Super-selective injection of propofol into the intracranial arteries enables Patient's self-evaluation of expected neurological deficit.

INTRODUCTION: It is hard to realize the extent of the expected postoperative neurological deficit for patients themselves. The provision of appropriate information can contribute not only to examining surgical indications but also to filling the gap between patient and expert expectations. We hypothesized that propofol infusion into the intracranial arteries (ssWada) could induce focal neurological symptoms with preserved wakefulness, enabling the patients to evaluate the postsurgical risk subjectively. METHODS: Presurgical evaluation using ssWada was performed in 28 patients with drug-resistant epilepsy. Based on anatomical knowledge, propofol was super-selectively infused into the intracranial arteries including the M1, M2, and M3 segments of the middle cerebral artery (MCA), A2 segment of the anterior cerebral artery, and P2 segment of the posterior cerebral artery to evaluate the neurological and cognitive symptoms. We retrospectively analyzed a total of 107 infusion trials, including their target vessels, and elicited symptoms of motor weakness, sensory disturbance, language, unilateral hemispatial neglect (UHN), and hemianopsia. We evaluated preserved wakefulness which enabled subjective evaluations of the symptoms and comparison of the subjective experience to the objective findings, besides adverse effects during the procedure. RESULTS: Preserved wakefulness was found in 97.2% of all trials. Changes in neurological symptoms were positively evaluated for motor weakness in 51.4%, sensory disturbance in 5.6%, language in 48.6%, UHN in 22.4%, and hemianopsia in 32.7%. Six trials elicited seizures. Multivariate analysis showed significant correlations between symptom and infusion site of language and left side, language and MCA branches, motor weakness and A2 or M2 superior division, and hemianopsia and P2. Transient adverse effect was observed in 8 cases with 12 infusion trials (11.2 %). CONCLUSION: The ssWada could elicit focal neurological symptoms with preserved wakefulness. The methodology enables specific evaluation of risk for cortical resection and subjective evaluation of the expected outcome by the patients.

Somatosensory evoked spikes in normal adults detected by magnetoencephalography.

OBJECTIVE: Somatosensory evoked spikes (SESs) have been reported only in children aged under 14 years and are considered as an age-dependent phenomenon. However, we detected SESs in adult patients with epilepsy using magnetoencephalography (MEG). The present study investigated whether MEG can detect SESs in normal adults. METHODS: Spontaneous MEG was recorded during measurement of somatosensory evoked fields (SEFs) for bilateral electrical median nerve stimuli in 30 healthy adults. RESULTS: Bilateral SESs were observed in 10 adults but none in the other 20 subjects. SESs consisted of one or two peaks, and the first peak latency corresponded to that of the second peak (M2) of SEFs. The first SES peak was identical to the M2 in isofield map pattern, as well as location and orientation of the equivalent current dipole (ECD). M2 ECD strength in the 10 subjects with SESs was larger (p <0.0001) than in 20 without SESs. CONCLUSIONS: All-or-nothing detection of bilateral SESs by MEG in normal adults must depend on the signal-to-noise issue of symmetrical SEFs and background brain activity. SIGNIFICANCE: Our results further confirm the higher sensitivity of MEG compared to scalp EEG for the detection of focal cortical sources tangential to the scalp such as SESs.

Language MEG predicts postoperative verbal memory change in left mesial temporal lobe epilepsy.

OBJECTIVE: To clarify whether preoperative language magnetoencephalography (MEG) predicts postoperative verbal memory (VM) changes in left mesial temporal lobe epilepsy (LMTLE). METHODS: We reviewed 18 right-handed patients with LMTLE who underwent anterior temporal lobectomy or selective amygdala hippocampectomy, 12 with (HS+) and 6 without hippocampal sclerosis (HS-). Patients underwent neuropsychological assessment before and after surgery. MEG was measured with an auditory verbal learning task in patients preoperatively and in 15 right-handed controls. Dynamic statistical parametric mapping (dSPM) was used for source imaging of task-related activity. Language laterality index (LI) was calculated by z-score of dSPM in language-related regions. LI in the region of HS+ and HS- was compared to controls. The correlation between LI and postoperative VM change was assessed in HS+ and HS-. RESULTS: Preoperative LI in supramarginal gyrus showed greater right-shifted lateralization in both HS+ and HS- than in controls. Right-shifted LI in supramarginal gyrus was correlated with postoperative VM increase in HS+ (p = 0.019), but not in HS-. CONCLUSIONS: Right-shifted language lateralization in dSPM of MEG signals may predict favorable VM outcome in HS+ of LMTLE. SIGNIFICANCE: Findings warrant further investigation of the relation between regional language laterality index and postoperative verbal memory changes.

