HGSI) and intermittent harmonic power Doppler imaging (HPDI) were performed on every tumor and the detectability of the two harmonic imaging modes were compared with that of dynamic CT. Results: Tumor vessels and tumor parenchymal blood flow were obtained in hypervascular tumors in the early arterial phase, and metastasis presented peripheral enhancement. When dynamic CT was taken as a gold standard, the sensitivity, specificity and accuracy of detecting tumor vascularity for intermittent HGSI were 55.6, 100 and 66.7%, and for intermittent HPDI were 83.3, 100 and 87.5%, respectively. The difference of detectability between the two modes was statistically significant (P<0.05). Depth of the lesion from the abdominal wall was a major factor affecting the detectability of tumor vascularity. Conclusion: With the administration of Levovist, intermittent HPDI was more sensitive than intermittent HGSI to demonstrate tumor vessels and tumor blood flow. Second harmonic imaging with Levovist would be a promising valuable means for investigating specific vascular features in hepatic tumors.

Purpose: To assess the effectiveness of contrast material-enhanced intermittent harmonic Doppler ultrasonography (US) in depicting tumor vessels and tumor parenchymal flow (stain) in hepatocellular carcinoma (HCC)., Materials and Methods: Fifty-eight patients with 65 HCC nodules were examined by using intermittent harmonic power Doppler US and digital subtraction harmonic B-mode US, both with intravenous administration of SH U 508A. Vascular findings at early arterial phase harmonic US were classified as positive enhancement or nonenhancement, depending on the tumor vascularity relative to the surrounding liver parenchyma. These results were compared with those of three-phase helical dynamic computed tomography (CT)., Results: For hypervascular HCCs, there was excellent depiction of tumor vessels and tumor stain with the two intermittent harmonic US methods. The sensitivity and specificity for depiction of tumor vascularity were 93% (41 of 44 nodules) and 100% (21 of 21), respectively, with intermittent harmonic power Doppler US and 86% (38 of 44) and 100% (21 of 21), respectively, with subtraction US, as compared with these values at dynamic CT. Attenuation was an important factor in the depictability of tumor vascularity at harmonic US., Conclusion: Contrast-enhanced intermittent harmonic US enables noninvasive demonstration of tumor vessels and especially tumor stain in HCC.

Objective: Our objective was to assess the usefulness of contrast-enhanced subtraction harmonic sonography in evaluating the treatment response of patients with hepatocellular carcinoma., Subjects and Methods: Thirty-two hepatocellular carcinoma lesions in 26 patients (age range, 44-85 years; mean age, 66 years) were examined with Levovist-enhanced intermittent harmonic imaging before and after therapy. A Toshiba Powervision 8000 was used. A subtraction image was obtained by digitally subtracting the last-frame harmonic image from the first-frame image when multishot mode was preset. Results of contrast-enhanced CT were compared with the results of subtraction harmonic imaging., Results: Before therapy, an enhancement pattern of tumor vascularity was seen for 93.8% (30/32) of hepatocellular carcinoma nodules on subtraction harmonic imaging. After therapy, subtraction harmonic imaging showed 46.7% (14/30) enhancement (incomplete tumor necrosis) and 53.3% (16/30) no enhancement (complete tumor necrosis). When dynamic CT was the gold standard, the sensitivity, specificity, and accuracy of subtraction harmonic imaging were 93.3%, 100%, and 96.7%, respectively. Intratumoral flow signals in hepatocellular carcinoma after therapy on harmonic imaging were used as a guide to target additional percutaneous therapy., Conclusion: Digital subtraction contrast-enhanced harmonic imaging can depict tumor vascularity in hepatocellular carcinoma after therapy sensitively and accurately. Because it is easy to perform and provides real-time needle insertion guidance, it may be preferable to perform after localized therapy to monitor treatment response, which will reduce unnecessary CT scanning.