Referral odyssey plot to visualize causes of surgical delay in mesial temporal lobe epilepsy with hippocampal sclerosis.

The "odyssey plot" was used to visualize referral delays in epilepsy surgery. Participants were 36 patients (19 males; 13-67 years, median 27 years) with mesial temporal lobe epilepsy with hippocampal sclerosis (HS) who underwent resection surgery. The "referral odyssey plot" included five clinical episodes: seizure onset (T1), first visits to a non-epileptologist (T2) and to an epileptologist (T3), first admission to our epilepsy monitoring unit (EMU) (T4), and resection surgery (T5). For each patient, we identified the first seizure type: the physician who first diagnosed focal aware seizure (FAS), focal impaired awareness seizure (FIAS), focal to bilateral tonic-clonic seizure (FBTCS), and radiologically suspected HS. Within the overall delay (T1-T5, median 18 years; interquartile range [IQR] 14), non-epileptologist's delay (T2-T3, 11.5 years; IQR 12.25) was far (p < 0.0001) longer than patient's (T1-T2, 0 year; IQR 2.25), epileptologist's (T3-T4, 1 year; IQR 4), or after-EMU delay (T4-T5, 1 year; IQR 1). FAS onset cases had significantly longer T1-T2 (N = 5, median 7 years; IQR 6) than FIAS (N = 22, 0 year; IQR 1, p < 0.005) or FBTCS onset cases (N = 9, 0 year; IQR 0, p < 0.001). FAS was correctly diagnosed first by non-epileptologists in 17.9%, by out-patient epileptologists in 35.7%, and at the EMU in 46.4%. FIAS was correctly diagnosed first by non-epileptologists in 94.4% and by out-patient epileptologists in 5.6%. Non-epileptologists diagnosed FBTCS in all cases. HS was diagnosed by non-epileptologists in 13.9%, by out-patient epileptologists in 47.2%, and at the EMU in 38.9%. Early referral to epileptologists is most critical for early surgery. Early utilization of the EMU is highly recommended because FAS is often overlooked by outpatient epileptologists. The odyssey plot will be useful to improve the healthcare system for other types of epilepsy.

Determination of language areas in patients with epilepsy using the super-selective Wada test.

The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the "super-selective Wada test" (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

Nanoscale-tipped wire array injections transfer DNA directly into brain cells ex vivo and in vivo.

Genetic modification to restore cell functions in the brain can be performed through the delivery of biomolecules in a minimally invasive manner into live neuronal cells within brain tissues. However, conventional nanoscale needles are too short (lengths of ~10 µm) to target neuronal cells in ~1-mm-thick brain tissues because the neuronal cells are located deep within the tissue. Here, we report the use of nanoscale-tipped wire (NTW) arrays with diameters < 100 nm and wire lengths of ~200 µm to address biomolecule delivery issues. The NTW arrays were manufactured by growth of silicon microwire arrays and nanotip formation. This technique uses pinpoint, multiple-cell DNA injections in deep areas of brain tissues, enabling target cells to be marked by fluorescent protein (FP) expression vectors. This technique has potential for use for electrophysiological recordings and biological transfection into neuronal cells. Herein, simply pressing an NTW array delivers and expresses plasmid DNA in multiple-cultured cells and multiple-neuronal cells within a brain slice with reduced cell damage. Additionally, DNA transfection is demonstrated using brain cells ex vivo and in vivo. Moreover, knockdown of a critical clock gene after injecting a short hairpin RNA (shRNA) and a genome-editing vector demonstrates the potential to genetically alter the function of living brain cells, for example, pacemaker cells of the mammalian circadian rhythms. Overall, our NTW array injection technique enables genetic and functional modification of living cells in deep brain tissue areas, both ex vivo and in vivo.

Possible spontaneous regression of hepatocellular carcinoma with unique histopathological features confirmed by surgical resection: a case report.

BACKGROUND: Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event, and its clinicopathological features and underlying mechanism are not fully understood. CASE PRESENTATION: An 84-year-old female with hepatitis C virus infection and diabetes mellitus was referred to our hospital for further examination. Abdominal ultrasonography showed a 3.4-cm solid tumor with a heterogeneous irregular center and no fibrous capsule in liver segment 8 (S8). An enhanced computed tomography (CT) scan revealed a tumor in S8 with heterogeneous enhancement in the arterial phase and washed out insufficiently in the portal and equilibrium phase. The enhanced pattern on magnetic resonance imaging was similar to that of CT. Although the imaging findings were not typical for HCC, liver resection (S8) was performed with HCC as the most probable diagnosis. Histopathological examination of the resected specimen showed that the tumor was well to moderately differentiated HCC with unique features. Approximately half of the tumor was composed of well-differentiated HCC that was focally accompanied by dense lymphocyte infiltration. The other half of the tumor was fibrotic tissue that resembled an inflammatory pseudotumor. Several foci of moderately differentiated HCC were scattered within the tumor with a nodule-in-nodule appearance, and the foci totally showed coagulative necrosis. On immunostaining, lymphocytes in the tumor stroma were positive for CD8 and programmed death 1. The expression of programmed death-ligand 1 was observed in carcinoma cells and macrophages specifically within the lymphocyte-rich area of HCC. CONCLUSIONS: We consider this case representative of spontaneous regression of HCC, and the immune response against HCC might contribute to tumor regression, leading to complex histopathological appearances. This case may provide insight into the mechanism of spontaneous regression of HCC.

Magnetoencephalography to confirm epileptiform discharges mimicking small sharp spikes in temporal lobe epilepsy.

OBJECTIVE: To determine whether magnetoencephalography (MEG) can identify epileptiform discharges mimicking small sharp spikes (SSSs) on scalp electroencephalography (EEG) in patients with temporal lobe epilepsy (TLE). METHODS: We retrospectively reviewed simultaneous scalp EEG and MEG recordings of 83 consecutive patients with TLE and 49 with extra-TLE (ETLE). RESULTS: SSSs in scalp EEG were detected in 15 (18.1%) of 83 TLE patients compared to only two (4.1%) of 49 ETLE patients (p = 0.029). Five of the 15 TLE patients had MEG spikes with concurrent SSSs in EEG, but neither of the 2 ETLE patients. Three of these 5 TLE patients had additional interictal epileptiform discharges (IEDs) in EEG and MEG. Equivalent current dipoles (ECDs) of MEG spikes with concurrent SSSs and IEDs showed no difference in temporal lobe localization and horizontal orientation, whereas ECD moments were smaller in MEG spikes with concurrent SSSs than those with IEDs. CONCLUSIONS: SSSs were more common in TLE than in ETLE. At least some morphologically diagnosed SSSs are true but low-amplitude epileptiform discharges in TLE which can be identified with simultaneous MEG. SIGNIFICANCE: Simultaneous MEG is useful to identify epileptiform discharges mimicking SSSs in patients with TLE.

Awake state-specific suppression of primary somatosensory evoked response correlated with duration of temporal lobe epilepsy.

Epilepsy is a network disease. The primary somatosensory cortex (S1) is usually considered to be intact, but could be subclinically disturbed based on abnormal functional connectivity in patients with temporal lobe epilepsy (TLE). We aimed to investigate if the S1 of TLE is abnormally modulated. Somatosensory evoked magnetic fields (SEFs) evoked by median nerve stimulation were recorded in each hemisphere of 15 TLE patients and 28 normal subjects. All responses were separately averaged in the awake state and light sleep using background magnetoencephalography. Latency and strength of the equivalent current dipole (ECD) was compared between the groups for the first (M1) and second peaks. Latencies showed no significant differences between the groups in either wakefulness or light sleep. ECD strengths were significantly lower in TLE patients than in controls only during wakefulness. The reduction of M1 ECD strength in the awake state is significantly correlated with duration of epilepsy. SEFs of TLE patients showed pure ECD strength reduction without latency delay. The phenomenon occurred exclusively during wakefulness, suggesting that a wakefulness-specific modulator of S1 is abnormal in TLE. Repetitive seizures may gradually insult the modulator of S1 distant from the epileptogenic network.

A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report.

Gastrointestinal stromal tumors are rare, and in pregnancy they are extremely rare. We present a case of a maternal gastrointestinal stromal tumor found in the second trimester of pregnancy. A 29-year-old woman, gravida 1 para 0, complained of bloody vomiting at 14 weeks of gestation. She had no significant medical history. We performed plain computed tomography and upper gastrointestinal endoscopy. Precise examination revealed a large mass in the stomach and an exposed blood vessel on the surface. An exposed blood vessel can be harmful for mother and fetus as it might rupture during the pregnancy. We performed a distal gastrectomy at 16 weeks of gestation. Histology confirmed a localized gastrointestinal stromal tumor with a high risk of recurrence, and adjuvant imatinib was recommended. The patient elected to delay adjuvant imatinib until after delivery. The postoperative and antenatal course was favorable, and the patient was followed up by ultrasound every 2 months after the operation. After she gave birth at 40 weeks of gestation, she started adjuvant imatinib 400 mg/day. There was no evidence of recurrence 1 year after surgery. There are no guidelines for the management of gastrointestinal stromal tumors in pregnancy. Given the treatment challenges, we believe that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine.

Sarcomatoid carcinoma of the pancreas with rare long-term survival: a case report.

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) tends to have similar or even worse prognosis than that of conventional pancreatic ductal adenocarcinoma. The clinical and pathological features of SCP remain poorly characterized owing to its rarity. CASE PRESENTATION: A 58-year-old man was admitted to our hospital with the chief complaints of upper abdominal pain and weight loss. Abdominal contrast computed tomography revealed a 5-cm low-density mass in the pancreatic body. Magnetic resonance cholangiopancreatography revealed an obstruction of the main pancreatic duct and a dilation of the distal main pancreatic duct. Based on the clinicoradiological findings, pancreatic body cancer was suspected, and the distal pancreatectomy was performed. A pathological examination revealed that the tumor was composed of an area of invasive ductal adenocarcinoma and an area of sarcomatous spindle-shaped cells; the latter component predominated. The spindle cells were immunohistochemically positive for both cytokeratin and vimentin, and thus, a pathological diagnosis of SCP was made. In addition, immunohistochemical analysis suggested the sarcomatous component might be derived from the adenocarcinoma component via the process of epithelial-mesenchymal transition. After the operation, the patient received 6 months of chemotherapy with gemcitabine. At 10 years after the operation, the patient is alive with no recurrence. CONCLUSIONS: The current case study presented a SCP patient with long-term survival after the operation. It was worth noting that the sarcomatous component of the tumor pathologically showed lower MIB-1 labeling index compared with those in previously reported SCP cases, which might account for the long-term survival of the patient.

Fundamental evaluation and optimization of porous spherical silica for developing functional fine particles via fluidized bed coating.

Particle coating, a taste-masking technique for drugs, is limited by its long manufacturing time, which is caused by the decrease in the spray rate required to prevent particle agglomeration. Mesoporous silica particles, which have a high surface area and pore sizes in the range of 2-50 nm, possess high surface free energy; they have attracted significant interest for numerous applications in adsorption, separation, and catalysis and drug delivery. A form of mesoporous silica, microbead silicate, can prevent particle aggregation because of its good water absorbency and drying properties. Hence, it has been suggested to be applicable for particle coating. This study evaluated the physical properties and drug release capability of microbead silicate with different pore sizes. Although microbead silicate with small pores displayed a rapid drug release profile, drug release was incomplete. Contrastingly, microbead silicate with large pores achieved complete drug release even with high drug loading. Furthermore, in the case of 100% layering, the porosity of microbead silicate was maintained, thus sufficiently preventing aggregation due to the prevention of formation of liquid bridging of the coating solution. These results suggest that using microbead silicate with large pores for particle coating enables complete drug release while improving manufacturability.

A comprehensive understanding of lowly-hydrolyzed polyvinyl alcohol-based ternary solid dispersions with the use of a combined mixture-process design.

We recently reported lowly hydrolyzed polyvinyl alcohol (L-PVA, 70-74% hydrolyzed, about 580 polymerized, JR-05) as a promising matrix for hot-melt extrusion (HME) due to its unique micelle formation ability compared to the most commonly used PVA (87-89% hydrolyzed, about 580 polymerized). In the present study, we focused on the effect of composition [indomethacin (IND), L-PVA, sorbitol] and process parameters (temperature and screw speed) on each response, i.e. processing torque, and physicochemical properties such as residual crystallinity, residual ratio, and area under the dissolution curve (AUDC) in supersaturated solution using a HME by applying the design of experiment (DoE) approach. To overcome the poor processability of L-PVA, given its semicrystalline nature, we applied sorbitol as a plasticizer and systematically and simultaneously evaluated its influence on the outputs based on the mixture design combined with process factors. Few studies have focused on comprehensive evaluation of the composition and HME process conditions because obtaining a design space requires numerous experiments. We found that incorporating sorbitol into the L-PVA greatly improved the processing torque. However, sorbitol negatively influenced the degree of residual crystallinity and the AUDC of IND. Lastly, we established a laboratory-scale design space that could achieve high supersaturation and ensure adequate miscibility between each component, using an acceptable processing torque for HME, by applying the minimum amount of sorbitol. These fundamental results suggest that sorbitol maximizes the potency of L-PVA as a carrier in HME.

Theoretical and practical evaluation of lowly hydrolyzed polyvinyl alcohol as a potential carrier for hot-melt extrusion.

Polyvinyl alcohol (PVA) is considered to be an unsuitable carrier for hot-melt extrusion (HME) due to its low processability. In this study, we focused on a lowly hydrolyzed PVA (JR-05, 70.0-74.0% hydrolyzed, L-PVA) to evaluate the potential use of L-PVA as a carrier for HME using the Hoftyzer and Krevelen method and thermodynamic models. These evaluations for drug-polymer systems based on the Flory-Huggins theory predicted the physicochemical properties of the solubility and miscibility between indomethacin (IND) and PVAs. Prior to initiating formulation studies, construction of IND and PVA phase diagrams provided guidance for design process conditions in HME. On the basis of the results of the validation studies, a conventional grade of PVA (JP-05, 87.0-89.0% hydrolyzed) is unlikely to be suitable as a carrier of HME due to its low plasticity, resulting in rapid recrystallization in the evaluation of in vitro dissolution and stability caused by poor miscibility. On the other hand, JR-05 demonstrated high processability, leading to the preparation of miscible extrudate with a high stability and an excellent in vitro dissolution profile due to its unique micelle-forming capability. These findings suggest that L-PVA brings about new carrier options among non-ionic polymers for HME.

[Neoadjuvant Proton Beam Chemoradiotherapy for Locally Advanced Gall Bladder Cancer-A Case Report].

A 67-year-old man visited our hospital due to progressing appetite loss and fever. He presented with a fist-sized palpable mass in his right hypochondrium. Abdominal CT showed a 10 cm diameter tumor that originated from the gall bladder infiltrating the abdominal wall, liver, duodenum, and colon. Blood tests revealed leukocytosis, elevated C-reactive protein level, and severe malnutrition. FDG-PET showed markedly high uptake in the tumor and diffuse uptake in the spine. Owing to the inability of oral intake, he underwent laparoscopic gastrojejunostomy and intraoperative tumor biopsy, which demonstrated pathologically G-CSF-producing carcinoma in the gall bladder. For the rapidly progressive tumor, he underwent proton beam chemoradiotherapy as preoperative treatment. The tumor markedly shrunk with dramatic improvement of his inflammatory and nutritional status. Consequently, R0 resection could be performed by combination surgeries of right hemi-colectomy, pancreatoduodenectomy, and partial liver resection. He received adjuvant chemotherapy and was alive without recurrence 12 months after tumor resection. To our knowledge, this is the first report of the use of neoadjuvant proton beam chemoradiotherapy in biliary cancer.

Identification of molecular-interaction sites between lowly hydrolyzed polyvinyl alcohols and indomethacin by NMR spectroscopy.

To evaluate the potency of hydrolyzed polyvinyl alcohols (PVAs) as matrices for solid dispersion (SD) formulations, we examined their inhibitory effects on precipitation of a poorly water-soluble drug, indomethacin (IND). Additionally, to clarify their mechanism, we investigated the intermolecular interaction of IND with PVAs in the supersaturated aqueous solution of IND. In the present study, we used five kinds of PVAs, i.e. JR-05 (70.0-74.0% hydrolyzed), JL-05E (80.0-84.0% hydrolyzed), JP-05 (87.0-89.0% hydrolyzed), JT-05 (93.5-94.5% hydrolyzed) and JF-05 (98.0-99.0% hydrolyzed). Of various PVAs, the lowly hydrolyzed PVAs such as JR-05 and JL-05E dramatically inhibited the precipitate formation of IND. Interestingly, the lowly hydrolyzed PVAs possessed micelle-forming ability, and inhibited the nucleation and crystal growth of IND. Moreover, strong hydrophobic interactions between vinyl acetate unit of lowly hydrolyzed PVA and hydrophobic moiety of IND were suggested based on the results of nuclear magnetic resonance (1H NMR) and nuclear overhauser effect spectroscopy (NOESY) in deuterium oxide. To the best of our knowledge, this is the first report describing the inhibitory effects of the hydrolyzed degree of PVAs on the precipitation of a drug, and demonstrating the intermolecular interaction between PVAs and a drug using NOESY in water.

Ultrastretchable Kirigami Bioprobes.

An ultrastretchable film device is developed that can follow the shape of spherical and large deformable biological samples such as heart and brain tissues. Although the film is composed of biocompatible parylene for the device substrate and metal layers of platinum (Pt)/titanium (Ti), which are unstretchable materials, the film shows a high stretchability by patterning slits as a "Kirigami" design. A Pt/Ti-microelectrode array embedded in 11 µm thick parylene film with 5 × 91 slits exhibits a film strain of ≈250% at 9 mN strain-force (0.08 MPa in stress) with a Young's modulus of 23 kPa, while the 3 × 91-slit film shows a Young's modulus of 3.6 kPa. The maximum strains of these devices are ≈470% and ≈840%, respectively. It is demonstrated that the Kirigami-based microelectrode device can simultaneously record in vivo electrocorticogram signals from the visual and barrel cortices of a mouse by stretching the film and tuning the electrode gap. Moreover, wrapping the Kirigami device around a beating mouse's heart, which shows large and rapid changes in the volume and the surface area, can record the in vivo epicardial electrocardiogram signals. Such a small Young's modulus for a stretchable device reduces the device's strain-force, minimizing the device-induced stress to soft biological tissues.

[A Case of Pathological Complete Response Following Neoadjuvant Chemotherapy with Gemcitabine plus Nab-Paclitaxel in Borderline Resectable Pancreatic Cancer].

We report a resected case with a pathological complete response(pCR)after neoadjuvant chemotherapy for borderline resectable pancreatic cancer(BRPC). A 67-year-old woman who had been treated for type 2 diabetes mellitus in our hospital presented with an exacerbation of diabetes. An abdominal CT scan confirmed a hypovascular mass in the pancreas body consistent with BRPC. After 3 courses of chemotherapy with gemcitabine plus nab-paclitaxel(GnP), her elevated DUPAN-2 level normalized. A follow up CT scan revealed that the tumor had decreased in size, and no distant metastasis was detected. Distal pancreatectomy with en-bloc celiac axis resection was performed. Histopathological examination of the resected specimens showed no evidence of residual cancer cells(pCR). The patient remains disease-free 8 months after surgery. Neoadjuvant GnP chemotherapy may be useful for BRPC.

Development of an ATP and hydrogen ion image sensor using a patterned apyrase-immobilized membrane.

A bio-image sensor using a patterned apyrase-immobilized membrane was developed to visualize the activities of adenosine triphosphate (ATP) and H+ ion in real-time. An enzymatic membrane patterning technique was suggested to immobilize apyrase on a specific sensing area of a charge coupled device (CCD)-type image sensor. It was able to observe the spatiotemporal information of ATP and H+ ion. The smallest size of a patterned membrane is 250×250µm2. The fabrication parameters of the patterned membrane, such as its thickness and the intensity of the incident light used for photolithography, were optimized experimentally. The sensing area under the patterned apyrase-immobilized membrane revealed a linear response up to 0.6mM of ATP concentration with a sensitivity of 37.8mV/mM. Meanwhile, another sensing area without the patterned membrane measured the diffused H+ ion from nearby membranes. This diffusion characteristics were analyzed to determine a measurement time that can minimize the undesirable impact of the diffused ions. In addition, the newly developed bio-image sensor successfully reconstructed ATP and H+ ion dynamics into sequential 2-dimensional images.

Nanoscale-Tipped High-Aspect-Ratio Vertical Microneedle Electrodes for Intracellular Recordings.

Intracellular recording nanoscale electrode devices provide the advantages of a high spatial resolution and high sensitivity. However, the length of nanowire/nanotube-based nanoelectrodes is currently limited to <10 µm long due to fabrication issues for high-aspect-ratio nanoelectrodes. The concept reported here can address the technological limitations by fabricating >100 µm long nanoscale-tipped electrodes, which show intracellular recording capability.